IRB review: A flexible process

by Andrea Johnson, JD, CIP, Regulatory Specialist, Oregon Health & Science University Institutional Review Board

I don’t think many will disagree with me when I say that the institutional review board (IRB) process is complex. While some of us, including me, find navigating complex regulatory schema to be an enjoyable challenge, the regulations governing human subjects research create practical hurdles that cost time and money, and some would argue that they may even hinder scientific progress. There is a clear need to balance the protection of human subjects with a process that is accessible, consistent, and efficient.

The reforms to the Common Rule proposed in the Department of Health and Human Services (DHHS) Advance Notice of Proposed Rulemaking (ANPRM) have this goal in mind, but it is anyone’s guess when, or if, these changes will materialize.  A summary of public comments compiled by Edward E. Bartlett, PhD, of the Office for Human Research Protections (OHRP) indicates that there is widespread disagreement throughout the research ethics community on a number of important aspects of the ANPRM.  In the meantime, what can IRBs do to simplify and streamline their review process without running afoul of the regulations?

One of the most helpful sessions I attended at the 2012 Advancing Ethical Research Conference was titled Finding Flexibilities in the Federal Regulations:  Advanced Considerations and Applications.  The presenters, Lois Brako, PhD; Moira Keane, MA, CIP; and Irene Stith-Coleman, PhD, did a great job of bringing the attendees back to the text of the Common Rule and reminding us that there is not a “right” and “wrong” for every aspect of human subjects protections. It was reassuring to hear about areas where other institutions had found flexibility, and there were several great ideas that I was excited to share with my institution. On a broader level, the session reinforced the concept that, when searching for ways to improve efficiency, it is helpful to start with the regulations themselves. It is important to note not only what they say, but also what they do not say.

The Common Rule articulates seven criteria in 45 CFR 46.111(a) that must be satisfied in order for a research study to be approved by an IRB.  Sometimes, just realizing that I can count the approval criteria on my fingers helps bring all the nuances of the review process back into perspective. The rule doesn’t provide a list of documents that are required to show that these criteria are satisfied. It doesn’t say that each investigator must complete a 20-page questionnaire in order to demonstrate compliance.  There is certainly room to optimize the way we collect information to evaluate these criteria. It is easy to assume that more guidance, more standardization, and more clarification will make things better, but this session on flexibility was a good reminder that gray areas can be embraced as an opportunity to customize rather than feared as an opportunity for mistakes.

Are those seven criteria the whole picture? No, certainly not.  But they are a great place to start. It is helpful to realize that, even if the ANPRM never evolves into a final rule, we can still work toward a more efficient IRB review process.

Research Ethics Roundup: Cancer patients left untreated in Indian trials, new evidence that mice may be a poor model for human disease, and much more!

Though there’s still snow on the ground across much of the country, baseball fans celebrated the start of Spring Training this week, signaling that warm weather is just around the corner. If you’re looking to get “ahead in the count” of your professional development, take a crack at this week’s Research Ethics Roundup.

Ethics of 2 U.S.-funded cancer studies in India questioned: Two separate U.S.-funded studies of cervical cancer in India are the subject of growing controversy. Researchers conducting the study neglected to screen members of the control group for cervical cancer and failed to obtain adequate informed consent from all those enrolled in the trial. According to this article, at least 79 of the women from the control arms of these studies have died from complications relating to cervical cancer.

Mice fall short as test subjects for humans’ deadly ills: A new study suggests that mice do not provide a good model for researching certain human conditions, such as sepsis and burns. This finding may have significant implications, as mice are heavily relied upon for preliminary drug testing. According to this article from the New York Times, “years and billions of dollars have been wasted following false leads.”

Redefine misconduct as distorted reporting: This article from Nature posits that the research community should redefine misconduct as “any omission or misrepresentation of the information necessary and sufficient to evaluate the validity and significance of research, at the level appropriate to the context in which the research is communicated.” Requiring researchers to be more transparent about their techniques and findings may provide a fairer method of curbing the unsettling proliferation of misconduct within the field.

Unethical stem cells?: According to a review of  human embryonic stem cell (hESC) lines approved by the National Institutes of Health, 49 stem cell lines currently in use may have been “derived from sperm or egg donors who did not give proper consent for the use of their biological material in research.”

