Research Ethics Roundup: Ethics violations in golden rice study, proposed changes from the USDA, and more!

Whether you have the time now, or need to bookmark this site for later, take a few minutes to catch up with the latest news in the research ethics world!

Treating Kids’ Cancer with Science and a Pocket Full of Hope: Pediatric brain cancer researcher Jim Olsen is developing an experimental product called Tumor Paint, a molecule that includes a dye that makes tumor cells glow during brain surgery. The goal is to make tumors easier for surgeons to remove. The first tests of Tumor Paint are scheduled for later this year.

Golden Rice Study Violated Ethical Rules, Tufts Says: Tufts University determined that its study of “golden rice” conducted in China failed to comply with federal regulations governing human subjects research. Tufts, after a year-long review, released a report that stated researchers failed to properly explain the genetic modification of golden rice, and made other changes in the study without obtaining IRB approval; however, they claim the scientific merit of the study stands.

Stephen Crohn, Who Furthered AIDS Study, Dies at 66: Stephen Crohn, whose immune system has been extensively studied by HIV/AIDS researchers because of his genetic resistance to HIV, recently died. Research on his immune system has led to numerous advances in fighting HIV, including the effective cure of the disease in a Berlin AIDS patient who received a bone marrow transplant from a donor with the same genetic mutation as Mr. Crohn.

Kenyan Patients Being Used as Guinea Pigs by Researchers: Somo, a Dutch non-governmental organization, released a report outlining research misconduct in Kenya, including allegations that researchers promised subjects that their participation would cure them of AIDS; that subjects were enrolled in research without their knowledge; and that blood samples collected from orphans were smuggled out of the country.

United States Department of Agriculture  (USDA) Seeks Comments Regarding Proposed Changes: The USDA is seeking comments on proposed changes to Animal Care Policy #3, which addresses veterinary care issues, including the use of expired medical materials, surgery, pre- and post-procedural care, pharmaceutical-grade substances in research, health records, euthanasia, and declawing and defanging practices in wild or exotic carnivores or non-human primates. Comments are being accepted through September 27, 2013.

Would you participate in your own research? Who Goes First explores self-experimentation

by Michele Russell-Einhorn, JD, senior director of the Office for Human Research Studies at Dana-Farber Cancer Institute

Imagine that you are an investigator and you have submitted a research protocol for review by the institutional review board (IRB) at your institution. The research involves a bone marrow biopsy. The approval comes back from the IRB with the following condition: The first subject enrolled in the research must be the investigator.

I will venture that the condition that the investigator participates in the research would be a surprise requirement for many IRBs and many researchers. Yet, that is precisely the prerequisite that Dr. Lawrence K. Altman, MD, proposes in his book, Who Goes First? The Story of Self-Experimentation in Medicine. “Why should a volunteer not connected with the research study go first and risk those consequences when the researcher has no valid justification for not having done so?” questions Dr. Altman (page 313).

Describing his own self-experimentation, Dr. Altman discusses his research into a rare genetic disease called pseudoxanthoma elasticum (PXE) that causes serious damage including blindness. The research required a skin biopsy which he did on himself first. He served as a normal control to those with the condition in the study. He explains the impact of his participation: “The fact that I had done it made it easier for me to explain the process to patients, and a bond developed between me and the people who volunteered for my research project” (Page 12).

That argument, though perhaps unsettling to many who review and approve research today, makes perfect sense once one reads this marvelous catalog of colorful stories about all of the discoveries that we may take for granted that indeed began with the investigator serving as the first human subject in the research. Dr. Altman takes us back to the life of Santorio Santorio, who lived from 1561 to 1636 and tested and retested various physiological and pathological conditions. He measured weight, fluid intake, the impact of the loss of waste and sweat—research all conducted on himself over a 30 year period. Other examples include Dr. Max von Pettenkofer who swallowed substances laced with cholera; Joseph Priestly who in the 1770’s experimented on himself with oxygen and nitrous oxide—important steps in the development of anesthesia; Dr. Werner Forssmann who in the early 1900’s inserted a tube through his elbow—on many occasions—to reach his heart and prove that a less dangerous route to treat heart conditions existed; and Drs. Kaplan and Koprowski who in the 1950s injected themselves with the first dose of an impure vaccine in research working towards a rabies vaccination.

