Increasing the Enrollment of African Americans in Cancer Clinical Trials

Natasha Blakeney, MPH, is the training director of the Education Network to Advance Clinical Trials (ENACCT). Founded in 2004, ENACCT is dedicated to improving cancer care and research through clinical trials. In this piece, reprinted from ENACCT’s blog, Natasha shares her perspective on increasing enrollment of African Americans in cancer clinical trials.

The National Cancer Institute (NCI) recently released a video discussing African Americans and their participation in cancer clinical trials. The video highlights some of the well-known challenges affecting this study participation, while noting the significance of cancer research in advancing the delivery of more personalized, state-of-the art cancer care to diverse populations. I appreciated NCI highlighting this important issue during Black History Month, drawing attention to the important role African Americans can play in cancer research. However, from my perspective as an African-American woman, this is a topic that should not be limited to acknowledgement once a year—it is a critical issue that needs attention all year long.

In my community, the topic of participation in cancer research can evoke a range of reactions, including distrust and fear on one end of the spectrum, and curiosity and enthusiasm on the other. Like the rest of the population, African Americans are not homogenous. This fact is important to acknowledge since there is a prevailing belief that we are not interested in research, are unwilling to participate, and may even be offended if given the option to take part in a clinical trial. A 2006 study showed that African Americans are just as willing to participate in medical research as others, but are less likely to be approached.

The bottom line? Cancer researchers cannot and should not make assumptions about our participation in cancer clinical trials. Not offering clinical trials as a treatment option to every eligible patient is a disservice and is disempowering. Ultimately, the power to decide whether to join a study should rest with the trial-eligible patient. Seen in that light, ensuring a culturally sensitive discussion presents an important opportunity to foster a greater understanding of the clinical trial process. Such a discussion may also highlight the existence of patient protections, with particular deference given to the concept of autonomy as detailed in the Belmont Report—every individual has the right to decide whether study participation is the right choice for her/him.

Does this mean that every African-American patient will say yes to clinical trial participation? No, it certainly does not. But one thing is certain; the prospect of African-American participation in cancer clinical trials is far greater when African Americans are asked, than when nothing is mentioned at all.

We can no longer accept simply despairing about low participation in clinical trials among African-American patients. Cancer researchers must take action by approaching all eligible patients, engaging in a meaningful, respectful dialogue about trials, and then letting the patient make her or his own choice. Now that’s making real progress in cancer care.

“Science Times” synthesis

As we hurtle towards summer, the research world is heating up! From contentious stem cell policies in Texas, to evidence of potential misdiagnoses in children, this week’s “Science Times” synthesis is full of controversial and eye-opening reports from around the globe.

Week of April 9

More brainpower seen in soccer’s top scorers: A new study finds that elite soccer players in Sweden tested higher than non-players in executive functions, the brain processes responsible for planning and abstract thinking.

Awake or knocked out? The line gets blurrier: This fascinating meditation on consciousness explores the boundary between wakefulness and unconsciousness, and the weighty consequences of getting it wrong.

Texas Board approves rules on use of stem cells: The approval of new rules on the use of adult stem cells by the Texas Medical Board has set off a firestorm of debate. Critics of the new rules cite lack of oversight and clinical evidence as the basis for their concern.

Tending a sick comrade has benefits for ants: By observing European garden ants, researchers have discovered that when one ant in a colony develops an infection, others will come to its side to lick the infection and remove the pathogen. This behavior, in turn, seems to have the beneficial effect of inoculating the colony. 

Week of April 16

Crowd-sourcing expands power of brain research: On Sunday, Nature Genetics published a series of studies on what appears to be a genetic basis for intelligence and memory. Data for these studies was contributed by over 200 scientists across the globe, leaving many wondering what role crowd-sourcing will play in research moving forward.

Attention problems may be sleep-related: Researchers in London have found evidence indicating that doctors may be wrongly diagnosing children with attention deficit hyperactivity disorder (ADHD)by not checking for sleep disorders first.

Trust acts to open research findings to the public: The Wellcome Trust, the second-largest nongovernmental funder of scientific research in the world, announced last week that it was considering sanctions against researchers who do not make their results freely available to the public.

