What does health care reform mean for clinical research?

by Emily Butler, content coordinator

As the dust begins to settle after President Obama signed into law the Patient Protection and Affordable Care Act and the Health Care and Education Reconciliation Act this week, the national news media are scrambling to answer the question that bill advocates and opponents alike are asking: What does health care reform mean to me?

While media attention is primarily focused on changes to the ways in which individuals will access and pay for health insurance, the bill carries several provisions that will affect the health care system as a whole, including clinical research. Even though many of these provisions will not take effect for several years, and even though many of the implementation strategies have not been fully defined, the research community is beginning to grapple with the laws’ potential impact.

The following provisions, pulled from the Kaiser Family Foundation’s “Health Reform Implementation Timeline,” represent a sample of the types of changes that could affect research:

2010

• Authorize the Food and Drug Administration to approve generic versions of biologic drugs and grant biologics manufacturers 12 years of exclusive use before generics can be developed.
• Support comparative effectiveness research by establishing a nonprofit Patient-Centered Outcomes Research Institute.
  

2011

• Impose new annual fees on the pharmaceutical manufacturing sector.

2013

• Require disclosure of financial relationships between health entities, including physicians, hospitals, pharmacists, other providers, and manufacturers and distributors of covered drugs, devices, biologics and medical supplies.

Recent articles published in Applied Clinical Trials and Kaiser Health News call health reform a boon for the pharmaceutical industry. But how might the changes affect other sectors of clinical research?

If you work in the field, we are curious to hear your perspective. How do you think health reform will impact clinical research?

The Immortal Life of Henrietta Lacks and its Relevance to IRBs

by Erica Heath, 2009 Advancing Ethical Research Conference Faculty Member

Late—very late—one recent night I finished Rebecca Skloot’s fascinating new book, The Immortal Life of Henrietta Lacks (hereinafter “TILoHL”). Before sharing my thoughts, though, I’d first like to tell you how the book came to my attention.

I was driving home from work one day listening to Terri Gross interview Ms. Skloot on NPR’s Fresh Air. Her account of the arduous process of getting permission from the Lacks family to write the book was compelling, and I drove straight to the local bookseller, but they were already sold out. I placed an order and left feeling disappointed.

Thereafter, it seemed impossible to escape the book’s presence: At my next IRB meeting, three members talked about the Fresh Air interview, and our chair was reading the book. A few days later, she loaned me her copy, and asked that I pass it on when I finished. The chair’s copy of the book is now being read by a friend’s daughter who is working with HeLa (short for “Henrietta Lacks”) cells in one of her college classes.

When I was about halfway through TILoHL, The bookstore called to tell me that my own copy had arrived. I picked it up, and it is now making its way through our office where I’m hoping my colleagues will get the same kick I did out of recognizing people and places from the annals of IRB history.

The book weaves the story of the Lacks family with that of the development, distribution, and use of the HeLa cell line. Among the themes that are relevant to IRBs are those of informed consent, the commercialization of tissue (or other biologics), the treatment of donors, and resultant suspicion of biomedical research.

Jay Katz’s seminal book, Experimentation with Human Subjects, which Skloot cites, has been an occasional noon-time read of mine. The first part of his book contains original documents Dr. Katz collected from the Jewish Chronic Disease Hospital episode, in which an investigator injected live cancer cells into patients without consent. The Jewish Chronic Disease Hospital case was one of several revelations that spurred Congress to create the IRB system.

Whenever I read this section of the Katz book, I felt as though there was something missing in the Jewish Chronic Disease Hospital saga. When I read the account of that research in Ms. Skloot’s book, I experienced an “ah-ha” moment when I realized that the live cancer cells came from the HeLa cell line. I at last felt as though I had the rest of the story, and finally understood the investigator’s flawed rationale for his ethically objectionable study.

In the IRB world, we have ongoing arguments about when or whether researchers have any duty to determine if original consent was gained for secondary or tertiary use of tissue in research. Ethics and reality/practicality often conflict; some studies say donors desire an opportunity to give consent, while others don’t see the point of obtaining consent so long as the samples are anonymous.