These are but a few of the extraordinary stories  that are described in engrossing detail in Dr. Altman’s review of who has been, and his argument for who should be, the first human subject in the research we do today.

Look for the wiggle room: An interview with Kacey Feasel

by Megan Frame, Membership Coordinator

Welcome to another installment of our featured member interviews, where we will continue to introduce you to PRIM&R members—individuals who work to advance ethical research on a daily basis. Please read on to learn more about their professional experiences, how membership helps connect them to a larger community, and what goes on behind-the-scenes in their lives!

Today we’d like to introduce you to Kacey Feasel, CIP, institutional review board (IRB) analyst at the University of California, San Diego in La Jolla, CA.

Megan Frame (MF): When and why did you join the field?
Kacey Feasel (KF): I fell into the field in March 2008. I was sent to interview at an IRB office in Boston by a recruiter. The first time I had ever heard of an IRB was during my preparation for the interview. I thought it was something I would feel good about doing, so I tried to make a good impression. It must have worked because they hired me.

MF: What skills are particularly helpful in a job like yours?
KF: Communication and learning skills—being able to teach yourself something and then in turn explain it to someone else. The ability to write correspondence that is clear and direct. Learning to fit square pegs into round holes—being able to think creatively about how to apply the regulations and local policies to novel study designs. Most importantly, you need to know where to look for answers. You can't remember everything, but if you know where to look, no problem!

MF: Tell us about one or more articles, books, or documents that have influenced your professional life. 
KF: In the first few months of my IRB career, I read On the Take: How Medicine's Complicity with Big Business Can Endanger Your Health by Jerome P. Kassirer, MD. The book discusses the tension between the pharmaceutical industry's interest in profit and the development of drugs meant to save lives, and how people in the field (doctors, administrators, etc.) can become caught up in this tension. After reading first reading the book, I remember having a revelation—I was very new to the supply-side of the health field, and naively took for granted that some sort of benevolence and government oversight kept corporations and companies in line. Ultimately, the book made me interested in learning more about research and made me feel that I was contributing, at least in a small, administrative way, to something important and good. I think most people want meaningful work, and for the first time post-college, I felt like I was moving into work that would give me a taste of that.

MF: Have there been any PRIM&R events or talks that you have attended that have had a significant impact on your approach to your work? If so, what were they and how did they influence you? 
KF: When the councilwoman from the Havasupai tribe spoke at the 2010 Advancing Ethical Research Conference about the tribe's experience with the University of Arizona scandal, I actually cried. I have Native American heritage and hearing yet another story of America's first people being taken advantage of and disrespected, really broke my heart. It made me think much harder about secondary use of data and specimens. I've encouraged people I work with to take these types of projects more seriously and to give them a bit more thought because the consequences of not doing so can be serious.

MF: What advice have you found most helpful in your career?
KF: My former boss told me, "Don't drive people crazy." Also, my dad once told me, "Don't ever let anyone tell you they're smarter than you unless they prove it." I liked that piece of advice because I think we need both confidence and humility. I work with a lot of well-educated people with prestigious titles, but at the end of the day, they’re still people. Their accomplishments are not a commentary on my capabilities.

MF: What is something you know now that you wish someone had told you when you first entered this field? 
KF: Good relationships with your "clients" make life wonderful. Ultimately, we need to balance the authority of the regulations and being “the IRB” with the practical needs of getting research done. I think when I first began I was very rigid about every detail being just so, but over time I realized you need to stick to what can't be changed, but help researchers where you have wiggle room. When you start looking for that wiggle room, you find quite a bit of it. This goes back to "don't drive people crazy."

Thank you for being part of the membership community and sharing your story, Kacey. 

If you’d like to learn more about becoming a member, please visit our website today.

