Thursday, September 18, 2014

Petrie-Flom Center Launches New Book on Human Subjects Research Regulation

by Holly Fernandez Lynch, JD, MBioethics, Executive Director of the Petrie-Flom Center for Health Law Policy, Biotechnology, and Bioethics

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 US Public Health Service Syphilis Study at Tuskegee, conducted by US 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, it has significant flaws—including its potential to burden important research, lag behind developments in how research is conducted, overprotect some subjects and inadequately protect others, and generate inconsistent results.

A new book from the Petrie-Flom Center for Health Law Policy, Biotechnology, and Bioethics at Harvard Law School, titled Human Subjects Research Regulation: Perspectives on the Future, documents some of the issues that persist with the current system of research regulation. Invigorated by the US government’s first steps toward change in over twenty years, Human Subjects Research Regulation, which was co-edited by myself and the Center's faculty director I. Glenn Cohen, JD, brings together the leading thinkers in the fields of 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 protections.

The edited volume stems from the Petrie-Flom Center’s 2012 annual conference, which brought together leading experts in a conversation about whether and how the current system of human subjects research regulation in the US ought to change to fit evolving trends, fill substantial gaps, and respond to identified shortcomings. After reviewing the history of US research regulations and the 2011 Advance Notice of Proposed Rulemaking for revision to the “Common Rule”—in a chapter by PRIM&R’s own Elisa A. Hurley, PhD, and Amy Davis, JD, MPH—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 IRBs; privacy, especially regarding biospecimens and tissue banking; and the possibility of fundamental paradigm shifts.  

The book is currently available from MIT Press and Amazon, and its introduction can be downloaded for free here. We will be hosting a book discussion at Harvard Law School on October 22 (in Wasserstein Hall Room 2009 from 12-1:30pm), and in Baltimore on December 5 at PRIM&R’s 2014 Advancing Ethical Research Conference.

We hope to see you there!

Tuesday, September 16, 2014

PRIM&R’s Response to the FDA’s Draft Guidance on Informed Consent

by Avery Avrakotos, Education and Policy Manager

PRIM&R has long been committed to the protection of the rights and welfare of human subjects, and strongly believes that informed consent is an essential mechanism for providing potential subjects with the information they need to make considered, autonomous decisions about research participation.

In July, the US Food and Drug Administration (FDA) announced it was seeking comment on a draft guidance document titled "Informed Consent Information Sheet: Guidance for IRBs, Clinical Investigators, and Sponsors." The draft is a substantial revision to the FDA’s prior guidance on this topic, which was issued by the agency in September 1998. Yesterday, PRIM&R’s Public Policy Committee, which is composed of experts from a wide range of disciplines and institutional settings, responded to the agency’s request with a set of comments on the draft guidance.

In its response, PRIM&R commends the FDA for encouraging investigators to think of informed consent as not simply a form, but rather a dynamic process that can be adapted to reflect the unique needs of potential subjects, as well as local context. PRIM&R also thanks the FDA for its efforts to harmonize regulatory requirements and guidance for human subjects research put forward by the Department of Health and Human Services, the Office for Human Research Protections, and the FDA. PRIM&R’s comments also applaud the addition of expanded sections on informed consent with respect to vulnerable populations and the agency’s consideration of the use of new technologies for obtaining informed consent.

PRIM&R comments also identify several areas where further guidance could benefit IRBs, investigators, sponsors, and, ultimately, subjects:

The Consent Form Versus the Consent Process
In a recent blog post, PRIM&R’s executive director, Elisa A. Hurley, PhD, discussed how the language we use to talk about informed consent can have an effect on our general attitudes toward consent. Along those same lines, in its comments, PRIM&R urges the FDA to replace the term “consent interview” with the term “consent discussion,” which more accurately reflects the desired tenor—an exchange of information between two parties—of such interactions. PRIM&R also recommends that the FDA carefully consider how it explains the purpose of the consent form, as what is said in the guidance document is likely to have far-reaching effects on the content of consent forms. As a final point, PRIM&R asks the agency to provide greater clarity regarding the form and function of the consent discussion, as well as its relationship to the consent form.