What roles do IRBs play? It is easy and probably appropriate to determine if the de-identified specimens are not human research subjects and leave it there. IRBs could ask the end-user researchers if consent was given, but they often cannot know, don’t need to have IRB approval, and should not, therefore, be asked to bear the burden of consent. We can require repositories obtaining residual samples from clinical tests to assure consent was given, but outside of medical centers there may be no opportunity to do so. Or, we can require anyone transferring specimens to assure that consent was given, but few places have mechanisms to track it. Unless everyone involved in harvesting those specimens for research agrees that consent is a desirable norm, documenting consent will be elusive. The tragedy of the Lacks family’s experiences will endure until there is a clear and ethical policy.

The public is becoming increasingly informed about biomedical ethics and more and more people have heard of IRBs. I no longer automatically sigh when I am asked what I do; Skloot’s book is a bestseller. Michael Crichton’s book Next (certainly not his best, as it’s quite contrived, and as the science is questionable) was built around many of the same issues; it remains in many airport book stores. Both books have a must-read Afterwards by the authors.

Will we ever see a movement toward requiring initial consent for research use of tissue? It’s my opinion that, sooner or later, we will. What do you think?

In any case, I highly recommend both Skloots’ and Crichton’s books for all those interested in these issues. And, if you run across an old copy of Dr. Katz’s book, grab it for your IRB library!

PRIM&R’s Abstract Spotlight

In this series of Ampersand posts, PRIM&R touches base with those who presented programmatic and research-based findings at past PRIM&R conferences.

Spotlight on an abstract from the 2009 AER Conference

Title: Improving Turn-Around Time for Initial IRB Review of Minimal Risk Studies

Authors: Cerdi Beltre, CIP and Hallie Kassan, MS, CIP

Affiliation: North Shore-Long Island Jewish Medical Center, the Feinstein Institute for Medical Research

Abstract summary: This program sought to improve the turnaround time for initial IRB review of minimal risk studies. After evaluating the causes for delays, the authors identified the following improvements that could provide the highest benefit with the least amount of effort:

• Rotation of exempt studies among four (rather than one) IRB staff members for review;
• Increase use of all IRB committee members on expedited reviews;
• Develop reviewer sheet for expedited review to assist committee members;
• Develop office checklist to standardize initial review process;
• Establish process for coverage when staff is out of the office; and
• One-on-one meetings with the director to hold staff accountable and provide education.

After three months of program implementation the data was reviewed again. The average turn-around time for initial response on exempt studies decreased from 10.1 to 3.1 business days. The average turnaround time for initial response on expedited studies decreased from 14.6 business days to 7.5.

(View the full abstract here.)

PRIM&R Staff (PS): In the months since you presented this abstract at PRIM&R’s 2009 AER Conference, how has your program changed or evolved?

Hallie Kassan, MS, CIP (HK): The turnaround time in our office has improved significantly, especially for exempt studies. We are constantly working on our processes and trying to choose that which is most efficient.

To further improve efficiency, we have moved from a system in which the IRB staff reviews submissions based on submission type (such as new studies, progress reports, etc.) to a system where the IRB staff reviews submissions based on the department. Thus, each staff member is an expert in the departments to which they are assigned. This strategy should help to fulfill our turnaround time goals.

PS: What challenges have you faced in implementing this program?

HK: Workload is still a challenge. Depending on the week and month, some IRB staff are so busy that it is not possible to meet our turnaround time goals and still provide an adequate review. We are currently trying to work on ways to redistribute the work in a timely fashion.

For questions or comments about this program, please contact Hallie Kassan.

Interested in submitting an abstract to present at PRIM&R’s next animal or human research ethics conference? Please e-mail us for more information.

Live from the 2010 IACUC Conference!

by Kimberly Hensle Lowrance

Our 2010 IACUC Conference got underway on Saturday in Baltimore, Maryland. We’re thrilled to be in the land of crab cakes and to be so near to our nation’s capital. Nearly 620 attendees from eight countries and 42 states joined together and celebrated 25 years of the guiding principles for animal research, which also was our conference theme.

The gathering kicked off with two intensive pre-conference courses, IACUC 101 and Essentials for IACUC Administration. These sessions were terrific resources for those seeking the indispensable “must-know” information about animal care and use committees and also offered excellent networking opportunities. We saw attendees sharing what they’ve learned with one another, picking the brains of our expert pre-conference program faculty, and making arrangements to go out to dinner with new friends.