Exploring the world of the “professional” research subject

by Elisa A. Hurley, PhD, Education Director

The portrayal of research in popular media can offer considerable insight. To reflect on some of the lessons offered, PRIM&R staff have spent the summer reading and watching books, movies, and television shows that have generated conversation and debate around issues related to research ethics. Over the next several weeks, they will share their reflections here, so join us as we explore popular representations of the research world. 

Like its title, Roberto Abadie’s The Professional Guinea Pig: Big Pharma and the Risky World of Research Subjects is a provocative book. Abadie conducted 18 months of ethnographic research in a Philadelphia community of self-defined “professional guinea pigs,” individuals who regularly volunteer for, and in many cases make their livings from, participating in phase I clinical trials, largely sponsored by the pharmaceutical industry. The book draws on that research to argue that the current practice of paying healthy individuals to participate in phase I trials exploits them, commodifies their bodies, and “subverts basic ethical principles and guidelines regulating the participation of human subjects in research” (154).

Abadie points out that the practice of paying people to participate in clinical trials is relatively new, emerging in the 1970s when it was no longer considered ethically defensible to use captive populations such as prisoners, members of the military, or institutionalized persons, as research subjects. He suggests that the ongoing need for healthy subjects for phase I trials in the absence of these ready populations led to the creation of a “trial economy” in which individuals are “recruited on the open market.”

According to Abadie, the prospect of financial gain is most professional guinea pigs’ sole motivation for participating in phase I trials which, after all, offer no prospect of therapeutic benefit to them. This fact is the source of a number of overlapping concerns Abadie outlines. One is that when individuals give their bodies and time to the pharmaceutical industry in exchange for money, they are being commodified and dehumanized. Another is that the compensation offered adversely affects the way subjects perceive and manage risk. More specifically, paid subjects tend to discount or entirely ignore the long-terms risks of participating in trials, such as potentially dangerous drug interactions, because they are so focused on short-term considerations such as what they need to do, and what immediate risks they need to endure, to receive compensation for the trial at hand.

His third concern, and perhaps the most serious, is that “the existence of market-recruited subjects in phase I clinical trials defies the principle of justice.” He explains: “the involvement of professional subjects in trial research is unjust because it burdens a group of poor research subjects without offering them a therapeutic benefit” (154). Social inequalities mean that some individuals are particularly vulnerable to being exploited by the trial economy: their financial need makes them more likely to take on risks, and their dependency on trial income interferes with their ability to freely consent to participate in research.
                                             
Abadie’s claims are indeed provocative, and his book sheds important light on a little recognized—and perhaps actively ignored—aspect of the modern clinical trial landscape, namely, the fact that phase I clinical trials depend on a readily available pool of healthy volunteers who have the time and willingness to submit themselves to the often boring, frequently uncomfortable, and sometimes quite risky, work of participating in phase I research.

That said, the strength of Abadie’s case that professional research subjects are exploited and otherwise treated unethically, is undermined by the fact that the professional guinea pig community he studies is a group of white male anarchists whose ideology emphasizes independent, flexible work, and whose participation in phase I trials is, as Abadie himself describes, a lifestyle choice. Of course, the fact that someone appears to choose a form of work does not in itself mean that they are free from exploitation—having severely circumscribed options can, depending on what does the circumscribing, amount to exploitation. But throughout the book, Abadie makes it clear that the anarchist guinea pigs he lives with in West Philadelphia are an unusually well-informed and articulate group characterized by relative stability, low expenses, easy mobility, greater clinical trial opportunities than other subject populations, and ideological opposition to the pharmaceutical industry, which they often act on by trying to sabotage the trials in which they take part. Abadie’s argument that paying phase I subjects is exploitative and unjust would have been more convincing had he explored the lives of phase I trial subjects for whom volunteering is a necessity or best choice given limited options, rather than a lifestyle choice or political statement.