Cross-Cultural Dialogue: The Key to Enhancing Research Protections

by Elisa Hurley, PhD, Education Director

Last month, I had the opportunity to attend the second Asia Pacific Research Ethics Conference (APREC), which took place March 7-9 in Singapore. The meeting was organized by the National Healthcare Group (NHG), and PRIM&R was proud to serve as the meeting’s co-sponsor, as we did for the first APREC in September 2010. The three-day meeting brought together representatives from institutional review boards (IRBs), ethics committees, research and academic institutions, national health authorities, and the pharmaceutical industry, who hailed mostly from the Asia Pacific region, but represented more than 25 countries as diverse as Australia, Turkey, Qatar, and East Timor.

I wore several hats while at APREC; I served as the liaison between PRIM&R and NHG, staffed PRIM&R’s exhibit booth, and taught my first IRB 201 course.  It was a very full, very stimulating few days, and throughout my time there I was struck by how similar the issues are that human research protections professionals struggle with across the globe, even when the specific sets of regulations that govern them, the structures in which review happens, and the cultures in which the research takes place are quite different.

One perhaps unsurprising commonality I discovered was the need for more and better IRB education.  Attendees from the Philippines, Thailand, Malaysia, and Saudi Arabia approached me, eagerly seeking resources they could use to educate their IRB members and staff.  This sounds familiar, does it not?  As PRIM&R’s education director, I was excited but also overwhelmed by this need.  There is clearly still a lot more work to be done to ensure affordable, efficient, high-quality education is available to human research protections professionals everywhere. 

There were other commonalities as well:

• Professor Ryuichi Ida from Kyoto University explained that research ethics committees universally struggle with the issue of length of time for protocol review, regardless of their structure.

• Assistant professor Peter Sainsbury from the University of Sydney echoed the issues raised in the US Department of Health and Human Services Advance Notice of Proposed Rulemaking; he highlighted challenges surrounding the review of research in public health and the social and behavioral sciences using guidelines and systems of ethical review that were originally drafted with biomedical research in mind. 

• Professor Ezekiel Emanuel from the University of Pennsylvania gave a thought-provoking and characteristically provocative keynote address in which he laid out a method of assessing risk that does not vary by culture. He did, however, stress that since the harms of everyday life do vary—for example, the chances of being bit by a car are much higher in some countries than others—risk assessment must be sensitive to local contexts.

Dr. Ezekiel’s comments on the importance of local context were aptly reflected in my own experience at the conference. As a first-time instructor of IRB 201, I spent the months leading up to the conference preparing diligently. I was particularly proud of the case studies and interactive discussions I had planned throughout the day. The lively discussions that unfolded among small groups seemed to promise a lively conversation on a larger scale, but when it came time for attendees to share, silence. The chatter had disappeared, and try as I might, I could not coax any of the 75 participants to participate. Having been a teacher, I first thought I might try letting the silence linger for a bit—in a North American classroom, this usually forces some brave or impatient soul who cannot stand the silence any longer to raise his or her hand. It turns out this technique does not work with a primarily Asian audience. Five excruciatingly long and awkward silences later, and I had learned an incredibly valuable lesson that will not be soon forgotten about the importance of cultural competence in any cross-cultural enterprise.  

I returned from Singapore and my very first trip to Asia with a deeper appreciation for the value of bringing people from multiple countries, cultures, and backgrounds together in the shared pursuit of enhancing research. I welcome you to share your own experiences fostering cross-cultural dialogue about research protections in the comments section.

Concerns Over Coercion and Undue Influence are Slowing the Pace of Valuable Clinical Research

by Emily A. Largent and Alan Wertheimer, PhD

In a recent post, we presented some of the key results from a 2010 survey we conducted with randomly selected PRIM&R members. As described in our article in IRB: Ethics and Human Research, “Money, Coercion, and Undue Inducement: Attitudes about Payments to Research Participants,” the survey explored their attitudes as to whether and why payment of research participants constitutes coercion or undue influence. We were interested in asking these questions because institutional review board (IRB) members are crucial gatekeepers in the research enterprise. As a result, how they understand and apply the concepts of coercion and undue influence will have marked effects on the approval and conduct of research protocols.

