Proposed Changes to the Federal Regulations for Human Research (Common Rule) – Chicago

Proposed Changes to the Federal Regulations for Human Research (Common Rule) – Chicago


Good Morning. We are live from Evanston, Illinois just outside of Chicago with the fourth of five listening sessions regarding the proposed changes to the federal regulations for human research. Welcome Hello.Welcome live folks and welcome to those people live streaming in. Good Morning. As I said, this is the proposed changes to the federal regulations.the fourth of fifth, fourth of five listening sessions We want to get your comments and input and questions to our expert panelists regarding Common Rule and the changes that are being proposed during the open session. We have the agenda for today which may come upon your screen.There’ll be a break after our first two panelists and during that time, those of you who are streaming in will hear music, and trust us that we are still here. And there’s your agenda After our first few panelists, there will be a short break, you’ll hear some music. We will go back into our session at 10:15 and then there’ll be a working lunch again during that time you will also hear some music Rest assured that we are still here, and we’ll pick right back up at the time according to your schedule We are scheduled to go until two o’clock and we hope to hear from you. The goal for today’s meeting, of course we always encourage you to ask questions throughout the day. For the folks that are here live Getting some instructions here live. We do actually ask you to ask questions during the day. You can either comment those.You can ask them if you are here in person live, there’s two microphone stands that we have. We also have two podiums that have bowls with comment cards or question cards. Feel free to write those down and put those in the bowl and we’ll address those to the panelists. And for those of you who are streaming live, you can tweet your questions, you can email your questions. We’ll get to those the way that you can do those. The goals of today’s meeting are to provide helpful background information about the changes, provide overview of the proposed changes, review the changes related to the scope of the Common Rule the exclusions and the exemptions, and to provide some expert perspective on these changes. We encourage again you to ask questions. We want … our experts here in the house. And we want to promote and encourage you to officially send submissions and comments to OHRP. We do want to let you know that the comments and questions and discussions that occur during the live session and these streaming sessions are not official comments posted to the Common Rule or OHRP. To post a comment officially to the docket on line you have to go to http:\www.regulations.gov. You enter HHS-OPHS-2015-0008 in the enter keyword or id field and then click on “search.” On that next web page you can click on submit a comment and follow those instructions. That will formally your comment, your question, your concern into the formal proposed changes section which will be addressed by the OHRP. You may also mail those to the Office for Human Research Protection Jerry Menikoff, MDJD at OHRP 1101 Wooton Pkwy. Suite 200 in Rockville Maryland 20852 Again, you can post your comments or tweet them @commonrule2015 #asknprm We will get those live here and address those as time permits. or you can email your questions to [email protected] and we can again get to those immediately if we have time during today’s session. For those of you who are live here we have Hilton meeting network access for your smart products. User id is Vanderbilt1, password, Hilton1 if you forget that … the program today you can look at the back of your name tag. There is no prize there, but you can have free access. Wonderful. As we said, this is the fourth meeting. We have one remaining meeting on November 18. the wonderful thing is that you can actually go online If you’ve attended any of these sessions and … live stream as well as the presentations will be there for you so you can review information that’s been exchanged at any of these meetings and send in your comments as we’ve described. Ok, we’d like to acknowledge the partners today. Got the National Center for Advancing Translational Science, NCATSI am the chief program officer at Nashville Cares. We are very happy to be here. OHRP We also have from NIH, Michelle Culp here with us live we appreciate you being here helping us out. The CTSA Science Awards Clinical Trials Transformation Initiative The Center for Information and Study for Clinical Research Participation, and if I failed to mention them, The Genetic Alliance. OK Some quick housekeeping. Those who are here in person, up the stairs to the left are the restrooms. For those live streaming, do you best. If you missed anything these live, the live intersersections will be the live sessions that have been streamed can be restreamed and you can review those at your leisure. OK If we don’t have anything else we will get on with our first expert panelist to help us get some information and to hopefully elicit comments questions, concerns while we have folks here who can help answer those questions for those of you liveand for those of you who are streaming in today. OK. Our first expert panelist who will be talking about the changing landscape of research is Ms. Stephanie Guzik. Stephanie Guzik is the Director of Research Compliance and the Research Integrity Officer at Rush University Medical Center located in Chicago. In these roles, Stephanie oversees auditing and review of research activities to promote quality assurance and compliance with federal, state, and university policies for human subjects research. Ms Guzik has over fifteen years in research administration. And is involved with the development of research compliance policies and procedures in response to the rapidly evolving state and federal laws and regulations. She has substantial experience in internal investigation, external audits, interpreting complex federal and state statutes. In addition, Stephanie investigates allegations of scientific misconduct. Please give me your attention and you applause for our first speaker, Ms. Stephanie Guzik Thank you very much. I’m delighted to be here today. And I wanted to welcome all of you on behalf of the three Chicago-land area clinical and translational science award sites. Those sites are the University of Illinois at Chicago, Northwestern University and the University of Chicago, which our Rush University Medical Center is an affiliate. So today I’m going to talk to you about the current landscape for human research protection and give you some history on how those rules and regs came to play. So my talk today is very general and so…….in the know… but this talk is really geared towards our general population so they can be afforded the knowledge to make a public…of the changes of these rules so. Let me get started. So research has been going on for a very very long time. As early as 1747 where James Lind found that the addition of citrus fruit to the diet of sailors prevented scurvy. And what he did was very intuitive, where he took some different groups of sailors and he modified their diet. And he found that the diet of those sailors that had citrus as an addition to their diet did not have scurvy. And so it took about 50 years for the British navy to implement the lime juice to every sailor’s diet. So now we have that corpular phrase that says for the English we call them Limeys. So that’s how we came to that term. But what’s important to know about that research is that he took different groups and added therapies and determined that one therapy was better than the other. And so the other individual is James Amberson.. And Dr. Amberson and his colleagues were treating patients with tuberculosis. And so what he did was a five hundred bed unit and what they thought there was a therapy that was a gold derivative. And this derivative, they thought, could help patients with tuberculosis. And so what Dr. Amberson and his colleagues did was they flipped a coin, randomly assigning experimental therapy against current treatment. Current therapy at that time. And so in modern clinical trials we call that randomization. So that means by random assignment these patients will get current therapy vs. what’s current therapy – excuse me – experimental therapy versus current therapy. And so, some of the reasons why we have research rules and regulations today are because we have some black eyes in history. We have some unethical practices in the way that we have conducted research in the past. So I’m going to talk to you today about some examples of those unethical behaviors and testing on human subjects. And so one of them is called the The Tuskeegee Study of Untreated Syphilis in the Negro Man. And then, so this study was to treat syphilis and the life cycle of syphilis from early stages to the late stages. This study was conducted in Alabama on sharecroppers. And these, the study was supposed initially for six months. Alright, they were going to evaluate these individuals for six months. And what turned out was that they looked at these patients for forty years. And it was a government funded study. And there are some problems with this because these folks were poor. They were sharecroppers. And the study offered them for their participation in the research, free meals, free medical care, and burial expenses. And so for these individuals, at that time that seemed like such a great thing to get, cause they didn’t have a lot of resources. So today we would consider that a type of coercion.The other problem with this study was that these patients underwent suffering. They had what’s called, what they called at that time, spinal shots, which were really spinal taps though without anesthesia. And that’s a painful procedure.So they experienced pain and suffering as part of their participation in the trial. And so, what also is a very big problem in the conduct of this trial, is that during the course of the trial, forty years, they discovered a treatment for syphilis. And that treatment is penicillin. And instead of giving these patients penicillin, which they promised medical care, remember, when they signed up they said we’ll give you medical care They did not give them penicillin and they continued to monitor the late stages of syphilis and there were several men who died as a result. And those deaths could have been prevented if they would have received the treatment. Another black eye in history would be the Willowbrook School School hepatitis experiment. And these experiments were conducted on mentally challenged children. And so, what had happened in that time. There was a high incidence of hepatitis in that state school and it was really, not really a school, but a sanitarium. And these patients were mentally retarded, they had a high incidence of hepatitis. And what they determined was that, well, there’s a high probability that they’re gonna contract hepatitis, and so therefore we’re going to infect them with hepatitis. and see whether or not this proposed treatment would help or prevent hepatitis from being contracted. And so these children were not asked if they, they weren’t presented with a choice of participating in the trials. And that’s unethical ? indeed Another problem with some of the research we’ve done in the past would be the human experiments at the Holmesburg Prison. And there’s a book that’s called “Acres of Skin” you can see on the slide, and that was dermatological so skin treatments, that were performed on inmates. On prisoners. So these prisoners were paid for their participation in the trial. However they were compromised. They were prisoners. How could they say no? So what had happened during that time as well as the problem is that they suffered because they were subject to biopsies, and rashes, and awful experiments on their skin that were painful. So again, we placed these patients at higher risk and harm. And we shouldn’t be doing that in research. Which brings me to the book title that’s called Doctors’ Hell. Which was written by a woman named Vivien Spitz, who I was fortunate enough to meet before she died. And she was a court reporter during the Nazi trials. And I’m gonna talk to you in the next slide about what had happened. So during World War Two there were experiments on the prisoners in concentration camps. And there were 23 doctors and scientists that were accused of performing unethical behavior, in fact, torture, on prisoners in concentration camps. And so what had happened was in 1944 excuse me, 1945, a coalition of representatives the US government Great Britain, the Soviet Union, and France came together and formed a tribunal. A military tribunal, and they came together to prosecute the doctors and scientists that had conducted some of these trials. Now some of the information that we know today about certain things like hypothermia, blunt force trauma, how to treat a gunshot wound, These are some of the things that we know because of the experiments that were conducted on prisoners in the concentration camps. However it was unethical research. And so during this Nuremberg Trial formally the doctor’s trial that was called United States vs. Karl Brandt. Karl Brandt was the personal physician of Adolf Hitler. And so during the trial it brought to light some of the horrors of the medical experiments on human beings. And so one of the principals was there was no informed consent. We harmed people in the process and some of the experiments did not benefit anybody. And so, during the time of these experiments, Germany had already had an ethical code on how to conduct research. It was a code, it was a guideline, it was not law. However, what was found in the end during the prosecution was that the experiments that were done definitely did contribute to current therapies, however the were used in a way on human experimentation because of political and racial issues. Not because of the spirit of medicine. And so the defense’s argument was that the experimentation on human beings had been accepted medical procedure. They asked a question, they answered the question. However, the way they went about it of course was very wrong. And of the 23 scientists and doctors that were prosecuted, 15 were convicted of murder, torture, and other atrocities committed in the name of medical science. And so to address this, in 1947 the Nuremberg Code was established. And so to address these issues, this group of lawyers and judges from around the world met and created this code. And the code is named after the area where the code was formed in Nuremberg, Germany. And so the Nuremberg Code states that participation in the research trial is voluntary. That means that you don’t have to do it if you don’t want to. And that if you do participate you can withdraw at any time without penalty. When conducting research it must benefit society. It also must justify the risk that may be incurred as part of the trial. We should minimize risks to patients and their suffering at all times during the conduct of the trial. And that research should not cause death or debilitating injury. And that medical research needs to be done by those who know how to do it properly and ethically. So those scientists and researchers must be trained accordingly. And in 1964 it was the next major step to refining our research rules and regulations. And that was the declaration of Helsinki. And again, it was named after the city where these principles were added to the code. And the principles that were added were that the researcher has a duty to protect the life, health privacy and dignity of human participants. That the research must be sound based in science, on previous work in the laboratory and on animals, and then on humans. And that there needs to be a good balance of risk versus benefits. And so those principles that were added are the consent to be in writing . So a participant can look at it and refer to it. That the research should follow a written plan or protocol. And so that if there are changes to the plan or protocol it needs to be written down. Needs to be formalized. That research must use strong scientific principles and be based on previous studies. So again, from the laboratory, then on animals, then on humans. So we know a lot of the risk and benefit to the research based on past studies. Those risks outweigh, excuse me, the benefits outweigh the risks . And that this is the first time where we hear about an independent committee. S o an independent committee that’s not associated with the research that’s being conducted should review the proposed research study. And so at the time that the public became aware of the Tuskegee trials in 1972 the Belmont report was established. And the Belmont Report was really the fundamental guiding principle of what we have today in the Common Rule. And so, there are three guiding principles, and you’ll hear this today with changes to the Common Rule they’re based on these three principles. Number one is respect pesons. Respect for persons meaning that you afford them their right to have an informed choice in participating in the research. It further goes on to talk about the informed choice They need to have enough time to make that choice. They shouldn’t feel pressured or have coercion to make that decision. That there’s benefit.The benefit to possibly them or society in general. And beneficence also insuring that you are not harming them during the conduct of the trial. And that we’re protecting them. So in the example I gave you of Tuskegee, we didn’t protect those patients because we knew we had treatment for them during the conduct of the trial which was penicillin. And we didn’t protect them or help them we continued to research – do research on them. So, the last principle is justice. And justice means that there is a proper risk benefit based, based on equitable distribution of patients, meaning that you have a good representation of all of humanity in the trial and that regardless of their race or ethnicity. And so the Common Rule is our official federal law that implements those principles from the Belmont Report of beneficence, justice, respect. And so the law defines that research and human subjects it makes more definitions and I’m gonna talk about those definitions in a few minutes. And calls for the research institution to establish an oversight committee, which is what we know today as an Institutional Review Board or an IRB. Sometimes also know as an ethics committee. And so it describes about how the IRB needs to review and approve research, how the IRB should be composed, and it also outlines special protections for vulnerable subjects. And those vulnerable subjects include children, pregnant women, and prisoners. And so it also further goes on to provide guidelines for informed consent. And so there are several elements that need to be in an informed consent. Things like risk benefit ratio, how long you’re gonna be in the study, and some of those elements. And so our current law has very prescriptive language on how those need be in place in informed consent. So I’m gonna go on to provide you with a few definitions of certain elements that pertain to research for those of you who are not familiar. What is the official definition of research? And I’m telling you that this is going to change, so you need to know what this means right now. So, research is a systematic collection designed to contribute to generalizable knowledge. It means that if we talk about that there’s a protocol a protocol, a design, that is systematic you’re collecting data in the same way for every patient throughout the conduct of the trial, that’s the systematic collection. And it’s aimed to help society. Ok, and that contributes to society through scientific knowledge. And what we do with that information is we provide it to when we find new therapies. We publish those things in journals, in medical journals and scientific journals. We present to our colleagues physicians present, educate each other on new therapies. And so that’s really what research is aimed to do. Translational research however is kind of what is the forefront of what is going on right now. And that is really applied research in real time. It means that sharing this knowledge with more than just the scientists and the physicians it means sharing it with the community members. Because the community members and community organizations know what’s happening in their communities. And so that’s what’s changing the landscape right now. And helping to bring therapies at the bedside to the community. So the definition of a human subject well, this is a key point. That it is a living person OK. A living person about whom a researcher obtains their protected personal information and private information that can be connected to the person. And so what that really means when we’re doing a clinical trial we’re looking at a therapy and we’re testing the therapy. And we’re making sure that it is safe and effective. And during that time we may do tests. We may do chest x-rays we may do EKGs or blood draws. And those things are looked at to understand whether it’s safe and effective. In the traditional sense that is clinical research. It also extends to looking at medical information, medical charts, data. And so we call that a retrospective chart review. It means that we look back in time. We look at charts, we take data and we look at trends in data to find out whether or not there are some common themes or common questions that we can answer. So what is an IRB. An IRB or ethics review board is an independent, remember independent from the study. The composition of that should be at least one community member. And also depending on the type of research that is being reviewed there needs to be expertise. So that means that when an IRB is reviewing a cardiology research so a heart research study somebody who knows cardiology or heart problems, heart research needs be represented in that committee review. The IRB has different layers of review and I’m gonna talk about that IN a couple of slides. That they, their first bite of the apple, the first time that they review a research study that’s called initial review. And they need to make sure that the principle that we talked about, risk, benefits, informed consent, elements that are there to protect human subjects ethical conduct, proper recruiting practices, there’s no coercion. These are elements that the IRB is going to be looking at during initial review. But always to make sure that risks do not out-weigh the benefits. The IRB also has responsibility for on-going review, so not just initial the first time, but on-going. Which means at certain time points the research must be reviewed. And it needs to be reviewed at least on a yearly basis if not sooner. It can also, the IRB has the responsibility of reviewing certain things during the conduct of the trial. They, for instance, if there are adverse events, if there are unexpected problems during the course of the trial, the IRB needs to look at those to find out and see whether or not that risks benefits ratio is still there. Also if there are changes to the protocol, changes to the conduct of the research study. Remember we talked about a systematic collection. You want to make sure that the research is valid. If we change it we need to have the IRB approve the changes and those changes are called amendments. So I think I’ve covered this and it may be a little redundant, but the IRB is charged with insuring that risk outweigh – excuse me, benefits outweigh risks. And that the risks are reasonable compared to expected benefits and if there’s no benefit to the single patient who’s participating that that patient subject knows that. That knows that while they might not benefit today that their participation may benefit society in general. Is the selection of participants fair and equitable? And theis is really important because when we’ve done research in the past if there is not a proper representation of male, female, minorities these can skew the way that treatments are made. For instance we know that there are some hypertensive drugs that do not work in the same way on the African American community as they do on the Caucasian community. So we need to have proper representation of all human subjects participating in research. How will the informed consent be done with each participant? And so there should be some kind of script that the IRB sees when the informed consent discussion is happening. And they’re responsible for making sure that there is no coercion. Especially when you see advertising out there about participating in a trial. That advertisement gets reviewed by an IRB to make sure that we’re not promising things that to people for their participation in the trial. Ok. And that’s what’s really important, especially now, about privacy. Privacy and PHI. PHI is protected health information and it means that we are during the conduct of the trial putting in special protections to maintain privacy and confidentiality. You can imagine that there are still stigma associated with certain types diagnoses, like mental health, and HIV research. And so the IRB understands and recognizes that those types of research need to have special protections in place. And for those vulnerable subjects, officially that we know as children, pregnant women, and prisoners that there are special protection in place when those individuals are participating in research. And is the study consistent with the values and need of the community? And so what’s important for the IRB to consider is that what may be a consideration in the community of Chicago may not be the same in rural Kentucky. And so those are things that an IRB or ethics review should take into consideration. So ther are three types of review that the IRB is responsible for and pay special attention to this because this is going to change in the proposed rule. So there are three layers of review, the first layer is full board review, meaning all the people come together including the community member as well as the expert for the research. And that means that it is more than minimal risk. And this is outlined in our federal regulation. Typically these are drug devised biologic studies that pose more than minimal risk to those people who are participating in the trial. The second tier is expedited review. And expedited review is less not greater than minimal risk and it fits into some categories that the federal regulations state. Those are things like collection of biospecimen. So in a non invasive way, meaning you’re not going in and opening up the chest just to take a specimen. It’s more something like a blood draw, so it’s not invasive. And then exempt review would be something like I talked about like a retrospective chart review and so you can see that it goes from very high risk to very low risk. Why should we make the changes now? So if you take this presentation as a whole you can see that we’ve refined our rules and regulations over time based on what we believe is ethical behavior. And so a lot of things have changed now most notably the way that we collect medical information. We do that in and electronic way. Before everything was paper. Today it’s at our finger tips. Ok, Everything’s at our fingertips. And so we need to make regulations and safeguards in place to make sure that we don’t have unethical research today based on our electronic medical records system. Another reason why we need to make changes is because we found out some very interesting things about our genome. And based on our genes and what we know about our genes we can take that information and develop therapies based on that information. And so genetic studies we need to have more oversight and specific oversight to insure human subjects protections when doing that research. And then the rising cost of health care. And we want to make sure we can bring new therapies to the bedside quicker and faster to reduce the costs. We also have a growing population so a lot of our folks out there are over 65 and they have more than one problem. So many have multiple problems and those problems may affect each other. And so we need to research more about those types of patients in our patient population. We also have a huge number of research that we are doing now compared to what we were doing 60 years ago. And so because of that we need to make sure that we are protecting human subjects on site. Any questions? OK. Thanks very much. Thank you, Stephanie. If you are just now joining via live streaming or hear in person We’re in Evanston, Illinois with the fourth of five listening sessions during the 90 day open comment period on the proposed changes to federal regulations for human research. We have expert panelists here to share information. We have folks fro the Office of Human Research Protection online to take your questions. And we have various videos from the previous sessions available to you for your review so that you can be well informed on the changes to these regulations. And to elicit your input and comments. About concerns regarding the advances of science and how these