Surprisingly, when it comes time to make recommendations, Abadie does not suggest that we do away with phase I trials—he recognizes how important they are—or with paying people to participate in them. Rather, he suggests that we need to better and more systematically recognize phase I volunteer participation as labor, and to provide better working conditions and proper compensation for that work. Abadie is not alone in this suggestion. Holly Fernandez Lynch, JD, MBE, of the Petrie-Flom Center at Harvard Law School has recently taken this idea to its logical conclusion, arguing in a recent article that human research subjects should be reconceived as human research “workers” and protected by extensions of labor and employment laws.

Thus, though I was unconvinced by many of the book’s central arguments, I acknowledge that Abadie leaves us with some thought-provoking questions about the ethics of phase I clinical trials. For those who will be at the 2013 AER Conference in Boston this November, I hope you’ll join me and your fellow attendees on Thursday, November 7 to further discuss Abadie’s work as part of the research ethics book group lunch!

Modeling kindness and respect in patient care

by Joan Rachlin, JD, MPH, Executive Director

I spent several days recently at the Jewish General Hospital (JGH) in Montreal, Canada, where my 95-year-old father-in-love (he started out as my father-in-law, but that status quickly changed), Sam, had been admitted for a host of medical problems.

Sam began his life in a Polish shtetl where he learned about caring, community, and devotion to friends and family in ways that have both benefited and inspired everyone who knows him. He worked as a peddler in the French Canadian community for nearly 50 years, and befriended all his customers. Sam was known for extending credit where none might have been due, and for his unending gentleness and kindness. He had many stories to tell, but after decades of heart problems, successive pneumonias, and a stroke, he has now been robbed of both speech and mobility. Nothing, though, can take away his incredible goodness, and that's what makes our family's vigil by his bedside a labor of great love.

I remember reading an article by Atul Gawande, MD, MPH, in The New Yorker several years ago titled “The Way We Age Now” that spoke about caring for the elderly. Dr. Gawande (who, by the way, will be one of the keynote speakers at PRIM&R’s upcoming Advancing Ethical Research Conference on November 7-9) wrote about how so few caregivers want to care for aging patients because they're often hard of hearing, poorly groomed, low-income, and generally afflicted with a host of chronic medical issues that, at best, can only be marginally improved. He talked about the manner in which a health care professional can tell a lot about an elderly patient's overall status by looking at their feet, since many of them can no longer continue the previously simple act of clipping and cleaning toenails or removing calluses once arthritis, spinal stenosis, or other orthopedic travails set in.

During Sam’s most recent hospitalization at the JGH, my admiration for the care he received was taken to new heights. The first thing that impressed, scratch that—stunned me—involved Dr. Luc Trudeau, the director of the hypertension clinic and an internist who has been at the JGH for more than 30 years. I had previously met Dr. Trudeau almost a year ago when Sam was hospitalized following a stroke.

During that time, Dr. Trudeau and I had a few conversations that I considered to be as good as it gets when dealing with physicians. Not only was he competent and attentive, but he was also consistently respectful, patient, vigilant, responsive, empathic, and determined to help Sam regain as much post-stroke strength and mobility as possible. When I saw him again recently, I reminded him of our earlier interactions and he said, without missing a beat, "Oh yes, I remember. Your father-in-law was in room 622, in the bed next to the window." His instant recall reinforced my observations of this uncommon man from our earlier encounters, and I immediately decided that if Dr. Trudeau could be cloned, I'd willingly surrender my opposition to human cloning.

Then there is David K. Williams, one of the nurses who took care of Sam. David is responsible for a large number of patients, but each time he comes to see Sam, it's as though he has no one else in the world to worry about. And when David is caring for Sam, he sees just a man, rather than a man who is very old and very sick; the removal of those “old and sick” modifiers makes all the difference. Like Dr. Trudeau, David is gentle and kind, and they both follow the well-known medical corollary of the golden rule: Treat every patient the way you’d want your parents to be treated. David told me that his mantra is, "take care of one patient at a time,” and I know that he means that in the both the literal and figurative senses. He is an intentional, mindful, and present man, who is both competent and caring.

