Here is HHS’s own summary of what has changed and what it thinks is most important:
The U.S. Department of Health and Human Services and fifteen other Federal Departments and Agencies have announced proposed revisions to modernize, strengthen, and make more effective the Federal Policy for the Protection of Human Subjects that was promulgated as a Common Rule in 1991. A Notice of Proposed Rulemaking (NPRM) was put on public display on September 2, 2015 by the Office of the Federal Register. The NPRM seeks comment on proposals to better protect human subjects involved in research, while facilitating valuable research and reducing burden, delay, and ambiguity for investigators. It is expected that the NPRM will be published in the Federal Register on September 8, 2015. There are plans to release several webinars that will explain the changes proposed in the NPRM, and a town hall meeting is planned to be held in Washington, D.C. in October.Read More
In her recent publication, On The Run, University of Wisconsin sociology professor, Alice Goffman writes about embedded research from 2002-2007 in a “ghetto” community she names 6th Street (located in Philadelphia). The African American residents of this community are mostly poor and tethered to the criminal justice system as parolees, on probation, and in and out of jail. Goffman’s human research subjects comprised the jailed, imprisoned, and minors–IRBs generally describe these populations as “vulnerable.”
On The Run is hailed as original, creative, and transgressive because of Goffman’s lengthy stay in such a descriptively chilling, dangerous, and Black neighborhood–where frequent gun battles teach kids to dive for cover, the women are teen mothers or crack addicted, and law enforcement incessantly polices the community. Indeed, she moves into the neighborhood and lives with three of the 6th Street boys. Much could be gained from documenting the challenges in such a community, particularly given the troubling patterns of mass incarceration in the U.S. However, the book raises questions about what represents credibility, quality, and rigor in social science research; the book lacks an index, bibliography, and meaningful citations. I write about these concerns and more in a forthcoming Texas Law Review essay, which can be found here.
Reviewers lauded the rigor and ignored ethics of the book, agreeing with Goffman’s Princeton advisor, Professor Mitchell Duneier, and his NY Times assessment that “[t]he level of immersion is really unusual,” because “[s]he got access to the life of the ghetto and came to understand aspects of it we don’t ever get to see.” Yet, therein resides a significant problem. Fascination with the ghetto and perceptions that life in inner-cities is so bad that researchers can’t possibly expose those human subjects to risks and harms may have blinded the book’s many reviewers to the fact that Black lives matter, including in human research. It might have also implied a lower standard for rigor; it is rare that an academic book lacks a bibliography and index. Goffman also destroyed her field notes. These concerns becomes starkly relevant when she writes about her desire and collaboration with “Mike” to kill a man from the neighboring 4th Street.
A remarkable new “sting” of the “diet research-media complex” was just revealed. It tells us little we didn’t already know and has potentially caused a fair amount of damage, spread across millions of people. It does, however, offer an opportunity to explore the importance of prospective group review of non-consensual human subjects research—and the limits of IRBs applying the Common Rule in serving that function in contexts like this.
Journalist John Bohannon, two German reporters, a doctor and a statistician recruited 16 German subjects through Facebook into a three-week randomized controlled trial of diet and weight loss. One-third were told to follow a low-carb diet, one-third were told to cut carbs but add 1.5 ounces of dark chocolate (about 230 calories) per day, and one-third served as control subjects and were told to make no changes to their current diet. They were all given questionnaires and blood tests in advance to ensure they didn’t have diabetes, eating disorders, or other conditions that would make the study dangerous for them, and these tests were repeated after the study. They were each paid 150 Euros (~$163) for their trouble.
But it turns out that Bohannon, the good doctor (who had written a book about dietary pseudoscience), and their colleagues were not at all interested in studying diet. Instead, they wanted to show how easy it is for bad science to be published and reported by the media. The design of the diet trial was deliberately poor. It involved only a handful of subjects, had a poor balance of age and of men and women, and so on. But, through the magic of p-hacking, they managed several statistically significant results: eating chocolate accelerates weight loss and leads to healthier cholesterol levels and increased well-being. Read More
The Risks of Biotechnology, with George Church Monday, Oct. 20, 5.30pm, Sever 102
Genetic manipulations can reintroduce extinct viruses or create viruses much deadlier than ever before. What are the dangers associated with biotechnology? Can a mistake in a lab lead to a global pandemic? Can this technology be used by terrorists? What would be the implications? And is humanity doing enough to avoid these threats?
