Weighing the benefits and risks of post-conference contact

On my desk, I have a pile of business cards from my trip to the 2010 Advancing Ethical Research Conference in San Diego, CA. After the conference, I thought I would be on top of things, calling and emailing each individual that I met. I planned to establish relationships between my institution’s IRB and others. However, reality hit with the holiday breaks and the general daily work of an IRB.

Last week, I noticed the business cards again and thought to myself, "it only takes a few minutes to email someone." Now, if you are like me and have more than 30 business cards to go through, those minutes add up. Perhaps more importantly, you have no clue who some of these people are or where you met them, making things even more challenging. So like many IRB members out there, I decided to weigh the benefits and risks.

Some risks of contacting these 30 people included:

• Receiving no response
• Feeling fairly silly about not knowing who you are talking to

Some benefits of contacting these 30 people included:

• Obtaining new resources
• Understanding alternative procedures and practices
• Sharing my own expertise

The benefits definitely outweighed the risks. So, I decided this was a feasible task and e-mailed five of my fellow attendees. The response rate was excellent. Within a matter of days, I was having calls discussing differences in our procedures, how we share the same issues and how we have each managed those concerns, what worked and what didn’t. What took me weeks to initiate ended up being a very beneficial conversation with an IRB several states away.

I strongly encourage my fellow IRB colleagues to pick up the phone or write a post-conference e-mail. It’s hard, I know, especially if you’re the type to eat lunch and work at the same time! However, when I realized it took just minutes, and the benefits of reaching out were so great, I knew that it was worth it. My goal this year (is it ever too late for a New Year’s resolution?) is to continue this outreach and stay connected. That’s why the business cards are sitting on my desk, right by my computer screen, as a reminder to stay in touch.

"Science Times" synthesis

Welcome to another week of the "Science Times synthesis"! Please enjoy our favorite articles from the New York Times science section from the past two weeks.

January 18, 2011

Heavy doses of DNA data, with few side effects: New York state banned the direct sale of DNA data tests to consumers, and many questions are arising.

Close look at orthotics raises a welter of doubts: An orthotics researcher is questioning if the shoe inserts help or harm those who use them.

Trial in a vaccum: study of studies shows few citations: Researchers are looking at how often clinical trials are addressing issues that may have already merited trials.

January 25, 2011

Harnessing the brain’s right hemisphere to capture many kings: Researchers explore the brain’s pattern recognition ability as a skill in thoughtful games such as chess.

With poem, broaching the topic of death: Health workers are using Navajo traditions to advance end-of-life care in their communities.

A pound of prevention is worth a closer look: Authors explore what happens if you and your doctor have questions about modern medicine.

Birth control update, in thousands of interviews: The National Center for Health Statistics conducted thousands of interviews to provide an updated picture of the country’s birth control methods.

Introducing the 2010 Pillar of PRIM&R

We are pleased to announce Dr. Amal Matar of Egypt as the recipient of the 2010 Pillars of PRIM&R Award.

Dr. Matar, who received her medical degree from Ain Shams University in 2000, is a graduate student in Biotechnology and Mass Communication and Journalism at American University in Cairo, Egypt. She will use her award to further the research she is conducting for her Master’s thesis, which will identify and assess the perspectives of and challenges facing IRB chairs at Egyptian institutions. Dr. Matar, who plans to conduct between 10 and 12 in-depth interviews for her thesis, hopes to ultimately be able to extend her study to include other countries in the region, including Lebanon, Qatar, Saudi Arabia, and Jordan. Dr. Matar’s project will be conducted in conjunction with the IRB at the University of Maryland at Baltimore. PRIM&R would like to congratulate Dr. Matar on her pioneering work in the research ethics field.

We look forward to Dr. Matar’s presentation of her work at the 2011 AER Conference in National Harbor, MD, and we hope you will be there to join us!

Since its founding in 1974, PRIM&R has been infused with the wisdom, devotion, and vision of a number of highly respected and uncommonly committed directors of the board, members, and volunteers. In recognition of these contributions, in 2007, PRIM&R established the Pillars of PRIM&R Memorial Fund to recognize those who hold the same values, principles, and commitment to research protections. The Pillars of PRIM&R Memorial Fund provides awards to qualified applicants whose scholarship in the field of research ethics reflects PRIM&R's mission and core values. It is our hope, through this initiative, the unique spirit and principles of those designated as Pillars will inspire the next generation of leaders in the field. To learn more about the Pillars of PRIM&R, please visit our website.