regulations may benefit or not benefit you and your res.. your positions of research enterprise in the community at large. This is again the fourth of fifth – fourth of five listening sessions brought to you by the Office of Human Research Protection and in particular the Vanderbilt institute of Clinical and Translational Research, CTSA Consortium Coordinating Center. The amazing people there have done a number of these sessions and have facilitated them so that you can have access to this information. We just heard from Stephanie Guzik The director of medical research compliance at Russ University Medical Center. She gave us a broad overview of the research landscape. Up next is Mr. Taunton Paine, to give us an overview of the proposed revisions to the Common Rule. I want to remind folks that you may provide comments or questions on social media. You can Tweet those questions to @commonrule2015 #asknprm. You may also email your questions to [email protected] during these live streaming sessions while folks are talking. For those of you in person you may step to the microphones to ask questions. We also two podiums with commentor question cards that you can place in the basket if you don’t want to ask those live. OK. Our next speaker is Mr. Taunton Paine. Taunton Paine is a science policy analyst in the Office of Science Policy at the National Institutes of Health Office of the director. Mr. Paine is involved in a variety of science policy issues including developing policies for human subjects protection, particularly for the protection of participants’ privacy and confidentiality in informed consent for research as well as policies for oversight of genomic data sharing dual use research and increasing public access to scientific data. Mr. Paine joined the Office of Science Policy in 2011. He holds masters degrees in history from Columbia University and the London School of Economics. Joining Mr. Paine via live stream and on the phone for your access to have questions are staff from the Office of Human Research Protections at NIH. Please join me in welcoming Mr. Taunton Paine. Well, thank you for that introduction. I’m Taunton Paine and I’m going to be giving you a brief overview of the proposed changes to the Common Rule in the Notice of Proposed Rule Making. So first I’ll go over some background on what the Common Rule is and the NPRM. I won’t say too much about this because we’ve already covered a lot of it. And then I’ll go over the major proposals that are in the NPRM. And then last I’ll just give a brief explanation of what the public comment process is and how it works and how to submit a comment. Ok, so first, the Common Rule, I think we’ve heard a lot about what this is, but just very briefly, it’s sort of the shorthand name for the body of federal regulations that establish protections for human subjects in research. And there are sort of two major components of it . One is that it requires informed consent for participation in research. and the second is that it requires that research be reviewed by Institutional Review Boards . An NPRM is a Notice of Proposed Rule Making. This is something that is issued by the government to explain forthcoming changes or new regulations whenever they are to be issued. It’s published in the Federal Register, which is the government’s official publication. And the goal is to allow public comment for a set period of time, usually 90 days. And we recognize that these changes have a lot of implications for people in different sectors, be they investigators, institutions, IRBs, research participants or patients themselves. And we also recognize that the Federal Register is not necessarily the most widely read publication, so we really … to sort of get the word out and raise awareness of the and to hopefully encourage people to submit their comments and their ideas. So the Common Rule is called the Common Rule because it is actually followed by 18 different federal departments and agencies. Including the one that I work for NIH. You won’t find NIH or FDA or CDC on this list because they are part of the Department of Health and Human Services . And it will be joined for the first time when it becomes final by a 19th which is the Department of Labor. We’ve heard quite a bit about the history here, so I’ll actually just skip to 2011 which was when the Advanced Notice of Proposed Rule Making was published that describes in general terms the changes to the Common Rule that were published on Sept 8th this year. It didn’t include a regulatory text but it asked a number of questions and solicited public comments. Those comments were considered and used to revise the ANPRM into the text that was published on September 8. And if all goes according to plan there should be a final Common Rule published that will incorporate the public comments received on the version published on Sept. 8 sometime in 2016. OK, so, when you’re looking at the NPRM this is just to give you some background of what’s in there, there’s an executive summary, there’s a section that has a sort of extensive rational for the modernization of the rule, and then it goes through the major proposals one by one that are in the rule including what the current Common Rule says, what the ANPRM proposed and what the public comments on this proposal said, if there was proposal about that. What the NPRM is proposing and then it asks 88 questions in total on specific issues in the Common Rule. Then there’s also a summary of all the comments that were received on the ANPRM. Then there’s a regulatory impact assessment which is just a way of estimating the quantifiable and unquantifiable costs and benefits of implementing the rule as is proposed. And then finally there’s the actual proposed regulatory text itself at the end of it all. So, I think we’ve also heard some about why modernization is considered to be necessary. I think we can all agree that in 1991 research and society have changed dramatically. Just to be very brief, there’s been a expansion of the number of clinical trials that are being conducted around the country. There’s been a diversification of social science research methodologies that involve human subjects. More research is being conducted in clinical settings and in fact in some cases the boundary between research and clinical practice may be blurring. There are more studies now that involve multiple institutions. Now at NIH approximately half of studies funded do involve multiple institutions. There’s substantially greater scientific data sharing going on and more mandates for greater scientific data sharing can be expected in the future. And last there’s an increasingly sophisticated ability to extract information from biospecimens that’s more commonly being used in research. And finally, there are new initiatives such as the President’s Precision Medicine Initiative that are advancing a more participatory model of research that really treats research participants as partners in that research. So there are two overarching goals behind this modernization. The first is to enhance safeguards for and respect for research participants. And the second is to simplify the current oversight system and reduce inappropriate and unnecessary administrative burdens, both for institutions, for researchers and for research participants themselves. Also IRBs, of course. Ok, there are sort of six major reforms that can be categorized from this NPRM. The first is to match the degree of oversight of research to the level of risk associated with that research. That is the risk for participants. The next is to require consent for the research use of all biospecimens regardless of whether they are identified or not identified. There’s also an allowance for and a description of what has to be included in broad consent for future research using identifiable or non-identifiable biospecimens or identifiable information. There’s an effort to simplify consent documents and processes in the rule as well. In addition to establishing privacy and security standards both for identifiable biospecimens or, well for both identifiable and non-identifiable biospecimens as well as identifiable information. And last there’s a number of proposals that would streamline IRB review of research. So I’m going to be focusing on matching the degree of oversight to the level of risk today. And I think that’s what this session in general will be about. OK, so this set of reforms is achieved through first expanding the scope of the rule to include some areas of research that have not been regulated before. To establish a number of exclusions which is to say types of research that are not subject to the rule in any sense, there’s no requirements for them in the rule. And last to establish a number of exemptions which would require they follow only some of the aspects of the rule based on the level of risk associated with them. So this graphic just sort of illustrates the general trend that I just described. Which is that it introduces a degree of oversight based on the level of risk to research while expanding it to certain areas that may not have been regulated before. OK. So the first change the expansion of scope. The NPRM proposes to expand to include clinical trials that are not previously been subject to federal regulation that are conducted at any institutions that receive federal funding for nonexempt human subject research. And if those institutions are in the US. So there are a number of exclusions in the rule that are established because they are deemed not to meet the definition of research for the purposes of this regulation. So the first one of those categories is oral history journalism, autobiography and historical scholarship that focuses on specific individuals. The collection of data and biospecimens for intelligence national security or homeland security activities. The collection of data and biospecimens for criminal justice activities by or on behalf of a criminal justice authority. Public healthe surveilence by by a public health authority. And the collection of data and biospecimens for a institutions own internal monitoring and program improvement. And if you read the preamble to the NPRM you’ll see that this really focuses on the idea that this kind of research would not be generalizable. And last, there’s an exclusion for quality assurance and quality improvement activities for the delivery of an accepted practice or service. An this rally focuses on delivery of that service rather than the service itself. So if you read the preamble again there’s a brief example given that an educational a study to evaluate the effectiveness of an educational practice for implementing an accepted medical practice could be potentially excluded from the rule. Whereas a study to evaluate the effectiveness of that practice itself would not necessarily be excludable from the rule. That would not necessarily meet the definition of QI. OK, there’s a number of exclusions that are also established because they are considered to be low risk. And this includes research involving the collection of er the use of information that was originally collected for other purposes, either research or clinical purposes. If the information is publicly available or is non-identified and the investigators using it will not attempt to contact or the re-identify the people from whom it came. There’s also an exclusion for research gathering non-identified or non-sensitive information that’s collected through educational tests, surveys, or interviews, or observations of public behavior. Non this term non-sensitive does not appear in the regulation, this is just shorthand for my presentation. What it events mean is that this kind of information if it was disclosed or released to the public, would be unlikely to pose any risk of criminal or civil liability or damaged financial standing, employability, opportunities for educational advancement or the reputation of the people from whom it was collected. And just to remind you, all of the types of research in these excluded categories are not subject to the Common Rule whatsoever. Ok there’s also another sort of set of excluded research which is excluded because it is already subject to another set of rules that establishes protections or requirements that are similar to the ones required by the Common Rule. So there’s two kind of categories here that fall into a set of requirements established by the Paperwork Reduction Act, the eGovernment Act and the Privacy Act. And both of these types of research that are subject to these are largely activities that are conducted by the government. But this would include the gathering of identifiable sensitive information through educational tests, surveys or interviews, or observation of public behavior. Or research that is conducted by a federal agency using information generated or collected by the government for non-research purposes. Which could include criminal history data. Again provided that both of these types of research were subject to the Paperwork Reduction Act, which has a notice in it the eGovernment Act or the Privacy Act both of which require the establishment of certain standards for the protection of information. And last research involving the collection or analysis of identifiable health information if it was regulated as either health care operation research or public health surveillance by HIPAA would also be excluded. OK, there’s one final category of of excluded research in the rule. And this includes research with non-identified biospecimens that will not reveal new information about an individual. This includes tests and assay development and validation, quality assurance and control activities, and proficiency testing typically for laboratory or test performance. And what this is trying to get at if you had a set of non-identified biospecimens where you knew that one did not have a certain disease, and you knew that the other set did have a certain disease, and you wanted to develop a test to determine whether a given biospecimen had that disease you could do that because you would not be revealing new information about the individual you would simply be using information that already existed. OK, so there are also a number of research activities that are exempt from most or some of the requirements of the rule, provided that they have certain protections in place. The one that is common to all of the types of exempt research is that a standard tool for the exempt… that will be used to determine whether research could be exempt would have to be used. And that an expert with knowledge of the Common Rule would have to determine the exemption status and that the outcome of using this tool has to be kept and recorded. In some cases there might be a requirement to apply safeguards such as information security to protect the information and biospecimen. In other case there might be a limited IRB review of the consent processes. And in some cases there might also be a requirement to have obtained broad consent using a template that would be published by the Secretary a sort of standard approved template. OK, so the first set of exemptions is just for low risk research. This includes research in sort of standard educational settings looking at standard educational practices provide that that they would be unlikely to adversely impact students’ opportunity to learn or for the evaluation of teachers. This would also include research in demonstration projects supported by the federal government to evaluate public benefit or service programs. This is already an exemption currently the only difference is that it under the current Common Rule it applies only if the government itself is undertaking this activity, but would now apply if the government funds research that would undertake this evaluation. There’s a new exemption also which is for research involving what the rule defines as benign intervention or video recording if the information in non-identified or not sensitive. And a benign intervention is typically something which is like taking a test or solving a puzzle. Something like that. It’s not something that is intended to have any sort of lasting permanent effect on somebody. And last, there’s a existing exemption category which is being carried over for taste and food quality evaluation. In all of these cases the only requirement that the NPRM would propose is that the a exemption determination tool would have to be used. And that the outcome would be kept and recorded. OK, there’s also a new category of exemptions that has somewhat more requirements on it. Which is research with identifiable sensitive information. And I want to be clear when I say sensitive here, this is not the opposite of the non-sensitive that I was referring to earlier. Sensitive is used in the rule here there’s not really a definition around it. So the first sort of type of research that would fall under this exemption category is non-interventional research that gathers identifiable sensitive information through educational tests surveys or interviews, or observations of public behavior. And the second category would be secondary research, meaning that you’re not gathering information directly. Somebody else has already gathered it and you are using it. That would be identifiable and sensitive but it would have had to have been collected for non-research purposes. So it couldn’t have been generated from somebody’s being involved in a study. And it would also require that prior notice has been given to individuals that the information could be used in research. And the secondary investigator who gets that information could not then use it for a different set of research than what they proposed to do with it. And for both of these types of research you would again have to use the exemption determination tool and record the outcome but you would also be required to apply information security standards that are established later in this rule. And there’s one last set of exempt categories research. And this is for research using biospecimens and identifiable information so it’s for the collection and the secondary use of it. So there’s sort of two parts to it. First there’s there’s the collection part, the exemption for the collection is for both biospecimens and identifiable information if you’re going to establish a data base or biobank. Or you are just collecting biospecimens or identifiable information with the intent that they will be available for secondary research. Other investigators can use it later. If this was your intent you would have to, first as with all the other types of research. use the exemption determination tool and record the outcome. And you would also have to have safeguards for the protection of information of biospecimens. You would have to obtain broad consent using a template. And there would also be limited IRB review to insure that the context in which the broad consent was collected was appropriate. So broad consent could be collected in clinical settings and there might be some clinical settings that would be considered inappropriate for the collection of broad consent. So that would be a case where the IRB would look at it and decide whether or not the context for asking for consent was appropriate. There’s also an exemption for the secondary research use of those biospecimens and identifiable information that were collected this way. Now if they have been collected as the previous type of research required, then the only requirement on the use of that biospecimen or information would be that the exemption determination be made and recorded and that the person using it has safeguards in place to protect information and biospecimens. There’s a number of ways in which this applies to vulderable populations, so all of these exclusions can apply to research with that involves vulnerable populations except that non-interventional research involving educational tests, surveys, interviews or observations of public behavior cannot involve children. All of these exemptions apply to research involving pregnant women. And certain research involving children cannot be exempt including the research involving the benign interventions, as well as the non-interventional research gathering identifiable tests and information. And last, research involving prisoners can never be exempt unless the research incidentally involves some prisoners, and what’s mean by that is that the prisoners are not your main population under study. There just might accidentally be some prisoners in the population you’re studying or some of the population you are studying might become prisoners after you started your study. There’s a requirement to obtain consent for research with biospecimens in the rule. This is one of the biggest changes in the rule, so I think it bears some discussion. This is accomplished by changing the definition of human subject that we heard about earlier. To require consent when and investigator obtains uses studies or analyzes biospecimens or research regardless of whether that biospecimen is identified or non-identified. With a couple of exceptions that we went over earlier. where there’s an exclusion of exemption. This would not apply to the collection and use of biospecimens for non-research purposes unless your intent was to use it for research. So biospecimens being collected in the clinic and for clinical purposes are not going to be required to get consent unless those research, those biospecimens would be used for research. There are also two alternative proposals in the rule that would establish somewhat narrower requirements. Alternative A is probably the narrowest in the sense that rather than requiring consent for the use of all biospecimens it would only require consent for the generation and use of whole genome sequence data, while alternative B would only require consent for research involving the generation or use of data from individuals that are considered to be unique could be potentially be re-identified if used in combination with other sorts of data. There are changes in the way in which waivers can that- IRBs can issue waivers of consent. Specifically, these are intended to insure that the requirement to obtain consent for biospecimens is observed. And so there are two additional criteria for research with biospecimens. And this includes that you have to show compelling scientific reasons for the use of those biospecimens and that the research could not be conducted with other biospecimens for which there was consent. And last there would be prohibition on waiving consent if the individual was asked to participate in research and declined. So the general idea here is that waiving consent would be rare. There’s also an allowance to use broad consent which simply would use a template that would be developed by the Secretary and published for public comment, so the public would have an opportunity to say what they would like to see in a broad consent. There are a number of elements that are intended to appear in consent that are listed in the rule. These are just the major elements and I won’t go through them all now, but they are in the rule there’s about potentially 16 in total, depending on the context in which you are collecting them. The idea is that it would be general and not specific to any particular research. So it would be for future use of biospecimens and data. There’s a number of efforts to simplify consent documents. Including that the informed consent documents can only first include the required elements of consent that are listed in the NPRM. So other elements of consent that are included by institutions or by IRBs could only be included as appendices to the main element of consent. There’s also a requirement that participants have to receive the information that a reasonable person would need in order to make an informed decision about whether to participate in research, and that they be given an opportunity to discuss that information. There are also a number of security standards and safeguards for biospecimens and identifiable information that are established by the rule. There are specific measures that have not yet been developed but would be developed by the Secretary that will be published. But this requirement could also be satisfied by following the measures in the HIPAA privacy and security rule. And there are also a number of sort of limitations on how sharing of biospecimens and identifiable information can be done. In general the idea is that IRB review of safeguards for information and biospecimens would not be required. Well for these effencies those safeguards would not be required. And there’s a number of elements to attempt to streamline IRB review. The biggest and this is one of the most significant proposals in the rule, is that multi-site research, that is research that involves multiple institutions would only be allowed to use a single IRB unless local IRB review is required by law. Or the federal department or agency that is funding the research decided that it wouldn’t be appropriate for that particular study or that particular site to use a single IRB. There’s also a change that IRBs rather than research institutions will be held responsible if the IRB failed to follow regulations. There’s a number of IRB review effencies that are included including that IRBs will not review grant applications. The continuing review of research would be illiminated in certain cases, where for example the research is eligible for expedited review. Or the study has progressed to the point where they’re, they’re sort of past the interventional stage and they’re just looking at data that has resulted from that research. And in cases where IRBs do want to do continuing review they’d have to sort of provide a rationale for it and document it. There’s s number of other effencies as well, I won’t get into all of these right now. There are some important transition provisions in the rule, so once the final rule is published, the effective date, which means the rule will not take effect until one year after it is published. Research that has been done before the effective date would not be subject to the new requirements in the rule. Biospecimens that were collected before the effective date would continue to be used without the new consent requirements provided that they are non-identified. And there would be a compliance date of three years after publication of the rule allowed for the new consent requirements for biospecimens. And for the mandate for single IRB review. So the public comment process works like this. The NPRM was published on September 8 for a 90 day public comment period that closes on December 7 of this year. Once the public comments are all received they will be considered and they will be published. And then federal departments and agencies will work together to revise the NPRM based on what the public comments said. The final rule will be published once that process has completed. We’ve already talked about the number of stakeholder meetings that are going on, but just to let you know, there’s one more coming up in Philadelphia that will focus on consent. And when you’re commenting, this is a general guide, just so you know, you can really comment on anything that you want. You can comment on specific aspects of the rule. You can comment on the idea behind the rule, you can say whether you think the modenrization is needed or if the changes are actually adequately addressing the needs. And there are 88 comments that you can answer if you want, you don’t need to answer any of them. Just remember that when you’re submitting a comment the comments will be published, so don’t include any information that you wouldn’t want to be published. There’s a number of different ways you can submit a comment. You can go to the regulations .gov website here. You can actually also go to the Federal Register website, there’s an option to submit a comment through there. And you can send by fax and mail. So thank you very much, and please do submit your comments. Thank you, Mr. Paine. Just a second, thank you. We have just heard from Stephanie Guzik, the director of research compliance at Russ University Medical Center, and Mr. Taunton Paine, policy analyst Office of Science Policy at the National Institutes of Health. They have gone over the research landscape and an overview of the Common Rule. We’ll now take some questions here from our live in person audience. Good morning. Morning That was a fine presentation. Basically, I just want to know ? real good right. Everybody hear this microphone? We can hear you. Oh OK. We’ll get people to talk like they’re kissing a baby. Sir, to our right. ?? Northwestern University. I’ve got lots of questions ?? but the first one I want to know is, has OMB or anyone like that looked at the economic impact of these regulations? Because on face value it looks like at least NIH’s research productivity per dollar is going to drop significantly because of the extra paperwork and greater difficulty getting both specimens and subjects. Right so, as part of the law that requires us to through this public comment process there is actually a regulatory impact assessment, which is essentially an economic assessment of the costs when they are quantifiable