Presentation of Risks
In the draft guidance, the FDA acknowledges that reducing length may increase the readability of consent forms. PRIM&R commends the agency for this recognition, but cautions that the call for disclosure of any reasonably foreseeable risks associated with the medically recognized standard care and appropriate alternatives seems likely to perpetuate the problem of overly long and complicated forms. PRIM&R believes the consent form, as well as the consent discussion, should focus on presenting potential subjects with the information that is most likely to be significant to their decisions to participate in research. In its comments, PRIM&R also recommends a framework— making a distinction between “risks” and “side effects” associated with a clinical investigation—that investigators, IRBs, and sponsors can utilize when determining which risks should be considered “reasonably foreseeable,” and thus, most likely, germane to a potential subject’s decision to participate.

Responsibilities of Investigators
One of the strengths of the draft guidance is the addition of clear information on the respective responsibilities of IRBs, investigators, and sponsors for informed consent, as all of these parties have an essential role to play in the informed consent process. In its comments, PRIM&R offers several additional recommendations with respect to the responsibilities of investigators. PRIM&R asks the FDA to consider requiring investigators and/or research staff to attest that they have discussed the risks, benefits, and alternatives and provided the potential subject with an opportunity to ask questions, and that, in their judgment, the potential subject understands the information that has been presented and has voluntarily chosen to participate in the clinical investigation. PRIM&R also asks the FDA to encourage investigators to consider the order in which information is presented in the consent discussion and to utilize alternative approaches to information disclosure that will enhance the discussion, such as videos or online resources.

Understandable Language
From the outset, the FDA recognizes in the draft guidance that the health literacy and numeracy (quantitative literacy) of many US adults are at a basic level. In its response, PRIM&R commends the FDA for recognition of this fact, and makes several additional recommendations intended to ensure that language used throughout the consent process is understandable to potential subjects. As a starting point, PRIM&R asks the FDA to recommend that scientific and medical terms only be used when necessary and, whenever possible, as parentheticals to ordinary language descriptors. Given the limited quantitative literacy of many US adults, PRIM&R also asks the FDA to provide clearer guidance on the presentation of quantitative information to potential subjects, for instance, the most effective way to present the likelihood of potential risks and benefits. As a final point, PRIM&R asks the FDA to ensure that all sample language provided in the draft guidance is consonant with its recommendations regarding the use of understandable language.

Enrollment of Non-English-Speaking Subjects
The principle of justice requires that no specific population either be unfairly excluded from the potential benefits of research or unduly subjected to its burdens. When barriers to enrolling individuals from a specific population, such as non-English speakers, are high, concerns related to the principle of justice arise. In its comments to the FDA, PRIM&R raises concerns about certain requirements for the unexpected enrollment of non-English-speaking subjects—including the post-hoc provision of a translated long form to subjects who have already participated in a consent discussion and enrolled in the research—which PRIM&R believes may carry significant financial and administrative burdens, without evidence that such requirements will enhance subject protections. PRIM&R asks the FDA to reconsider these requirements with the principle of justice in mind.

I encourage you to take a moment to read PRIM&R’s complete response to the FDA, and to share your thoughts about PRIM&R’s comments or the FDA’s draft guidance below.

Thursday, September 11, 2014

Finding Empowerment at the 2013 AER Conference

by Betty Kalama, Senior Community Facilitator at the Kenya Medical Research Institute Wellcome Trust Research Programme

As a community facilitator within the Kenya Medical Research Institute (KEMRI)-Wellcome Trust Research Programme, my primary responsibility is supporting community engagement. From workshops for community members to staff training sessions on research ethics and communication skills, I work frequently with researchers and community members to strengthen the relationship between the programme and the community. In addition, I participate as a member of the Consent and Communication Committee, which aims to support ethical research by advising on locally appropriate strategies for communicating with participants and the wider community about research.

Given my professional responsibilities, I was very pleased to be able to attend PRIM&R’s 2013 Advancing Ethical Research (AER) Conference through the organization’s Global Research Scholarship Program. The conference provided me with an opportunity to learn in greater detail about the convergence of ethics with medicine and research. Furthermore, I was able to expand my understanding of the diverse ethical challenges that can arise in the review of research. The experience solidified for me the idea that, while the principles of research ethics may be global, careful attention needs to be paid to the research setting to ensure the appropriate application of those principles. By sharing experiences with other scholars and conference attendees, I discovered how complex ethical principles can be applied in a variety of settings. The conference also provided me with new strategies to tackle the challenging issues inherent in human subjects research.