There are so many caregivers like David and Dr. Trudeau at the JGH, including one nurse who came in to insert an IV, and found that Sam's veins were very thin and mostly collapsed. Instead of repeated poking, which would have caused Sam pain, she went to get warm compresses, which she then gently applied, reheated, and reapplied until she found a vein that could accept her needle. Or the nurse's aide who spent what seemed like an hour comforting a scared and crying patient. All of this tender, loving care reminded me of a well-known Boston Globe Magazine piece entitled “A Patient’s Story,” written by Ken Schwartz, a Boston lawyer who died of lung cancer almost 20 years ago at age 42. He wrote a deeply personal and professionally piercing account of his illness in which he described the power of the human connection between patients and their caregivers. Ken Schwartz reminded caregivers to stay in the moment with patients and how “acts of kindness —the simple human touch [of ] caregivers—made the unbearable bearable.” Thanks for your small, medium, and large acts of kindness and compassion, Dr. Trudeau, Dr. Hockstein, Dr. Henault, Dr. Edwards, Dr. Lachleban, Dr. Langlois, Dr. Goldstein, David, Theresa, Valerie, Linda, and the many other wonderful members of the JGH staff.

Although this is not a research ethics post, it is about the truism that treating people with respect, kindness, and justice is a universal need, no matter the setting or circumstance. It's so easy to dismiss the elderly when we pass them on the street, see them in a store, or encounter them in a healthcare setting, but I am increasingly reminded that someday, all of us "boomers" will be at risk for playing out stories like Sam's in hospitals and nursing homes across this country. I know that other cultures and countries have different attitudes toward caring for the elderly, but the United States has a long way to go.

This is thus a gentle plea to remember that each elder is a unique individual with a back story, a family that loves them, and with the universal hope that their dignity will be maintained and protected by others once they lose the ability to preserve it for themselves.

Research Ethics Roundup: Controversy over a research study in India, bias in animal research, and more!

It’s back to school and back to work! Get into the swing of things by catching up on the latest news in the research ethics world (which never goes on vacation)!

Aveo Reeling after FDA's Rejection of Kidney Cancer Drug: Aveo Pharmaceuticals spent seven years and $300 million developing tivozanib, a kidney cancer drug, which was recently rejected by the Food and Drug Administration (FDA). The panel cited concerns about the trial design, the data, and the interpretation of the data. Critics of the ruling claim that the FDA unfairly changed the criteria that Aveo needed to meet in order to gain approval. The FDA’s decision prompted Aveo to let go of more than 60 percent of its staff, and shareholders have filed lawsuits claiming the company issued misleading statements about the drug.  The Securities and Exchange Commission is now investigating.

Questions in India Cancer Study Still Lingering: A National Cancer Institute (NCI)-funded study of cervical cancer screening in India continues to generate controversy as questions about the trial design remain. Researchers conducted simple, inexpensive vinegar tests to screen for cervical cancer on half the enrollees, and the remaining subjects were placed into an unscreened control group. In 2012, the Office for Human Research Protections (OHRP) found that the informed consent documents used were inadequate because they did not explain to enrollees in the control group the alternatives for receiving cervical cancer screening; this problem has since been corrected. Many believe that it was unnecessary for researchers to have an unscreened control group; however, investigators, as well as NCI, have defended that decision, arguing that “since the standard of care for cervical-cancer screening in India is no screening, [researchers] were ethically justified in having a no-screening control.”

Scientists to Sequence Genomes of Hundreds of Newborns: The Genomic Sequencing and Newborn Screening Disorders multi-site research program, funded by the National Institute of Child Health and Human Development and the US National Human Genome Research Institute, will sequence the genomes of 480 infants, half from healthy babies, and half from babies in neonatal intensive care units. The aim of the study is to see whether full genome sequencing is better than conventional newborn screening for detecting genetic disorders that affect drug metabolism, immune function, and hearing. Different sites will report different information to the parents of enrolled subjects; some will follow the American College of Medical Genetics and Genomics recommendation to report results of mutations in 57 genes, which are linked to various health conditions, even if they are not linked to subjects’ diagnoses. Other teams are planning to give parents information on genetic defects relevant to babies’ diagnoses and other mutations which might be “medically actionable.”