Speaking of expert faculty, the IACUC 101 team also did double-duty, welcoming attendees, and as seen in the picture below, distributing certificates of attendance to the participants.


Look for more posts, including a profile of the main conference’s first day, and the keynote address!

PRIM&R’s Abstract Spotlight

In this series of Ampersand posts, PRIM&R touches base with those who presented programmatic and research-based findings at past PRIM&R conferences.

Spotlight on an abstract from the 2009 AER Conference

Title: Implementation of the University of California System's IRB Memorandum of Understanding

Authors: Rebecca D. Armstrong, DVM, PhD and Lisa Voss, MPH

Affiliation: University of California, Berkeley

Abstract summary: This program sought to evaluate the success of the University of California (UC) System's IRB Memorandum of Understanding (MOU). The MOU was endorsed in 2006 with the goal of decreasing the number of UC IRBs that need to review collaborative research taking place at multiple UC sites, thereby reducing the burden on principal investigators and increasing the speed of study implementation.

The authors’ findings indicate the MOU saves principal investigators hours in IRB preparation and review. In addition, an unanticipated benefit is an increased understanding of each others’ policies, procedures and institutional climate—along with more cooperation among IRB offices.

(View the full abstract here.)

PRIM&R Staff (PS): In the months since you presented this abstract at PRIM&R’s 2009 AER Conference, how has your program changed or evolved?

Rebecca D. Armstrong, DVM, PhD (RA): Due to increased institutional concerns about liability and post-approval monitoring within our system, the UC IRB directors placed a temporary “hold” on relying on each other’s full committee reviews system-wide.

The “pilot” group of institutions (UC Berkeley, UC San Francisco, UC Davis, and Lawrence Berkeley National Lab) that began this level of reliance are continuing to rely on each other for full committee reviews. Another change pertains to the UC Office of the President (UCOP) that had been maintaining a central database and website about this MOU. The IRB directors decided that the original purpose of such a database and public website was not being met, and that the effort to keep the website updated was not worth the time involved. Therefore, the website has been taken down, although UCOP will continue to be notified of MOU projects and a standardized protocol identification system has evolved to facilitate tracking.

PS: What challenges have you faced in implementing this program?

RA: The biggest challenge has been the administrative management of this reliance process given the system-wide furloughs, layoffs, and budget cuts. This has resulted in some schools wanting to streamline our documentation even more in order to reduce the staff workload.

For questions or comments about this program, please contact Dr. Armstrong.

Interested in submitting an abstract to present at PRIM&R’s next animal or human research ethics conference? Please e-mail us for more information.

An interview with PRIM&R’s 2010 IACUC Conference keynote speaker

PRIM&R is pleased to welcome Andrea Amalfitano, PhD, DO as the keynote speaker at the 2010 IACUC Conference in Baltimore later this month. On Monday, March 22, Dr. Amalfitano will commence the conference program with a discussion titled, “Biomedical Research into Treatment of Genetic and Infectious Diseases.”

Dr. Amalfitano is the Osteopathic Heritage Foundation Endowed Professor of Pediatrics, Microbiology, and Molecular Genetics at Michigan State University (MSU). As a clinical pediatrician and geneticist, Dr. Amalfitano sees patients and families who are affected by a multitude of diseases for which there are no cures.

As a result, he has set out to pursue basic biomedical research in an effort to help these situations. For one particular project, he co-led a team using the first-in-man therapy for a muscular dystrophy known as Pompe Disease. As a result of that pioneering trial, Myozyme is now an FDA-approved drug for the treatment of all patients with Pompe Disease. In addition, Dr. Amalfitano’s research laboratory has attempted to focus its efforts upon determining the feasibility of gene therapy to cure human genetic and non-genetic diseases, and to eventually translate that knowledge into the clinical realm.

PRIM&R Staff (PS): Can you tell me a little bit about your planned remarks?

Andrea Amalfitano, PhD, DO (AA): One topic I plan to address is the relationship between my clinical activities and my basic lab research. These two aspects of my work are intertwined, in that I am constantly applying findings from one arena to the other.

