Planning Committee Profile: Michele Russell-Einhorn, PC Co-Chair

Planning Committee (PC) Profile: Michele Russell-Einhorn, 2010 Advancing Ethical Research Conference PC Co-Chair

How might you explain your work to someone who is new to the field of research ethics?
Everything I do is geared toward making sure that any research conducted within the Dana-Farber/Harvard Cancer Center (DF/HCC) is scientifically sound and that the people who are asked to participate will only be exposed to risks that are reasonable and will be monitored carefully.

What motivated you to choose a career in research ethics?
I fell into it! I had previously been involved in human rights work in the 1970s. Sweeping ahead to the 1990s, I had an opportunity to participate on the NIH subcommittee relating to the radiation research experiments sponsored by the Department of Energy. During this time, I discovered that I had a real interest in learning more about the participation of human subjects in research.

What’s the most rewarding part of your job?
I truly love working with people who really care about finding a cure for cancer as well as caring about the subjects involved in cancer research. I am awed by the dedication of the IRB chairs, members and investigators within the DF/HCC community who will drop everything to deal with some unforeseen issue involving the safety of a human subject in an ongoing research protocol.

How did you become involved with PRIM&R?
The first day I started work at the Office for Protection from Research Risks (OPRR), Office for Human Research Protections (OHRP) being its successor, I was sent to an animal research conference in San Diego hosted by PRIM&R. Because of my work with the government, I participated in many of PRIM&R’s meetings from the earliest partof my work in the field.

What are your goals for the 2010 Advancing Ethical Research Conference?
To expose people to some of the cutting-edge issues in the work that we all do, and to help people use the conference as a place to network and develop connections.

Which topics will the conference program address that you find most intriguing, or in need of attention, especially given today’s ever-changing regulatory environment?
I find the issue of personalized medicine to be one of the most difficult. Technology has given us access to information that we may not know what to do with. Tissue banking and research on clinical data is critical to advancing research, but how do we really describe the risks and the “down stream” issues that any participant may face? Conference speakers will give us a lot of food for thought in this difficult area.

In addition to the keynotes, panels, and sessions, our conference has so many other highlights (i.e., networking events, book group discussions, meet-and-greets). What are you most looking forward to?
I’m looking forward to networking. I’m a real people person and I enjoy seeing people I know and don’t often get a chance to see; and, I enjoy making new friends!

Where is your hometown? New Haven, Connecticut

What’s playing on your iPod? (What music do you listen to?) Simon and Garfunkel

What are you reading? The Girl with the Dragon Tattoo

What is your favorite type of food? Chocolate

If you had to choose one…

Classical music or rock? Rock

Circle or square? Circle

Dogs or cats? Dogs

City or country? City

Silver or gold? Gold

Swimming or hiking? Hiking

Sweet or salty? Salty

Thanks, Michele, for sharing your thoughts. See you in San Diego!

Center’s Studies Suspended Due to Impure Injections

A July 17, 2010 New York Times article revealed that research at the Kreitchman PET Center at Columbia University has been suspended.

An Food and Drug Administration (FDA) investigation alleges that at least 10 batches of drugs, called radiotracers, violated protocol and were subsequently injected into human subjects. The Center also allegedly falsified documents in an attempt to hide their drug’s impurities, according to the FDA.

The Center, widely regarded as a premier research establishment based on its use of positron emission tomography (PET) for psychiatric research, is alleged to have repeatedly violated the FDA’s regulations for more than four years.

Radiotracers are meant to gather in the specific area that researchers are studying, which in the case of the Kreitchman Center, was the brain. These compounds are considered very safe, but have a short shelf life and degrade quickly. As such, centers like Kreitchman may create their own radiotracers under strict FDA guidelines.

The Center’s protocol violation also raises questions regarding informed consent and vulnerability, as the study participants were mentally ill, diagnosed with disorders like schizophrenia and depression.

What do you think of the Kreitchman Center investigation and allegations? Is this a “slip-up,” or a more pervasive issue? How might this affect the work of researchers in comparable centers, or those that aspire to the status of the Kreitchman Center?

PRIM&R's International Spotlight

In this new series of Ampersand posts, PRIM&R will feature an international perspective on the field of research ethics.