and the benefits when they are quantifiable, of implementing the regulation. It’s actually in the NPRM so you can look at that if you want. There are of course a number of costs and benefits that sort of defy quantification, I think and or it would be very difficult to determine how how expensive or how much money they would save. So actually one thing that you know if anybody does have better data that they think was used in the RIA we would welcome comments on that as well. I think, you know, yes, there will be costs associated to it with a lot of these changes,. I think some of them also will save a significant amount of effort in the long run especially. So.. Another question. Good morning. I have like a two part question that’s not necessarily related to one another but my first question is I have a condition called neurosarcoidosis Which is an offshoot of sarcoidosis which is an autoimmune disease. It’s not heavily researched but in my case because it’s located primarily in my brain they’re saying that the only thing that can help me would be like stem cells. Um. How realistic would it be for me to become a part of a trial and are you aware of anything as far as you know the research of more uncommonly known disorders? That was the first question. OK The second question is in reference to you know drugs are advertised regularly every day ok. And they you hear the side effects of those medications on television. Those side effects, are they is that good research? You know or is that the least possible scenario of side effects or is that just a matter of getting something to the market? Well, I’ll answer the first part of that question. In terms of clinical trials, I don’t know of one off the top of my head that are specific to that condition, but there is a website called clinicaltrials.gov and if you go to it you can search for it. And there’s a number of different ways you can search for both ongoing and actively recruiting clinical trials. So if, I think it would be it would be worth looking at that, at that website. In terms of what the NPRM does for changing the balance of sort of focus on rare diseases, I think that’s not really a change in the NPRM. So, you know, it really has to do with the processes through which people can be recruited into a trial rather than what kinds of trials will be funded necessarily. So there might be changes in it for how people would be involved in a clinical trial and how that clinical trial would be reviewed by an IRB but I don’t think it would really change what federal departments and agencies would fund in terms rare disease or clinical trials or research for rare diseases. We also want to acknowledge from the Office of Human Research Protections Lauren Hartsmith, Ivor Pritchard, Irene Stith-Coleman Julia Gorey and Julie Kaneshiro are on the line. If you have specific questions for them. And our next – Did you have anything to add to that? Yeah, I was just gonna take the second part of your question in regard to the way clinical research is conducted and looking at adverse advents and side effects. And so the process really is we touched briefly on today with the the risk benefit ratio. And that when clinical trials are being conducted , you know they’re first discovered and researched in the laboratory, and then tested on animals. And then there are four phases of research that occurs in humans. And so during those phases we are always looking at risk and safety. And so at high points during the conduct of the study patients will come in and we’ll make assessments assessments and those assessments include adverse event reporting. And those adverse event reporting, the higher, the ones that occur in the ma – the majority of occurrences, so let’s say it happens at, I’m just giving an arbitrary number here like 50 % of patients who got drug A had headaches.. And so therefore the side effect on that drug when it – if it gets FDA approved would be headaches. So that process is not gonna go away as a part of this change to the rules. And we’ll take one more question here. Hi, My name is Michelle Bradley and I’m with Northwestern University. I had a question about the biobanking. So currently we collect samples from patients and we bank the samples and the investigators are able to talk to the PI about doing research and patients know when we consent them they don’t necessarily know what the samples are gonna be used for. And then we get requests from PIs to get women who are age 40 who have a GFR of whatever and we send those samples out. So with the changes, are we now gonna have to do another consent process with the patients for those samples before we send them to the investigators? So it sounds to me like you’re actually already collecting broad consent for secondary research. (Correct) for those samples. So all that the NPRM is requiring is that that consent be obtained for the use of specimens. But it can be broad. So this would allow any future use. So the consents that you’re using right now to get those, that itself might have to change to conform to what the NPRM says is broad consent, there’s a … DROPPED SIGNAL …and of course researchers charged with making that determination themselves, it’s so scary not only for us, but for the researchers themselves that it opens up a whole possibility of not knowing what’s going on in the institution. And so without specific ?? particular parts of the exclusion my concern is (excuse me) the liability of things taking place without knowing what they are because people believe truly or misguidedly that they do not, that they don’t fall under IRB or institutional review it’s very worrisome. And also I see no accommodation in the exclusions for interviews or surveys that involve greater than minimal risk in the taking of the survey. The so-called talking writing watching, whatever they legitimize it as certainly if you ask people how long … in the waiting room, how come they… DROPPED SIGNAL …first comment, that is correct. The excluded categories of research there’s not really a process you know, in the NPRM for how you would determine that your research is excluded. There is a process for determining whether it’s exempt. And presumably in some cases you’re going to go through that process and find out that your research is exempt, or It’s excluded, sorry. So, but if that’s a concern to you or if you think it should work differently or that the exemption tool should apply to the use of excluded categories as well, I would just encourage you to submit a comment. And for the sort of second part of your question about whether the information is greater than minimal risk that’s being collected. The excluded categories are, I think, pretty clear that they involve information that’s non-identified. So that’s generally why it’s considered to be low risk. Or it is considered to be, if it would cause any sort of harm to come to ?? It’s the process of being asked that’s troublesome.These kinds of interviews and surveys at our institutions currently have counseling support you know at the ready to should some participant need some kind of extra help. You know it’s not answering the question it’s not the answer, or the identification with the answer, it’s the process. Right. It’s the interaction . Right. I think there, I was there at the town hall meeting and my takeaway from that is there’s some flexibility in the process of how institutions will get that information. However what I planned to comment on would be looking at the safeguards that are proposed in those situations and those have not been shared with the public at this point. Is OHRP on the line? Hello OHRP. Anyone. Julia, Julie? Irene? Can you hear? Yes. Yeah. I just wondered if you had anything to add to that comment. This is Ivor Pritchard I think one thing that’s noted is that what the question asked about the process for exclusion is status quo. It is already the case that the regulations are silent with respect to what policy or procedure is used to decide whether something is or isn’t research. Or whether there are human subjects involved or not. And presumably if an institution is concerned about how that decision is being made they can identify what kind of policy or procedure they want to use at their institution to draw that line. With respect to the issue of opening a survey I believe that the Proposal of the Notice of Proposed Rule Making is essentially saying that adults are capable of deciding for themselves whether they wish to respond to questions based on whether they are sensitive or not. And lastly I would just encourage the commentor to provide whatever comments they would like to make both about whether there ought to be procedures related to determining exclusions and for the circumstances in which surveys or interviews should or should not be some requirements of some sort or another. Thank you. Any other comments? OK. You are in session with the fourth of listening sessions for the proposed changes to the federal regulations for human research. None of the comments here are formally submitted comments to the docket. The instructions to do so are on your screen. We are going to take a 10 minute break. We will resume our program at 10:45 You may tweet your questions @commonrule2015 use the hashtag #asknprm. Or email your questions to [email protected] We’ll be back in a minute. OK. We’re back. For the in-person folks, could you please take your seats. And welcome back to folks online. We’ve still got some music playing. That’s always nice as folks take their seats. We need that little chime thing that people… Lots of lively activity here in person So please have that as well on your live stream. OK. Once again you are tuned in to the fourth of five listening sessions regarding the proposed changes to federal regulations for human research. Today’s session is focusing on revising and expanding the scope of the Common Rule. We have expert panelists here to give out information and hopefully to solicit comments concerns questions regarding these changes . You can do lots of different things you can read the regulations that’s quite task handy. Or you can listen to these sessions and present your comments and concerns. You can join us on social media @commonrule2015 #asknprm if you want to tweet your question in. You can also email your question to [email protected] Please be reminded that this is not an official comment submitted. If you have a question comment or concern you go to the livestream or you tweet or email or the discussion here in person, these are not formal submissions of comments. To do that we’ll give you instructions later in the program on how to do that.. For our next sect… our next section, the expansion of the Common Rule, we have Dr. Stephanie Solomon Cargill. Dr. Cargill is assistant professor of health care ethics at the Albert Gnaegi Health Care Ethics at St. Louis University. With a secondary appointment at the center for research ethics at Washington University’s Institute for Clinical and Translational Research. She holds a PhD in philosophy from Emory University. Dr. Cargill’s area of expertice include institutional review board policies, research ethics with vulnerable populations, and collaborative research methodologies involving community partners and the public. Such as community based participatory research and public deliberation. She has done extensive work on research ethics and community engaged research including developing a research ethics training for community partners in research that translates IRB requirements into a language that’s more appropriate for research done in community settings. Her two most recent projects focus on biobanking consentand involving the public in research spending decision making. Please join me in welcoming Dr. Cargill. Hello and welcome. Good morning. Hopefully you got some coffee and you’re getting some energy going back to your system. So a couple of disclaimers that I want to make. I mean I’m being called an expert here. I do research ethics but I am not a regulatory expert. I had nothing to do with the development or articulation of these policies. And I basically was exposed to the exact same policies as you have and I am just doing my best to make sense of of them to myself and to you. I also … (quotation) marks on the word expansion up here because it’s kind of an interesting question in the scope of the whole NPRM whether they are actually expanding or contracting. I’m going to talk about the part of them that is expanding but whether things that we learn about this afternoon, like the exclusions and the exemptions end up contracting more than it’s expanding. I think is a really open question. So a little bit of background about this idea of expanding the Common Rule. So first of all, the current federal regulations only apply, or only must apply to human subjects research that’s funded by federal dollars. So we were talking about this morning with the other Stephanie what human subjects research is and how it’s defined, but it also has to follow the train of federal funding dollars for a kind of a jurisdictional reason. But that being said, a lot of academic institutions voluntarily apply these regulations to all of their human subjects research whether or not it is federally funded. But at least in the way that I read the NPRM, this would no longer be an option. But if you are an institution that receives federal funding then these regulations would apply to all of your human subjects research or at least a subset of them regardless of funding. So… Ok, so, I’m not very good at graphics but I’m also a very visual person. So this is the way I visualize to myself the current state affairs. Which is that, you know, that kind of Leonardo vision is my image of human subjects research and it’s currently being funded either federally or not federally. And those actually are opposites, unlike sensitive and nonsensitive. And so then the question is we have human subjects research going both sides so it could be risky or not risky, but the code of federal regulations really currently, and this is somewhat of a simplification applies to that that is federal grant-funded. Whereas we have a big question over whether and what is covering those types of human subjects research that are not being funded by federal grants. Now this doesn’t mean they’re not being covered by any regulations and there’s no protections, it’s just that what protections there are are sometimes unclear it’s highly variable, it depends on institutions, it depends on organizations or other oversight over this research. And so really this expansion is about trying to deal with that question mark area. So the controversy about expanding the Common Rule is not new. It’s not from 2015. People have been arguing about this at least since the 90s. Probably longer than that. And the controversy looks something like this. On the one side you have a group of people that say human subjects deserve to be protected. And whatever standards at which they should be protected we believe ethically are the levels they should be protected at. It shouldn’t depend on where the money is coming from. That some people are protected at this level and some people are protected at this level. It should be ethically irrelevant where the money is coming from. Human subjects should be protected across the board. And so the kind of conclusion from a lot of these arguments is that the federal regulations should cover all human subjects in research regardless of funding. And this argument has been made by lots of people It was made by President Clinton. It was made by the Committee on Radiation Experiments, back in the 90s, it was made by the National Bioethics Advisory Commission and lots of scholars have been arguing for this for years. But there is another side to this which I think is worthy of at least consideration. Which is that we’re in a system where ethical standards are different depending on who’s funding the research. But it’s kind of an open question whether the federal regulations either before or now do a better job than other regulations or other ways that human subjects may be protected. And because it it’s kind of an open question whether the federal regulations do it best, then this idea of broadening the federal regulations doesn’t necessarily mean we’re protecting people better. We may just be protecting them more. And so, there’s and the other part of this is a jurisdictional question and I’m not a lawyer and I barely remember how a bill becomes a law. But there’s an issue about federal funding and what the federal government has a right to control. And the idea historically has been like where the federal government is paying for things they have a right to control it. And when they’re not paying for things they have less of a right to control it. And I want this to be clear because I think the NPRM is trying to kinda trying to forge a middle path between the going anywhere and everywhere no matter what money’s involved and only covering things where they are directly paying for it. So they’re kinda trying to forge a middle ground between these two sides of this historical controversy. And other people who are just very critical of the current federal regulations say we’re just taking a bad system and making it broader and that we shouldn’t spread the federal regulations because they’re already a mess. I mean it’s interesting cause I see work on Medicaid expansion policy and you get a lot of similar arguments there. Like you shouldn’t expand Medicaid because it’s already a broken system. So I think asking yourself if it’s a good system or at least if it’s the best system we have, and then it should be expanded or whether it’s problematic more than it’s helpful and I think that’s an open question, or at least one you should reflect on. So the proposal the proposal I’m gonna be talking about today in the NPRM is the proposal to extend the Common Rule to all clinical trials with exceptions. A couple things that are important in this, even just this title, It is an extension. No one’s lying about that. But it’s not to all human subjects research. I think it’s important to know this. It’s not to all human subjects research, it’s only to all clinical trials. And I’ll talk about that in a minute. So we’re not extending the regulations to any and all human subjects research. So the purpose, and I think this has already been talked about quite a bit but I’m just going to rephrase it, what I would say is the implicit purpose here is not explicit in the reg- the NPRM is to expand but to limit that expansion to legitimate federal jurisdiction. So where can the federal regulations legitimately cover and protect human subjects? While actually upholding what I would say the whole NPRM is aiming to do which is increase coverage for high risk research while reducing coverage for low risk research. And reducing burdens for low risk research. So I’d say kind of a key question here is to ask yourself whether these two purposes are achieved or how it could be phrased better or problems with it being achieved and how it’s currently being phrased or planned. So how is this proposed to be done. OK, so instead of the regulations following the money directly so federally funded research is covered by the federal regulations. The proposal is to have it go to institutions that receive federal funding. So, and at this point the bar is at like a dollar of federal funding, so if an institution receives any federal funding for research, not in general, but for research, then any human subjects research that constitutes a clinical trial, and we’ll talk about that in a minute, should also fall under the Common Rule. So here’s another bad picture that I made. So let’s think we’re in an institution, and this is not to scale because different institutions have more or less federally funded research, but let’s say the institution has some combination of the both and currently some subset of the funded research is human subjects research by the current regulations and that, that is federally funded and defined as human subjects research that’s what’s covered currently by the regulations. And then as I said before many academic institutions and others voluntarily cover that second part of the blue box but it’s their choice to do so. So this is the proposed change. So we still have a combination of federally and non federally funded research. We still have a subset of that that constitutes human subjects research. Although if you notice I made that box smaller because at least ostensibly the NPRM is trying to restrict what’s defined as human subjects research. and say that some of it that is currently defined that way is not defined that way any more. So that box is ostensibly smaller now and then like before humans subjects research that’s federally funded will still be covered, that hasn’t changed, but now there’s this new concept. somewhat new, at least in the regulations that a subset of that this is why I had to draw a picture, because my mind was kind of exploding here, a subset of that is gonna be called clinical trials. And things that satisfy that definition are covered even if it’s not federally funded. So this is my really sad picture from PowerPoint. I hope it’s helped a little bit. And we’ll revisit this in a minute after I kind of help with some of the definitions. So a clinical trial seems very key to this whole plan. What is a clinical trial. I mean obviously in lay, you know, conversation, those of us who are in this world talk about clinical trials all the time. but this is a very specific definition. So in the NPRM a clinical trial means a research study which has one or more human subjects and I think it’s interesting that it could be one, who are prospectively assigned, so this doesn’t necessarily cover retrospective studies, one or more interventions. So it could still be one. So we could have one person prospectively to one intervention, although I don’t know quite scientifically why that would be helpful. And then it has to evaluate the effect on biomedical behavioral or health related outcome. So this is verbatim, I just broke it up into bullet points, but verbatim what the definition of clinical trial is. Now this isn’t a new definition I went looking and it’s pretty identical to the NIH definition of clinical trial. It’s also very close to the WHO W H O World Health Organization definition, but notably it’s different from the FDA definition. And whether or not that’s something important I think is just something to think about, I’m not gonna, I don’t know the answer to that. But it’s different from the FDA and also a propos our earlier conversation, it’s different from clinicaltrials.gov definition. So I think for those of you in the regulatory world whether that difference makes a difference I think is something to reflect on. I went and talked to my IRB head staff person because I’m not an IRB administrator and said, like, what do you think about this whole thing? She basically saw this part as being awhole bunch of problems. Trying to figure out how to define this consistently and distinguish it from other definitions of clinical trials. Oh, and just to be clear, FDA calls it a clinical investigation, not clinical trial, but they’re usually synonymous. OK, so, which clinical trial, so not all clinical trials are even gonna be covered. So like I said before, they have to be at an institution that’s receiving research support from a federal department or agency. And one of the questions in the NPRM , I’m sorry this is small, is whether there should be an upper time limit or a lower financial limit to this. So I guess what their thinking is on this, so you’re an organization like a community hospital or even a community college or something and you got a federal grant like 20 years ago for a pilot project and haven’t gotten federal money since then, does this apply to you. Or you, you know, got a really minuscule financial grant, or lots of very minuscule ones for research does it apply to you? So I think that’s a question that the NPRM wants people to reflect on is whether there should be a threshold for this. It’s not applying to clinical trials subject to the Food and Drug Administration regulation. On the one hand this could be really helpful because a lot of institutions have trouble trying to follow all these different regulations. They have the Common Rule they have the FDA , they don’t always align with each other and it causes people to get very frustrated. you know. But on the other hand, one of the questions about jurisdiction is what is this going to now cover? So any kind of pharmaceutical company that doesn’t get federal dollars is most likely already going to be subject to FDA regulations. So this wouldn’t actually extend an apply to that. So I think that’s important to think about. It has to be domestic, so it has to be conducted within the US. And it doesn’t qualify exclusion, exemption or already subject to independent control. I’m not gonna belabor this because I think whether it falls into that category we’re gonna be talking about pretty much for the rest of the day. But especially when it comes to the question about behavioral health research. A lot of people are concerned that it’s going to try to cover low risk behavioral and social research. And the question is it would, the answer is it would only cover those that don’t qualify for these exclusions or exemptions. And whether that’s appropriate or not. How many, so what difference is this going to make? Turns out very very hard question to answer. According to the NPRM, and I’m not sure maybe we can have different people answer this question where got this data, so the NPRM actually tries to answer this question. And they say that HHS, sorry typo, HHS supports 909 clinical trials a year I guess on average, of which 575 are regulated by the FDA. So the estimation in the NPRM is that there are 1399 active clinical trials not currently overseen by either the Common Rule or the FDA. Which is a lot, I mean it’s more than what’s currently being covered if this is accurate information. I don’t know I can’t speak to where this data came from but that would be a big coverage. But as this stuff is unregulated it’s really hard to know and measure because no one necessarily has to register the trials with anyone to have a kind of over-arching number. So who would this affect?This is also, I struggled with answering this question. In the non-academic sector I’m not totally sure, I probably just heard of people in the audience or in the listening audience about who this may affect, who is not currently affecting. Some of the suggestions I’ve heard are community health centers who may not regularly get research dollars or like community academic centers like community colleges, things like that that don’t do a whole Lot of research, but maybe some. Another example from my IRB staff person was something like nurses for new-borns or something like that that’s trying to get something evidence based and may have some federal money involved in their institution, but I think this is an important thing to think about. Though I don’t actually know the answer. In the academic sector I do know the answer. Which is that all universities who have not already voluntarily covered their non federally funded research by the Common Rule will now be covered by the Common Rule. And this in academic speak is called unchecking the box. These are institutions that have chosen only to apply the Common Rule in its entirety to federally funded research then they kind of explore flexibility with other types of funded research. Often times with empirical kinds of evaluations. Like what if we add an exemption category. What if we allow two years of continuing review instead of one. They try out different alternatives that are not necessarily allowed currently in the Common Rule to see if lessening some of the regulations is OK. In terms of numbers on this, according to an IRB advisor article in 2013, 37% of research programs uncheck the box and another 32% on top of that 37% uncheck the box on all but subpart A. So that would be the vulnerable population section of the regulation. So that may be a lot of people i guess is my point here. It’s a lot of institutions, It’s kind of a surprising amount of institutions. And they’re often very big institutions. They’re like University of Michigan, Harvard, others. Other institutions like my own I found out actually have unchecked the box but they don’t actually don’t do anything about it. They actually in practice apply the Common Rule to everything but they like having the flexibility and the limited oversight so they uncheck the box and then apply everything. So the question for the public is is this a good idea? And some of the consideration I want to bring up that were put into the ANPRM, and so I think it’s interesting to ask whether the NPRM resolved them or responds to them, are some that I’ve said already which is that the Common Rule already has problems and we shouldn’t extend them. Now the commonly touted problems with the Common Rule are how it handles informed consent it’s not very good necessarily distinguishing high risk from low risk research. IRBs often have lots of critiques and problems with