What’s in a name? Research “participant” versus research “subject”

by Ali Hall, Educational Programs Assistant

At a recent discussion at one of PRIM&R’s staff meetings, we took up the issue of how to refer to those who volunteer to participate in research. More specifically, our conversation started with the fact that PRIM&R uses the term “research subject,” rather than the term “research participant.” The significance of this very conscious choice of language had previously managed to escape me, and so I found the ensuing discussion incredibly enlightening.

While research “subject” is the more traditional of the two terms, there has been a shift over the past 25 years or so to use research “participant” when referring to individuals who take part in research, because, many argue, it is more respectful of research volunteers. This shift can be directly traced to the work of the HIV/AIDS activist and cancer survivor communities in the 1980s and 1990s, who demanded not only access to clinical trials, but participation in setting research agendas. I saw first-hand evidence of this shift recently when I received a request from a conference faculty member to change the title of a session at PRIM&R’s 2013 Advancing Ethical Research Conference—specifically, to replace the word “subject” with the word “participant.” In making the request, the individual expressed to me that the term “subject” tends to perpetuate an unhelpful view of the research enterprise and is most likely part of why only 5% of individuals participate in clinical trials nationwide. This person felt strongly that, because it emphasizes the passivity of the individual who is taking part in research, using the term “subject” discourages people from taking part in research and thereby slows the rate of scientific discovery.

I must admit, I found this argument compelling. So why does PRIM&R continue to refer to volunteers as “subjects,” I wondered. Well, what I learned during our staff meeting is that PRIM&R uses “subject” rather than “participant” for a number of carefully considered reasons. For one, the term “participant” is not found anywhere in the federal regulations governing human subjects research, known as the “Common Rule.”  For another, and more substantively, PRIM&R’s view is that the term “subject,” far from being disrespectful of those who volunteer for research, much more accurately and honestly represents the true nature of the research enterprise, including the fact that there is always a power and knowledge differential between those conducting the research and those on whom the research is conducted. In addition, using the term “subject” to refer to those who volunteer to take part in research makes salient the fact that, due to their position of relative vulnerability within the research enterprise, there need to be independent mechanisms to ensure the individuals who volunteer for research are respected and protected. We do not, of course, wish to diminish or ignore the potential for exploitation of research subjects (especially since that is something PRIM&R actively works hard to prevent); indeed, we believe that use of the term “participant” to refer to research volunteers may leave them more vulnerable to exploitation, since it may obscure the need for formal protections.

Now, this doesn’t mean, I also learned, that PRIM&R believes that the term “participant” is never appropriate when referring to those who volunteer for research. In the context of community-based participatory research, for instance, where communities who will be the subjects of the research are integrally involved in both designing the research study and in carrying it out, it seems appropriate to refer to those individuals as “participants” in the research. In addition, we’re currently seeing a rise in “participant-led” and “participant-centered” research, where those being studied act as a driving force behind the research. Examples include self-surveillance, analyses of genomic data, and genome-wide association studies, to name a few, all of which represent a more bottom-up approach to research, as opposed to the more top-down approach favored by traditional scientists.

While I can see why people may think the term “subject” is disrespectful, or even pejorative, when describing people who take part in research, I now understand and appreciate PRIM&R’s choice to stand by it. Being forced to stop and consider the potential implications of using one term over another, has also raised a series of questions relating to human research subjects and the part they play in the overarching research apparatus for me. For instance, are there additional arguments for using one term over the other? Do most researchers think the choice of terminology has significant bearing on the decision of the average individual to participate in research? Please share your thoughts.

Data in the Cloud

by Julie Fine, BS, Legal Specialist, Worldwide Research and Development, Pfizer Inc., La Jolla, California

While the 2013 Advancing Ethical Research (AER) Conference has drawn to a close, PRIM&R is pleased to continue sharing reflections from members of the PRIM&R Blog Squad to provide our readers with an inside peek of the conference.

During the 2013 Advancing Ethical Research (AER) Conference, I attended two panels that challenged conventional wisdom about transparency, control, and crowdsourcing of research data. The first, Panel VII: Data Sharing on Steroids: Demands for Transparency of Subject-Level Research Data, touched on the increasing demand for transparency in clinical research on a broad scale, and included representatives from an institutional oversight organization and a pharmaceutical company, and a patient advocate, who shared their insights into data transparency.