Spotlight on India

Clinical research is booming in India. Recent reports indicate the Indian clinical research industry could garner as much as $1.5 billion in funding from the US and Europe this year. While it is difficult to determine the exact number of clinical trials and institutional ethics committees (IECs)—also referred to as institutional review boards (IRBs) or research ethics committees (RECs)—tracking and monitoring of clinical research involving human subjects is on the rise.

PRIM&R is pleased to introduce S. Swarnalakshmi, Ph.D., IRB manager at the Y.R. Gaitonde Center for AIDS Research and Education (YRG CARE) in Chennai, India. Swarna may be a familiar face in our community; she attended the 2009 Advancing Ethical Research (AER) Conference as an international scholar.

PRIM&R Staff (PS): Please share with our readers your story: How did you come to the field of research ethics?

S. Swarnalakshmi, PhD (SS): Prior to joining YRG CARE as a research associate in 2001, I had no previous training in research ethics. After assuming the role of IRB coordinator in 2003, I became fascinated with the discussion of ethical issues during the IRB meetings. With institutional support, I started attending national and international workshops, conferences, and seminars in research ethics, and learned more about the latest trends and issues in the field. I then became even more involved after completing an intensive training program in bioethics organized by the Indian Council of Medical Research (ICMR) and sponsored by the National Institutes of Health (NIH) in 2007. I now organize the annual bioethics symposium at YRG CARE, and speak in research ethics workshops at other institutions.

(PS): Please tell us a little bit about the history of human subject protections and RECs in India.

(SS): Historically, physicians have referenced the texts from traditional systems of medicine in India, Ayurveda and Siddha, which offer guidelines for how physicians should conduct themselves, keeping in mind the welfare of patients. In 1980, the ICMR developed the first version of the Ethical Guidelines for Biomedical Research in Human Participants (ICMR Code).

The ICMR Code was then revised in 2000, and the current and latest version came out in 2006. However, these ethical guidelines do not have legal sanctity as in the US. Many institutions now feel the need to protect the interests and welfare of human subjects, and have started establishing IECs. However, as discussed in this editorial, there have been no systematic assessments of the number of IECs in India. According to the Office for Human Research Protections (OHRP) website, India has as many as 278 IRBs registered as of July 2010, of which 57 have been deactivated. The actual number of IRBs is likely higher, as this list only includes projects that are US government-funded.

Efforts are also underway to track and monitor clinical trials with a national registry. The Clinical Trials Registry-India (CTRI) began tracking clinical trials in 2007, and as of June 2009 it became mandatory to register trials before enrollment of the first participant. A recent article in The National Medical Journal of India states that the CTRI had registered 298 trials in 23 months before June 15, 2009, while 551 trials were registered in the following nine months.

(PS): Please share one unique challenge and one unique asset you and your colleagues face in protecting human subjects in India.

(SS): In international collaborative research projects, it is a challenge to balance the national good clinical practice (GCP) and ethical guidelines with the international regulatory requirements. For example, the informed consent forms administered to the study participants are translated in the local language, but great care has to be taken to ensure the study participants understand the complex and detailed technical information in these forms.

One unique asset at YRG CARE has been the commitment and dedication that IRB members exhibit. They vigilantly ensure that the rights and welfare of the study participants are well protected before, during, and after a research project ends. The institution has also been supportive of the IRB work and at present, we have two full-time staff members devoted to IRB work. This is not very common in India, as IRB members generally serve on the IRB in addition to their routine responsibilities.

(PS): How do you see the field of research ethics changing in India?

(SS): There is growing awareness of bioethics in India, and many research institutions like YRG CARE are organizing workshops and symposia to foster awareness of research ethics among investigators and students. The Indian Journal of Medical Ethics organizes the National Bioethics Conferences, and ICMR conducts several research ethics workshops. Though not on the level of PRIM&R’s Advancing Ethical Research Conference, there is increasing interaction and active participation in bioethics conferences and symposia in India, and I am confident that India will reach that level in the years to come!

Furthermore, more institutions in India are starting IRBs and streamlining the operations of these committees. I am hopeful that there will be further positive developments when an ICMR bill, the Biomedical Research Human Subjects Promotion and Regulation Bill, reaches legislative sanction. This bill will establish a Biomedical Research Authority, through which all ethics committees will be required to register.

(PS): Thank you for taking the time to share your perspective with the PRIM&R community, Swarna.