them and defining research and non-research. I know Ryan’s gonna talk about quality improvement as one of those major issues of defining research and non-research is a big problem. And I think one thing to ask yourself is does the NPRM solve a lot of these problems? Because if it does, then extending is much less of a problem than before when the existing Common Rule has been criticized for these things. And the other point is the loss of flexibility. So that data about unchecking the box a lot of them belong to something called the Flexibility Coalition which is a group of academic institutions who all kind of share strategies of what to do with non-federally funded research. Mostly, though they deal with different ways of regulating minimal risk research. So the question once again is fi the NPRM does a good job of kind of taking the Common Rule out of the issues of minimal risk research then this might not be as much of an issue. So for example a lot of institutions who haven’t checked the box add expedited and exempt categories but so does the NPRM. So I think it’s interesting to ask whether that kind of solves that problem. Longer approval times. NPRM actually does some of this as well. Different consent requirements for children, often times is minimal risk research. Things to think about in terms of flexibility. Couple other arguments is the worry about burdening low risk research. Especially some of the behavioral research funded by the non-profit sector. A lot of people are worried about this. They mention this in the ANPRM comments so I think it’s important to ask whether the NPRM deals with this. Greatly relieving burdens without affording sufficient protections was mentioned in the ANPRM. I think once again it depends on how you feel about the rest of the shebang here And overreach and federal oversight, I think the argument coming from the NPRM is that because these institutions receive federal funding already and also have an IRB already in most if not all cases, that it’s not going to increase the burden a whole lot because the IRBs are already there. And that the oversight is legitimate because those institutions already have a kind of financial agreement with the federal government. Whether or not that’s convincing is up to you. And the other thing is to ask whether this is going to actually solve the underlying problem which is, remember that first picture I had with the question mark about unregulated research are we really getting at unregulated research here? We’re getting at research that’s not federally funded at academic institutions but outside of that I think it’s an interesting question whether we’re actually getting at unregulated research and how much. And people were worried about making industry comply with multiple sets of regulations. The FDA kind of caveat here might solve that problem. It might not, I don’t know. So that’s pretty much my critique, I just want to show you my lovely picture again because I’m not actually that proud of it, but seeing this visually is important. So think about those critiques and to look at what we’ve done with this NPRM and say, OK, are we shrinking human research to ? all together in which case this expansion might not be actually that much of a burden or that much of an expansion. Is it a good idea to carve out clinical trials. Is it term clinical trials going to focus us on high risk research which is also explicitly the purpose of what’s going on here. Which is to say we don’t want to extend the Common Rule to low risk research that’s not federally funded. The purpose really is to focus it on in the language of the NPRM focus it on unregulated clinical trials actually, I mean like drug clinical trials. Is it a question does this definition get us there? And so this is the picture, the yellow is what would be added here in this expansion. I just want to leave you again with the expansion address does it address the arguments? Here are the questions. Some of them are actually explicitly the public questions in the NPRM. Does the definition of a clinical trial make sense? Hopefully it does because the NIH is implementing it all over the place. But are there ways that it could be clarified that would be helpful? Does it serve its purpose? Which I take to be the focus on higher risk studies. And the essential question is having that kind of behavioral health clinical trial in there. Is that acceptable, does it still focus on high risk because as we noticed in the back of the room earlier. Behavioral research and social research can be high risk. It’s not just an issue of identification all the time. Does the inclusion of behavioral health outcomes raise concerns? Is it clear? They ask if they need to define it further. Does the exclusion of FDA related research solve the multiple standards problem? That the industry was very worried about. Does the limitation of the expansion to institutions that receive federal funding, and I guess the one thing I haven’t said is it has to be federal funding for non exempt non excluded research. So if you’ re receiving federal funding for things that under the new regulations would fall outside of kind of expedited or full-board review then it still wouldn’t be covered. But does it create a balance between filling in some of these gaps that we talked about at the beginning and not federally over-reaching too much? And I think a key to think about through the rest of the day is sort of other assessments and do the other changes about you know biospecimens, about consent, about exemptions Do these things make expansion more legitimate than they might have been before when people had grave issues with a lot of the ways that the Common Rule was applied? So in the long sheet of feedback that you were given these are questions number 85, 86, 87 loosely. so if you want to comment on any of these issues you have to kinda go to the end of the numbers of public requested comments, and then I will open it up for questions. Thank you, Dr. Cargill. Just quickly I want to remind folks. From the world you may tweet in your questions or comments. @commonrule2015 #asknprm. You may also email your questions to [email protected] org. In person please make you way to the microphones or you may submit written questions at the podiums in the back. Our first question, gentleman to the right. So, just so I’m understanding this exactly. I at an academic medical center, right. We extend the Common Rule to everything now. This exclusion of FDA means all of our commercial trials are now completely outside of the Common Rule? No. No. So if you already voluntarily apply, so you would have – the FDA exclusion is only, as far as I understand it only for non-academic centers. so, you want to speak to this? Well I think that that particular exclusion is a limitation on this expansion. They can’t hear you. Oh. So that particular language on not applying to FDA regulated clinical trials is a limitation on this expansion. So if you’re already applying it, this wil not bu, this NPRM will not apply it, but i , if you’ll if it already is applied either because it has to be be or because you’ve done it voluntarily the NPRM won’t change that. Right, but thius This seems to create, one, a very strong incentive for institutions to carve out their commercial research because you really have, you got your federally funded research. You’ve got your commercial research, and then your other clinical trials are often internally funded. So many institutions you know defacto run the same rules across all of them. But you seem to be creating an incentive for academic medical centers to carve out their commercial research separate from the other two categories. Is that how this can work? What do you mean exactly by carving out? Well, we have a whole number of you know rules on consent and data handling and you know number of changes. But you’re saying that if quote FDA regulated, so your 21CFR studies become No, so so. That is not intended to exclude things that are currently subject to the Common Rule from being excluded on the basis of being also regulated by the FDA. That’s an expansion or it’s a limitation on the expansion that is proposed in the NPRM. But I see what you’re saying. So say I’m an academic institution that has not checked the box. And currently I only apply the Common Rule to federally funded research. I apply the FDA rule to to FDA funded research and then I kinda do whatever I want with non federally funded and not FDA research would this expansion only cover that third category? Or are the things that are under the FDA at my academic institution also gonna have to go under the Common Rule? My understanding is that it would be the third category as you described So I think your exempted question is an interesting one. Yeah. Our next question. Hello, once again. my question is this. Do you think it’s almost like a Pandora’s box being opened with the extension of the Common Rule? Because it’s almost as if it’s gonna be a class based issue with exclusions. Cause those institutions that receive federal funding are more than likely going to go for the high budget conditions. Cancer, heart disease, so on and so forth. Where consent is usually easier to get and the exclusions are not a really big issue. Whereas as you know we get more get more integration. We have these new diseases and it’s more difficult to cure the common cold, it might not get the research or the look necessary to kinda help solve those problems. And it’s usually in a more in the population is more susceptible to to those conditions It’s just a comment. I was just curious to know if that is something that you see with this expansion of the Common Rule. I mean once- I think it’s an interesting question for me that I think about when it comes to whether this expansion will apply to say service organizations that want to become more evidence based. And so say I am serving an HIV positive population in you an inner city area and we’re all being encouraged to kinda do research to see if our interventions are successful, But if I get any federal funding for anything at my institution, now I have maybe the burden of going through this whole kind of Common Rule process and it may, it may. I guess this is an open question to me whether those organizations can kind of partner with an academic institution and get the kind of infrastructure they need or whether this would disincentivise either doing research or just doing research with the federal government. I don’t know. you know, I think we- how this would burden kind of community organizations that focus on the underserved is a really key question for me. Yeah, Um. I would just add to that if you think that this is going to create a disincentive to do that kind of research, please do submit a comment to that effect. Thank you. Any other in-person questions or comments. Anything from OHRP who is still on the line and listening? Thank you Dr. Cargill Moving right along before lunch. Our next speaker is Dr. Zachary Schrag. Dr. Schrag is a professor of history at George Mason University. He received his doctorate in history from Columbia University. Dr. Schrag studied cities, technology and public policy in the United States in the 19th, 20th, and 21st centuries . Much of Dr. Schrag’s work is focused on the operations of institutional review boards and how these boards, which were established to govern medical and psychological research affect the work of scholars in the social sciences and humanities, as well as journalism. He’s the author of the book Ethical Imperialism: Institutional Review Boards and Social Sciences 1965 – 2009. Dr. Schrag also maintains a blog providing news and commentary about IRB oversight of humanities and social science research. Please join me in welcoming Dr. Zachary Schrag. Thank you very much. It’s a pleasure to be here. So we’ve had some really good questions already from people in the audience. 5 or 6. Of the people who asked questions already, how many got IRB approval to ask those questions? No right? We have the example of Dr. Cargill just before me. She goes to her IRB office and says, what do you think of the NPRM? So did you get approval from the IRB to ask that question? No. I’m not being facetious here. This has been a problem for half a century. Is trying to draw some kind of distinction when we know that there really is a continuum between these kinds of questions people ask each other every day to more sensitive questions like asking about someone’s sexual history or reviewing her medical records to distressing questions of the sort that were raised earlier. To the actual physical interventions, like the spinal taps or murder of clinical research that began our conversation today. So we’ve got a real problem. How do you draw the line between those techniques that need review and those that do not? And the NPRM is just the latest in a very long effort to draw those distinctions. So what I’m going to try to do is explain where it fits in compared to earlier efforts. And how those proposals for exclusions for exemptions that we talked about try to address problems that have arisen in those previous regimes. So why do we need to limit the scope of IRB review? The NPRM starts with the premise that IRB review protects the rights and welfare of participants in human subjects research. Dr. Cargill expressed some skepticism about this basic premise.A skepticism which I share, but if you believe as a starting premise that IRB review helps people you might well ask, well why not expand it to everything? Or do as much of it as possible? and there are three basic reasons that regulators and others have come up with. The first is to eliminate absolute silliness. Like demanding IRB review of Dr. Cargill’s question. In the 1970s the University of Colorado told researchers to get permission before going through a phone book and copying down names. In the 2000s UCLA issued instructions on how to read published letters to the editors in the newspapers. So, like, oh my god. I got the newspaper today. I so I ought to call the IRB before I read it cause I might find out sensitive information. So one of the points here is to try to reduce this kind of absurdity. The second one and this is the main one that has been emphasized in the NPRM is to reduce IRB work load. Basically if we swamp IRBs and IRB offices with every question that any sociologist or public health researcher or quality control person is going to try to ask, we will give them a mountain of work and those truly problematic studies will get buried. It’s the boy who cried wolf problem we’re gonna try to stop that boy from crying wolf unless there really is a wolf and the only way to do that is to shut him up from time to time. And then the third reason, and this is unfortunately barely mentioned in the NPRM is this little work called freedom. We live in a society that is dedicated to freedom, right. We have freedom of press in our constitution and our and the UN declaration of rights there is freedom to seek information. And a lot of people are uncomfortable with the idea of prior restraint of questioning. This is particularly true when we get into journalism, which I’ll come to in a moment. But once you say, well journalists should be able to ask questions freely. You start to ask well who else are like journalists, maybe historians, biographers, we could ask political scientists, law professors. And a lot of people think there are serious concerns about putting too many rules on asking these questions. So we do have to draw the line somewhere. And I’ll tell you right off that wherever we draw the line it will include , impose some burdens on research that shouldn’t get it while freeing up some research that might benefit from review. There is no line you can draw that will magically slice right between the more ethically hazardous and ethically safe proposals. And as Linda Brodski mentioned before, researcher- questions about quality of life for people with diseases is a good example of questions that are not regulated now that are not going to be regulated under the NPRM. I’m not sure regulation is the best way to address them, but some kind of information for researchers and resources for participants would be a great idea. We have some empirical research on this. But currently those are not regulated, and so we have research that shouldn’t get regulation that’s getting it and research that should get it that isn’t. So how do we go about limiting this? There are various ideas that have been tried from time to time. The first one that Dr. Cargill just mentioned is funding. And this goes to the 1960s. The very first IRB regulations, rules applied only to projects that directly got funded by the public health service. that includes the NIH and FDA. If you actually read the statute that justifies IRBs passed in 1974, it only applies to the public health service. So among other things I would say that the expansion to clinical trials regardless of funding is illegal. And if you – well anyway. The, Dr. Cargill also I think very ably explained the problems with the funding. It makes a lot of people uncomfortable to think that if you get your money from the federal government you’ve got these ethical requirements. If Bill Gates of someone funds you, do whatever the heck you want. That’s a little scary. So in general the movement has been away from saying it’s only the funded research that gets oversight. It, it doesn’t smell good. Another early effort was to try to base review on risk level. This is the 1974 regulations they say it applies to any activity involving human subjects risk. This was a terrible risk cause it’s circular. The whole, one of the reasons we have IRB review is to determine what’s risky. So to have someone say, well if it’s risky, you’ve gotta review, well if that tells you it’s risky doesn’t make much sense. That was scrapped pretty quickly. And then a third option, one that has not been tried in this country but has been tried to some degree in other countries, particularly continental Europe, is to narrow the definition of human subjects research. So we have a much narrower definition of clinical trials that specifically looks at health outcomes. A lot of European countries only regulate health research. They don’t try to do behavioral and social research for example. And this is what a lot of Americans would like to see but that was rejected in the 1970s and again rejected in this most recent round. So all kinds of things start out as research. And so what we have instead, and this is what we got in 1981 and what we continued with and what is proposed continuing with is a very broad definition of human subjects, a very broad definition of research, but then all of these exceptions or carve-outs as we are calling them here. Saying, oh yes that would be research except here’s a special get out of jail card for you. And so we started off in 1981 with five exemptions. In 1991 when the department of agriculture joined in we got the sixth one for food quality. And but basically these exemptions come out of 1981 in what I call —– dropped signal— where the promise made in the federal register was that by exempting a number of types of low or no-risk research the largest protion of social science research will not be subject to IRB review and approval. OK, and what that meant was fifty percent or eighty percent or ninety percent they were never terribly clear, but the idea was that most social scientists would simply not call up the IRB office. And that actually worked for fourteen years from 1981 to 1995. I think I have a photo of it, there we go. –dropped signal— a hassle with each other. Contrary to some expectations the anthropologists did not impose a reign of terror on the United States. the geographers didn’t murder too many people. So that kind of worked for 14 years. But then it broke. I’ll spare you the whole details, but this is the document that broke it. The OHRP, the Office of Protection in Research Risks sends out this newsletter and says, guess what. New idea. Investigators should not have the authority to make an independent determination of what’s exempt and should check with the IRB or other designated authority. And so what does this do? This basically tells researchers you need to write a proposal and get review to see if you need to write a proposal and get a review. Technically, not a requirement, but if you make a suggestion to institutions that depend on you for your support they’re going to do what you suggest. And so since 1995 overwhelmingly academic and medical institutions have followed this advice. They put some kind of formal requirement on the exemptions. And already by 1998 nearly three quarters of IRB administrators said that their IRBs were routinely involved in deciding on exemptions and less than half the protocols eligible for exemption were actually getting it. And that’s pretty much the world we’ve been living in for the last 20 years. So for example my old employer, ? College puts up — dropped signal– if I am exempt does that mean I don’t have to go through IRB review. No. You still need IRB review. So exempt doesn’t mean exempt. We had this in our first presentation, right? It was a slide showed you those levels of review and exemption was one of those levels of review. That’s a pretty good depiction of the way the system is working now. It is also complete betrayal of the promise made in 1981. So, we’re the exemptions are just broken. This could be justified if IRBs and IRB staff had some magical book that told them that some things deserved exemption that the researcher just didn’t have access to that information. And if you look at the defenders of the current system, they suggest that. Researchers don’t know what the exemptions mean, but IRB staff do. There is no evidence for this. We, if you actually look at studies that have you put the same proposal to multiple universities for example you find wildly inconsistent results from IRB different IRB offices about what is and is not exempt. Or the wild over-regulation. For example, at my old university we had an IRB meltdown a few years ago. The consultants came in and found that most projects that deserved exemption were not getting it. So IRB staffs don’t know what they’re doing, researchers don’t know what they’re doing, we’re basically all guessing together. So that was the main thing that happened to break the compromise of 1981 was that exempt no longer means exempt. The other thing that happened was, again due to federal pressure, IRBs started reviewing kinds of things like oral history and journalism that had simply not ever been reviewed. Not in the 1960s not in the 1970s not in the 1980s. There were some efforts to carve a work-around about this. One of the things that happened was journalists and historians in particular sorta said well, we might be doing research but it’s not research as defined by generalizability. This was pretty nasty. Cause, we love research, right? This is what historians and biographers do. But we don’t like these rules It’s it’s awkward to say that we’re not doing research and it’s largely ineffective. A few universities have freed up their oral historians. Most of them have not. And so we’re in this kind of Alice in Wonderland world. Mitchell Seligson a political scientist has a nicely titled article from a few years ago. Exempt is non-exempt and research is non-research. And that’s pretty much the world we live in now. Where the current categories have been tortured beyond regula – regular meanings of the words. And that’s what the NPRM I would say is designed to fix with its new processes of exclusion and exemption. So as you heard, this process started in 2011 with the Advanced Notice of Proposed Rule Making that acknowledged the problem of over-regulation. And continues with the 2015 NPRM. And what the NPRM tries to do is expand and clarify that list of activities that either do not need any kind of review or needs much less review than they are currently getting. And it always, you know, The NPRM is very hard to read. there are all sorts of cross-references but by my count I believe there are something like 11 categories of excluded right – excluded activities and six of exempt activities. And I want to just go through some of these efforts to return us to that earlier stage of lessened regulation. So to start with the excluded ones, One thing the NPRM is trying to do is restore the meaning of the term research. And they use this term excluded, which is sort of an odd term. Because usually excluded means that you’re not getting into something. Oh, I got excluded from the night club. Not, oh I got excluded from paying taxes. you know when you get away from paying taxes you say yay, I’m exempt. So in some sense exempt would be a better word for this if 20 years of mis-regulation hadn’t beaten that word into the mud. We’ll go with excluded for now. And as you heard, this included a bunch of routine government work. Like law enforcement and intelligence gathering public health surveillance. It specifically includes oral history, journalism, biography and historical scholarship that focuses on individuals in part, and again they don’t use the word freedom, they say in part because these individuals deserve public scrutiny. We just have a great example of this. There’s a new biography of the first President Bush that’s about to come out. And it’s all based on on-the-record interviews with him and it may damage his reputation. You know it, he says terrible things about Dick Cheney and Michael Dukakis and so forth. And if that damages his reputation, that’s fine, right? That’s part of living in democracy is you get to say bad things about former presidents. Or current presidents. So one of the things the exclusions would do would be to free up this kind of question asking that is not designed to do no harm. As the first slide said. Right? It may be beneficence in the biggest picture, but we’re not trying to let people avoid accountability for their public actions. And then it also included a bunch of low risk activities that you’ve heard about. For example if you’re not collecting identifiers or not gathering sensitive information. So a lot of the work load disappears from th IRB in boxes right there. The second slice as you’ve heard are these exemption categories. Some of these are in there, for example , if you’re trying to figure out classroom instruction and want to do a test it’s exempt now, it will remain exempt. Same with taste and food quality. A very big one that we’ve heard a little bit about are these benign interventions. The puzzles and the games, why do we need that? Well a lot of our IRB work now is covering these routine psychological experiments often done on or by undergraduates where they have you estimate the – how much you would pay for a piece of chocolate. Or, you know, have you walk down the hallway, or something like that. And so this is a huge burden on IRBs that probably doesn’t really have to happen to protect anyone. We’ve got difficult wording of further exemptions on talking to people. If you just did the NPRM town hall on October 20 there were a couple of questions about ethnography as done by sociologists and anthropologists. And ethnography, the word does not show up in the NPRM. But Julia Gorey at OHRP explained that it might well be exempt or excluded under some of the NPRM provisions. And for part of the same reasons as we’ve discussed already If you don’t like the question don’t answer it. So this could again take away a lot of the burden from IRBs. One problem that we’ve seen with IRBs is that the federal inforcement only goes one way. IRBs are too lax down comes the hammer. If they’re too strict their faculty aren’t happy, but the federal government doesn’t care. And there isn’t much in the NPRM to really relieve that problem except perhaps this idea of a web-based decision tool, where, you know, a researcher –currently the researcher has to fill out a lot of forms, go through a lot of training that may be completely inappropriate. Exemption can take a few hours it can take up to four weeks at a lot of institutions, it’s a major hassle. The proposed decision tool researcher is sitting there in his pajamas at 2AM goes online, fills out some yes and no questions and the exemption is now on record. So that if the institutions adopted that, that could really reduce a lot of the burden on the researcher and allow these projects to proceed. So I’m somewhat hopeful that we can get back to the state where historians, sociologists, political scientists, folklorists, linguists, geographers law professors, anthropologists, and all others who — in the latest —- FDA regulation without waiting for weeks to get approval. some of these scholars will have to spend some time on computer screens, others will be excluded entirely, But I hope that the majority of them will no longer be subject to the delay, and quite frankly the crease that they now face when submitting their proposals for review. Now there will be controversy, again. I promise you wherever we draw the line i t will make some people unhappy. And there will be some controversies over specific projects. The most recent one from summer 2015, the controversial book was On the Run by sociologist