Category Archives: REND

Research Ethics News Digest

On and Off and On Again: Human Embryonic Stem Cell Research

The ethical and legal issues of human embryonic stem cell (hESC) research seldom fail to stir public debate. Recent events, however, have (in addition to producing a deluge of news items on the topic) resulted in weekly changes in the prognosis for the future of federally funded hESC research. Here is a summary, by date, of what has transpired in response to the case of Dr. James L. Sherley, et al., Plaintiffs, v. Kathleen Sebelius, et al., Defendants. Civ. No. 1:09-cv-1575 (RCL).

August 23, 2010: Judge Royce Lamberth, of the Federal District Court of the District of Columbia, granted an injunction preventing the NIH from using federal funds for hESC research. The plantiffs in the case (James L. Sherley and Theresa Deisher) argue that funds from the NIH are supporting research with does not conform with the Dickey-Wicker Amendment. Although interpretations vary, the Amendment prohibits the NIH from creating or harming human embryos for research purposes. The injunction sought to stop hESC research until the case of Sherley v. Sebelius is resolved in the courts. (See: Sherley v. Sebelius, Dist. Court, Dist. of Columbia 2010.)

August 31, 2010: The U.S. Department of Justice (DOJ) filed a motion to stop the injunction on the behalf of the NIH, the Defendants’ Emergency Motion to Stay Preliminary Injunction Pending Appeal and for Expedited Briefing and Consideration. In the Motion to Stay the defendants (NIH) disagree with Judge Lamberth’s interpretation of the Dickey-Wicker Amendment. The NIH insists that the Amendment does not prohibit research involving pre-existing hESCs. The NIH also argues that research using hESCs can be distinguished from research to create new hESC lines.

Francis Collins, in a declaration attached to the Motion, also pointed to the public costs of the ruling. According to Collins, the injunction would “result in [the] immeasurable loss of valuable and one-of-a-kind research resources”. Part of this “immeasurable loss” includes the waste of “over $546 million dollars of public funds” already spent on hESC related research. (See Motion to Stay, available from: http://www.nih.gov/about/director/stemcell/stay_08312010.pdf.)

September 8, 2010: Judge Lamberth rejected the DOJ’s request to temporarily lift the injunction. In his response to the Motion to Stay, the Judge wrote: “a stay would flout the will of Congress, as this Court understands what Congress has enacted in the Dickey-Wicker Amendment … Congress has mandated that the public interest is served by preventing taxpayer funding of research that entails the destruction of human embryos.” The DOJ continued its appeal in the Court of Appeals for the District of Columbia. (See: Rob Stein. Judge declines to lift stem cell funding ban. The Washington Post. September 8, 2010.)

September 9, 2010: The U.S. Court of Appeals for the District of Columbia granted the Motion to Stay. The temporary order allows federally funded research using hESCs to continue while the court hears the appeal to Lamberth’s decision. The Court requested additional information from the parties by September 20, 2010. Afterwards, the Court will determine whether the order to stay the injunction will remain in place for the duration of the case before the District Court. (See: Gardiner Harris. Stem cell financing ban ends, for now. The New York Times. September 9, 2010.)

September 9, 2010: Plaintiffs filed a Motion for Summary Judgment in the District Court. (See Motion for Summary Judgment, available from: http://docs.justia.com/cases/federal/district-courts/district-of-columbia/dcdce/1:2009cv01575/138107/55/.)

September 10, 2010: In addition to generating media coverage and frustrating researchers, the legal dispute has spurred other public developments. While the temporary stay is in place, the NIH is “rushing” to fund hESC research. According to Science Insider, the NIH hopes to expedite funding for 24 ongoing grants (due for renewal in September and October). The funding, however, comes with a caution to exercise “prudence in resuming experiments.” (See: Gretchen Vogel and Jocelyn Kaiser. NIH rushes to hand out stem cell grants during temporary stay. ScienceInsider. September 10, 2010.)

September 13, 2010: Reacting with similar urgency, legislators have renewed the push to legalize hESC research. In the Senate, Arlen Specter introduced S. 3766: A bill to amend the Public Health Service Act to provide for human stem cell research, including human embryonic stem cell research, and for other purposes. Meanwhile, Diana DeGette has introduced H.R. 4808: Stem Cell Research Advancement Act of 2009—the House version of Thomas Harkin’s S. 487.Versions of similar bills were passed by Congress, but vetoed by President Bush in 2005 and 2007. (See: Karen Kaplan. Congress registers its support for human embryonic stem-cell research. Los Angeles Times. September 13, 2010.)

September 16, 2010: Senator Thomas Harkin will hold a hearing on “The Promise of Human Embryonic Stem Cell Research” before The U.S. Senate Committee on Appropriations. The hearing will be available as a webcast at http://appropriations.senate.gov/ Speakers include: Francis S. Collins, NIH; George Q. Daley, Children’s Hospital Boston; Sean J. Morrison, University of Michigan; Jean Peduzzi-Nelson, Wayne State University; and Cody Unser, Cody Unser First Step Foundation. (See: U.S. Senate Committee on Appropriations. Committee Schedule for the Week of Sept. 13th. Press Release. September 13, 2010.)