George Church, Professor of Genetics at Harvard Medical School and the world’s leading expert on synthetic biology and security will share his insights on these issues.
The research assistant will work with the principal investigator Nir Eyal and collaborators from the Harvard TH Chan School of Public Health, Duke University, Massachusetts General Hospital, and the Brigham and Women’s Hospital as well as the ACTG HIV trial site network. The multidisciplinary team uses methods of clinical epidemiology, economics, simulation modeling, and normative theory to predict risks in early-phase HIV cure studies, assess how much likely candidates for participation understand those risks, and make ethical recommendations on the conduct of HIV cure studies.
The research assistant will help prepare, conduct and analyze a pilot survey expected to take place in a US site of the AIDS Clinical Trials Group (ACTG). The survey will assess perceptions of HIV cure and of cure study risks. The research assistant will also promote other research and grant-related activities, through literature reviews and assistance in the preparation of abstract, poster, and manuscripts for publication, grant applications, a simple project website (using Harvard’s user-friendly OpenScholar platform), and slides for lectures and seminars. The research assistant will be in touch with top researchers in HIV cure, medical decision making, and ethics from around the country, to facilitate our meetings, a workshop, and regular conversations to plan the research and debate ethical issues around early-phase HIV cure studies.
The book is currently available from MIT Press and Amazon, in hardcover and paperback. We will be hosting a book discussion at Harvard Law School on October 22, and in Baltimore on December 5 at Public Responsibility in Medicine and Research (PRIMR)’s annual Advancing Ethical Research Conference. Details will be announced shortly.
From the book jacket:
The current framework for the regulation of human subjects research emerged largely in reaction to the horrors of Nazi human experimentation, revealed at the Nuremburg trials, and the Tuskegee syphilis study, conducted by U.S. government researchers from 1932 to 1972. This framework, combining elements of paternalism with efforts to preserve individual autonomy, has remained fundamentally unchanged for decades. Yet, as this book documents, it has significant flaws—including its potential to burden important research, overprotect some subjects and inadequately protect others, generate inconsistent results, and lag behind developments in how research is conducted. Invigorated by the U.S. government’s first steps toward change in over twenty years, Human Subjects Research Regulation brings together the leading thinkers in this field from ethics, law, medicine, and public policy to discuss how to make the system better. The result is a collection of novel ideas—some incremental, some radical—for the future of research oversight and human subject protection.
After reviewing the history of U.S. research regulations, the contributors consider such topics as risk-based regulation; research involving vulnerable populations (including military personnel, children, and prisoners); the relationships among subjects, investigators, sponsors, and institutional review boards; privacy, especially regarding biospecimens and tissue banking; and the possibility of fundamental paradigm shifts.
Contributors Adam Braddock, Alexander Morgan Capron, Ellen Wright Clayton, I. Glenn Cohen, Susan Cox, Amy L. Davis, Hilary Eckert, Barbara J. Evans, Nir Eyal, Heidi Li Feldman, Benjamin Fombonne, Elisa A. Hurley, Ana S. Iltis, Gail H. Javitt, Greg Koski, Nicole Lockhart, Holly Fernandez Lynch, Michael McDonald, Michelle N. Meyer, Osagie K. Obasogie, Efthimios Parasidis, Govind Persad, Rosamond Rhodes, Suzanne M. Rivera, Zachary M. Schrag, Seema K. Shah, Jeffrey Skopek, Laura Stark, Patrick Taylor, Anne Townsend, Carol Weil, Brett A. Williams, Leslie E. Wolf
For a more information, including the full table of contents, check out the book on the MIT Press website
“aims to remedy the shortcomings of the existing Clinical Trials Directive by setting up a uniform framework for the authorization of clinical trials by all the member states concerned with a given single assessment outcome. Simplified reporting procedures, and the possibility for the Commission to do checks, are among the law’s key innovations.”