2011 – The Year of the Rabbit… and the biospecimen repository?

by Sylvia Baedorf Kassis, MPH

Happy New Year! Although one of the characteristics of the Year of the Rabbit, according to the Chinese Zodiac, is supposedly a decrease in rules and regulations, I don’t see any shortage of discussion of research ethics and regulations in my future.

In fact, since my return from the 2010 Advancing Ethical Research Conference, it was not long before I put my conference experience, especially what I learned about biobanks, to good use. Four investigators have already contacted me for guidance on how to proceed with their research projects that include the use of previously stored samples or the prospective storing of samples for future research.

Repositories also seem to be on the minds of regulatory and ethical professionals at academic institutions funded by the NIH’s Clinical and Translational Science Awards (CTSA). I just participated in a national teleconference where more discussions about biobanks took place; repositories seem to be a hot topic—both at my institution, and beyond.

Post-AER, I have become particularly concerned by the banks that house "discarded" clinical samples without any kinds of approvals for research use in place. We are hearing more and more about physicians storing biospecimens collected for clinical purposes during routine care (without necessarily having any research intent) rather than discarding them when clinical testing is finished. It is hard enough to create guidances and policies for the repositories we know about; how can we even begin to uncover all the informal, unregulated 'banks' in hospital freezers around the country?

Over the past year and half, two cases related to the storing of biospecimens for research purposes have had very different outcomes. At the end of 2009, the Texas Department of State Health Services (DSHS) settled a lawsuit by agreeing to destroy more than five million stored newborn blood spots because parents did not give consent to do so. Consider, however, that similar litigation took place in Minnesota and that case was dismissed by the court in 2010. If it hasn’t already, it won’t be long before this issue of researchers wanting to access stored samples hits an IRB near you.

There are many factors that your institution will have to consider when deciding whether to approve tissue banking-related research. I simply want to leave you with the reminder that repositories are made up of samples and data collected from people who may or may not have been informed that their samples were going to be used in future research.

The aforementioned cases, as well as the story of Henrietta Lacks' family and the Havasupai tribe, prove that people have very strong feelings about the storage of their samples. As noted by PRIM&R's education director Elisa Hurley, in our efforts to advance ethical research, it is essential that we listen to the voices of research participants. Only then can research guidances, policies, and regulations be meaningful, relevant, and protective of the research participants who enable the promise of scientific progress to become a reality.

'Science Times' synthesis

As Mother Nature reminded us of her power here in Boston (and around the country as well), we were grateful to have our favorite science-related articles to keep us busy while we were snowed in. We hope you’ll enjoy the latest edition of our New York Times ‘Science Times’ synthesis. And, no matter where you are, stay well and virus-free!

January 4, 2011

Study linking vaccine to autism was fraud, journal reports: The first study linking vaccines to autism may have been doctored, according to a report.

Many defibrillators implanted unnecessarily, study says: Thousands of patients who do not need high-tech heart devices may still be receiving them.

Grasping another’s point of view at an early age: A study examines infants’ ability to understand someone else’s perspective.

Evidence of mammals and legumes, 22 years old: Scientists share their 22 million year-old findings from the field.

January 11, 2011

Cancer can develop in catastrophic burst: Scientists examine cancer cells with new rapid methods of decoding DNA.

Preventing heart risks at the root: childhood: Two recent studies suggest that heart disease prevention should begin in early childhood.

RNA game lets players help find a biological prize: Researchers are using an online game to create and study RNA designs.

Inactivity is harmful, even with trips to the gym: New research suggests that squeezing in short trips to the gym may not be enough to combat a day’s worth of inactivity.

Depth of kindness hormone appears to know some bounds: As researchers continue to study the chemicals that create kindness and love, they begin to discover the boundaries of these chemicals.

And one final article: Though this is not an article from the Science Times, we’re nothing if not flexible here at PRIM&R. We therefore hope you will enjoy this additional article from the Boston Globe on Sunday, January 9, regarding the same study concerning the link between autism and vaccines referred to in the January 4 summary above.