The demand for public access to aggregate research results has lead biotech companies and the European Medicines Agency (EMA) to rethink the way in which data can (and should) be shared. Greater openness could generate opportunities to reassess research results and perhaps expand the utility of secondary analysis. It is important, however, that the process of gaining access to the data also be transparent.

The initiatives of the EMA and other biotechnology companies highlight the merits of legitimate, purposeful data sharing. That is to say, if a qualified researcher with a well-defined research proposal has no significant conflicts of interests and possesses the requisite skills to conduct the proposed analyses of the data, the sharing of research results can be highly beneficial. Still, such transparency does raise concerns, several of which were discussed by the panelists. For example, scientific inquiry and the public good may not be well served if uncontrolled open sharing leads to misuse or junk science.

The second, Panel VIII: Taking Control: Ethical Challenges for Participant-Centered and Participant-Led Research, examined instances in which participants become the driving force behind the initiation of, and at times actually take an active role in the conduct of, research projects. With the help of social media and other digital technologies, online communities can engage in projects with their own data outside of standard regulation-controlled research. Though crowd-sourced data and self-policed affinity groups may be a novel approach with certain advantages, it’s difficult at this stage to envision an FDA-approved drug entering the market from this model. What do you think?

Please note that the views presented here are Julie’s own and do not reflect the positions or policies of Pfizer, Inc.

Research Ethics Roundup: New recommendations on incidental findings, considering personhood, and more

by Maeve Luthin, JD, Professional Development Manager

Oh, the weather outside is frightful, but Research Ethics Roundup is so delightful! So, we hope you’ll bundle up, hunker down, and enjoy some of the research ethics stories that are making headlines this week. We, here at PRIM&R, wish you a joyous holiday season and good health in the New Year and always.

GM Maize, Health and the Séralini Affair: Smelling a Rat: The Food and Chemical Toxicology journal retracted a September 2012 study that suggested genetically modified maize causes cancer. Critics of the article complained that the rats used already had a pre-disposition to cancer, that too few animals were included in the study, and that researchers did not distinguish between spontaneous tumors and those that may have been caused by the maize. The publisher said there was no evidence of intentional misrepresentation of the data or fraud. Some members of the scientific community have been concerned that the backlash against genetically modified food has undermined efforts to use genetically modified food, such as Golden Rice, to feed children in resource-scarce nations.

Harvard Fined for Violating Animal Welfare Law in Care of Monkeys: The United States Department of Agriculture fined Harvard Medical School $24,000 for eleven violations of the Animal Welfare Act in its care of nonhuman primates used in research. These infractions, which occurred in 2011 and 2012, led to the deaths of four monkeys. Earlier this year, Harvard announced it would shut down its New England Primate Research Center by 2015.

Medics Should Plan Ahead for Incidental Findings: Earlier this month, the Presidential Commission for the Study of Bioethical Issues (PCSBI) released a report outlining how researchers, physicians, and companies should handle incidental findings discovered in the course of genetic analyses, imaging scans, and other tests. PCSBI contends that researchers have a duty to plan for how they will handle incidental findings.

Rare Cancer Treatments, Cleared by Food and Drug Administration (FDA) but Not Subject to Scrutiny: The New York Times explores the challenges of the FDA’s humanitarian device exemption policy, which was implemented in 1997 and grants companies permission to sell products that are safe and have a “probable benefit” for the treatment of conditions that affect less than 4,000 patients annually—a subject pool generally not large enough to warrant clinical trials. Under the policy, companies are not required to collect safety and efficacy data.

What is Personhood?: The Nonhuman Rights Project (NhRP) filed a series of lawsuits in New York courts demanding writs of habeas corpus, which challenge a person’s alleged imprisonment or unlawful detention, on behalf of four chimpanzees. NhRP contended that the chimps qualified as persons with a fundamental right to freedom because of their autonomy, self-determination, and self-awareness. In response to the lawsuit, James Carroll, a columnist for The Boston Globe, considers the issue of personhood in this thought-provoking piece.