PS: In addition to talking about your research, can you share a bit about the kind of advice, strategies, and direction you will be providing the audience about the ethical and policy issues related to gene therapy or other cutting-edge research?

AA: There are many fantastic lab-based studies, but quotes from scientists claiming the science is close to clinical application, such as “we are 2-5 years away from clinical use,” more often than not mean the scientists do not have a clue when the research will reach this stage.

There are so many steps to bringing the science to the patient. Gene therapy is a classic example. Early on there were wild claims about revolutionizing medicine. I was in the middle of this, and was more naïve than I am now. Unfortunately, I now see these same claims being made in regard to the "potential" of various stem cells.

There needs to be a greater understanding on the part of the laboratory scientists in regard to the complexities of translating findings made in a research laboratory into clinical reality. In my experience, there is a great disconnect. If scientists are not involved with patient care, they many times are not aware of the multiple practical problems (scientific, medical, as well as pragmatic) that are associated with bringing the research observations (and their potential applications) into clinical fruition.

PS: Since the March audience will be primarily composed of those who are working with animals, how would you characterize your experiences with Michigan State’s IACUC? Such as, have you found them to be educated about and sensitive to the highly technical and sensitive nature of your work? Have you found their responses to your protocols reasonable?

AA: I think I've been able to see all the facets of this issue. I sat on an IACUC for eight years and am very familiar with this side of the equation of doing animal research. While I see the strengths and weaknesses of IACUC oversight, the bottom line is that the necessity is there.

If we desire to move novel, cutting-edge applications into human use, we need to minimize the numerous risks involved. We always consider computer modeling, tissue cultures, and other types of alternative strategies in these sorts of studies. Only when these systems fall short are we justified in moving into animal models. Our specific type of research combines genetic technology with genetic diseases interacting with a living, extremely complex immune system.

These complexities are not matched by current computer models or tissue culture systems. Animal models are the next best option. However, we are always conscious about humane end points, and thus research animals are always treated in a safe and benevolent manner.

My experience with the IACUC is that they offer valuable education to researchers and provide alternatives that will foster both the acquisition of important research results, alongside the ethical treatment of animals. I see this as a win-win situation. It’s a necessary part of doing research. If you want to really make a difference, these are the hurdles we must overcome.

PS: As PRIM&R’s mission is to advance ethical research, and as the fields in which you are working represent the cutting edge of research, what do you consider to be the most challenging ethical issues when moving from the lab to “first-in-human” studies?

AA: I teach a course about translational medicine. If there’s a great clinical need and the risk suggests it’s reasonable, this leap can sometimes be made without fully understanding the molecular mechanisms of a putative therapy. This empiric approach has its limitations, as each clinical situation is a moving target, and every situation is unique. There are many variables at play to decide whether you are ready to make that jump.

PS: Do IRBs and regulations guide that process effectively?

AA: I think so. I have been on IRBs in the past and understand how they work. The process, while it might seem cumbersome, is absolutely necessary. It’s important to instill the public with trust. There were a couple cases in the late 1990s where I feel this public trust was breached, but IRBs and clinical researchers responded appropriately by becoming more diligent. The process has to be vigorous.

PS: Thank you for taking the time to speak with us, Dr. Amalfitano. We look forward to hearing more about your exciting work at the 2010 IACUC Conference later this month.

Meet the Henry Spira Memorial Lecturer

We are honored that Dr. Tom Beauchamp, an eminent leader in the field of research ethics, will deliver the Henry Spira Memorial Lecture at the 2010 IACUC Conference.

Widely known for his breakthrough work on The Belmont Report, which he co-authored in 1978, Dr. Beauchamp has propelled ethical issues to the forefront of the research field for more than 35 years. He has helped to set the basic guidelines and principles regarding both human and animal research subjects, and continues to make an impact in the bioethics arena.

Currently, he serves as professor of philosophy and senior research scholar at Georgetown University’s Kennedy Institute of Ethics, where he has worked since the mid-1970s.

In 2004, Dr. Beauchamp was given the Lifetime Achievement Award by the American Society of Bioethics and Humanities for his outstanding contributions and significant publications in bioethics and humanities.