Research in the midst of tragedy

by Wendy Tate, PSM, CIP

I live in Tucson, AZ. Located 60 miles north of the US-Mexico border, 1 million people and the University of Arizona call Tucson home. Tucson is known as a large city with a small-town feel. On Saturday, January 8, 2011, when a single individual shot 19 people, including my congresswoman, Gabrielle Giffords, this small town became the center of the nation’s focus.

Like many of you, I have been keeping up on the medical updates regarding Rep. Giffords. As I hear about the amazing feat of surviving a point-blank gunshot to the head, I am reminded of two areas of science that have driven medical care to the point that surviving such a traumatic event is even a possibility: combat care and research. The relationship between combat care and emergency medicine is clear, but now, I would like to focus on research and its role during these events.

This is a time when research is put to the test. Emergency response requires methods that are quick and effective. While research studies often allow for careful and methodical procedures in controlled situations, the field has real-world expectations that are often not as forgiving. Emergency medical personnel perform cutting-edge procedures to try not only save a person’s life, but to preserve its quality. Psychologists utilize revamped testing and counseling methodologies to help victims cope with their experiences. Like everything in life, affected populations’ responses cannot be predicted accurately 100 percent of the time. Research results must be robust enough that when they are made into standard practice, they hold up to the variability that life guarantees.

At the same time research results are validated in the field, researchers are tested. Tragic events provide a plethora of opportunities to study everything from medical and environmental technologies to human responses and emotions. While the purpose of research is to answer a scientific question, researchers must remember the populations with whom they are working, and the delicacy of the situation that they are approaching.

Communities that have experienced a devastating event are vulnerable for a substantial period of time, making informed consent difficult, if not impossible. While the research subjects may be competent and cognitive, they are no doubt still vulnerable. Researchers must build safeguards into their protocols to ensure that unnecessary risks are not introduced. Asking questions that seem to have minimal risk may cause psychological damage, therefore having a greater risk. Asking a person who just finished watching a war movie what emotions and images come to mind when hearing the sound of a gunshot is much different than asking a person who recently witnessed a shooting in real life.

Our community is vulnerable right now. I have no doubt that our IRB will be seeing research proposals looking at the fallout of this past weekend’s events, and that research on tragedies such as this produce good findings. However, I know that the IRB will be very concerned about what research subjects are asked to do.

This event has become part of Tucson’s local context for research, even though the reason behind this tragedy had nothing to do with research. Everyone involved, researchers, IRB members, human research protection programs, research administration, and the community at large must take a stand and only allow research that follows the ethical principles of the Belmont Report. Respect for persons must be upheld, especially when those persons are in a vulnerable situation and may not have the capacity to decide what is best for them. Risks, including psychological, must be minimized; and no risk is justifiable when there is no potential for benefit. Justice must be preserved. Individuals and communities should not be asked to participate in research if there is no benefit to their population. They must reap from the contribution that they make.

I want to close this article by thanking my colleagues across the United States. Over the last two days, members of my office have received several e-mails and phone calls sending well-wishes and condolences to our community. We cherish them all, and thank you for keeping us in your thoughts and prayers.

Listening to the voices of research in the New Year

By Elisa Hurley, PhD, education director

As we begin the New Year, I continue to reflect on themes that emerged during the 2010 Advancing Ethical Research Conference in early December. There is one theme in particular that I keep coming back to: listening to the voices of research participants. As well-meaning as we are in the human subject protections field, when we are faced with the mounting pressures to push research forward, to adhere to increasingly complex regulations and guidelines, and to manage overloaded IRB dockets, we may forget to listen to those we are tasked to protect. We were reminded again and again at the 2010 AER Conference the true value of the voices of research participants.

During the panel Hot off the Presses: Selected Abstracts on Innovative HRPP Programs and Research on Research Ethics, Susan Trinidad of the University of Washington gave a presentation titled Informed Consent in High-Throughput Genomic Research: Views of Health Plan Members. She and colleagues conducted focus groups asking people what they would like to see covered in consent forms for genome-wide association studies (GWAs). Many of us in the session were surprised to learn that, while information about the study purpose was important to respondents, information about risks—primarily risks concerning disclosure of identifying information—was not of particular interest or importance to them. In fact, they were more concerned about the risk of disclosure of their private banking information from routine financial transactions.