Looking for more news? PRIM&R members can visit our Knowledge Center to find more recent scholarly journal and popular media articles pertaining to research ethics. Not yet a member? Learn more about becoming a member by visiting our website.

Beach Blanket Bioethics

by David Perlman, PhD, President & Founder of E4-Eclipse Ethics Education Enterprises, LLC

I borrowed the title of this blog post from Nancy Berlinger, PhD, at the Hastings Center. Every spring, before the summer season, she writes a post for the Hastings Center Bioethics Forum about works of fiction that tackle ethical issues in research and medicine.

Bioethics as entertainment is nothing new. My personal Top 10 List of films, books, and television programs show research gone awry is:

1. Coma
2. Dark Angel 
3. I Am Legend
4. The White Plague
5. Limitless
6. The Strange Case of Dr. Jekyll and Mr. Hyde
7. Frankenstein
8. Jurassic Park
9. The Fly
10. The Hulk

These pieces of fiction are terrific for reflecting on research ethics. Fiction has an allure that fact lacks. With fiction, we can do the sorts of (thought) experiments that no institutional review board (IRB) in their right mind would ever approve. Stories resonate with our moral sensibilities. As I have written elsewhere, “stories are important tools for synthesizing universal truths from particular glimpses into our shared human condition.”

When I read a work of fiction that attempts to address ethical issues, I find myself using my moral imagination to play out the “what if” scenarios that confront the characters. Perhaps this is because, as a child of the 1970s, one of my first fiction reading experiences included the terrific Choose Your Own Adventure books. In this series of books, the reader becomes the protagonist and must confront moral choices. Some choices end badly; some don’t. Reflection on the likely consequences of one’s choices is at the heart of these books. In this way, these books, more so than straightforward works of fiction, help shape and sharpen one’s moral imagination and help to inculcate the habit of moral reflection. For this reason (and as a philosopher who studied the Ancient Greeks), I know Aristotle would have been pleased with the Choose Your Own Adventure series.

As an ethicist, I have often wondered why there aren’t more books about ethics that use this interactive format. So, I decided to write my own. Here’s a blurb I prepared to introduce people to the book, which takes place in the not-so-distant future:

My recipe for a creepy futuristic sci-fi novel: Take one part Robin Cook’s & Michael Crichton’s Coma, mix in one part Jessica Alba in Dark Angel. Stir in an organ transplant shortage, a devious surgeon, a nefarious body snatcher, and families of vegetative patients who would donate a kidney in exchange for perpetual life support. Whisk in the ability to choose your own adventure throughout and what do you get? A perfect “organ farm.” 

My novel, The Organ Farm, tackles issues of medical experimentation with patients in permanent vegetative state (PVS). The surgeon in the book trades the use of the patients’ bodies (as organ and tissue donors, especially ova for fertility experiments, which are fertilized then implanted back into the female PVS patients to gestate the fetuses) in exchange for continued medical maintenance of the patients. The description from Amazon.com says it best:

The year is 2022, and bioethics has come full circle. Learn how guerilla bioethicist, Maria Vasquez, infiltrates the medical tourist transplantation operation of Dr. Wallace Jefferson and what happens when she discovers that Jefferson's illegal operating room in former US base Guantanamo Bay has become a new base of operations for Dr. Zoltan Zaros' stateside fertility clinic Pregnancy Viability Systems, Inc.

I invite members of the PRIM&R community to check out The Organ Farm and leave a comment with your own Top 10 “Beach Blanket Bioethics” List of the books and films you would watch or read when on vacation and why.

Research as a tool for understanding gun violence

by Julie Fine, Legal Specialist, Legal Division, Pfizer Inc. (Please note: The views presented here are my own and do not reflect positions or policies of Pfizer.)

In the weeks following the 2012 Advancing Ethical Research Conference, what has lingered with me most has been the keynote speech on mental illness and stigma by Elyn Saks, JD, PhD. She discussed how a combination of good pharmacology and talk therapy has allowed her to be a high functioning woman and brilliant scholar. Despite having schizophrenia, her delusions are under control and her mind, with some minor memory lapses, is sharp. After her talk and after the horrific tragedy in Newtown, CT, I’ve keenly followed the debates in the media about our mental health care system and its relationship to gun responsibility.