In this follow-up post, we seek to outline the central argument of a follow-up article, now available online from Bioethics. We believe that our findings reflect views about offers of payment – widespread in the research community – that are based on misconceptions about coercion and undue influence.

Following the Belmont Report, which states, “coercion occurs when an overt threat of harm is intentionally presented by one person to another,” we believe that coercion always involves the threat of harm. On that view, offers of payment are never coercive. Moreover, and contrary to what a majority of our subjects believed, offers are not coercive simply because they get people to participate in research when they would otherwise not, or because people feel they have no reasonable alternative but to participate in research.

It is more difficult to provide a practically useful definition of undue influence. Many of the survey respondents expressed a belief that offers of payment constitute undue influence if they get people to participate in research when they otherwise would not do so or when subjects feel that they have no reasonable alternative but to participate. We disagree and instead argue that offers of payment constitute undue influence only when they distort a subject’s ability to perceive accurately the risks and benefits of research participation.

Although we did not explicitly ask survey respondents how they distinguish between coercion and undue influence, our reading of their responses suggests a third misconception: many seem to understand coercion and undue influence as lying on a continuum. By contrast, our view is that although both coercion and undue influence render consent invalid, they do so in ways that are quite distinct. Whereas coercion compromises the voluntariness of consent by the threat of harm, undue influence compromises the validity of consent by creating a cognitive deficiency or distortion in reasoning. The target of coercion may act involuntarily but perfectly rationally; individuals who are unduly influenced may act voluntarily, but their reasoning is distorted.

We do not know the extent to which these three misconceptions influence IRB decision-making.  If, as seems likely, these views do affect the decisions made by IRBs, they may limit payment offered to research subjects and could therefore slow the pace of valuable clinical research for ethically unjustifiable reasons.

Featured Member Profile: Beverley Williams

Welcome to another installment of our featured member profiles where we will continue to introduce you to more of 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 Beverley Williams, assistant director of human research protections at the University of California, Irvine.

When and why did you join the field?
I began my career in human research protections in 2000. I graduated with a Bachelor of Arts degree in psychology and, while considering graduate school, I decided to go ahead and enter the working world. I responded to a newspaper advertisement for an institutional review board (IRB) coordinator at Children's Hospital Los Angeles. Honestly, the job sounded interesting and so did the prospect of working for a children's research hospital. It has been 12 years since then, and to this day, I continue to learn and enjoy what I do.

What is your favorite part of your job?
My position focuses on educating the staff and research community as well as ensuring human subject research compliance at the University of California, Irvine. I enjoy meeting with members of the research community (faculty, students, and staff) and helping them understand the regulations and their importance.

What is the last movie you saw?
I just saw The Artist. I think it is one of my favorites of all time. Really a touching love story, and I loved the sweet dog!

What do you value in your friends?
Listening skills.

What are you reading?
Then Again, by Diane Keaton.

What is your idea of perfect happiness?
Being comfortable in my own skin.

Why did you join PRIM&R?
For the education and networking opportunities the organization provides.

What is your favorite member benefit?
My institution recently renewed our subscription to the Ethical Oversight of Human Subjects Research Course (Online Course). This online course serves as an additional training resource for our new IRB members. We even use it as part of training of new staff.

If you were planning our next conference, who would you select as a keynote speaker?
I would choose a research subject—a person with direct experience participating in human subjects research. I really appreciate first-person perspective presentations—they are inspiring and motivating.

Thank you for being part of the membership community and sharing your story, Beverley. We hope we that your staff enjoys our Online Course!

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

Back to School: A PRIM&R Staffer Attends Institutional Review Board (IRB) 101sm

by Megan Frame, Membership Coordinator

As a member of the PRIM&R staff, being onsite during our annual conferences constitutes some of the busiest (and most gratifying) parts of my year. Unfortunately, with so much to do, I often don’t have time to experience what so many of our attendees rave about: the incredible faculty, the thought-provoking discussions, and the diverse networking opportunities. But with the March Regional Program taking place in Boston, PRIM&R’s very own backyard, I was able to carve out some time to attend IRB 101sm, one of PRIM&R’s flagship programs. 