One year prior, he was presented with Georgetown University’s Career Recognition Award, which is given annually to a faculty member whose career is characterized by distinguished research initiatives. Earlier, in 1994, Indiana University awarded Dr. Beauchamp its “Memorial Award for Furthering Greater Understanding and Exchange of Opinions between the Professions of Law and Medicine.”

Dr. Beauchamp is the author or co-author of more than 140 scholarly articles and several books including Principles of Biomedical Ethics, the first major American bioethics textbook, A History and Theory of Informed Consent, and The Human Use of Animals, among others.

All work and no play? Not at PRIM&R!

by Joanna Cardinal, membership manager

Our 2010 IACUC Conference promises to be jam-packed with learning sessions. Here at PRIM&R we recognize the value of educational offerings, but we also know that our attendees need time to connect with colleagues both personally and professionally. That’s why we include numerous special events and networking opportunities. From our receptions to our breakfasts and lunches, we’re sure you will enjoy all we have to offer!

If you’ve recently joined the PRIM&R membership community, or are looking to connect with your colleagues, please join me on Tuesday, March 23, from 7:00-8:15 AM for the Member Networking Continental Breakfast. Simply let me know you’re coming and I’ll be sure to save you a seat.

Do you have questions about animal well-being, compliance, or IACUC operations? If so, please sign up for Speed Networking on Monday, March 22, from 6:00-7:30 PM. I know that you’ll enjoy having your questions answered by our distinguished mentors. And after you’ve had a chance to experience mentoring at this event, I hope your interest will be piqued and you’ll become part of the year-round PRIM&R Mentoring Program as either a mentor or a mentee.

For all of the book worms out there, we also offer a book group discussion lunch. This year’s selection is Adrian Morrison’s An Odyssey with Animals: A Veterinarian's Reflections on the Animal Rights and Welfare Debate. Alice Ra'anan, director of government relations and science policy at the American Physiological Society, and Claire Edwards, science policy web specialist at the American Physiological Society, will lead the discussion.

Finally, PRIM&R conferences would not be successful without your help. If you haven’t done so already, I invite you to peruse our volunteer opportunities and make the most out of your 2010 IACUC Conference experience. We need people interested in serving as:

• Common Ground Networking Luncheon Volunteers

• Conference Greeters & Keynote/Plenary Session Ushers

• PRIM&R Exhibit Booth Attendants

• Speed Mentoring Mentors

For more information on these and other special events at the conference, please visit our website. We strive to make sure you are happy with the benefits of PRIM&R membership. If you have any questions, comments, or suggestions please stop by the Help Desk and let me know. If you won’t be attending the conference you can always call (617.423.4112, ext. 16) or e-mail me.

I’m really looking forward to seeing you later this month!

What are the moral bounds of the field of bioethics?

By Emily Butler, content coordinator

Are bioethicists moral experts that can be called upon to shape policies and political agendas? Or, would such input constitute paternalism and moral policing? According to Sally Satel, a resident scholar of the American Enterprise Institute (AEI) for Public Policy Research, the answer is clear: The field of bioethics has overstepped its moral bounds.

In The Limits of Bioethics, an AEI commentary published on February 2, Dr. Satel critiques the expansion of the field of bioethics. She says bioethicists might offer valuable expertise in guiding the formulation of a moral decision, but offering concrete opinions on matters of right and wrong—on matters of life and death—implies an unsanctioned moral authority.

Dr. Satel argues that bioethicists are innately biased by their own moral philosophy; they might be skilled in framing the facets of a dilemma, but have no greater claim in deciding what is right or wrong than the rest of us. In Dr. Satel’s words, the role of bioethicists “should be to illuminate debates, not to settle them.”

Dr. Satel also critiques the institutionalization of bioethics in the name of human subject protections. While she concedes that “nobody denies the need for research oversight,” she argues that bureaucratic policies, unnecessary consent processes, and overzealous privacy protections waste money and impede medical progress.

The commentary offers no specific recommendations for how to resolve bioethical dilemmas in human subjects research.

The role of bioethical analysis in human subjects protections is up for debate. What are your thoughts on this article and these controversial questions?