Research into the public health effects of gun violence has been restricted since the mid-90s. On January 16, President Obama issued a presidential memorandum to lift these limitations and allow researchers to investigate trends in gun violence in an unprecedented way. If federal funds become available in support of gun research, ensuring unbiased study design for objective data collection will be of critical import as we begin to research whether the systems we have put into place are working effectively to combat this issue.

For instance, the Brady Handgun Violence Prevention Act of 1993 mandated the creation of the National Instant Criminal Background Check System (NICS). This system is currently used to determine eligibility to purchase a firearm in the US and contains information from criminal records and about individuals who have been “adjudicated as a mental defective or committed to a mental institution (18 U.S.C. §922 (g)(4)).” Federal and state agencies contribute the information which is protected by the Privacy Act of 1974. The only answers relayed by NICS to a request for a background check are either "Proceed," "Denied" or "Delayed.”

In the wake of recent tragedies, some have argued that more standardized and comprehensive mental health information should be utilized for NICS decisions. If the NICS were to be expanded to include all individuals who are mentally ill, presumably it would apply only to those individuals who have sought treatment for serious psychiatric disorders – not the undiagnosed and untreated. This kind of personal health information would likely need to be disclosed by health care professionals, a change that would bring with it many new questions. What type of permissions from patients would be needed to allow for that? What impact might the protections offered by the Health Insurance Portability and Accountability Act of 1996 have? The collection of this type of information would be unprecedented – and complicated.

My hope is that, as the debate surrounding this topic continues, mental health experts like Dr. Saks will be engaged in the dialogue and will be invited to help shape the country’s course.

Thinking like an AER Conference panelist

by Andrea Johnson, JD, CIP, Regulatory Specialist in the Research Integrity Office at Oregon Health and Science University 

It seems like just yesterday that I was walking around in beautiful 65-degree weather outside the San Diego Convention Center, overhearing discussions on the U.S. Public Health Service Syphilis Study at Tuskegee. The start of the New Year really has a way of making time fly, but I’m getting back in the swing of things.

In my office, we recently had a discussion about prioritizing some potential improvements to our institutional review board (IRB) process. One of the ideas we discussed was adding structure to the process through which researchers request a waiver or alteration of informed consent. Right now, researchers are simply asked in our questionnaire whether they plan to use a consent form, and if not, why not. If the questionnaire indicates that the researcher intends to waive or alter the informed consent form or process, the IRB makes a determination, based on the information provided in the questionnaire, the protocol, and other supporting documents, whether such a waiver or alteration meets the regulatory criteria. The improvement we considered involves creating a form for researchers to use when requesting a waiver or alteration that asks them to address each criterion specifically. As my coworkers piped up with pros and cons of each scenario, I thought, “Hey, this sounds like a session at the Advancing Ethical Research (AER) Conference!”

An interesting concern voiced by one of my colleagues regarding developing a more detailed form was that it may encourage researchers to seek a waiver when they don’t truly need one. Of course, the IRB must still find that all criteria are met, but if we start with the presumption that the researchers can obtain consent and leave it to them to tell us that they cannot, we may end up with a slightly higher bar for the “impracticable” element (45 CFR 46.116(d)(3)). But does that lead to better human subjects protections? Does it unduly hinder research? Our group didn’t really reach a consensus.

The benefit to maintaining our status quo is that, as I’m sure many of you know, researchers tend to provide much more information if you ask an open-ended question than they would if you hint at the answers that you are seeking.

On the other hand, the creation of a form that requests specific information relevant to each criterion for granting of a waiver or alteration of consent may offer an educational benefit. We hope that, such a form would also help guide the IRB by pointing reviewers directly to the information that addresses the waiver criteria. Finally, it would simplify and enhance documentation of the IRB’s determination. And yet, who really wants another form to fill out?

These puzzles are what keep me coming back to research ethics. Even a seemingly small issue has so many facets to consider.

I haven’t had a chance yet, but I am really looking forward to digging through the 2012 AER Conference Passport. Perhaps I will find some guidance on this issue and many others, and I’m sure I will come up with new questions and things to think about, too. Since you couldn’t clone yourself (yet…discuss!) and attend  five sessions at once, the Conference Passport is a great way to get a taste of the sessions you missed, as well as refresh your memories of the ones you attended.