Alice Goffman, who lived with and described the lives of impoverished residents in Philadelphia. And may or may not have driven a getaway car in a murder plot, as sociologists do. But this is IRB reviewed research. We’ve had controversies like this in the 1960s before the IRB system was extensive, we had them in 1970s during the first wave of regulation. We’ve had them in the 1980s when things were deregulated. We’ve had them since the 1995 repealed the compromise, we’ll have them in the future. Not very often, once in a little while that’s pretty unavoidable in a free society. What we don’t have is any evidence that any one of these systems are better or worse than another. So again, if you’re worried about researchers making these determinations I ask you to go back to that period of 1981 to 1995 Ask yourself was it really that bad. Again, you can certainly find examples in individual projects that could have been done better, but they are very rare and it’s very hard to write a regulation that takes care of the rare event without putting undue burden on the more common ones. So again, the IRB, NPRM justifies this reduction primarily in terms of work load. They want to reduce time and effort on the lower risk projects in order to focus more attention on the higher risk projects. And again, I think that’s a very noble effort if you think that IRBs protect people from more dangerous projects. I think there’s a lot of questions to be asked about that including questions from some people at NIH like Christine Brady, But at the very least it would be very nice to focus attention on the projects that could potentially benefit from the most review. And then buried sort of in the NPRM is the idea that enabling lower risk research to go forward is a good thing. And really buried even deeply there is this idea that it would respect autonomy. That’s kind of a code word, but it’s an important on for two reasons. First of all, autonomy is one of the magic word of research ethics. Since the 1970s it basically means that people would be allowed to make decisions for themselves. And in this case it specifically means that yes, people should be able to you know consenting adults should be able to decide whether they want to speak with other consenting adults. You get a survey on the phone oh, this is probably a push pull from an opposition research , well that’s ok I’m going to talk to them or you hang up the phone. Or this is a sociologist calling me up wanting to talk to me. Do I want to talk? Yes, no, it’s my decision not to interpose some university office between me and the researcher to make that decision. So when we say – when the NPRM says autonomy, it may actually be referring to this concept or it only appears once in the NPRM and then only in reference to the Freedom of Information Act, but there is this missing concept called freedom. And this may be as close as the NPRM gets to acknowledging the fact that freedom itself is an ethical value. So to sum up, for the past 20 years the federal government has not required but strongly suggested that universities review a whole lot of research in ways that has produced anger and despair, and it may be time to try something else. Thank you. Thank you, Dr. Schrag. Thank you all for joining us. We have just heard from Dr. Zachary Schrag, professor department of history and art history at George Mason University regarding proposed changes to the federal regulations on human research, specifically, exclusions, exemptions, and the determination process. We are now open for questions. Which I remind you you may tweet in @commonrule2015 use the hashtag #asknprm. Or you may email your questions to [email protected] Our first question the gentleman on the right. I guess, certainly I must say as a disclaimer, I am suffering from PTSD as a former IRB member. I guess one of the examples you gave, though were psych students and psych studies. And as somebody that looked at those, they are often of the form you can sign up for 2 one-hour studies or you can write a 40 page term paper. Your choice. So there – we have a lot of cases where, you know, and we are seeing this especially with our mobile society, where you want to do, you want to purchase something, well you have to sign up for binding arbitration by a religious court. We’re starting to see some of those occurring in some of the red states. And people say, well that’s, autonomy. You cannot buy that product. Or you can choose to not be a psych major. Or you know, at what point, we’ve had enough cases of researchers bending the line on what is autonomy that, are we really comfortable with giving them that freedom back? Because they have a his- part of the idea is you want to have a neutral observer to decide whether there’s coercion but in some ways it seems like we’re giving researchers the ability to just say no this isn’t coercive. I’ve seen many studies that come through that say, we’re only studying doctors, so it’s not human subjects research. Most of my doctor friends actually believe they are human. So, couple of great points here. First one is, I mean this really goes to the question of, do we think the system is currently working. And there are some good IRBs out there, there are some bad ones. One of the terrifying things, if you believe in the system is to realize how inconsistent it is. So, Laura Stark over there has done some research on this, gave the same proposal to 18 IRBs, got 18 answers more or less, right? So at some level if you really believe that requiring those psych majors to participate in that subject pool is coercive, doesn’t it terrify you that you’re doing you’re saying that at Northwestern and down at the University of Chicago they come up with a different answer? Right? That should be terrifying to you – that there is no central system for collecting this information. The ANPRM actually proposed some kind of central collection system, the NPRM syas nah, that’s too hard, never mind. So the IRB system as we now have it is not empirical. We don’t know if people who are being asked about quality of life after mastectomy are suffering. We have some information on it. IRBs are not required to act on that information. The claim earlier that you have to have a cardiologist on an IRB reviewing a cardiology study, that’s simply not true. It would be nice if it were true, but IRBs all round the country you could have an IRB follow people who have no idea what goes on in the psych major pool who are ruling on that study. So I don’t think the IRB has any magical power to decide what’s coercive or not. Robert (Sisman?) came up with a recent book. One of his examples there was a consent form that says either the consent form says you must fill out the form or you must complete the form. And the IRB said either that fill out was coercive and you had to change it to complete or complete was coercive and you had to change it to fill out. I don’t know cause they’re synonyms. But this IRB was just making stuff up. So there are a lot of things, if you really believe the IRB system worked then yes, the exclusion the exemptions are troubling. All the empirical research we have over the last 50 years tells us that the IRBs are pretty much throwing darts at the dart board. And so why not let people go. Yeah, I’ll leave it at that. The other point about binding arbitration, there is this concept of minimal risk. Based in part on everyday life. And one of the efforts of the NPRM is to say, yes, if a student goes through the day with the click through licenses and the arbitration agreements and you know I came in here in a taxi where the taxicab driver had both headphones on and no seat belt, right. Is it rally that awful to ask the student to decide you know, prisoners’ dilemma game? This is really not what we want to spend our public health and university resources worrying about. Next question. Hello, I first want to say that I really appreciate your participation on the panel. I looked at the schedule today and just nearly every presenter has a health background and is talking about research in health. And so, I do educational research , curriculum development and classroom and we are really overburdened by the medical model being applied to our work. I whined about it to my NSF program officer last year and he said, oh. I bet you’re at an institution that has a medical school, aren’t you. And yes, indeed I am, and I guess I won’t identify it because some of my complaints are specific to the institution, but I think part of the problem is that they really are just trying to do their job meeting federal regulations, which as we see by what’s being discussed really is built on the medical model. So I appreciate your comments. So one thing you said, it’s hard to draw the line and one thing it’s done is when you go to and there are two different review panels there’s the social and behavioral research, but I’d like to suggest that educational research is not doesn’t fit well in that. What’s going on in the classroom with kids is so, here’s an example. My, so we had a project where we give teachers they’re trying our new curriculum, so the school gets free books, it’s an after-school program. School gets free books, the kids can sign up to be in this after-school club and you know it’s all known about it. So we prepared our consent forms, submitted to our IRB. Three weeks later we get a response that says, oh, but what are you going to do to protect the confidentiality of the participants. Well, it’s not at all confidential. The teacher is advertising this club in her school. It’s not at all confidential. Everybody knows they’re in this club. But that was three weeks before we got that response so then we had to address the question. Then it was another 2 weeks before we got that response. It actually took us three months to get a minor revision in our consent documents this past year. So it’s just the burden of these kinds of things because we’re put into that model. Let’s see if I had another – – Oh, another thing, our teachers were classified as researchers. And the reason is, we’re going to pre-test and post-test to the kids. That means they are handling research data. Well in normal every-day classroom procedure teachers are handling exams. It’s part of their job. And they know how to do that in a confidential way. But because it’s now research data we are, there’s lots more paper- oh they’re researchers so then the school has to get a FWA number and you have lots more levels of certification. So I would like to make the point that oh, and why are we not exempt? –it’s very nicely laid out that if you’re doing normal classroom things that’s exempt. But as soon as the researcher wants to say anything in the classroom, maybe to co-teach with the teacher, then it becomes, it’s not exempt any more. And it’s expedited and you have to go through all the procedures and stuff, so that’s my comment and I appreciate your perspective. Let me just address a few of those. I can’t address everything. But first of all, The medical model maybe works at institutions with medical schools, but it is pretty much baked into the system because these regulations came out of public health service and have never really changed. And we saw a good example of this again at the previous NPRM event in Washington, where anthropologists had written some comments and Julia Gorey of OHRP said, very frankly, we didn’t address ethnography because we didn’t know anything about ethnography. Now at the ANPRM stage the anthropologists had written in and said, please leave us alone, essentially. We have the sort of book length proposal ? from the National Research Council that came out in response to the ANPRM that proposed more of an expert body on social research. NPRM ignores that. So a lot of this stuff is actually coming down from the feds. And this required training at many universities with or without medical schools is the city program, which was developed in a medical school. So the medical model is deep here. Very hard to get out. The second question is sort of about exemption and one of the issues here, again, is that the regs currently promised expert review but don’t deliver it because you have an educational project being reviewed by someone who has never done that research. And one of the flowers that might bloom in the sunshine in the NPRM would be to have an exemption and a real one where you click on the computer screen and then you’d actually go to a department committee that would know stuff about educational research. So at McCalister College which is an undergraduate institution, I’m not sure if they get any money, they have their undergraduates have their projects reviewed by people in their field. So if you’re doing a geography project you talk to geographers and say what are the ethics of geography and not try to ask the nutritionist and the cardiology and the community member what do you think we should do. So it would be great if deregulation did not mean a lack of oversight but rather a shift to truly expert oversight. And then, finally, again, if you’re wondering about the decision tool, why it is the way it is, one of the ideas is to get rid of that three month delay because that is unconscionable. And we’ll take one more question. Here or here. to out right. I really appreciate Professor Schrag’s allegiance to autonomy and I’m for autonomy too. I mean autonomy is a great thing and for interviews and surveys you know, people can hang up the phone, walk out of the room, tear it up, that’s great. So much of the exclusion. Let me back up for just one minute to say that you present data to indicate that when people submit for an exemption half of the exemptions are denied. And additionally there are there’s evidence that enormous inconsistency between IRBs and what they judge to be exempt. And you conclude from that that the system doesn’t work and we should step away from the system. To me it’s terrifying to think that half of the people who already go through exemptions believing that they are exempt do not get exemptions, that doesn’t lead me to a direction to think we should then exclude these categories and allow them to make the decision to exclude themselves in the new classification. I’m led to the opposite direction, and not back to the autonomy which autonomy works beautifully in 99.9% of surveys and interviews. I agree with that completely. So much of the exclusion and exemption, though, is in situations the use of data where surveys and interviews are not really in play. And it’s the use of your data without consent, which actually is a reduction of autonomy. And speaking to whether this is an expansion or reduction of rules, I would argue very much a reduction, and this autonomy part comes in in particular where we used to have a waiver, we’re saying now that we’re having additional protections without the waiver but in fact, waivers required that it not be practicable to get consent.And that is a very simple and obvious test. You’re doing a retrospective chart review, not practical. I would say across the board, not practical, even though there are many cases in which it is. So let’s just say, not practicable. You have somebody in your office and you’re going to use their data, in my opinion, with respect to autonomy, there’s every possibility of asking that person’s permission and no excuse not to. So… Yeah. So on the first part, the studies that I refer to don’t show the researchers have made the wrong determination, They show that the research offices, the IRB staff are getting it wrong. Now what does wrong mean in these contexts? A lot of these exemptions are terribly written. And so you know some level is, there’s not really a right answer. But to the extent that someone with maybe a little more expertise comes in and reviews, well here’s what the researcher said, here’s what the IRB office said. What they are finding is that the IRB office is getting it wrong. Again, what wrong is is kind of blurry here, but that’s what the limited data that we have has found. Now I’m blanking on the name, but there was a posting a few years back on the ? bill of health, where one of the members of ? which is one of the federal advisory commissions said, you know. Researchers don’t have the knowledge to make the exemption. And I see it all the time at my IRB and I dared her online to tell me which exemption cause there are six. I said if you really have this data, tell me which exemptions the researchers get wrong. She didn’t answer, cause she was making it up. I’m gonna say that right now. I will bet her a box of chocolates right now that she did not do that study and was just making up the claim that researchers were getting this wrong. So these are good chocolates ? good chocolates. Now, uhm – I could tell you right off but the rule was changed, but with the existing Common Rule one that got wrong continuously is identifiers. Whether something is identified or not identified. You will ask them not only is this identified is it identified by code or by or blah blah blah– You’ll say does it include any of the 18 HIPAA identifiers and they you’ll say does it include names? does it include medical record numbers? Does it include date of birth or any other elements of birth. No no no no. You look at the data collection tool first thing there is name, second thing there is medical record number. You go back to the researcher but you said it’s not identified. Oh no no no I’m not using identifiers I’m just keeping my records straight. Or I’m you know I would never think of putting this in an article. Have you published that finding? That researchers regularly get identifiers wrong. What was that? Have you published that finding? Oh, sure. I haven’t published it but I’d be happy to. Please do. I mean this is the thing. We’re talking about this. The whole system, we’ve had this 50 years and have almost no information on how it’s working or failing. Correct. We’re in agreement there. Thank you Dr. Schrag. Can I get a round of applause for all of our morning panelists. We’d also like to move right along here to the break. We’re about to take a break, but I want to acknowledge OHRP who is on the line and taking questions and listening to comments and so forth. We are here in the fourth session being produced by the amazing people at Vanderbilt CTSA Consortium Coordinating Center. and we’re talking about the proposed changes to the federal regulations and soliciting comments and discussion around these changes. And have expert panelists here to give us this information to kind of get the brain thinking and to get things moving along. We’re about to take … couple of housekeeping things. One. Any of the discussion comments other types of questions that you’ve sent in via twitter and email or put in the bowl through written comments or in person comments these are not formal submissions. Comments to the proposed changes to the federal regulations for human research. To do that you must go online On your screen is regulations.gov. It gives you the directions there on how to do that. You may also do it by mail, you may also do it by fax. The other thing is that we want to make sure everybody has an opportunity to look at all of the sessions that have been produced. You can go online to do that. For your participation today you will be sent an evaluation and assessment. And that will include a link for you to go back and check all of these the various sessions that have been recorded. To have comments and questions from all of our panelists from all of these sessions with the fifth session happening in a week to two weeks. OK. We’re taking a break. Fifteen minutes we will resume at 12:15. For the folks that are here in person, up the stairs and in the lobby are your boxed lunches. for those streaming in stretch your legs, get a drink, do what you need to do. We’ll be back at 12:15. Thank you so much. Welcome back. Thank you for being so prompt and for getting back. for those live streaming in, we are back Again this is the fourth of five listening sessions regarding the proposed changes to federal regulations for human research. We are are live from Evanston, Illinois. Just outside of Chicago. To remind you the 90 day open comment period for the Notice of Proposed Rule Making changes is open and we’re providing these sessions to make sure everybody has information so that they can use to make comments regarding the proposed changes and have access to our expert panelists as well as experts and distinguished associates at OHRP who are on the line as well. A quick reminder. You may tweet us your questions @commonrule2015 #asknprm. You may email your questions to [email protected] Another public service announcement. Comments made here or questions that you send in or have written are not formal comments to the docket. to do that you must go online to regulations.gov. We have the instructions there for you on the live stream. There’s also a fax number that you can use. We want to make sure that we get those comments. We’ve had great discussions so far and so let’s get right into our afternoon program. The next session is on quality improvement in the NPRM. We have Dr Ryan Spellecy. Dr Spellecy is associate professor of bioethics and medical humanities and psychiatry and behavioral health at the Medical College of Wisconsin. Dr Spessecy received his PhD in philosophy from the University of Utah. He has authored and co-authored numerous peer-reviewed articles in the area of research ethics and informed consent, ethical issues in psychiatry and community involvement in research. Dr. Spellecy is the co-PI for the Blood and Marrow Transplant Clinical Trials Network for the study evaluating a novel easier to read consent form for blood and marrow transplant trials, and he has served as an IRB chair at the Medical College of Wisconsin for ten years. Please join me in welcoming Dr. Spellecy. Thank you. Am I close enough to the mic for the folks in the back? Get a little closer. OK. I’ll get as close as I possibly can. So thank you to NCATS and C4 for putting this on. I’m very excited to be here. I bring, to NCATS I bring greetings from the northern CTSI, the Southeastern Wisconsin CTSI where I’m located. And I want to talk briefly today about quality improvement in the NPRM and some clarity that I see arising out of the NPRM when we make these determinations around quality improvement and human subjects research. And I that this definition has been addressed earlier in the morning but I want to bring it up again because this is important and I want to focus in on certain aspects of the HHS definition of human subjects research. And I’m using the HHS definition under the current regulation of human subjects research because when we’re talking about quality improvement and whether something is quailty improvement that does not require IRB or a quality improvement activity that is human subjects research and thus requires IRB review we’re usually talking about HHS regulations. So I’ll use the HHS current regulation, explain what we’re talking about. And then I want to move into how things, I see are different under the NPRM. So IRBs as we all know are charged by the federal regulation with the review of, I commonly put it simply, research involving people, but it’s not that simple because we have some very artful definitions that we have to apply to whether IRB review is necessary or not. It’s really a question of human subjects research where a human subject is defined as a living individual about whom an investigator is conducting research, obtains data through interaction with the individual, or identifiable private information. CThat’s the easy part for my discussion today on quality improvement. The trickier one is research. And research under the HHS regulation is defined as a systematic investigation including research development, testing and evaluation designed to develop or contribute to generalizable knowledge. And I think the key under the current regulatory scheme of – for us when we’re talking about is it a quality improvement endeavor that requires IRB review or not. It’s gonna hinge on that last part. Designed to develop or contribute to generalizable knowledge. It’s largely a quesion of design on that last portion of the definition. And I often phrase this in terms of the purpose or intent where if the primary purpose or intent is to contribute to generalizable knowledge it is probably research. And that’s where we draw the line between human subjects research and quality assessment as it’s sometimes called or quality improvement. Here I’m using a definition from a common IRB reference book. We call it Amdur in the field. And it says that activities that are designed to determine an aspect of medical practice are being performed in line with established standards is called quality assessment. when an activity is specifically initiated with the goal of improving the performance of medical practice in relation to an established standard the activity is called quality improvement. And the key there is, I think, in relation to an established standard. There’s a sense in which all medical research in which we engage is intended and initiated with a goal of improving the performance of medical practice. That’s why we conduct medical research is to make the practice of medicine better. What distinguishes research from quality improvement then is not just that it’s intended to improve medical practice. If that was the definition much of what we do in medical research would be quality improvement and not research. But rather if that this is initiated with the goal of improving the performance but in relation to an established standard. So there’s some national standard. Some consensus guidelines what have you. And we are initiating something to see alright how well are we hitting those targets spelled out in this agreed upon established standard? Now. IRBs, and there is much consternation about this and angst, and I’ll be using consternation, angst and anxiety a lot today. but IRBs typically would apply intent litmus to determine if what you were doing was quality improvement that is not subject to IRB review or quality improvement that is human subjects research and is subject to IRB review. And the way a lot of IRBs my own included when I started off, use to make this determination was a sort of a look. Investigator coming into my office. If you think there’s a chance anywhere down the road that you you might publish this or present it at a regional or national meeting we’re gonna have to call it research, you’re gonna have to submit your application, we’re gonna have to review it. Fortunately that’s the sort of old litmus test that we don’t use any more at most IRBs around the country that I talk with. And this is anecdotal conversation, but most of the IRBs which I’m familiar with don’t use that If you ever think you might publish we’re gonna call it research. Rather, we’re looking at things like, and this is from that, we heard about that flexibility initiative earlier, this is looking at the primary intent. And looking at the design question in that HHS definition of human subjects research. We tend to now say look at the primary intent of the project is to create generalizable knowledge it is likely research. If however the primary intent is to internally assess or improve your practices, or check whether you’re hitting those metrics or agreed-upon guidelines then it is likely quality improvement. Now the important distinction there is and often-times when we’re having conversation with study staff or investigators or colleagues we’ll say look. Just take them aside and say look, why are you doing this? If at the end of the day when you undertake what you’re calling a QI project and if at the end of the day you are able to assess whether you’re in line with the national guidelines around something like cardio-pulmonary resuscitation, and you’re able to assess that for your organization but you never find anything to get published and you never find anything that’s really worth presenting at a national meeting will you still feel like you were successful. And probably in the majority of cases if the answer to that is yes, what you’re doing is something like quality improvement and not research. Because your primary intent is to assess or improve your practices. You might find something along the way in implementing this national agreed-upon standard that you think is worth sharing with other institutions for your experience in trying to meet this standard or evaluate this standard, and if that’s the case, we want you to share that. We want you to publish that. Again, because we want to make the practice of, in my experience medicine, but others as well, we want to make the practice of medicine better. We want to improve things. So if you find something out you might want to publish it, come back and check with us as the IRB and we’ll help you along that process. That’s the goal of how we look at quality improvement versus human subjects research today under the current regulatory scheme up. And in keeping with Dr. Cargill’s slide, I too have limited skills and in word art, but this is how I describe it. You’ve got your venn diagram with your domain of human subjects research. Not all human subjects