Since joining PRIM&R last autumn, I have been fascinated by the work of IRBs, and I was eager to learn more about the issues they face. Sitting in the classroom on the day of the course, I felt fortunate—what better way to achieve a greater understanding of research ethics than to immerse myself in a lively discussion led by two experts in the field, Elizabeth Bankert, MA, assistant provost at Dartmouth College; and Dean Gallant, assistant dean at Harvard University.

As we went around the room to introduce ourselves, I was struck by the diversity of positions that the attendees held, and I grew excited to hear more about the specific concerns that each deals with at their institutions. The morning session was spent reviewing the history and development of IRBs, and then discussion shifted to the current regulatory system. In the afternoon, we delved into case vignettes based on studies that had previously been subject to IRB review.

Instead of feeling nervous about my lack of experience with the subject matter, I felt encouraged by how much I could understand as a layman, and I was struck by how relevant the concepts and areas of concern for IRBs are to all aspects of life.

As we wrapped up for the day, one idea stuck with me. In response to a lengthy discussion over a particular case study, Elizabeth Bankert encouraged the group to think in “probabilities, not possibilities.” She urged the audience to focus on what is most likely, as opposed to considering everything that could occur. It is clear to me that adapting this type of mindset is necessary when reviewing protocols. There are undeniable risks associated with research, and it is the IRB’s job to make sure those risks are minimized and/or eliminated wherever possible. However, if we focus on the extreme possibilities, and cite every proposal as being too risky, research will halt in its tracks. So, while I do not serve on an IRB, spending the day in IRB 101sm has certainly given me a lot to think about.

Enhancing Awareness Regarding Use of Non-Pharmaceutical Grade Chemicals in Research with Vertebrate Animals

The 2012 Institutional Animal Care and Use Committee (IACUC) Conference hosted several forums that provided insight into complex issues in the field of animal care and use.

One such topic that was discussed at the conference was a webinar, Use of Non-Pharmaceutical-Grade Chemicals and Other Substances in Research with Animals, which was held several weeks earlier, on March 1, 2012. The goal of this webinar, jointly presented by the United States Department of Agriculture (USDA), the Office of Laboratory Animal Welfare (OLAW), and the Association for Assessment and Accreditation of Laboratory Animal Care (AAALAC) International, was to clarify the expectations of the three sponsoring organizations regarding the use of non-pharmaceutical grade substances. The discussion on this topic by OLAW, USDA, and AAALAC representatives continued throughout the 2012 IACUC Conference.

Per USDA Animal Care Policy Three, investigators are expected to use up-to-date, pharmaceutical-grade medications whenever they are available, even in acute procedures. The USDA policy further states that the use of non-pharmaceutical-grade compounds should be limited to situations involving scientific necessity, unavailability of acceptable veterinary or human pharmaceutical-grade compounds, or specific review and approval by the IACUC. Cost savings alone are not considered adequate justification for the use of non-pharmaceutical-grade compounds in laboratory animals.

In congruence with the USDA policy, the Eighth Edition of the Guide for the Care and Use of Laboratory Animals (Guide) also indicates that pharmaceutical-grade chemicals should be used, when available, for all animal-related procedures. It goes on to recommend that the use of non-pharmaceutical-grade chemicals or substances be described and justified in the animal use protocol and approved by the IACUC. The Guide further indicates that, when establishing and reviewing a proposal, the investigators and the IACUC should consider the grade, purity, sterility, pH, pyrogenicity, osmolality, and pharmacokinetics of the non-pharmaceutical grade substances to be administered, as well as any animal welfare and scientific issues relating to their use.

It is important to understand that these guidelines pertain to both active and inactive components of chemicals administered. Therefore, the vehicle used to facilitate the administration of a compound is just as important as the active ingredient in the compound. In accordance with USDA and OLAW guidance, a pharmaceutical-grade compound is a drug, biologic, or reagent that is approved by the Food and Drug Administration (FDA), or for which a chemical purity standard has been written/established by a pharmacopeia, such as US Pharmacopeia and the National Formulary (USP-NF), British Pharmacopoeia (BP), and/or Pharmacopeia of the Council of Europe (EP).