Reflecting on Therapeutic Misconception

by László M. Szabó, Esq., Director of the Office of Research Regulatory Affairs at Rutgers, The State University of New Jersey

While the 2013 Advancing Ethical Research (AER) Conference is over for the year, PRIM&R is pleased to continue sharing reflections from members of the PRIM&R Blog Squad to provide our readers with an inside peek of the conference happenings.

On the second day of the 2013 Advancing Ethical Research (AER) Conference, I attended Paul Appelbaum’s keynote address, Therapeutic Misconception in Clinical Research: A 30-Year Retrospective. Dr. Appelbaum is an expert on informed consent, decisional capacity, and related issues, and has written widely on research ethics. Importantly, Paul was the first to identify the phenomenon of “therapeutic misconception” about 30 years ago, and reflected upon the matter with his depth of experience.

Therapeutic misconception takes place when a research subject incorrectly attributes therapeutic or ordinary treatment benefits to participation in research, thereby misconstruing the intent of research and treatment. Obviously, the impact on the informed consent process is substantial. Therapeutic misconception can be triggered when established treatment options are lacking or when a research study is similarly designed to clinical care. For the latter, subjects often either underestimate the risks associated with the research or are overly optimistic about the outcomes of the research.

Because the informed consent process is so vital to overcoming therapeutic misconception, it is important to convey several points to subjects to construct a clear distinction between research and clinical therapy:

• Explain that research = experiment = unknown/untested methods. Research is intended to test hypotheses (it is, after all, an experimental undertaking) that will ideally lead to theories that can be translated to clinical treatment. 


• Clearly define how the research differs from treatment (e.g., the use of placebos), and incrementally prompt the subject for understanding. A recommended way to accomplish this is to have fewer open-ended prompts and, instead, more structured assessments.


• Explain that one key aspect of how research differs from treatment is that the protocol spells out what needs to be done for research, whereas in treatment the treating physician has greater professional discretion to decide on a course of treatment. The effects of this, for example, may be that if the subject needs more medication they may not be able to receive it because it may be prohibited under the research protocol.


• Limit the use of study acronyms that sound overly optimistic (e.g.,  “BEST”, “MAGIC”—both real acronyms).


• Pay attention to the connotations of verbiage. For example, many researchers avoid the term “experimental” in lieu of “study,” or “project,” which can increase the likelihood of therapeutic misconception.

A key consideration—really a threshold matter to address the possibility of such misconception taking place—is to first consider how close the research resembles treatment. This assessment, of course, should disregard the intent of the researcher and be made from the perspective of the target subject population.

So, what can you do to avoid therapeutic misconception? Clearly define ways by which the research is different from treatment (e.g., by explaining what random assignment is), pay attention to the verbiage used in the study, and conduct informed consent face-to-face to support a comprehensive understanding by the subject.

Resources cited by Paul:

• False Hopes and Best Data: Consent to Research and the Therapeutic Misconception

A Tribute to Nelson Mandela: An Exemplar and Inspiration to Us All

by Joan Rachlin, JD, MPH, Executive Director

The eight days since Nelson Mandela’s death on December 5 have been among the most inspiring of my life. The words and images that have poured forth from South Africa have caused me to experience several “driveway moments” (defined by NPR as those times when you’re driving along listening to a story, and although you reach your destination, you’re so riveted that you sit in your idling car to hear the piece all the way through).

I have long admired and been in awe of Mandela. In fact, the first protest to which I took my then two-year-old daughter was one urging the Commonwealth of Massachusetts to divest its holdings in South Africa. I also took my 11-year-old son, Micah, and one of his friends to hear Mandela speak at Harvard on September 16, 1998. The boys and I were quite close to the stage, and the combination of feeling Mandela's aura, hearing his powerful voice, and listening to his profound yet humble words, is among my most enduring and cherished memories.

I thus decided to write this post despite the lack of an explicit link to research ethics, but, as my PRIM&R co-worker, Avery Avrakotos, reminded me, there are echoes of what Mandela stood for in PRIM&R’s own core values. Although our work is only a thin link in the powerful global chain that Mandela created, I am struck by the manner in which both the Belmont principles and our organizational creed reflect his teachings.