Moreover, and very importantly, the Regulation seeks to improve transparency by requiring pharmaceutical companies and academic researchers to publish the results of all their European clinical trials in a publicly-accessible EU database. In contrast to earlier stipulations which only obliged sponsor to publish the end-results of their clinical trials, the new law requires full clinical study reports to be published after a decision on – or withdrawal of – marketing authorization applications. Sponsors who do not comply with these requirements will face fines.
These groundbreaking changes will enter into force 20 days after publication in the Official Journal of the EU. However, it will first apply six months after a new EU portal for the submission of data on clinical trials and the above mentioned EU database have become fully functional. Since this is expected to take at least two years, the Regulation will apply in 2016 at the earliest (with an opt-out choice available until 2018).
For those closely following the litigation over this clinical trial, a few updates. On January 22, the district court ruled on defendants’ motions to dismiss plaintiffs’ third amended complaint. That complaint named as defendants the director of the IRB, the chair of the IRB, the other members of the IRB (“the IRB defendants”)—all in their individual capacities; the PI of the trial, in his individual capacity; Masimo Corporation, the manufacturer of the oximeter used in the trial; and fictitious defendants (ABC Health Care Providers #1-100; ABC Individuals #1-100; and XYZ Entities #1-100). The complaint stated seven counts: products liability and negligence against Masimo; negligence, negligence per se, lack of informed consent, and breach of fiduciary duty against the IRB defendants and the PI; and wrongful death against all defendants.
Today, there are two big stories that relate to the “institutional corruption” of medicine (aka conflicts of interests). For those who have been working long and hard on these issues, they are cause for hope. The needle does move.
First, one of the biggest pharmaceutical companies, GlaxoSmithKline, has decided that it will stop paying doctors to promote their drugs. My prior work has shown that such payments are quite common (e.g., 61% of urologists and 57% of gastroenterologists taking money), and that they likely influence the prescribing decisions of the doctors who take such money. In recent months, Glaxo has made several such moves towards greater transparency and integrity, often as a result of threatened or actual criminal prosecutions. (See their newfound commitment to opening up their clinical trial data too.)
The NYT story quotes an industry consultant suggesting that the move to stop paying physicians is a result of the Affordable Care Act’s “sunshine” requirement that such payments will be disclosed, and that several other drugmakers are considering similar moves. I am a bit skeptical that the disclosure mandate had such an effect, since the disclosures were already required by Massachusetts and other states, and as part of the “corporate integrity agreements” that came of several federal prosecutions. My sense is that such disclosures are not likely to reach patients in a useable way, so its hard to understand how the transparency could really impose much of a disincentive on the companies. Yet, something has caused Glaxo to change course.
Second, the National Football League has decided to give the National Institute of Health $30 million to study brain injuries. The counterfactual is that the NFL could have kept the money, of course. But the more interesting alternative is that the NFL could have just spent the money itself, hand-picking the researchers and carefully specifying how the research should be performed, in order to buy the scientific conclusions that it preferred. This has been the classic strategy of industries facing litigation risk, from tobacco, to asbestos, and now the paper industry, whose law firm actually commissions scientific studies on its behalf. The NFL’s move instead proves that it is possible for a self-interested party to nonetheless fund independent, credible, gold-standard research, by using an intermediary, such as the NIH.
This is exactly the sort of reform that I have called for, as an alternative to the false dichotomy between public funding and private interest. For companies that have a bona fide interest in discovering and publicizing the scientific truth, a credible intermediary like the NIH can reassure consumers of scientific information that it is valid. Now, if only we can get big pharmaceutical companies to make the same move for their clinical trials and other scientific research studies. Perhaps the first-movers will be the most innovative companies who have bona fide products and are tired of them being lost in the cheap talk? If physicians making prescribing decisions continue to give greater credence towards NIH-funded research, such integrity could be rewarded.
EDIT: Corrected link to NFL story on NYT, and corrected amount from $100M to $30M. Also, disclaimer: I am not involved in this Petrie Flom Center collaboration with the NFL, and the views expressed here are entirely my own.
Additional information and registration available online.
The neonatal SUPPORT trial, which randomized extremely low birth weight infants to lower or higher levels of oxygen saturation as part of their ventilator management raised ethical issues that are turning out to be among the most controversial topics in research ethics in many years. Read More