Interested in sharing your story about research ethics in your country? Please e-mail us for more information.

Genetic testing at universities raises ethical dilemmas

Stanford University has joined the University of California Berkeley in inviting incoming students to participate in personal genetic testing.

According to an article in last week’s Scientific American, major ethical considerations are raised when students are given the opportunity to study their genotype: coercion, privacy, and adequately preparing students to interpret the results of their tests.

Because Berkeley is offering the genetic testing kit and support services free of charge, students may be compelled to participate without fully understanding the implications of what they are doing, including associated risks. It also remains to be seen how peer pressure might influence students’ decision to participate.

Stanford’s program, only available to medical and graduate students enrolled in a genomics and personalized medicine course, costs a deeply discounted $99. The tests usually cost about $600.
It is unclear how the universities will use the data that they collect. While Berkeley says the data will not be used for research, language in their consent form refers to the project as a “study.” And even though both schools promise to incinerate the DNA samples after use, results will be preserved electronically.

Students may also not be adequately informed to draw conclusions from their results, which could lead to “unwise lifestyle decisions.” Berkeley plans to prepare students with a series of lectures during orientation.

While the schools claim testing will be conducted purely for educational purposes, where is the distinction between treating students like students, or like research subjects? Have the schools taken the necessary precautions to balance the benefits and risks inherent in genetic testing? How might universities work to address privacy concerns, and prepare students to make decisions based on the test results?

Life as an IRB Administrator: Advocate or Advisor, Protector or Promoter?

by Cynthia Hahn, PRIM&R member and guest blogger

A robust human subject protections program is one in which the system is set up from the start to facilitate the ethical conduct of research.

News of the Physicians for Human Rights (PHR) request that the Office for Human Research Protections (OHRP) investigate the Central Intelligence Agency (CIA) alleged torture “studies” has generated a lot of discussion in the Institutional Review Board (IRB) community. In a recent meeting at my institution, members of our IRB staff wondered whether OHRP has jurisdiction to conduct such an investigation, and if so, what they could do about the “studies.”

Then we asked: what if an IRB had reviewed it? Could an IRB ever have approved any aspect of the research? For example, could an IRB have determined that the monitoring of individuals undergoing torture was, in fact, for medical purposes, and that the collection and analysis of the data was the sole research intention? Could an IRB see this case as a secondary review of data collected for performance improvement?

Allegations like PHR’s raise questions not only about how IRBs might handle this case, but also about the roles IRB members play. What would you do as an IRB administrator if an investigator at your institution came forward with a retrospective review of existing data for a procedure that was (in your IRB’s opinion) morally objectionable, but approvable under the existing federal regulations?

What if that investigator argues he/she performed the intervention for the treatment, monitoring, or diagnosis of individual patients, and not for research? What if you find nothing counter to this point? What if your IRB thinks that it would be important for this information to become public?

The discussion could go on for hours, and in angst the committee may turn to their IRB administrator and ask, “What are our options?” IRB administrators would hold a lot of power in that moment.

Resources exist to guide IRBs in ethically challenging situations. For example, projects like the Clinical and Translational Science Awards (CTSA) consortium, the Federal Demonstration Partnership (FDP), and the OHRP’s and Secretary's Advisory Committee on Human Research Protections (SACHRP)'s work on IRB Authorization Agreements all strive to provide innovative strategies to improve IRB efforts. Additionally, the programs seek something often referenced as "reducing administrative burden." But how can we balance this reduction of burden with the history of high-profile IRB shutdowns in the late 1990’s, the tragic deaths of Ellen Roche and Jesse Gelsinger, and the Illinois White Paper on IRB Mission Creep?

Websites such as IRBwatch, as well as many IRB administrators in the field, raise concerns about this balance in the investigator community. IRB administrators walk a tightrope between protecting human subjects, protecting their institution, and reducing administrative burden for investigators. As a result, most academic medical centers today offer IRB services, through IRB administrators, to help investigators achieve compliance. These services range from writing consent forms to providing IRB pre-submission assistance, and assisting with protocol development. While these services are almost always helpful, the questions remain: Do they help investigators develop an ethically responsible protocol with the least amount of paperwork, or do they help him/her craft a good argument around the regulations?

So, what is the role of an IRB administrator: ethicist, or administrator? Advocate for subjects, or the investigator? Can they be all of the above?