Bias Detection: Study Identifies Instruments for Evaluating Animal Studies: University of California, San Francisco researchers have identified 30 assessment instruments to evaluate the risk of bias in animal research, including randomization, concealment of allocation, blinding, and accounting for all animals. The study team searched 3,371 articles from the past 45 years of MEDLINE in compiling their data. Commentators have called the study an important step in reducing the risk of bias.

Risk in comparative effectiveness research: Reflections from DHHS public meeting

by Elisa A. Hurley, PhD, Education Director

As I shared in yesterday’s blog post, I had the privilege of attending the Department of Health and Human Service (DHHS) public meeting in Washington, DC, on “matters related to protection of human subjects and research considering standard of care interventions,” which was convened to address some of the issues raised by the Surfactant, Positive Pressure, and Oxygenation Randomized Trial (SUPPORT).

Yesterday I mentioned the surprising areas of convergence among the 27 presenters who took their turn at the podium. Today I will focus on some of the areas of disagreement. One issue that continues to provoke widespread disagreement is how to conceptualize and assess the risks of comparative effectiveness research. David Magnus, from the Stanford School of Medicine, for instance, argued that when there is no evidence of an increase in risk for individuals enrolled in a study versus those not enrolled, the research is appropriately classified as minimal risk, regardless of what risks are associated with each arm of the study.

On the other hand, George Annas, from Boston University School of Public Health, claimed that randomization always harms the subject by depriving her of the doctor-patient fiduciary relationship in which her physician is obligated to act in her best interest, and so, presumably, enrollment in a randomized study of any standard of care interventions could never be classified as minimal risk.

Steven Joffe, from the Perelman School of Medicine, made a characteristically articulate and concise case that the definition of minimal risk in the regulations is woefully unclear, perhaps contributing to much of the confusion about how to assess comparative effectiveness research, and proposed guidance clarifying that assessments of minimal risk should be made based only on risks that result from research, and not therapies that the subject would receive if not involved in the research.

John Lantos, from Children’s Mercy, and Nancy Kass, from the Bloomberg School of Public Health, provided the most eloquent, persuasive, and provocative challenges to the assumption that participating in research is always riskier than receiving conventional treatment, or that receiving individualized care is always better than receiving care through research. Both went so far as to suggest that we should, through informed consent forms, be more transparent about the fact that receiving unvalidated therapies may be riskier than participating in randomized research.

Of course, many other fascinating questions and issues came up on Wednesday, and I encourage anyone who wasn’t at the meeting or watching it via live stream to watch the archives to get the full flavor of the richness and collegiality of the discussion, the graciousness and astoundingly thorough preparation of the panelists, and the mutual respect this community has for one another, regardless of where we all stand on the issues. It remains to be seen what the policy outcome of this special meeting will be, but there is no doubt in my mind that this was public policy deliberation at its very best, and it was a privilege to be part of it.

Finding common ground on SUPPORT: Reflections from DHHS public meeting

by Elisa A. Hurley, PhD, Education Director

Last Wednesday, August 28, 2013, the Department of Health and Human Service (DHHS) held a public meeting in Washington, DC on “matters related to protection of human subjects and research considering standard of care interventions.” It was an unprecedented event on a historic day—the 50th anniversary of the March on Washington—and I was lucky enough to attend the event as a representative for PRIM&R. Over the course of two posts, I want to share some of my reflections from this remarkable day.

Those of you who have been following events for the past five months know that this meeting was scheduled following the heated public debate that erupted in response to the Surfactant, Positive Pressure, and Oxygenation Randomized Trial (SUPPORT), which we’ve been covering on Ampersand. The debate around SUPPORT has illuminated deep disagreements within the research and ethics communities about how risk should be assessed and disclosed to subjects (or their surrogates) in randomized studies on interventions that are used in standard care, but about whose relative effectiveness there is widespread disagreement (often called “comparative effectiveness research”). The lack of consensus within the field about this growing area of research prompted DHHS to announce, in late June, that it would hold a meeting to “seek public input and comment on how certain provisions of the [DHHS] requirements related to the protection of human subjects should be applied to research studying one or more interventions which are used as standard of care treatment in the non-research context.”