research is quality improvement. You’ve got your venn diagram of quality improvement, not all quality improvement is human subjects research. But you’ve got overlap in the middle. And this is where the anxiety lies. This is where, as one of the commentators in the morning session pointed out, there’s a lot of, I believe it was it was investigators thought that it was scary to make determinations like these themselves. It wasn’t specifically in the context of QI but I’ve heard this anecdotally from colleagues at my own institution. People are nervous. And they want the IRB to weigh in and say, yeah, yeah. You’re OK. It’s quality improvement. You’re fine. It’s that gray area that overlap of the diagrams that causes a lot of anxiety or angst among IRB members and IRB folks because we don’t want to give the wrong advice. And among investigators as well because they don’t want to run afoul of regulatory schemes or IRBs. And its this sort of overlap area that was discussed in a previous session that NCATS put on about the now-famous life-saving checklist with Hopkins and Michigan Hospital in which they rolled out a check-list that involved such benign interventions as reminding surgeons to wash their hands to try improve the practice of medicine. But the way it was conducted was in that sort of gray area, that overlap where is this human subjects research or is it quality improvement. Why does it matter? Well if the project is QI, if it’s in that zone of QI that is not human subjects research, certain federal regulations governing conduct of researchers don’t apply. And they might determine, or you might consult with your IRB, and we might say, yeah. You’re not human subjects, your project is pure QI. It is not human subjects research. And as a result you’re not under those regulations that require things like informed consent or at least applying for a waiver of informed consent. And an informed consent that has to have certain elements. And continual review where you check in with the IRB at least once a year and let them know how your project is going. So there’s a lot resting on this as to whether or not currently under the regs something is QI in that pure sense as in not human subjects research or if it’s in the overlap area of QI and human subjects research. And I see as I read the NPRM in the majority of cases, I see the NPRM as it relates to quality improvement as an attempt to pull quality improvement out of the realm of human subjects research by exclusion. So that we can avoid that anxiety and that confusion of those overlap areas where we have projects that seem to be both. Unburdening researchers and IRBs as well, and the issue of what if I find something in the course of something that’s QI that I think is worth sharing my experience with other institutions publishing, presenting what-have-you. Still improving the practice of medicine sharing our experience but not having that undue regulatory burden. Sorry. And again, I think this comes down to intenet. If you see now we’re moving into what we see in the NPRM again, this comes down to intent. As we see in the NPRM this category and that’s QI, and by the way QI is the first… the first category of projects that is granted an exclusion I don’t know if there’s any significance to that, all I know is it wasn’t done alphabetically, but this category is excluded because these activities are designed for various administrative purposes related to using information to improve quality of services provided by a specific institution and are not designed to produce generalizable knowledge. And as I read that, that doesn’t say and ye shall never publish anything you find so help you God. But rather, this is a question of intent and design. So if it designed to produce generalizable knowledge if that’s the purpose, the primary intent, it’s gonna be human subjects research, but if the primary intent is to, as the NPRM says, improve the quality of services provided by your institution, it is excluded. So, an example. Here’s an example of what I think would be QI under the NPRM. Let’s say we want to look at our national guidelines for how we conduct CPR at a hospital. And we know what the national recommendations are, we know what the national guidelines are, but what we want to know is say, when somebody comes into the emergency department with a cardiac event that requires CPR, how well are we performing CPR as we’re supposed to be performing it. According to the national guidelines. If you wanted to institute a project like that to assess how well you’re doing it, or institute a project to bring yourself up to that standard, as I read the NPRM, that would be excluded as QI and not subject to IRB review. However, the NPRM helpfully gives us examples of projects and activities that would not meet this QI exclusion and this is tough, I think this is a great example because my colleagues who do QI, there are certain buzzwords in here that would lead one to believe that this example could be QI but the NPRM is very clear in saying no, no. This is not being quality improvement. And it says, an example of an activity that would not satisfy this exclusion, this quality improvement exclusion, is a prospective observational study of patient treatment to analyze the comparative effectiveness of two different standard of care treatments frequently used to treat the same medical condition. Now what makes that look like at first glance something that might be treated as quality improvement is things like comparative effectiveness. And two different standard of care treatments. And what that’s getting at is, look these are two different treatments that are routinely used standard of care. In fact, you might get one or the other depending on which physician happens to be on call when you enter the emergency department with a cardiac event. However, according to the NPRM you are doing a prospective observational study of those treatments to analyze their effectiveness. And they’re two different standard of care treatments it would not meet the quality improvement exclusion. Sticking with CPR, imagine a you want to do a randomized trial. You have two different ways of performing CPR. Say for example you’ll give a certain number of chest compressions in a ratio to breathing. How many chest compressions to how many breaths you give, say that there are two different sort of standards out there that people routinely include, and this is the case, especially in ?? and EMS systems that can vary depending on where you happen to find yourself when you suffer a cardiac event. So some emergency medical systems will use one ratio of chest compressions to breath and another one down the road, say you have a cardiac event here in Evanston, you might have one ratio of compressions to breath and then if you have one up in Milwaukee or down in Chicago with a different EMS, you could very well get different form of CPR. A different model of CPR. Still CPR, but we don’t know which one’s best. They’re both sort of standard of care because they’re standardized in those different locals, But you want to randomize people to find out once and for all which one’s better. That’s not gonna meet the quality improvement exclusion. You’re doing a prospective trial of two different standard of care interventions. I threw in randomization to make it more stark, but that’s not going to, even though, even though we’re trying to improve the practice of medicine and find out which way of CPR is best, it’s not going to meet the criteria for the exclusion. And it’s going to be under the NPRM some for of human subjects research. So, I see some benefits to this in the NPRM. Excluded versus not human subjects research it’s less confusing for researchers. Researchers who continually conduct quality improvement, as Dr. Schrag helpfully pointed out, I wrote it down cause it’s just perfect. He said it’s awkward to say we’re not doing research we call it not human subjects research in Europe. whether you’re a historian or a sociologist or a quality improvement specialist, when we carve out what you’re doing and say, oh, you’re not doing human subjects research. It sends a bit of a mixed message to the researcher, the researcher who publishes this, who writes these papers, presents at national meetings an it counts as research for our job, for our career, but then it sends this odd mixed message of this sort of artful term of human subjects research to say you’re doing not human subjects research. I think it’s a little more simply helpful to call this excluded than not human subjects research. Maybe in ten or twenty years from now we won’t think this is helpful, but at this, from this vantage point I think that’s a helpful move. Two: hopefully this will allow IRBs, this will free up their time to focus on higher risk research. So if they’re not reviewing excluded quality improvement where you’re looking at a national standard and trying to bring your practice in line with a standard, as opposed to in someone’s clinical practice they might decide, you know I think it would be better if we did this procedure or this drug in this way. I’m going to test to see if that improves it. That’s coming up with your own standard. We’ve got a national standard based on evidence, based on consensus, that’s difference than an investigator initiating a trial, and IRBs can be freed up to focus more on that higher risk research. And lastly, I think one of the benefits is less confusion for IRBs and investigators on that determination of if, when it’s both quality and human subjects research what am I supposed to do with it? Where do I fit in that venn diagram world of QI and human subjects research? I see the NPRM as making those lines much more clear between quality improvement and research and that, too, I think is a good thing in the NPRM. I have a few concerns that I want to throw out there. And this has been voiced before. The determination of whether something is meets that QI exclusion will largely be left to the investigators. There’s a proposal for a checklist or flow chart which is great if done correctly and Professor Schrag rightly admonishes us with evidence from… with evidence from the literature that IRBs are very often inconsistent at making such determinations themselves. That’s true. We don’t have any evidence, though that investigators, that I’m aware of are necessarily better at making these, these determinations themselves. And so we have excluded activity that doesn’t require things like consent, doesn’t require on-going oversight, which can be problematic. I would say let’s be very careful about how we train our colleagues and our investigators about making these exclusions. But then I’m reminded that IRBs have lots of training on how to apply these exemptions currently and we are, as a whole, as demonstrated in the literature, not the best at applying these exemptions. And so I have some concern that investigators I have no reason to believe, I should say, that investigators will be any better or any worse at applying these exclusions. But the last one is a more ethical concern. And that’s informed consent. And so, in quality improvement and a number of the other exclusions, as a result of being excluded, informed consent would not be required. And my concern here is informed consent is one of the primary ways in which we uphold the ethical principle of respect for persons. It’s got elements of freedom, it’s often a synonym for autonomy. But it’s the idea that if we are doing research excluded research, but still research, on your data to improve the practice of medicine typically we think that we ought to somehow engage you in that process, to let you know that we’re doing it. Maybe we don’t need to get your permission in terms of consent, but this is an opportunity to hit a pause button and say, OK, how can we more meaningfully engage the public that comes through our doors and we’re going to use their data and their experience to improve the practice of medicine, how can we better engage them in the discussion around this . If we’re not going to get their consent to make sure we respect them as human beings, and the… their right to control their information to some extent. Even if it’s not with informed consent to adhere to respect for persons. And I believe yeah, that’s the last of my slides. We’ve just heard from Dr. Ryan Spellecy, Assoc. Professor of bioethics and medical humanities and psychiatry and behavioral health in the medical college of Wisconsin regarding quality improvement in the NPRM. We are now open for questions, comments, both in person at a live mic or written and deposited in one of our bowls at the podium. Or from the world, you may tweet your questions to @commonrule2015 #asknprm or email your questions to [email protected] Our first question. Hi, thank you, Ryan. Maybe this, I struggle with this distinction a lot and I feel like you said things that sounded clear but I don’t know that they clarified it for me, so I want to kind of push you a little bit, and more to say like how do you think the NPRM may clear this up? So it seemed like in the examples you gave there were kind of three qualities that were compared. One was whether things were randomized. Where it seems like whether or not there’s an established standard of care you could randomize two things to improve something, a fact about the standard of care. Like a check list. You could randomize some people to having a check list, some people to not have a check list see which one gets you closer. The prospective aspect of it seems an element, but it also seems you could do prospective things and have an established standard of care. And then the other was kind of having an established consensus about standard of care and as we’ve seen with like the support study and other things it seems like whether there’s an evidence based standard of care whether there’s standard care, whether diverse standards of care, whether there’s even, you know, I was on the IRB recently where the standard of care was one thing and what the kind of pediatric recommendation policy was with another thing and we were sitting here, and they wanted to compare them. And we’re like, well are they comparing two standards of care? We didn’t know what they were doing. So I guess I want you to kind of help me understand which of those things are essential elements to making something not quality improvement? Right. Thank you, Stephanie, that’s a , I think that’s a really great question and really driving at the heart of if the NPRM is going to make it easier for IRBs and investigators to figure out whether or not what they’re doing is quality improvement and not human s- that is excluded for whether it’s human subjects research, how is it gonna do that? And I would welcome OHRP if they’re on the line or Taunton if you have any insights on this to chime in. But as I see it I don’t see, I see in that definitional slide with things like well I threw in randomization to make it more stark, but in the NPRM it talks about prospective and comparison of standards of care. I don’t see any of those , and this is just my reading, I don’t see any of those as being sufficient to trip the switch as it were into human subjects research. I think it goes back to if the primary intent to improve the practice of medicine. But, and those issues like prospective and issues like comparing consents to standards of care or randomization are all helpful illustrations of things that begin to move the litmus over into human subjects research and not quality improvement. But I think what we’re really trying to get at here is, what is and I think this is the right way to go, is to say listen what is the purpose of what you’re doing. If the primary purpose is to improve the practice of medicine in relation in relation to some standard care, you rightly point out that when we talk standard of care there’s different ways that standard of care gets established. Sometimes it’s local consensus, sometimes it’s a consensus guidelines of a national body. Sometimes it’s evidence based. Sometimes it’s not. And so I don’t want to go into that mine field, per se, but suggest that these are helpful ways for us to think about what is quality improvement to get at the intent of the project. And that’s what is going to be more helpful to parse those human subjects and quality improvement that’s excluded out. Mr. Paine Yeah. I’d just like to add to that that randomization is not sort of a criteria for any of the exclusions or exemptions. There might views at different IRBs about what randomization means in terms of whether something is minimal risk or not, but that, again is not a criteria for any of those excluded categories. Now this particular one that we’ve been talking about, this this category, generalizability, I think is kind of an underlying principle and the preamble talks about that. So that’s sort of a main kind of criteria for it be cause it does talk about un institution’s own sort of internal monitoring program improvement processes and things like that. So really it’s kind of centered on, you know, this issue of generalizability. But there’s actually, there’s another category of excluded research as well which really focuses on implementation of certain practices rather as and also sort of the evaluation of different methods for implementing certain practices. And it would not exclude you know, comparative effectiveness of the of those practices themselves. And, so I think kind of the issue there is less about generalizability and more about sort of the implementation of it. Now in the process of understanding whether something is being effectively implemented you might you know need to do research that was like a health outcome and things like that that could begin starting to become kind of closer to human subject research, but I think that sort of determination would really hinge on whether it was an implementation of the effective of the process. That’s being discussed or not. And that is for sort of standard medical practices as well. For those streaming in, that’s Mr. Taunton Paine Policy Analyst for the Office of Science Policy at the National Institutes of Health. Our next question here to my left. Yes Ma’m Just a question. For those those programs that are in the QI category. What level of oversight is being prepared for those foundations that have sufficient enough funds not to go into the standard of care category. They can really just stay in limbo in quality, in QI. And and really just without oversight. Just go kinda wlly nilly for lack of a better word, in experimentation. Is there a certain level of oversight prepared for those institutions that don’t necessarily rely on federal funding? And to a certain extent I’ll play devil’s advocate. I think that’s a good question. Thank you As I see it, though, it’s not the quality improvement question whether and institution, whether someone can say of their project that this project is quality improvement and so I don’t need to submit it to the IRB. It’s excluded under the NPRM. Isn’t really a question of funding where institutions with more or less funding could somehow avail themselves of that, but rather it’s a question of it can quite helpful to institutions with less funding as they, they look at are we supposed ot send this to the IRB or not.So I don’t think that funding is is the defining characteristic of whether something is quality improvement or not. If I understood your question correctly. Next question or comment I’m not sure this line is getting as bright as you think, and I think technology may be part of your undoing In two angles. One, we now have electronic health records. And many places have data warehouses. So my prospective comparison of two treatments I simply wait six months and do a query to data warehouse, and now it’s a retrospective quality study. And our EDW reports to me, I have seen a data request come in . We said where’s you IRB. They said oh, never mind. The exact same data request came in with a big “q” stamp on it so you know our physicians are resourceful. The other thing is, you talked about specific institution but we now have a large number of multi-institutional quality consortia that are comparing between institutions. Does that stop being quality and if it doesn’t how does that specific institution clause apply in a quality consortium? That’s a. The second question, they’re both great questions. The second question, I don’t know that I have an answer for you, to be honest with you. When it looks at at your own institution so if I were to hypothesize on this. Perhaps if you were looking at… It would depend on how people defined institution, and so if we were going to say OK, if part of you, as you said I think quality improvement consortium and if you wanted to look at quality improvement across the consortium as opposed to just at my local hospital, am I doing a sort of end run around the quality improvement exclusion. I don’t know how that would be treated.I think that, honestly , is a great question to submit to the NPRM as something that need further clarification. the first question on – let’s say that I want to do a prospective was it two drugs or something? OK, so if I want to do a prospective trial of two drugs and see which one’s better at treating whatever condition, with these large clinical data warehouses that most of us are probably familiar with, this is where with the medical health records we can link to other institutions and have what’s called big data, where multiple institutions are linked together, and we can look at the electronic health care records not and the data not from just one institution, but rather from multiple institutions, and really have exponential data there. You could simply wait six months, a year, year and a half, two years, whatever the case may be until enough patients have gotten those two drugs and do a retrospective chart review of that, I think that’s a , two points on that. One, I think that’s a question of in a sense it’s really a question of scale. I think you’re right that the electronic health records help us with larg institu, or multi institutnonal data warehouses does present new challenges, but we currently do that or sorry, we did that before we had multi-institutional data warehouses with retrospective chart reviews, and I don’t think that was necessarily quality improvement. Because if we’re looking at which drug is better, it’s going to come under probably, as Taunton pointed out, the , a different exclusion. So I don’t think that would be an end run around the quality improvement exclusion, but if somebody did try to do that an IRB office, if they went to them, would probably say good news and bad news. Bad news first, it’s not quality improvement. Good news, it’s behind this exclusion behind door number two and you can still do your project. Is the way I think it would go. Mr. Paine? Yeah, I just want to point out that for the exclusion for the study of the effectiveness of implementation of accepted medical practices. That the number of institutions involved and the generalizability of those findings wouldn’t have a bearing on whether it is elligible for that exclusion or not. It’s for the sort of program improvement where we’re talking about un-institution, that’s where generalizability comes in . That’s a different exclusion. And in that case, it does say un-institution, I mean it doesn’t provide a hard number for what, you know how many institutions can be involved. But presumably if you had more than one institution in it, you might be starting to become more generalizable. As you added institutions to that. So, I mean, there’s that principle behind it that I think is sort of the the defining criteria there. So yeah so that category of excluded research would be kind of bound by the number of institutions that were involved. Next question to our left. Thank you. Forgive me if I’m repeating. I might have heard my answer already. Quality improvement the exclusion piece of that, What if, I’m trying to share that, the things that didn’t work for quality improvement. Do those, does that funding of that piece, will that always still get funded? Can you tell me, so, what if you do a quality improvement project and it doesn’t work? My question is basically, and anybody on the panel as well. I mean if you excluded something of of quality improvement, would that, that particular piece still get funded by the government or institution? So if I understand your question, It could be, yeah. Just because it is, are you asking if something is deemed excluded from the regulation it gets that quality improvement exclusion could it still get federal funding? Yes. Other questions, comments? OK, thank you Dr. Spellecy, don’t go too far. For those just tuning in, we are in the afternoon session. We’re talking about the proposed changes to federal regulations for human research, revising and expanding the scope of the Common Rule. We’re moving into a session with three speakers. We will do these sequentially and then have a follow-up question period for all of the speakers, so please write down your questions as they come up. As a reminder none of these comments or questions are formal comments to the docket. To do that you have the information posted on your screen of how to do that and follow up with that as well. For those of you live streaming in you can tweet your questions to @commonrule2015 #asknprm or email your questions to [email protected] . OK, the first person for our how do the proposed expansion exclusions and exemptions to the Common Rule affect research participants the review process and researchers is Dr. Laura Stark. Dr. Stark is assistant professor at Vanderbilt University Center for Medicine Health and Society. She holds a doctorate in sociology from Princeton University. She’s the author of Behind Closed Doors: IRBs and the Making of Ethical Research. The first book to meld first had observations of IRB meetings with the history of how rules for the treatment of human subjects were formalized in the United States in the decades after World War II. She has published several other works on the history of medicine, morality and the modern state. and pieces on social theory. Her current research explores the lives of normal control research subjects enrolled in the first clinical trials at the US National Institutes of Health from World War II to the present. Dr. Stark currently serves as the associate editor of the journal, History and Theory. Please join me in welcoming Dr. Stark. Hi, there. Can everyone hear me? Am I loud enough? Yes in the back, thumbs up. I hope out in the aether everyone can hear me as well. OK, so my name is Laura Stark I’m at Vanderbilt University in the Center for Medicine, Health, and Society. I’m really grateful for the invitation to talk to you today and I’m looking forward to the conversation. So I am a social scientist and my own research is on research. I’m currently working on the research recruitment process, but I recently completed a large-scale multi-site study of how IRBs go about making decisions. So part of my research on IRBs has been archival, which is to say that I examined the historical documents from the 1950s through the 1970s. And my aim was to understand not just why we got regulations. And Dr. Guzik covered that really nicely for us today. Instead, what I wanted to do was try to understand why we got these particular sets of regulations. So there were alternatives and why did we come up with these rules? What was interesting to me and what I found in the archives was that these rules originated not in Congress but at NIH in the 1950s But it focused on, we saw a shift in the focus on consent in paper, on paper rather than in conversation before the declaration of Helsinki. And it was to deal with a new kind of human subjects. Not sick people, but healthy human subjects. Through NIH and their own expanded funding of extramural research, these rules that had been specific to the NIH clinical center and broader campus actually got attached to the money that went elsewhere and were eventually institutionalized in different rules. In the late 60s the NIH rules were absorbed into public health service and from there this is a really crucial turning point, in ’74 there were two options. There was a federal, a proposal for a federal set of rules, a set of rules in which the federal government would have a more centralized role in the review process. Or a more decentralized one. this is the one we ended up getting, which makes liability for the federal government a lot easier because institutions that are not the federal government are responsible for the research. The rules, however, were the ones that had originated in NIH, at NIH in the 1950s. In addition to this archival research my work also involves ethnographic research. And I studied, which means that I did observational research and also interviews. I studied three IRBs over the course of one year, although the medical wards I observed a bit more briefly because frankly they wore me out. They’re very long more regular meetings at variously locations on the East Coast within driving distance of my institution at the time. And so I was able to audio recorded these meetings and what I was interested