The emphasis on use of pharmaceutical-grade compounds serves to ensure that substances administered to laboratory animals meet established standards of purity and composition, and ultimately, to assure animal welfare and scientific validity of experimental results. The use of lower grade chemicals or compounds containing higher levels of impurities or poorly formulated preparations may introduce research complications, unanticipated variables, and/or adverse effects. The USDA and OLAW have indicated that the wording of these regulations provide some room for professional judgment. This flexibility establishes an expectation that the IACUC and investigators will work together to determine the best way to conduct experiments within the context of humane animal care.

One of the discussions on this topic that was of particular interest to me at the 2012 IACUC Conference focused on how an IACUC can best meet its responsibilities regarding the use of non-pharmaceutical drugs in research with animals. There are a variety of administrative methods an IACUC may use to review and approve the use of such agents, including the establishment of an institutional set of acceptable scientific criteria, in place of criteria arrived at  on a case-by-case basis. Some institutions address this issue in the IACUC application and/or in the veterinary consultation phase of the proposal review.  An institution may also consider developing an IACUC policy for the use of non-pharmaceutical-grade compounds in laboratory animals. Institutions and organizations are expected to make investigators and research staff aware of the new USDA/OLAW requirements. Whether information is provided through newsletter announcements, policy updates, board meetings, email outreach, online training and/or semi-annual site visits, enhancing awareness is key.

Please feel free to share via this blog platform any protocols, ideas, and/or processes that your organization has developed in order to comply with the new guidelines and regulations regarding the use of non-pharmaceutical grade compounds in laboratory animals. Please don’t hesitate to include information on your experiences, challenges, and solutions.

“Science Times” synthesis

Spring is here, and much like the flora outside, the news is abloom with tales of research! Take some time out from smelling the roses and check out this week’s installment of the “Science Times” synthesis.

Week of March 26

Panel says flu research is safe to publish: The National Science Advisory Board for Biosecurity has recommended that controversial data from a research study on the H5N1 virus, which was originally withheld due to public safety concerns, be published.

Surgery for diabetes may be better than standard treatment: Two recent studies, published by the New England Journal of Medicine, have concluded that bariatric surgery may be more effective than standard medical therapies in the treatment of Type 2 diabetes.

Doctors have feelings, too: In this poignant and compelling piece, a doctor meditates on the latent role emotions play in the practice of medicine.

Week of April 2

The ABC’s of the health care law and its future: With uncertainty surrounding the Affordable Care Act, Jonathan Oberlander, author of the Political Life of Medicare and a professor of social medicine and health policy and management at the University of North Carolina, Chapel Hill, provides a succinct summary of what’s at stake in the Supreme Court’s decision.

Study says DNA’s power to predict illness is limited: The increasing ease of DNA sequencing has brought with it hope for the future of personalized medicine. New research suggests, however, that an individual’s full DNA sequence has its limits in predicting disease.

Scientists link gene mutation to autism risk: Several scientists conducting research into autism have reached a shared conclusion regarding several gene mutations that may increase the probability of a child developing autism.

Feeling Around the Edges of Cultural Competence Through Performance and Discussion

by Catherine Rogers, Marketing and Communication Design Manager

For researchers, understanding cultural competence means more than just knowing about historical and current contexts. It means putting down the clipboard, taking off the lab coat, and connecting with others through thoughtful, respectful exchanges.

As demonstrated recently through two one-act plays at the Dana-Farber Cancer Institute in Boston, MA, the edges of cultural competence can be blurred by our assumptions, past experience, and personal biases. The core, however, remains clear: Cultural competence helps build a firm foundation upon which public trust in research can be built.

The two-hour symposium featured The Bok Players, an interactive theater group that examines complex issues of human interaction, and a panel of experts from areas such as health disparities, human subjects protections, and research subject advocacy.

Through the two distinct pieces, and the discussions, questions, and role-playing that followed, the nearly 100 research professionals in the audience explored the various challenges that arise in the subject recruitment process. Although each plays’ characters were different—one featured the mother of a potential subject and a researcher, the other brought to life an investigator, a research assistant, and a leader of a Jewish philanthropic organization—they both demonstrated the extent to which lack of respect, empathy, and honesty can give rise to distrust, frustration, and coercion.