Mandela’s life was a paean to ethics, justice, and humanitarian ideals, and he innately embodied so many of the fundamentals on which our field and this organization are based. For example, the Belmont principles of respect for persons, beneficence, and justice were tightly woven into the fabric of Mandela’s life and legacy. His thirst for dismantling apartheid (which literally means “apart-hood”) so that black South Africans could be free of white minority rule represents respect for persons writ large.

His beneficence is legendary, and the example that has awed me most is a story I heard from a guide at Victor Verster Prison, from which Mandela was released after more than 27 years in captivity (20 years of which were spent on Robben Island, off the coast of Cape Town). I learned that Mandela, when he was told he was to be released the next day, declined to leave until a few days later because he needed time to “thank his jailers for caring for him.”  Mandela even invited a few of those jailers to his inauguration, and later appointed F. W. de Klerk, the last state president of apartheid-era South Africa, to join his cabinet.

Yet another example of Mandela’s beneficence is captured in the film Invictus, which tells the story of his actions following the mostly-white South African team’s victory in the 1995 Rugby World Cup. Finally, his formation of the Truth and Reconciliation Commission is representative of his determination to keep bitterness and conflict at bay despite his many reasons for feeling, or fueling, both.

Nelson Mandela’s every act reflected his commitment to and passion for justice. His speech on April 20, 1964, at the Rivonia Trial changed the course of South African history because of its moral force and the case it made for justice, which of course was to be delayed for him for 27 long years.

I’m grateful that PRIM&R’s core values are also reflective of this once-in-a-generation man. I’ve included our list of values below, with a Nelson Mandela quote on each:

• Excellence: “There is no passion to be found in playing small—in settling for a life that is less than what you are capable of living.”


• Community: “Let there be justice for all. Let there be peace for all. Let there be work, bread, water, and salt for all.”


• Diversity: “If you talk to a man in a language he understands, that goes to his head. If you talk to him in his language, that goes to his heart.”


• Integrity: “If I had my time over I would do the same again. So would any man who dares call himself a man.”


• Knowledge: “Education is the most powerful weapon you can use to change the world.”


• Respect: “For to be free is not merely to cast off one’s chains, but to live in a way that respects and enhances the freedom of others.”


• Social Responsibility: “I hate race discrimination most intensely and in all its manifestations. I have fought it all during my life; I fight it now, and I will do so until the end of my days.”


• Creativity: “If you want to make peace with your enemy, you have to work with your enemy. Then he becomes your partner.”

Although the latter quote is not about traditional forms of creativity, but rather about ways of creative governance, there has been much talk since Mandela’s passing about the art, music, comics, and movies that he inspired. Two poems that I have found incredibly stirring include one written by Maya Angelou six days ago called “His Day is Done,” and another by Elizabeth Alexander titled “A Poem for Nelson Mandela.”  There are also poems that, while not inspired by Mandela, served as a source of comfort and strength for him during his imprisonment such as “Invictus,” by William Ernest Henley. Mandela embodied, and often quoted, an excerpt that reads:

It matters not how strait the gate,
How charged with punishments the scroll,
I am the master of my fate:
I am the captain of my soul.

If you’ve made it this far, I would like to thank you for reading Mandela’s extraordinary words. He walked the talk, and I hope to honor him by trying harder to do the same. President Obama urged those at the memorial service for Mandela on December 10 to apply Mandela’s lessons to our own lives—for if we do, it will be a far better world.

Rest in peace, Nelson Mandela. Thank you for inspiring and teaching us. We know that your immortal light will continue to shine brightly.

Introducing “Anticipate and Communicate”

by the staff of the Presidential Commission for the Study of Bioethical Issues

This piece, which originally appeared on the blog of the Presidential Commission for the Study of Bioethical Issues, has been reposted with permission. 

We all need to know how to better manage health information that we did not expect. Today, the Presidential Commission for the Study of Bioethical Issues (Bioethics Commission) released its report Anticipate and Communicate: Ethical Management of Incidental and Secondary Findings in the Clinical, Research, and Direct-to-Consumer Contexts. Commission Chair Amy Gutmann, PhD, discussed the report in a Policy Forum piece published today in Science.