The IRB Forum: One year later

by Anne Meade, Senior Manager for Website and Social Media

In early 2012, the IRB Forum, a resource-rich online community for human research protections professionals, found a new home at PRIM&R. We were (and are!) delighted to have this online community as a part of PRIM&R’s network of rich educational and networking resources.  The past year brought some changes to the IRB Forum, the most significant of which was a technical upgrade. The software that runs the Forum had been out of date for some time, and was updated in order to ensure the continued smooth operation of the Forum.

The technical upgrade had its challenges, but the IRB Forum now offers some beneficial new features that we wanted to be sure you were aware of:

• Daily or weekly digests: You can now receive daily or weekly digests of messages posted on the Forum. If you prefer, you can still get an email any time someone posts a new message or replies to a thread. Visit your Forum Subscriptions page to adjust your subscription settings.
• Email notifications: You can now sign up to receive email notifications for every forum, including Jobs, Events, Resources, and Discussions. Visit your Forum Subscriptions page to adjust these settings.
• Direct posting: Similar to the discussions forum, now you can post a message in every forum directly from the website, instead of emailing the moderator. Simply go to the forum where you want to post and click “New Topic.” 

At the end of November, we distributed a survey to IRB Forum members to get their feedback on the IRB Forum in order to understand what additional features they would like to see incorporated. Some requested features included: improving the search functionality, creating a repository of frequently asked questions, and reinstating the ability to submit a post via email. We will consider these and other features as we continue to improve the IRB Forum.

Lastly, I want to leave you with a sampling of some of the current discussions happening in the IRB Forum (Please note you will need to be logged in to the IRB Forum to see these discussions.). Questions currently being considered include:

• What criteria should be used to determine when a waiver of parental permission is appropriate?
• Can minors serve as research staff?
• What is the regulatory framework that supports the conduct of local review for research studies occurring internationally?
• Does auto-experimentation require IRB review? 

If you aren’t a member of the IRB Forum, you can go to the Register page to create a new profile.

For those who are members of the IRB Forum, I hope you continue to enjoy the discussions shared on the IRB Forum. If you have questions about the IRB Forum, or about the survey, please leave a comment below or contact me via email (ameade@primr.org) or phone (617.423.4112, ext. 113).

Research Ethics Roundup: Urging airlines to continue to transport research animals, the role of gender in scientific misconduct, and more!

Punxsutawney Phil predicted that spring will come early this year, so to celebrate we’ve brought together the latest stories in the world of research ethics! In this Research Ethics Roundup installment, learn about burgeoning discussion of the use of placebos in developing countries, recent reports of government agencies funding redundant protocols, and much more!

Ethical controversy in human subjects research: The use of placebo as a control in clinical trials is typically considered unethical if an effective treatment for the condition under study already exists. However, in resource-scarce countries, individuals outside of clinical trials may not have access to those treatments. This blog post from Ruth Macklin, PhD, considers whether the standard of care against which new treatments are compared should be universal or specific to the resources available within the country where the research is taking place.

Humane transport of research animals: In this post from the blog Bill of Health, Suzanne Rivera, PhD, argues that airline companies should not succumb to pressure from animal rights activists to ban the transport of research animals. According to the author, airline travel is the most humane means to transport animals for medical research. She argues that a ban on research animal transport not only causes unnecessary harm to the animals, but also hinders research which may benefit animals and humans alike.

Twice the price: This editorial from Nature comments on two recent articles alleging that many federally funded studies bear remarkable similarity to other federally funded protocols. The post cites the lack of a centralized list of government-funded studies and poor reporting procedures as possible explanations for the duplicated efforts.

The unfair sex: men 'are behind most research misconduct': A recent study has found evidence suggesting that men are disproportionately more likely to commit scientific misconduct than their female colleagues reports Times Higher Education. The data suggests that the greatest disparity occurs within academia, where men represent 70 percent of faculty in the life sciences, but account for 88 percent of misconduct.

Looking for more news? PRIM&R members can visit our Knowledge Center to find more recent scholarly journal and popular media articles pertaining to research ethics. Not yet a member? Learn more about becoming a member by visiting our website.