The day-long meeting was held at DHHS’s headquarters, a stone’s throw from the United States Capitol. Two hundred and twenty individuals were registered for the meeting. Twenty-seven presenters, including me, were on the agenda. Each one of us was allowed seven minutes to present our comments in response to DHHS’s request, and five minutes to answer questions from the DHHS panel, which included Jerry Menikoff, director of OHRP; Kathy Hudson, deputy director of science, outreach, and policy at NIH; and Robert Temple, deputy director for clinical science at the Center for Drug Evaluation and Research at the FDA. Presenters included parents of children enrolled in SUPPORT, bioethicists, representatives of public advocacy organizations, SUPPORT investigators, neonatologists, and other researchers, and represented the entire spectrum of views on both SUPPORT and the broader issues regarding research on standard of care.

That said, one of the many remarkable aspects of the day was how much common ground there was, even among those who seemed, at the height of the controversy, to be at the starkest of odds with each other. While some, including representatives of Public Citizen and the Alliance for Human Research Protection, continue to argue that SUPPORT was an unethical study to conduct, the majority of presenters agreed that SUPPORT, and studies like it, are worth doing and, more generally, that we collectively should be committed to addressing the alarming fact that much of what is done as a matter of routine clinical care is not supported by good evidence.

There was also surprisingly widespread—though not unanimous—agreement around the idea that respect for persons demands a comprehensive informed consent process, a view that cut across very different conceptions of the level of risk involved in research on standard of care interventions. For one thing, most presenters seemed to agree that the informed consent documents used in SUPPORT were woefully inadequate, precisely because they did not mention what was known at the time of the study about the risks to premature infants of receiving the oxygen levels under study. More generally, many suggested that what is included in consent forms and processes should serve the goal of transparency about precisely what is being asked of subjects and their surrogates, and what it might mean for them—whether or not those elements are “novel” to the research context or not—rather than follow the letter of the law, i.e., regulations that explicitly require only the disclosure of the nature, risks, and benefits of research procedures. Some of the strongest presentations on this topic were those by Peter Vasilenko, from Alion Science and Technology; Lois Shepherd, from the University of Virginia School of Law; and David Forster, from WIRB.

I was particularly pleased to see this consensus emerge, because it is very much in line with PRIM&R’s own recommendations. In our comments, we proposed a framework to guide institutional review boards (IRBs) when they are asked to review research on standard of care. According to our framework, IRBs have a responsibility to make sure that individuals being asked to enroll in studies examining standard of care interventions are adequately informed about all of the following:

• The nature, potential benefits, harms, and burdens of the interventions being compared
• The fact that they’re being asked to participate in research
• That they have a choice, with regards to the specific interventions being studied, between remaining in a therapeutic, doctor-patient relationship, and entering an investigator-subject relationship, in which the physician will not routinely be making personalized clinical decisions about the use of the interventions under study
• That the research may impose particular burdens and potential harms beyond those involved in receiving the interventions solely as ordinary care, and what those specific burdens and risks are

An even more surprising theme regarding informed consent also emerged on Wednesday, namely, that consent may be wholly inadequate in the context of clinical care, given that, in many cases, there is a lack of certainty about which intervention physicians might choose from a set of generally accepted alternatives, and that when there are multiple standards, their profiles of risks and benefits may differ in ways that are of import to patients. It would be hard not to emerge from the day thinking that physicians ought to be talking about alternatives with their patients much more regularly than they currently do—though what sort of policy implications such a conclusion has was, of course, outside the scope of this group’s purview.

While there was a surprising amount of convergence across the perspectives shared last week, there were also, of course, areas of disagreement. I will highlight some areas of contention that arose at the meeting in a second blog post, tomorrow.