in doing was understanding the patterns in decision making in the review process. So again, these areas of archival research and ethnographic research, I think they can help us understand the problems that the NPRM is trying to address right now. What are they trying to overcome and how does it really get institutionalized. So our topic for today is the proposed expansion exclusions and exemptions that would change the Common Rule. And my task in particular is to consider the changes and the consequences for research participants themselves. So my aim here is just to frame a few broad issues. I’ll be drawing from my own research in order to do this. Here’s my starting point. What is it that research regulations do? Well they do a number of things. But I want to propose one way of thinking about them. In most cases, as we all know, the specific individuals who will eventually serve in research aren’t known individually at the time research is reviewed. So one of the biggest challenges for research regulations ond one of the areas the NPRM is trying to address is how to go about making closer the review process and the actual individuals who are serving. So what research regulations fundamentally do, is they assign other people to stand in for research participants. In other words, other people to represent their view. They give people the specific, the authority to imagine priorities, perspectives and feelings of research participants. And here I want to really emphasize the word imagine. As sort of unscientific and and maybe uncomfortable as it sounds, Applying regulations really is a big act of imagination if you’re trying to prospectively consider who these people will be. So the question is, who gets to make this choice, who gets to imagine. And over time there’s been a variety of ways of answering this question. In 1954 the US federal, the US National Institutes of Health much to their credit created the first review committee. Sort of a proto IRB before the word had actually been coined. And so here they are mostly in their team-issued white coats. One of the things I also just want to flag as we also consider the ways in which the composition of IRBs is being changed or not changed through the NPRM. Just to notice the composition of this board in particular. And one of the things that the reasons why this review committee was created to deal with this new kind of research participants that they needed. So researchers and researchers basically had pretty well established its tacit standard for how to deal ethically with people who were sick. So, patients. But there was a new kind of research participant and this slide is an example of one of them. It was a large scale research on people with absolutely no debt to the State who were totally healthy. And yet you would actually be doing experiments on them. And so this is also the way in which we can see social sciences research being slid into rules that were often intended originally for medical research. The reason why there are so many more research participants who are healthy, no debt to the State was because of the rise of the randomized controlled trial as the gold standard of research in the ’70s. So what I want to flag here and this is the point, is NIH’s creation of the first proto-IRB was a shift from letting researchers decide or to stand in for research participants and to start to allow review committees to be the ones who are standing in for research participants. And what the NPRM is trying to dial back the restrictions from letting researchers stand in for research participants. And one way they’re doing this is through the decision tool that we’ve heard a little bit about. And I think deserves additional or would merit some additional conversation as well. So we know that H, uh Health and Human Services is creating a model consent but there will also be a, a decision tool that will be produced that will allow researchers to try to devise for themselves which category their work should fall into, and therefore the level of regulatory oversight it should have. So this is a recognition of a shift away from trust in researchers, which is what happened in the 1950s. And that’s an over-correction and that actually researchers do deserve to be able to make these decisions in some cases. Since the 1970s IRBs there’s also been another way in thinking about who might legitimately stand in for research participants. And these of course are other community members, or the people who don’t have an institutional affiliation with the board, itself. So in my own research, and now I’m referring to my ethnographic research. I’ve found that actually representing the views of research participants were not necessarily the roles they actually played. Many of these people were scientifically well-read and quite sophisticated in these dimensions. And yet they had a very hard time advocating for their position. Why was this? Well in order to do this I’m just very quickly going to introduce a term called a warrant. And warrants are things in conversation that are basically, you can think of them as justifications or reasons. It could be excuses in some cases. So you give a statement and then you give a reason for your opinion. And in my analysis of the ways in which these board meetings, the review meetings happen, IRB community members were not as effective in, their positions was related to matters of fact and matters of science were not as effective as scientists themselves. So the example I have from my field notes actually comes from a report of an adverse event. A woman on a study got pregnant. And it was for,it was a drug study and she was not supposed to get pregnant. The issue was whether to have the protocol changed for the researcher which of course would fundamentally change the recruitment process and the size of the study. When the community member tried to defend sort of an actual user perspective this was not effective, so the board ended up being much more restrictive. So there’s different ways that people could warrant their views. They could use scientific matters of fact. They could their private experience, what you know from being a member of a family or a member of a community. But also, and this was the one that was most persuasive, professional scientific experience. And this is the area where people who are community members were at a distinct disadvantage because they’re entire claim to authority was that they had no scientific professional experience. So as we consider who might legitimately stand in for research participants, we just want to think not only in terms of what the NPRM already includes, but also other possibilities. And it really matters who stands in for research participants. Because these are the people whose decide of course what the levels, what they think the levels of risk are for their research that’s being considered as well as the benefit, as well as the kind of information that needs to be shared with research participants. And one thing that we know for sure is that these definitions of risk change over time. And also that there is another matter that can tend to be spoken about less often and that’s simply the issue of rights. So I think that in our discussion today research methods that are common to social sciences like interviews, questionnaires, ethnography have been getting their due. And this is important and I think dialing back the research regulations in these areas are a legitimate and good area for conversation. A noteworthy feature of the NPRM is that in the sections on exemptions addresses quite a, quite a wide ranging bundle of research methods, and I’m thinking here of biospecimen collection storage and research. The one big question mark on the research front, and it’s sort of an exciting question mark is what can be done and what can be learned from the biospecimen collection and research on storage. And so this raises questions about commercial interests. I think the concerns of the research community, the research participant community, are not often fully understood in this area. So there are three real areas that have been flagged. The first is just the issue of privacy when you think about biospecimens. And this seems to be well covered and well updated in the NPRM. In addition to that there is the concern about, or there can be a sense that research participants want benefits in the form of financial benefits. But this is something that also seems to be managed. They want a cut of any commercial products. That kind of thing. But actually, the big area of concern is, again, a much less regulatory sounding one and it’s one of the classic moral questions of just how people want to live in the world. They want to be contributing to private capitalism to commercial interests or do they take themselves in the broad consent for biospecimen collection and storage to be actually participating in something that’s a public good and not intended for commercial interests. I think this is a legitimate area of question that many people could comment on fruitfully. So research regulations fundamentally assign other people to stand in for research participants. There’s a variety of ways that this could be done as we’ve seen historically and can imagine other ones as well. And this really matters because these people are the ones who define the risk as well as well as the right that future research participants will want to have and to know. So one of the other areas that we also know quite a bit about is that definition of rights and of risk change over time. One of the curiosities of the NPRM is that despite the fact that we know that we’ve changed from the past there’s no anticipation that what we’re doing in the present day will actually be appropriate based on any empirical evidence that we generate that will be successful and also we know that through all of the exciting changes in research we will need new rules to accommodate them in the future. So when will the rule be reviewed again? So as a historian and an ethnographer the vision of ourselves and what we will look like from the perspective of the future is one of the things that would be worth considering. So there’s a lot more to say. I’m looking forward to keeping the conversation going, and I thank you very much. We are going….Spellecy ..[intermittent] …..psychiatry and behavioral health ….thank you. Alright. So thank you… gonna speak to you a bit on just a few points from an IRB chair’s perspective. On the NPRM. I’m an IRB chair, I’ve been an IRB chair for around a decade. And I want to highlight three issues. There’s a litany of issues, in talking to fellow chairs, what do you think about the NPRM. And a large confrence of IRB professionals is happening next …week in Boston. There’ll be much discussion about this. So these are just three that I picked after my own reading of the NPRM as well as discussions with colleagues about they thought was particularly interesting or salient in the NPRM. From the perspective of an IRB chair. And the sky is not falling according to myself and my colleagues. I have a bit of cautious optimism about the NPRM. And I want to talk about that cautious optimism in regards to three domains. The expanded definition of human subjects research and tissue banking. What are the expansions? Earlier I talked about exclusions now I want to talk about an expansion. The concept of broad consent and generally efforts to improve consent in the NPRM. So. I want to clarify what I mean by this expansion. And I am going to refer to this as tissue banks or tissue banking and when I say that I mean research on tissue, blood, what have you that’s collected now for future unspecified and perhaps currently un-imagined research. So you go in for knee surgery. There’s some left over tissue. They want to keep it for future research, they don’t know what they’re going to do. But they wanted to save that cartilage because perhaps it might be useful for some research in the future. Or you go into your annual physical. Your physician orders a blood test. They check your cholesterol, whatnot blood left over. Hey can we keep that blood in case it would be useful for research in the future? We don’t know what we’re gonna do with it in the future, but may we keep it? This is that sort of future unspecified and quite honestly as Dr. Stark pointed out, we may not even know what is to come and what we might be conducting research on in the future. Now, importantly, the sort of tissue banking I want to talk about today is. These are samples, tissue, blood, whatnot, that are collected without what we call identifiers. And what that simply means is, the tube of blood that we have left over that we want to store for future research, If it’s stored without identifiers it has nothing on it that can identify whose blood that is. There’s no, as we heard earlier, there’s no name medical record number all of those identifiers, so we can’t tell whose blood that is. And that’s important. I’m talking about saving extra tissue, blood samples, whatnot for future research that we don’t know what it is right now. And the way that we’re saving it is without anything that identifies whose blood or whose cartilage it is. Under the current research regulations, we could call that not human subjects research because it’s being stored without those identifiers. And as a result, as I said earlier, if it’s not human subjects research, a litany of requirements no longer apply, including things like consent. We would not have to get consent for that. We would not have to get consent for that. Because it’s not human subjects research and we would not be obliged to follow those regulations. And many institutions around the country currently have this as a practice. They might notify people that they’re doing this but they don’t require consent. Under the NPRM that distinction is removed. And so. And I apologize. I tried to think of a better way to say this because there’s a lot of nots in there. But as I read the NPRM, de-identified tissue research is no longer not human subjects research. Basically (I know) it would fall under human subjects research. As a result of that, consent would be required. Not for every project. We’d be looking at initial consent, so when we, when you go in for your physician’s visit, and we anticipate that there may some left over blood from your annual blood work. We might have what ‘s called a broad consent and I’ll talk in a bit about what that is. We might ask for your broad consent for that sort of future unspecified research. We would not be reauired to get consent in the future, so when someone goes to that tissue bank as I called it earlier to get some blood to do some research we wouldn’t have to recontact you to say, hey researcher X is looking at whatever the project may be. But upon initial collection we would ask for what is called broad consent. Broad consent, I want to point out two things. One, it can be done. My own institution, I believe Vanderbilt does it as well. Many institutions around the country, even though it is not required, because this is not human subjects research, many institutions around the country currently do get broad informed consent for, and we heard it from the audience earlier when someone described activities they were undergoing, and we were talking that that sounded to me like you’re already getting broad consent. It’s possible. So the idea that, oh, we can’t get broad consent whatever that is, we can’t get it for tissue banking. It’d be too cumbersome, too onerous, That’s not the case because it’s being done. At my own institution, our assistant dean for clinical research who oversees all of our IRBs, a guy named David Clark got together with the chair of pathology and they sat down and decided, you know what? There’s a point of contact which we come into contact with these folk where we can ask them. Is it ok if we keep your left-over cartilage from your knee surgery. Is it OK if we keep your left-over blood for future unspecified research. And you come up with a very short consent form that explains what we want to do, how long we want to store it, things like that. We can’t tell you what we’re gonna do with it because we don’t know yet. But the important thing is here, from the literature we know people’s perspectives on this. People are supportive of this. People want this sort of research to go forward. They’re generally supportive. They want to be asked, which we can do, but the general public is supportive of this kind of research. But there’s an important point. Some of the general public, some folks out there have specific moral objections to certain kinds of research. Cloning is an example that is often used. And there’s a great article that recently came out by Christine Grady at NIH with this notion of broad consent with the possibility of an opt out. So yeah, we can’t specify all the kinds of research we’re gonna do with these tissues, but people want this research to go forward. And they typically have the attitude of well, I guess you know, once you take my blood and you have some left over, I’m not gonna use it, so go ahead. Do research with it. But they might be opposed to something like say cloning. And say, well, research is good and I want to further medical science, but I have real issues with cloning, and so you might be able to delineate specific research that a sizable minority are opposed to and allow people to opt out of that kind of research. It’s something worth considering as we move forward, but this notion of broad consent for tissue banks, once and this is far better than my not not human subjects research. As I see the NPRM when we look at that practice of tissue banking of saving that left-over blood, cartilage, for future unspecified research currently, this is the current picture. You’ve got that tissue without identifiers being stored for future unspecified research, you’ve got human subjects research over here. They are distinct under the regulation. Under the NPRM it would actually move it back in. Earlier I gave the example of moving things further apart. Under the NPRM as I see it much of that would be moved under the guise of human subjects research and regulated as such. Not regu– In a new way, though. So not the full – when you get informed consent for research there are certain elements that are required. Such as the purpose of the research is one of the first things we have to tell people in a research protocol. We have to tell them here’s what we’re doing in this research, so you can decide for yourself whether you want to support that research. With tissue banking we don’t know what that future unspecified research is. What we can tell you is we don’t know what that future unspecified research is, but here’s what we would like to do. We’d like to save the extra stuff that we don’t need for your clinical test and use it in the future. So it’s not full consent, but it’s this sort of broad consent. Might not be full IRB review, it might be limited IRB review. But it is in the realm of human subjects research under the NPRM. So there’s tissue banking being with the expanded definition of human subjects research. There’s broad consent for that tissue banking. And the last thing I want to talk about is improving informed consent. Which would apply to that expansion of broad-of tissue banking and broad consent but would also apply to other areas of research as well. For an attempt to improve how we conduct informed consent with special emphasis played on the consent form. From the NPRM it says that information should be organized and presented to facilitate the potential subject’s decision to participate or not. That’s getting at this idea of respect for persons. the ethical principle that who better than you to decide whether to participate in this research for yourself. And we need to get you the information and not just the information but we have to organize it and present it in such a way to facilitate your decision to participate or not. And present the information regarding the study first and other information as an appendix. When you hear stories about clinical trial consent forms that are 20, 25, 30 or more pages long and the risks and the purpose of the research are buried in other information that isn’t pertinent to the research, subjects have a hard time figuring out what the point is and what the decision is that they’re making and they just gloss over. So the NPRM as I see it would isolate that information and bring it to the fore and present it to people. And not just, and this is important from an IRB perspective, from an IRB perspective when we we review a consent form, unfortunately often-times we are looking for completeness. We are looking to to make sure all of the elements of informed consent are included. And that’s important. What we’re looking less at is whether that information is organized and presented to facilitate a decision of whether or not to participate. So I see this as an improvement. Because the information will be there. They will have the information they need. And we’re going a step beyond, hopefully. to present the information and organizing it in a way that is easier for them to comprehend and make a decision. And ultimately adhere to respect for persons. It strikes me as reminiscent of the NCI recommendations which were joined with OHRP and the FDA to recommend a consent form template. How we do consent, how we organize and present information. Be shorter, simplified, easier to understand and yet still incorporate the federally required elements of informed consent. I see this as in line with that recommendation which unfortunately we have not lived up to from way back in 1998. But I do have as I conclude, just a few words of caution. The literature around informed consent is littered with the corpses of attempts to improve written informed consent. We’ve tried all kind of things. Just do a lit search and most of them failed. Some of them not only failed, but failed spectacularly. In such that we devised some intervention to improve informed consent, and when we tested it to see if people understood the research better, it was worse. People understood the purpose – people understood less. Or they, it resulted in lower recruitment rates. So I think it’s important to look to the empirical literature to see both what works and what does not work. There are certain things like consent form length we know. The shorter the consent form the better the comprehension. When information isn’t buried. Using things like plain language and the active voice. Or even two column format. Think for a second. How many of you have clicked on the iTunes agreement? Right? It’s this massive monolithic block of text that no one reads. Remember your mortgage when you signed your mortgage? Massive amounts of single column text that no one can understand. And you just hope that the lawyer that’s telling you to initialize those things is being trustworthy. Then think of things that are presented in two columns. Things like the magazine at the doctor’s office. Or the newspaper. Two columns is easier to digest and, and this has been proven empirically shown. A two column format of a consent, sorry, a two column format presentation of text is easier to read and easier to digest and easier to make a decision about. Looking back to the NPRM, a better way to present and organize to facilitate a decision than that monolithic single column which we use. And lastly, Even though all of the focus is on the consent form, the piece of paper, I would encourage us not to forget the conversation that occurs that is also part of the decision of whether to participate or not in research. That’s the conversation with the principle investigator, the physician, the study nurses, whatever, what-have-you. We need to look at the entire process of informed consent and not just the piece of paper if we really want to really facilitate informed decisions for certain participants. Thank you. And our final panelist is Dr. Emily Anderson. Dr. Anderson -dropped–intermittent — she holds a PhD in health care ethics from St. Louis University and a masters of public health and community health services from University of Illinois at Chicago. Her areas of interest and expertise include ethical issues in research with vulnerable population, research ethics and institutional review board policy, ethical issues relating to emerging bio-technology, issues in public health and health disparity, and the application of qualitative research techniques to the study of research ethics. She has served on six IRBs over the last ten years, bless you, and is frequent presenter at public responsibility in medicine and research commonly known as primer meetings. Please join me in welcoming Dr. Anderson. Thanks. Hopefully everyone can hear me. Thanks. I’m really excited to be here. It’s great to be the last speaker at the end of a long day like this. Both an honor and a challenge. I’m gonna try to keep my remarks succinct so that we can allow time for dialogue but I have to admit that my head is sort of exploding with all of the food for thought that I have been fed throughout the day, so I hope I can stay on task. Thank you for the lovely introduction. I want to tell you a little bit about, more about myself where I start. This is not to brag about myself or to gripe about how overextended I am, but to just let you know that I’ve been asked to provide the researcher perspective, but I am only one researcher and one kind of researcher. As we have discussed today, research is not monolithic . There are lots of fields and methods and populations and we also know that institutional interpretations and applications of the regulations vary. And so the researcher perspective is a very perspective, I mean, I’m gonna try to do justice to that, but I also want everyone to remember that I am just one person. One researcher. My own research, I am hopeful a lot of my research falls into the category of behavioral and social science research that will hopefully decrease burden on me with the exclusions and the exemptions, but I’m not just a researcher, I’m also a research ethicist and an IRB member and I serve as formal and informal consultant to a lot of other researchers so my remarks are sort of based on a variety of sources. So, before talking about the proposed changes, I want to sort of lay out the researcher perspective more broadly. What do researchers want? Researcher’s primary interest is in doing their research. Right? And most researchers have very good intentions for wanting to do this research. And I think it’s important to be explicit about this. Researchers want approval as soon as possible, they have obligations to sponsors, they have career interests and they have limited resources. And this is their primary interest in sort of the research ethics, IRB review, Common Rule, context. But I think it is also really important remind everyone that researchers are genuinely concerned with protecting research subjects. Despite all of the examples of atrocities that we’ve heard about and that we know about, 99.9999% of researchers want to protect research subjects and I think’s important. It’s common and can sometimes be fun to set up a battle between researchers and IRBs, but I think we do ourselves a disservice when we do that. I also think it’s important to state that researchers really want to be compliant. They mostly just want to follow the rules and they want to do the right thing. But researchers can be very frustrated when rules aren’t clear or when there’s a perception that what is right is at odds with the rules. And I think you know, we’ve gotten into the situation where this is the source of frustration for a lot of researchers. So researcher’s criticism of the Common Rule and IRB review are many. Burden are not – burden is not commensurate with risk. The review process is very slow. Guidance is unclear and decisions are inconsistent. There’s a sense that the IRB review process is a black box. What you put in goes through something that you don’t understand and you don’t really know how you got, why you got the letter that you got back. And this is a common complaint that researchers have. Related to this is the fact that there is no appeals process. So you have to respond to what the IRB tells you and you don’t really get to appeal that like you do in other justice systems. Somebody mentioned this earlier, there’s a perceived prejudice against certain disciplines. And this has to do sort of with the dominance of bio-medical model. I would say that everybody who doesn’t fit that bio-medical model of the randomized control trial, which interestingly is the higher risk level of research, feels that they are under increased scrutiny by the IRB, sort of round peg, square hole. Round hole square peg, square hole round peg problem I have a little cartoon on the end that I have included in most of my talks about IRB review at this point. But it’s a pervasive problem and it creates a lot of ill will among researchers. But the final thing that I want to point out the researcher criticism of the Common Rule and IRB review and this is sort of gonna be the main take-away point of my presentation, is that there’s limited evidence of the effectiveness