Here are a few other take home lessons from the performance:

• Watch your assumptions. Just because a woman has a child doesn’t mean she’s a “Mrs.”
• Show how you’re alike. Get to know the population you’re working with and emphasize your similarities. Trade a lab coat for street clothes or business attire.
• Take your time. Don’t rush a visit with a potential subject or their advocate.
• Be respectful with how information is presented. Even though more than half of the population has limited health literacy, strive to give full disclosure and accurate information about risks and side effects.
• Make it personal. Try to validate a patient’s concerns rather than gloss over them. It’s OK to say, “this must be really hard for you.”

What suggestions do you have about achieving cultural competence? Please let us know!

What Boundaries Have You Drawn Between Research and Practice?

by Amy Davis, JD, MPH, Senior Director for Programs and Publications at PRIM&R

Remember the Johns Hopkins-Michigan study in which the Michigan Hospital system implemented an intensive care unit-based check-list system for inserting a catheter to reduce central line infections? The project was submitted to the Johns Hopkins Medical Institution’s (JHMI) institutional review board (IRB) in 2004, who categorized the project as “exempt” from the federal regulations at 45 CFR 46 because data provided to Johns Hopkins researchers was de-identified and the project posed minimal risk.

Based on this determination, the project leaders did not ensure that the hospitals in which the study was conducted were federally approved to conduct “research” with “human subjects.” Neither did they obtain individual, written informed consent from the patients who were part of the pilot program. In 2006, OHRP received a complaint that the project violated federal regulations, and the rest is history.

The John Hopkins-Michigan study highlights the difficulty of determining the line between research and practice, or in this case, between research and quality improvement. The case is neither unique nor new. This issue was discussed prominently in the 1979 Belmont Report and over the years, examples that do not fall tidily within the definition of “human subjects research” have raised ethical questions about ethical oversight: activities that occur in the practice of public health, quality improvement, clinical innovation, and community-based health initiatives, to name a few.

The fact is that sometimes people carry out activities that resemble both ordinary practice and the development of generalizable knowledge, a central characteristic of research. These individuals, and the human subjects office at their institutions, then find themselves wondering “does this activity require IRB review?” Such longstanding ambiguity and confusion leads to wasted resources at a minimum, and exposure to undue risk at worst. It is time to provide more guidance to institutions, practitioners, and IRBs about how to manage the ethical issues that lie at the border of research and practice.

This is the goal of PRIM&R’s project titled “The Boundaries Between Research and Practice.” This initiative was launched last year when PRIM&R hosted a meeting on the topic facilitated by PRIM&R board members, Alex Capron, LLB, Scott H. Bice Chair in Healthcare Law, Policy, and Ethics in the Gould School of Law at the University of Southern California; and Hugh Tilson, MD, MPH, DrPH, Adjunct Professor and Senior Advisor at the University of North Carolina at Chapel Hill School of Public Health. That meeting led to a follow-up gathering in National Harbor, MD during the 2011 Advancing Ethical Research Conference, titled Town Hall Meeting: “Bumping Into Things: What are the Boundaries of Research and Why Might We Want to Know?”

During this dynamic event, the moderators and participants discussed examples of borderline situations from different areas of practice, and discussed the salient characteristics that define them as either “like” or “unlike” research. Characteristics such as level of risk, extent of deviation from common practice, nature of potential benefit, and extent of systemization have emerged from the discussions to date. Participants also discussed alternative review mechanisms that they have used for non-research activities that raise ethical concerns. Review systems such as ethics audits, human subjects office staff review, and consultations with ethicists were described.

The participants were gratified to learn how their peers were handling borderline cases, but they confirmed the need for effective guidelines that advance ethical conduct and encourage creativity and action. The more information that we receive about these experiences, the better informed we will be to develop useful guidelines. So we are coming to you to ask for your input. Please contribute your expertise, your questions, and/or your experiences with managing cases at the “border.” Here are some questions to prompt your thinking.

• As a practitioner, have you struggled with the question of whether your IRB should review a project before its implementation?
• As an IRB member, have you heard about a project that was not submitted for IRB approval that you thought should have been? Or have you been asked to review a project proposal that you felt was outside the IRB’s jurisdiction, but that raised ethical questions requiring oversight?
• As an administrator, have you established or employed alternative systems for review?
• What project characteristics do you believe should determine whether an activity requires ethical oversight and what kind of entity would you recommend for this purpose?

Please share your thoughts here.