Upon returning home, I shared the knowledge I gained with other staff in my organization. Through my participation, my colleagues were able to learn about new things, including the use of placebos in clinical trials and recent changes to the Declaration of Helsinki. This knowledge empowered my team to address ethical issues in protocol review, trainings, workshops, outreach efforts, and regular interactions with both the staff and the community. Thanks in part to the knowledge I gained at the conference, I was also able to advance: I was nominated to serve as secretary of the Consent and Communication Committee.

I am grateful to PRIM&R for the opportunity to attend the conference. I am also thankful to the KEMRI-Wellcome Trust Research Programme for encouraging me to attend.

Registration for the 2014 AER Conference, which will be held December 5-7 in Baltimore, MD, is now open. Please visit our website for more information.

Tuesday, September 9, 2014

Consent and the Autonomy of Human Subjects

by Elisa A. Hurley, PhD, Executive Director

We all know that designing a mechanism for obtaining valid informed consent is a perennial challenge, but it seems to be receiving special and renewed interest lately.

The United States Food and Drug Administration (FDA) recently released a draft guidance, Informed Consent Information Sheet: Guidance for IRBs, Clinical Investigators, and Sponsors, for public comment. The draft is intended to replace the FDA’s previous, and much briefer, guidance on informed consent, which dates from 1998. Throughout the new draft guidance, the FDA emphasizes that informed consent involves more than a form, and encourages investigators, IRBs, and sponsors to think of informed consent as a dynamic process that can be adapted to reflect the unique needs of potential subjects, as well as local context.

The introduction to the FDA draft states it plainly:
To many, the term informed consent is mistakenly viewed as synonymous with obtaining a subject’s signature on the consent form. FDA believes that obtaining a subject’s oral or written informed consent is only part of the consent process. Informed consent involves providing a potential subject with adequate information to allow for an informed decision about participation in the clinical investigation, facilitating the potential subject’s comprehension of the information, providing adequate opportunity for the potential subject to ask questions and to consider whether to participate, obtaining the potential subject’s voluntary agreement to participate, and continuing to provide information as the clinical investigation progresses or as the subject or situation requires. To be effective, the process must provide sufficient opportunity for the subject to consider whether to participate.
PRIM&R has long championed this approach to thinking about informed consent, and we commend the FDA for recognizing that this guidance document can be used to foster improved understanding of the purpose and goals of informed consent. PRIM&R will submit comments to the FDA on the draft guidance, and I encourage you to share your thoughts and comments on the guidance, along with those on other topics, at the end of this post.

Additionally, the Secretary's Advisory Committee on Human Research Protections (SACHRP), the body charged with making recommendations to the Secretary of Health and Human Services regarding human subjects protections issues, devoted a full quarter of its July 2014 meeting agenda to a discussion of the informed consent process, in a session aptly titled, Informing Informed Consent: Defining and Validating Comprehension.

There is a common thread between these two examples—a renewed emphasis on the role and importance of subject understanding in the consent process.

The FDA draft guidance focuses on the importance of consent documents being written in language understandable to subjects, and includes expanded sections on informed consent with respect to non-English speakers. The SACHRP session concentrated on barriers to subject comprehension, including the fact that therapeutic misconception persists despite increasingly well-informed efforts to educate potential subjects about the purposes of research.

These points are well taken: empirical research dating back to the 1980s consistently shows that research subjects have limited understanding of study information (Falagas et al., 2009; King and Heubi, 2014), and that consent forms are often to blame. Long, dense, and technically written consent documents do a better job of legally protecting research institutions than enabling potential subjects to make informed decisions about research participation. And while legal protection is important for both the subject and the institution housing the research, the focus on avoiding future litigation puts the interests of the institution above the interests of individuals who are being asked to take on sometimes significant risks for the sake of, at least primarily, generating scientific knowledge. Without subject comprehension, consent can’t meet its intended goal: to afford potential research subjects the opportunity to autonomously agree to participate in a research study, with full and well-considered knowledge of all that participation entails.