Research Day at Brigham and Women’s Hospital: An opportunity to engage the community in research

by Lesley Solomon, director of strategy and innovation at the Biomedical Research Institute at Brigham and Women’s Hospital, Boston

At Brigham and Women’s Hospital (BWH), we are constantly thinking about new ways to create conversations around our work—what it means to us, our patients and the community, and how we can strive to do better. It is in this spirit that we hosted our first annual Research Day on Thursday, November 15.

The goal of Research Day was to increase awareness of the breadth and depth of the outstanding research that happens at BWH. With more than 1700 attendees consisting of our patients, employees, researchers, clinicians, donors, and industry friends, we qualified the day as an incredible success and , participants agreed, according to the feedback they shared in a  post-event survey.

Highlights included a poster session with more than 150 posters and ten mini-symposia featuring “TED-like” talks and panel sessions on a variety of research topics; a keynote address from Atul Gawande, MD, MPH, on the importance of collaboration in developing innovative solutions to today’s health care challenges; a visit from Joseph Selby, MD, MPH,  executive director of the Patient-Centered Outcomes Research Institute; and the announcement of Dr. Robert Green as the winner of the $100,000 BRIght Futures Prize – an innovative hospital effort that used crowdsourcing to determine the winner. Of the three finalists, Dr. Green was named the winner after nearly 6,500 people from around the world voted online.

If you we unable to join us for this exciting event, we encourage you to check out this great short video summarizing the day’s activities. Videos from the different symposia on various topics from aging to obesity to cancer are also available on our website.

My sentiments, as I walked from one packed room to another on Research Day, are best echoed by one of our poster presenters who noted:

“Lay people interacting with poster presenters and speakers was my favorite [part of the day]. It snapped me out of my focused little research box and made me look at the problems we are trying to solve in a different light.”

Engaging our community and the public in our research is a priority for us. Our next Research Day will be in November 2013. Stay tuned for details!

Reflections on my 2012 AER Conference experience

by Royell Sullivan, Institutional Review Board (IRB) Education Specialist at the New York University (NYU) School of Medicine 

2011 was my first time attending PRIM&R’s annual Advancing Ethical Research (AER) Conference, and I have to admit, I was a tad bit lost. I had this feeling that the information was just over my head. Attending the conference for the second time this past December, however, let me know how far I’ve come in my understanding of the field and  the PRIM&R community. I felt more at home, I knew what to expect, and I chose sessions that were more in tune with my daily course of work.

Soon, I will be presenting a staff education session to my colleagues on research involving vulnerable populations. Attending The Basics and Beyond: Research with Children, Pregnant, Women and Fetuses, and Prisoners (C12), led by Julia Gorey, JD, and Robert J. Levine, MD, helped highlight things I need to mention during my own session. I plan to stress the importance of direct benefit for vulnerable populations. I also want to bring more attention to prisoner representation on IRBs. After attending the session, I know that it is not enough to have a prisoner representative serve as a consultant. I also know that the Office for Human Research Protections requires that the prisoner representative be an actual voting member on the IRB when research involving prisoners is being reviewed.

Similarly, Essential Documentation (A12), shed light on the importance of how information is captured during IRB meetings. Jean Toth-Allen, PhD, declared, “the minute taker is not a transcriptionist.” She continued by reviewing all of the elements that  minutes should include. I kept this in mind recently when I presented an education session on IRB records.

The poster presentations were also an eye opener for me. The day before the conference, I attended the pre-conference program IRB 301: An Overview of the Criteria for Approval of the Research. During the course, we had a debate about the primary and secondary reviewer system (check out my blog on the debate). Later in the conference, I read a poster presentation about IRB administration at WellSpan Health. WellSpan went into their database and discovered that most of their IRB members were not opening studies unless they were assigned to them. They used this information to ask their board members how they could better assist them so they could review all studies. They are now moving forward with implementing some improvements. I thought that was wonderful.

I made new friends while attending Developing and Implementing an Educational Program at an Institution with a Small Research Program (B25), led by Eric Allen, CIP, CPIA, and Michelle Feige, MSW, LCSW-C. We had a chance to vent about our frustrations at work and share a few ideas.

I came, I saw, I conquered, and I walked away more knowledgeable than when I arrived. I met some great people, and the sunny San Diego weather in December was definitely a plus. I cannot wait to see what is in store for this year!