No one is immune from the prospect of discovering something unexpected when undergoing a routine test at the doctor’s office, participating in research, or even submitting a cheek swab to a direct-to-consumer (DTC) company for analysis. Regardless of the setting or the test or procedure, when it comes to incidental findings, the Bioethics Commission offered this piece of overarching advice: anticipate and communicate. The Bioethics Commission recommended that all practitioners anticipate and plan for incidental findings so that patients, research participants, and consumers are informed ahead of time about what to expect.

Incidental findings, traditionally defined as results that arise outside the purpose for which a test or procedure was originally conducted, give rise to a range of practical and ethical challenges for recipients and practitioners. Secondary findings, like incidental findings, are not the primary target of a test or procedure but are actively sought in the process of testing. Incidental and secondary findings can be lifesaving if their discovery leads to treatment that would not otherwise have been possible, but also can lead to uncertainty and distress with no corresponding benefit if they identify conditions for which no effective treatment is available.

The Bioethics Commission concluded that certain actions should be taken regardless of where incidental or secondary findings arise, and made five recommendations intended to apply across contexts. The first overarching recommendation aimed to ensure that individuals are informed about the possibility of incidental and secondary findings before they are tested, and of any plan for disclosing and managing these findings. Because of the fundamental importance of informing potential recipients—including respect for recipient autonomy, beneficence, and informed decision making—the recommendation was further specified and applied in the clinical, research, and DTC contexts.

The Bioethics Commission also recognized the importance of developing an evidence base to inform decisions about how best to manage incidental and secondary findings. In its second overarching recommendation, the Bioethics Commission called on professional groups to develop guidelines to categorize the findings likely to arise from each diagnostic modality and develop best practices for managing these findings. The third recommendation called for research about the types and frequency of incidental and secondary findings; the costs, benefits, and harms associated with these findings; and recipient and practitioner preferences with regard to these findings.

Informing individuals works best when those involved—both practitioners and potential recipients—are informed about the consequences of incidental and secondary findings. Accordingly, in its fourth recommendation, the Bioethics Commission called for the preparation of educational materials to inform all stakeholders—including practitioners, institutional review boards, and potential recipients—about the ethical, practical, and legal implications of incidental and secondary findings.

Finally, the Bioethics Commission recognized that existing disparities could lead to inequitable access to the counseling and care needed to appropriately manage incidental and secondary findings. In its fifth recommendation, the Bioethics Commission noted that the principle of justice and fairness requires affordable access to quality information, both before and after testing, about incidental and secondary findings that could arise.

These overarching recommendations are supplemented by recommendations specific to the clinical, research, and DTC contexts that will be described in subsequent posts on the Bioethics Commission's blog.

2013 AER Conference: What You Liked

by Maeve Luthin, JD, Professional Development Manager

For the second post in our two part series highlighting the evaluation results from the 2013 Advancing Ethical Research (AER) Conference, I'll be sharing your favorite parts of the meeting. We hope that we will be able to recreate some of these successes (and that you’ll be with us to witness them!) in Baltimore, MD, on December 5-7, 2014 for the 2014 AER Conference!

Finding Posters: We tried something new, and you told us that it worked! (We love it when that happens.) We’re talking about a new series—titled “Innovations in…”—that featured individuals who submitted exemplary poster abstracts as panelists. These sessions focused on controversial topics, genomics and biobanking, influences on research participation, and communication with research subjects. You enjoyed hearing the authors present their work and take questions on their research, and, as one of you shared, this format “does the presenters and their material far more justice” as compared to poster sessions in the past.

Star Wars: Our keynote speakers brought energy and inspiration to the podium! You cited Atul Gawande as a master storyteller; George Demetri as brilliant and inspiring; Paul Appelbaum as fascinating and enlightening; Esther Duflo as engaging and impressive; and Joan Rachlin as moving and motivating. We hope that next year’s slate of keynote speakers meet the high expectations set by this year’s group.

A Few Good Arguments: There was a lot of enthusiasm about the moderated debate on risk and consent in standard of care interventions. Why? Mostly because it was a true debate—the kind in which the speakers don’t agree with one another. Moderator Jeremy Sugarman and panelists Leonard Glantz and Robert Truog outdid themselves with their whip-smart, witty dialogue in their discussion about this controversial topic.

Once again, many thanks to everyone who shared their thoughts about their time in Boston!