This finding is striking in the context of informed consent. From the conference’s first debate, Be it Resolved that Consent Forms are an Obstacle to Informed Consent and Should be Abolished onward we heard repeatedly that the current process for obtaining and documenting informed consent is in need of a major overhaul. Consent forms get longer and more complicated every year, and yet, as Dr. Ezekiel Emanuel pointed out in his plenary, the forms do not get any better at disclosing information relevant ito making an informed decision about participating in research. Part of the problem, it seems, is that consent forms contain information investigators think participants ought to know, rather than the information that potential research participants want and need to know. The work of Ms. Trinidad and her colleagues suggests that the research protections community’s ongoing struggle to develop meaningful informed consent would benefit from conducting more empirical research on what is truly important to potential participants; in other words, from listening to the voices of those whose consent is required.

The most common sentiment Ms. Trinidad and her colleagues heard in their focus groups was “we just want to be asked.” Participants were less concerned with the details of a study then with the idea of being asked, and thereby being shown basic respect and appreciation for their willingness to participate. How would the lives of Henrietta Lacks and her family have been different if she, or they, had just been asked their permission for keeping , replicating, and distributing Ms. Lacks’ tumor cells? How different would the Havasupai tribe’s relationship with medical researchers be if they had been asked to specify the kinds of DNA research for which they would allow their blood samples to be used? Listening seems like such a simple thing; perhaps, every once in a while, we just need to be reminded of its concrete value.

New Year, new perspective

By: Walter Straus, MD, MPH, PRIM&R Board Chair

I am beginning the New Year by fulfilling a resolution. Perhaps it’s a sign of age that I no longer race to embrace the latest technological breakthrough. So, here goes my first foray into the blogosphere.

My career has revolved around improving human health, through clinical medicine, public health work domestically and internationally, and, for the past dozen years, research to develop new drugs and vaccines. I have always focused on issues important for human health. I had recognized the importance of attending to animal welfare requirements in bioethics, but had not appreciated this on a personal level.

This past weekend, my family headed off to New Hampshire for a skiing vacation. We left Abbie, our six-year old German Shepherd, at home in the care of dear friends. For much of her life, Abbie had been a difficult dog. She had some alpha tendencies, and didn’t care much for other dogs. In her puppyhood, she had eagerly taken on some large and mature German Shepherds, to establish her dominance. My wife had patiently trained her during her first two years, but general puppy training wasn’t rigorous enough for Abbie. She found it a bit trivial, and required a more authoritative instructor along with a different set of peers. Soon she was in a dedicated German Shepherd class, consisting of 8-10 dogs, marching in procession through a local park. Onlookers wondered whether we were conducting police K-9 training, and always provided us a wide berth. She developed good manners, and was a very smart dog. She could put on a serious expression that I always interpreted as soliciting assignments more complicated than "fetch." At night, I would put on a mock serious expression, stare her in the eyes, and instruct her to “secure the perimeter.” She seemed delighted to have a worthwhile assignment, and would eagerly run out, bark at the moon, and confidently return to the house.

Abbie was always concerned about the pecking order at home. For several years, we had to be a bit cautious when our young daughter was around Abbie’s food bowl. But over time, she became a wonderful companion to our family and was always attentive to our security. In fact, we would easily recognize whether a knock at the door was by a friend or a stranger based on the cock of Abbie’s head and the directionality of her marvelously expressive ears, and then by her pace to the front door. Whenever one of us was ill, Abbie would instinctively lay at the foot of the bed. And whenever we had overnight visitors, she would station herself midway between guests and family, before falling into a light sleep (keeping one eye open for the unexpected).

One night into our ski vacation, we received a tearful call from our friends. They had returned to our house, and found her dead. The next 12 hours were a blur. A veterinarian performed an autopsy, and made a definitive diagnosis of "bloat." In human medicine, bloat is a term for volvulus, a paradoxical twisting of the intestines, which results in strangulation, and may lead to death. Bloat is a leading cause of death in dogs, especially large ones. With only subtle warning, Abbie, who had been in wonderful health, had become acutely ill, and then died.