of our current review system in meeting its stated goals. So what are some of the results of researcher dissatisfaction? Limited trust and sense of loss of control. IRBs unfortunately have come to be seen by researchers as impediments rather than colleagues and partners who can help improve research. I’m an idealist and I would like to see this changed in my lifetime. I think it’s important to note that there has some people have hypothesized that when certain individuals are dissatisfied with a system and perceives it to be unjust, there’s a potential for there to be rule breaking. This has been raised and empirically proven in other contexts, not in the research context, but I think it’s something to be mindful of as part of the conversation. But there’s, a couple people have talked about you know, this discussion, whether or not researchers can be trusted to make determinations on their own, and I think that we have created a problem with over-regulation that we’ve almost encouraged researchers to become what I might call ethically lazy. We have discouraged researchers from thinking robustly about the ethics of their own work, and gotten to a point where a lot of researchers say, I’m just submit my protocol and let the IRB tell me what to do. They’ll tell me what I want and I’ll just do that. And I really want to point out or sort of echo Dr. Schrag’s comment that potentially one of the upsides of deregulation could be sort of a return to a more robust ethical discussion about research within communities of researchers and experts. So, that’s just sort of a canvas, I just wanted to put that out there. We talked about the stated goals of the NPRM to modernize strengthen and make more effective the system of review. I think these goals are great, but when I put on my researcher hat I… it leads me to ask, you know, what are the benchmarks? What are we measuring, how are we measuring them? So I think, given the researcher viewpoint and the criticisms and the goals of the NPRM, what researchers want from the revisions are reduced burdens, faster time to approval, and more clarity and consistency. But I think the research community also would like to see revisions based on good evidence, on-going data collection to assess whether changes to improove… to assess whether the changes improved protections and meet other goals. As well as a commitment to respond to identified gaps in meeting their goals. And I think, you know another thing I’ve been thinking about throughout the day is that kind of an elephant in the room is that there’s actually data to show that research is extremely safe. Again despite these instances of harm. Research is very safe. And we spend a lot of money and resources trying to prevent what are really rare events that may not be preventable for a lot of reasons. Dr. Schrag talked about how wherever you draw the line you’re going to miss something. And I think that’s something that’s important to keep in mind. But researchers are also taxpayers and so again, sort of in the spirit of show me the money, I would like to see some data to show me that these changes are working and all of these researchers are worth it. When I first started putting this talk together I thought that I was going to be able to say some really I was going to be able to confidently say whether or not some of the proposed changes were going to meet the goals and I tried to look at the NPRM and identify changes that would reduce burdens on at least some investigators. Points of improved clarity. Points of continued or increased muddiness changes which may increase burden or the effects of which are unclear. And I have to say that as I worked on this things moved around a lot. And as I talked to people different kinds of researchers things moved around a lot. And as I sat here today things have moved around a lot. So I’m hesitant to even go through my slides. They all, many of them already have a lot of question marks on them. But I think, you know, very briefly, if you’re a historian you have a lot to be – optimistic about. I looked at Dr. Schrag’s blog in the last couple days and I believe the headline is historians love the NPRM. Or something like that. So that’s one kind of researcher who feels one sort of way. Who has one sort of perspective on the proposed changes. I think if you are a behavioral social science researcher who does, you know, low risk, however you define that kind of research, you have a lot to be optimistic about in terms of potential decreased burden on you with some of the proposed changes around determinations and the tool and things like that. But it depends on the populations that you are working with. And the kinds of data that you’re going got be collecting and the kinds of methods that you’re going to be using. I think if you’re a researcher that does work with biospecimens, you’re pulling out your hair and experiencing a great deal of frustration right now. And a group that we haven’t talked about you know, one of the proposed goals of the NPRM that IRBs will now have time, more time to spend scrutinizing research that poses significant risk. Which you know, there’s a feeling now that that is lacking in our current system because there’s so much time spent on low risk research. So I tried to think about, you know, that sort of a, it’s very implicit in the regulations but there’s nothing explicit that tells that are doing high risk but also potentially high reward randomized clinical trials. What’s gonna change for them with all of this free time that IRBs are going to have now to provide increased scrutiny to their work. So that’s sort of hidden thing that occurred to me as I was sitting here. But the bottom line, you know, your perspective on these proposed changes really depends on the kind of research that you do. And so a theme I think that’s come out today is that we’re both expanding and excluding and it’s really unclear where those boundaries are changing. So I talked about, you know, I mentioned a couple things that I think should release the burden on many investigators, exclusion of oral history and biography. Public health surveillance. I think a lot of the the elimination of the continuing review requirement for a lot of different kinds of research I think is something that a lot of researchers will benefit from. As well as sort of the shift in terms of evaluating things that are now excluded and exempt that were fell in, now fall into being exempt or expedited. But I think, and I think there are a couple points of improved clarity and consistency although again my view on this has changed as I’ve been sitting here. I think I am very hopeful for the web based automated decision tool for exemptions. I’d like to see something like that extended to the exclusions as well. Some people say there’s a brighter line between QI and QA in research. Other people don’t. I think you know, I’m sort of less clear after hearing the conversation on that today than I was before, but I already had a question mark on it. Increased muddiness. There is like very very long, but I think I’m not the only person to say that I feel that there are some poor language choices with exclusions including low risk activities that use the definition of research. And now we have exemptions having to meet additional requirements. And some things like that. So I think I’ll just sort of. Lot of things unclear. And I think I’ll leave it at that. But summary, again, I think from the researchers’ perspective there are reasons to be hopeful and there are reasons to be concerned. But I think improving researcher trust and satisfaction is going to require revisions based on solid evidence, systematic data gathering to assess the impact of changes. And I think there’s a lot of opportunities but there’s not mention of that in the NPRM. And that’s something that I plan to comment on. But we also need community determined standards against which to measure progress. We need benchmarks. And also a plan for evidence based responses. So when we do hopefully collect this data and we find gaps and we find that changes haven’t met our goals what’s gonna be done to try to close that gap? And I think having a plan, such a plan in place would go a long way to insuring researcher trust in the regulation. So end there and I’ll look forward to our discussion. Thank you Dr. Anderson. So. To get us back on track we will have a question period for this session but we’d like to combine it with the entire panel discussion to get us as close to the two o’clock stop time as possible. So I’d like to invite back up our previous panelists. Stephanie Guzik could come up please. Mr Paine is here, Dr. Cargill. If you could join us please. Dr Schrag. As they’re making their way up I will remind folks that we are looking for your questions comments and concerns regarding the NPRM. You can do that in a number of ways. If I can find my correct sheet here. I will give you the email and the twitter. It’s the join-athon social media page. Tweet your questions @commonrule2015 #asknprm. Email your questions to [email protected] Another reminder that the comments, questions, concerns, inputs that we’ve gotten both live and through twitter or email are not formal comments to the docket. To do that you have instructions there on your screen. regulations.gov. enter those letters and numbers. Get to the search and on that page you can submit your comment formally. Certainly you can do it by mail at the address you see there. There’s also a fax number. OK. So we’ll now open it up for either questions comments from the final session or anything you have from the day. Our first question here to the right. Ok. I have both a comment and a question. So I’ll start with the comment and I think it’s addressing something that Dr. Spellecy mentioned. You were I think if I understood you, you were saying you were looking forward to the opportunity that the IRB would be able to be more involved the organization or yeah, commenting on the organization and clarity of the consent document. I think there’s a real concern for over-involvement there. Just a little anecdote, I recently submitted consent forms for approval. We got the response that a particular sentence needed to be put in bold. And I don’t know where in the federal guidelines it gives my university the authority to tell me what I have to put in bold in my consent documents. I think that’s just going way overboard so there’s a risk there that that’s overstepping the IRBs authority I think. So OK comment. But then question. I really do have a question about something I think it was said this morning. You showed a graph in an earlier presentation about I think that there’ll be levels in the exempt category and I’m wondering if we could hear more about that. so, for example, I would be really excited to hear if So for example in an educational setting, if you are just doing testing and things that are part of normal classroom procedures, that’s considered exempt.The participation’s exempt. If you want to bring in a video camera then that is that goes up to expedited. Which I think is very appropriate, the use of video taping of children should be reviewed and so I approo- I don’t object to that. but as soon as we do that then the whole thing gets reviewed. Where those tests that were exempt before are now subject to review, and the standard classroom procedures that wouldn’t have needed the extra burden of oversight now have to be the whole project gets reviewed. So is it possible to just review the use of the more risky procedure, namely the video tape, but assume that everything else is trusted as before we had the camera, so you could trust us now. So that’s the question could someone speak a little bit more on the levels proposed of those different layers of expedited review. So those different levels are meant to indicate kind of the degree of oversight that would be required for types of exempt research. So typically what that’s referring to is the different requirements that would have to be put in place for research that was exempt. So currently when something is exempt it has no requirements, but under the NPRM there’s multiple categories of exempt research, and based on the level of risk associated with them there’s a couple of different requirement. And the most basic requirement and the one that would be involved with the educational exclusion would be the use of the decision tool in recording the outcome of that that decision tool and keeping a record of it. Now for your other question about whether you can simply subject some parts of the research to a higher level of review, the NPRM doesn’t really get at that. So I think if that is something that you think might become more standard practice with the ability to kind of select well to apply a sort of higher standard for review for parts of research that are riskier than other parts of that same research, then i would, you know, encourage you to submit a comment to that effect. I’d like to remind folks that our distinguished colleagues at OHRP are also on the line. And OHRP if you have comments or would like to insert a comment please go ahead and do so. Our next comment here in person from the floor Maureen Moran, Northwestern University. My really comment probably in response to Professor Spellecy is. If better informed consent leads to lower enrollment in human subjects research, is that really a bad thing? No. For the reasons I think we probably already know. If the consent is truly better in the sense that it’s better informed and we present the information better and people are better under- better able to understand the risks and benefits and make their own decision in that, were that to result in lower enrollment, I Cmean that’s a system, I would say that’s a good thing because it’s in keeping with the rights of the individual and their autonomy. It’s not a zero sum game, though. Because that could potentially slow the pace of research. I just kinda wanna add to that because, and I wanna I know I’m not in the audience but I have a question for Dr. Stark. One of the things I’ve been thinking we keep saying is can we trust researchers, can we trust researchers that it seems like one of the reasons even to have a scientific review in the original IRBs and then moving to what we have now, is the worry about the conflict of interest. That as a researcher, even if I want to protect my participants, I also want to enroll them. And that’s the conflict of interest that you historically has made us say we need someone who has at least a little bit of distance from this study to be able to assess it. And I guess I’m one under, I think, you know, researchers are smart people. It’s not like they can’t figure out if it fits the exemption or exclusion definition. I think the worry comes with the conflict of interest and whether the shift to trusting, trusting researchers which, I think I do trust researchers in a lot of ways, but where they’re pushing a lot of these determinations to researchers risks involving these conflicts of interest that we kind of moved away from by having IRBs and having less, you know having community members on IRBs and things like that, and so I guess I wanted you to reflect a little on that. So I think the ques– issue is what will be the default setting. So either in the former set of regulations or the new one that will be forthcoming we all hope in 2016. The previously the default for a lot of research that’s now being pushed outside of the rule was the default was the review committee. And now there’s a shift with these new exemptions, extensions, to actually having the default be trust the researchers. And then in specific cases to go with the review committee. So for me it’s just a question of or I try to recognize the question of how the default is being set. So from a starting point they’re saying we trust researchers. If I could just make a comment on your comment on your comment on the potential for improved informed consent to decrease enrollment. There’s actually some evidence that shows that people refuse participation because of poor understanding. Particularly in research that could have direct benefit. So again it’s not a zero sum game, and I think that’s something to be really cognizant of as we think about providing equal access to the potential benefits of research and sort of getting away – swinging the pendulum towards a less protectionist stance so I just wanted to put that out there. thank you. I want to make sure we get to unless there’s other comments on that we get to a question that’s come in from the world. Number one. The broad consent requirement is very vague at this point. A and this only goes to C. Why can’t this content be part of the current proposed rule? Or at least that there be a clause allowing for the use of interim broad consent content that can be implemented until the Secretary finalizes it? Anyone? That’s for everyone. So let’s see. It is vague, although there is a rubrick for what it should look like. And some specific comments about, actually it says things like you know how long you would store material would have to be part of that broad consent. So there some elements. What is not included is you know, there’s a promise that some sort of a template will be developed. And that’s fair. There’s a promise for a template and we need to be careful about what that template looks like. But the last point about why there can’t be an interim, I think the answer to that is, people are currently getting broad consent for tissue banks, my own institution, the Medical College of Wisconsin does it, Vanderbilt does it.At least one person in the audience, their institutions does it as well. So there is nothing preventing an institution from getting broad consent right now for this sort of tissue banking endeavor. Sorry, Nothing in the regs. Mr. Paine, did you have anything to add? No I would just say that yeah there’s a detailed list of the content of broad consent that would have to be in there which would certainly be reflected in any template that was developed. Although we don’t have any template right now we have a pretty good idea of what it would look like. And the final part to that was and/or finally that there be some deadline for the Secretary to release the Broad consent content consistent with a three year implementation plan. Is that kind of subsumed within your answers. Well, there is no deadline included in the NPRM, but for I think practical purposes it would certainly have to be within that time frame. Our next question, gentleman to the left. I just want to thank the panel. Y’all did a wonderful job, thank you so much. Very informative. I have a somewhat outside the box silly question. I’m glad the young lady said about conflict of interest. This question is what role will insurance companies participate in this venture. Or is there a role for insurance companies? That’s my question. Anybody can answer. Well, the NPRM doesn’t regulate insurance companies per se. It’s more about spen – I mean they may be partners in research in some studies, I suppose that’s a possibility. I think, I think well, it wouldn’t really regulate that either. But I think in terms of insurance companies having access to information there are certain requirements now that information that’s identifiable to an individual would have to be controlled to some extent. You know with standards for ID security put into place and that there would be sort of restrictions on the way in which you could share that. The new requirements for consent and for notification in some areas would make so that you have a better idea of where your information and your specimens are going. And another question here in person. This is really for the OHR folks out in the aether. Most of our panelists have commented on the rip-roaring inconsistency across IRB panels. And we’ve also had comments early on about how an IRB will never be punished for accelerating research, right. They will be punished for not being rigorous enough but they will never be punished for torturing their own researchers. So we’re now giving them more time to focus on a particular class of studies. Are there, you know, part of this is the fact that scared individuals and groups become inconsistent. This is, you know, they’re unpredictable. Is there any plan to encourage consistency or reduce this fear based behavior of our IRBs as a way of inducing better behavior and more consistency? We want to give the first shot at that to our folks at OHRP on the line. Hi, this is Julie Kaneshiro, ??? if they want to join in. See I just get a ?? that to the extent that the of the proposal is to make the lines brighter about what is and is ?? the scope of the evaluation that what is not ?? exclusions and exemptions is one way we try to clarify what the IRB has regulatory oversight on and what it does not.You know, In addition the exemption tool that’s been discussed is another way in which we’re hoping to try to clarify that line. And at least to the extent that the IRBs are reacting out of concern or fear we’re hopeful that if the lines can be appropriately clarified they’ll be less apt to do that in the future. You know they think the issue will always remain to some extent. Quite frankly I don’t it’s something we could eliminate entirely. We do you know now get questions along those lines on occasion and we do try to clarify for institutions and investigators where the line is so at least they understand that they’re not necessarily following what needs to be followed when they choose to go beyond the regulatory floor. And some choose to do that voluntarily because they think it’s important to do so. You know. And we may well continue to see that. Other comments from the panel. Well I think one stakeholder that I don’t think we discussed today are the institutions and the staff of IRBs. because I mean one thing to say is that IRB members chairs have to kind of make sense of these regulations but it’s the IRB staff and the institutional lawyers who are worried like if someone fills out this tool and it says it’s exempt and then something goes wrong and they want to sue someone are they suing the funders or are they suing the institution? If they’re suing the institution then the institution says well we want to have some oversight over that whatever the tool says. And I’ve heard that quite a few times, about would they really relinquish oversight of things. And the answers I get are only if we’re protected in some sort of greater legal sense. And I don’t know what to do about that, but I think it needs to be said. And we shouldn’t forget that the protections are these federal regulatory rules that we’re supposed to obliged to as an institution. There may be state and local laws that we have to adhere to when conducting research on human subjects. I will add that there were two provisions in the advance notice of proposed rule making that at least were pushed back some. One was the proposal to collect data on adverse events nationally so that would provide some kind of empirical base for IRB decisions and reduce some of the arbitrary decision making that we’ve seen. And the NPRM says no that’s just too hard, we’re not gonna try that. And then the other one was to provide an appeals process at every institution. This is something that the Canadian system already guarantees. This is something that was endorsed by the National Research Council. The NPRM drops that proposal and makes no explanation of why. So if nothing else, that would provide some kind of paper trail where these researchers could have said I don’t know why you are making me put this sentence in bold. And maybe the IRB has empirical data on it,probably it doesn’t. Probably they’re just making it up. But the appeals process if nothing else would have documented those kinds of conflicts and we could work to try and address it. So the NPRM is a big retreat from the advanced notice of proposed rule making in terms of due process protections. And I would ask if OHRP cares to comment, first of all why are there no due process protections for researchers in the NPRM and secondly , more candidly, why can’t we do more like Canada? They revise their guidelines every 2 to 5 years, they do a major overhaul every 12 years. they provide rapid and helpful and easy to understand guidance in both English and French. And what we’re talking about as Professor Stark pointed out, is the possibility that this may be the last revision of these rules for another 35 years. I mean the next NPRM at this rate is gonna come out in 2048 with a notice of proposed rule making in 2050 and the final rule in 2051. That’s a very long time to wait if we get things wrong now. Why can’t we have a more nimble revision process? Does OHRP want to chime in? We would just encourage that that be submitted to the docket. Those are important points and we will certainly consider them. These were in the docket for the ANPRM three years ago. I don’t really know why you expect us to accept that answer when previous submissions the previous docket have been ignored. I mean I really I know that some things in the NPRM reflect submissions to the previous docket, but there are a lot of people in the ANPRM docket saying yes, give us an appeals process. The NPRM says no dice. No explanation and then you tell us to comment again. Ok. We’re gonna wrap this up. But you’re not off the hook yet. You all have one thing about the NPRM that you can provide a comment on, what is it? We should not have to wait another 35 years for revisions. They should be revised at least every 12 years the way that Canada does it in light of experience both in terms of what rules don’t make sense and as Prof. Stark points out, in terms of changing social norms about risk and research there should be a continual revision process that gets better all the time. That and collection of evidence and application of evidence to those frequent revisions and changes. Greater specification of how the decision tool will be made, who will be involved in it and how testing of this very important decision tool will be implemented. This wasn’t at all in the topic for today, but I found that the very broad vague comments about informed consent were incredibly unsatisfactory considering we all know that it’s a broken system. It doesn’t work in telling people just tell people the essential things when no one really knows what the essential things are is not very helpful. I’m not going to submit any comments, but I look forward to seeing all of yours. I’m going to be the optimistic person in the room, and say that I appreciate the changes into the continuing review and that it is for oncology studies that follow patients for survival. They will have a reduced burden of regulatory paperwork and so I welcome that change. I’m going to be somewhat optimistic as well, although I I would echo everything that my colleagues on the panel have said, especially why do we have to wait 35 years. Let’s make our revisions empirically informed, but I do like the way things are heading. Something is better than nothing. And as regards informed consent. It’s near and dear to my heart. I would like to see us be aggressive in the way that we overhaul informed consent for research and that what we do be empirically informed with what works. There’s a lot of evidence out there about what works. There’s a lot of evidence about what does not work and we should pay attention to that. And if we have, if there’s gaps when we’re revising the consent process and we don’t know what doesn’t work we ought to find out. And lastly any final comments that you’d like to make, brief as they will be? Historians love the NPRM. I just want to, as someone who’s very invested in communication between science and the public I want to just say thank you for having these sessions and that the public has at least some opportunity to hear what’s going on. Get a little feedback. OK. It looks like we’ve put a wrap on this fourth session. You can go online to view these. You can also sign up for the fifth one, I believe it’s November 18th. Because you are participants today you will get a followup email and you’ll have an opportunity to both assess this, access the previous sessions as well as sign up for the upcoming session. Let me just get down through my big list of thank yous. Can we get a big round of applause for all of our expert panelists here. They’ve done a wonderful job. We’d also like to thank NIH and the OHRP for both being here in person as well as on the line. Thank you so much. The unhearlded heroes from the Vanderbilt Institute for Clinical and Translational Research. C4 Coordinating Center, thank you so much. Both those of you who have live streamed thank you for coming. Again, remember that any of these comments are not formal submissions on your screen is the way to submit your comments formally. You have until, I believe, December 7 is the closing date for comments. The last session again as I said is 11-18. You’ll get the online assessments and the link to the streaming sessions. If you did not get to your question or comment you will be responded to, so hang in there and somebody will get that to you. That’s a wrap. Thanks for coming.

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