None of this is news, of course. And valiant efforts are being made to offer empirically grounded recommendations about how to improve both consent forms and processes, precisely to increase subject comprehension (Nishimura et al., 2013; Koyfman et al., 2009; Stunkel et al., 2010; Kass et al., 2011). But attending the SACHRP meeting and then shortly afterward working on PRIM&R’s comments on the FDA guidance, got me thinking about the tenacity of the problems around subject comprehension in informed consent. This led me to reflect on another practice around consent I’ve noticed and always objected to: the use of “consenting” as a transitive verb – as in, “we consented the subject into the study….” This may seem like a minor detail; in fact you hear it all the time. But I think this way of speaking reflects the same general attitude toward consent that results in overly lengthy, poorly constructed consent forms: that it’s something done to subjects so that research can get started.

Thinking this way does real violence to the very idea of what consent is supposed to do: respect, acknowledge, and invoke the agency of potential research subjects as they think about and knowledgeably decide whether they want to participate in research. Again, the phrasing may seem like a small detail, but words matter. They convey an attitude. In this case, it’s an attitude reflective of a more general corruption of the spirit of informed consent, namely, that in practice, on the ground, there is not enough regard for its role as our primary mechanism for respecting the autonomous, informed choices of individuals to participate in this important endeavor we call research.

What do you think? Is this an issue of mere semantics, or a point requiring a culture change? What are your reactions to the FDA’s draft guidance? And what are some best practices you’ve seen or used to foster subject comprehension during the informed consent process?

Friday, August 22, 2014

Patience and persistence: An interview with Jami Peelle

by Megan Frame, membership coordinator

Welcome to another installment of our featured member interviews where we introduce you to our 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 Jami Peelle, faculty grants and fellowships coordinator and IRB administrator at Kenyon College in Gambier, OH.

Megan Frame (MF): When and why did you join the field?
Jami Peelle (JP): I am a librarian by training, and when I first agreed to do grants work at my institution ten or so years ago, I joined a wonderful network of people who do grant work for small colleges. At my first gathering with these incredibly generous colleagues, they were all talking about IRBs and IACUCs. I finally had to ask what in the world they were talking about. I returned to my campus to find out that we didn't really have a formal IRB. I was assigned to set ours up and soon found that PRIM&R was the leader in providing education on the protection of human subjects in research and the operations of an IRB.

MF: What skills are particularly helpful in a job like yours?
JP: Ability to find information, patience, and persistence.

MF: Tell us about one or more articles, books, or documents that have influenced your professional life.
JP: I love the book The Immortal Life of Henrietta Lacks, and was thrilled when the author, Rebecca Skloot, gave a keynote address at PRIM&R’s 2010 Advancing Ethical Research (AER) Conference. The book helps start discussions on many topics pertinent to the college community, including the ethical conduct of research. A number of faculty here find Laud Humphreys' Tearoom Trade an interesting case study for thinking about potential problems in social science research.

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?
JP: I have been to a number of PRIM&R’s annual conferences which are always interesting and useful, but the most important PRIM&R conference I have attended was the 2007 Social, Behavioral, and Educational Research (SBER) Conference. There is always an SBER track at the AER Conference, but having SBER front and center was terrific. The SBER focus made networking easier.

MF:  How has membership in PRIM&R’s community of research ethics professionals helped you to advance in your career?
JP: I found the At Your Doorstep program very helpful in designing and providing an IRB program for our college consortium. It was tailored and presented beautifully for us by the dynamic J. Michael Oakes, PhD. We found Professor Oakes' experience with IRB review of undergraduate research invaluable.

MF:  What is your proudest achievement?
JP: I am very proud of the establishment of our IRB and our website. I believe we provide our students with an excellent foundation in the ethics of human subjects research, which will serve them well as they continue on to graduate programs. It is my belief that the IRB review of undergraduate research projects results in higher-quality research experiences.

MF: Is there anyone, living or dead, who has inspired you in your career and/or in life?
JP: There have been many who have inspired me in one way or another: friends, colleagues, family, and teachers. In my work with responsibility in research, I owe much to our first IRB chair, Ric Sheffield, JD, and to my Colleges of Liberal Arts Sponsored Programs colleagues.

Thank you for being part of our membership community and sharing your story, Jami. We hope to see you at future conferences, including the 2014 Advancing Ethical Research Conference, where representatives of the Henrietta Lacks family will be joining us for a conversation on the importance of the Henrietta Lacks case and its legacy for the research community.

Additionally, PRIM&R will host the 2015 SBER Conference on November 12, 2015, in Boston, MA. Mark your calendar and stay tuned for more details about the conference!

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