In the past two days, I’ve had a rush of memories about Abbie, and more generally about dogs. Isn’t it remarkable that this species of once wild animals has permitted domestication? Isn’t it also remarkable that certain breeds of dogs instinctively dedicate themselves to protecting their owners, even at their own risk? With those thoughts, as well as our own love for her, we feel terribly guilty at having let Abbie down during the moment when she needed us. We wonder whether we might have been able to save her had we been present, and been able to quickly transport her to the veterinarian. Though that is not likely, we’ll always be troubled. This experience has made me appreciate our moral responsibilities to animals in a new and deeply personal way.

All of which brings me to PRIM&R and the Pillars program. Apart from its leadership in human bioethics, PRIM&R is dedicated to advancing the field of ethics in animal research, which benefits both humans and animals. I have made a contribution to PRIM&R’s Pillars program, and have done so in the hope of supporting future research to advance bioethics – so that future human and animal research can be supported with the highest ethical standards.

Interested in supporting the Pillars of PRIM&R program? Learn more.

Another look at the Guatemala research revelations

By: Leonard H. Glantz, Professor of Health Law, Bioethics and Human Rights at Boston University School of Public Health, PRIM&R Board Member

Professor Susan Reverby’s important discovery and disclosure of experiments in which American public health doctors intentionally infected Guatemalan prisoners with syphilis has been received with shock. Some commentators have described this as worse than the Tuskegee syphilis experiments in which black men afflicted with syphilis had effective treatment withheld from them by US Public Health physicians. But grading atrocities is not a worthwhile exercise. Rather such revelations should remind us of the need for vigilance over these activities. Sadly, Professor Reverby’s discovery is not unique but rather one more addition to the growing collection of examples of the misuse of human subjects.

In the early 1900s Captain Richard Strong infected 900 condemned Filipino prisoners with plague to determine if he could invent an effective plague vaccine. During World War II and later, prisoners in American correctional facilities were infected with malaria, typhoid, dysentery, malaria and a number of other dangerous diseases. Indeed, the Maryland House of Corrections had something called the "Infectious Disease Area" where these studies were conducted in a thirty-three bed ward. As in the Guatemala case, these healthy subjects were intentionally infected with a serious disease to enable researchers to test hoped-for treatments. During the Nuremberg trials, which resulted in the execution of several Nazi doctors for their heinous use of Jewish prisoners for their experiments, Dr. Andrew Ivy, an expert witness for the prosecution, was cross-examined about the malaria and plague research conducted in US prisons. The Nazi’s defense lawyers claimed their clients’ research was similar to that in US prisons. Ivy argued that the American researchers didn't actually harm their subjects and obtained their consent. When asked why Strong only used condemned prisoners for his plague research Ivy responded "I do not know."

Only a little more than a decade following the hangings of the Nazi doctors, Dr. Chester Southam injected live cancer cells into incompetent residents at the New York Jewish Chronic Disease Hospital for research purposes. During a state disciplinary hearing Southam argued that the injections were risk free. He was asked if had injected himself with this risk free substance. He replied he had not. In 1965 Southam was placed on licensure probation for a year and allowed to continue to practice. In 1968 his colleagues elected him president of the American Association for Cancer Researchers.

We should not think of misuse of human subjects as an historical oddity. It is only this year that the US Environmental Protection Agency decided to ban experiments in which investigators knowingly expose human subjects to toxic chemicals to determine just how toxic they are. Until this year researchers could, and did, such experiments.

In 2003 both the FDA and a number of institutional review boards across the country permitted researchers to withhold available blood from unconscious patients suffering from hemorrhagic shock who had been taken to emergency rooms. Emergency room doctors were permitted to administer an unproven blood substitute to determine if that substance was as good as human blood, the proven, effective treatment for this deadly condition. Neither the subject nor family member consented to this research which presented a deadly risk. The research showed that the blood substitute was inferior to blood and resulted in an excess number of deaths. The research imperative once again dominated our notion of ethics and human rights.

Putting the Guatemalan research revelations in historical context in no way excuses the atrocious behavior of those researchers. Rather, it once again demonstrates our ability to misuse human beings in our efforts to make scientific advances. It is all too easy for scientists, their institutions, and their sponsors to believe that their unethical means justify their desirable ends.

Professor Reverby’s important historical work should remind us that those who do not know history are doomed to repeat it. But knowing it obviously does not mean we won’t.