Related Links:
NIH Stem Cell Information
Stem Cells: The New York Times
Insoo Hyun. Stem Cells. In From Birth to Death and Bench to Clinic: The Hastings Center Bioethics Briefing Book for Journalists, Policymakers, and Campaigns, ed. Mary Crowley (Garrison, NY: The Hastings Center, 2008), 159-162.
Andrew Siegel. Ethics of Stem Cell Research. The Stanford Encyclopedia of Philosophy (Fall 2008 Edition), Edward N. Zalta (ed.)

Other Research Ethics News

Editorial: Bank of infant blood spots is valuable resource for medical research. The Detroit News. September 5, 2010.

Timothy Caulfield. [Commentary] The cure for MS includes healthy skepticism and a dose of hope. The Globe and Mail. September 2, 2010.

Dan Frosch. Will Aging Chimps Get to Retire, or Face Medical Research? The New York Times. September 1, 2010.

CIHR Press Release. CIHR makes recommendations on Canadian MS research priorities. CIHR. August 31, 2010.

Henry I. Miller. [Commentary] Anti-drug fear factor trumps facts. The Washington Times. August 24, 2010.

Kaiser Family Foundation. Study Examines Movement Of Pediatric Drug Testing Outside The U.S. Kaiser Daily Global Health Policy Report. August 24, 2010.

Gina Kolata. What to tell the patients after a trial goes awry. The New York Times. August 23, 2010.

Scott McLemee. The mild torture economy. Inside Higher Ed. August 18, 2010.

Eugenie Samuel Reich. High price to pay for misconduct investigations. Nature News. August 17, 2010.

International Clinical Trials and the Challenges of FDA Oversight

The Department of Health and Human Services Office of Inspector General (OIG) recently released a report [PDF 1.8 MB] raising doubts about the FDA’s capacity to monitor the safety of clinical trials conducted in foreign countries. According to the report, the FDA needs to:

1. Improve electronic reporting: many international trials reported safety and human subjects data in database-unfriendly formats;
2. Increase the monitoring of foreign clinical trials: the FDA is 16 times less likely to inspect foreign research sites than domestic sites;
3. Look for new ways to expand FDA oversight of foreign clinical trials, including: building new agreements with national regulatory agencies and creating new oversight programs.

While the FDA agreed with all three OIG recommendations, the agency may not have the money and staff to do the job. Inspecting research sites in other countries is logistically difficult and expensive. (According to one FDA source, inspections cost “about $40,000 each”.) With a growing number of multisite trials (with subjects enrolled in different cities, countries and regions), the cost of ensuring the safety of international medical research is indeed a high one. On the other hand, the benefits of conducting trials at non-U.S. sites are enticing. In addition to easier recruitment, diverse populations, and lower financial overhead, the Association of Clinical Research Organizations (ACRO) press release insists: “globalized trials can reduce development time by more than half”. With these and other incentives, the percent of international clinical trials has doubled in the last decade. As would be expected, while the number of FDA regulated investigators in non-U.S. countries has increased by 15% each year since 2002, the number of non-U.S. subjects enrolled in international clinical trials has also grown. In the year 2008, 78% of all human subjects participating in FDA regulated clinical trials were enrolled in foreign sites.

The impact of the OIG’s report may lead to new or increased scrutiny of how these clinical trials are conducted and regulated. While some of this increased scrutiny may come from the FDA, other government agencies, including the Department of Justice (DOJ) may get involved. An advisory [PDF 532 KB] written by Kirk Ogrosky (the former Deputy Chief for Health Care Fraud in the DOJ) and attorneys at the firm of Arnold & Porter, encourages researchers to: prepare for heightened FDA inspections; strengthen internal oversight of CROs; and ensure that research-related payments “pass muster” under anticorruption laws, including the FCPA. According to Arnold & Porter, the DOJ will be interested in payments that “may have been used as an incentive to inappropriately increase subject enrollment” and will examine “differences in payments among investigators in varying locations, and between sites overseen by … local CROs”.

For its part, ACRO stands behind a July 2009 report it commissioned on the ethics and safety of international clinical trials. In addition to restating its findings, ACRO responds to the OIG report by calling for: fully funded FDA oversight, improved research infrastructure, and universal protection of human subjects, including by the standards of the International Conference on Harmonisation’s Guideline for Good Clinical Practice [E6(R1) – PDF 380 KB].

In an editorial published in The Washington Examiner, two ethicists expressed similar confidence in the safety of international research, but worried that the public might miss the fact that a disproportionately large portion of clinical research is currently conducted in the U.S. In their assessment, to effectively and fairly address global health disparities, the number of international clinical trials should (by necessity) increase in the coming years.

In the absence, however, a simultaneous and proportional increase in FDA and other oversight, the risk that foreign clinical trials may be conducted in an unsafe or unscrupulous manner will remain unknown. At the very least (rightly or wrongly), without transparent oversight, public perception may increasingly reflect the sentiments of Adil E. Shamoo in The New York Times. Shamoo, on thinking about the “potential problems” of accountability in international research and the allure for CROs, noted: “There is less liability, patient recruitment is far easier, the concept of informed consent is not well established, and it’s cheaper.”

References:

ACRO responds to HHS report on FDA inspection of foreign clinical trials. Association of Clinical Research Organizations. 2010 Jun 22. Available from: http://www.acrohealth.org/acro-responds-to-hhs-report-on-fda-inspection-of-foreign-clinical-trials.html

Clark, Todd D. The case for globalization: ethical and business considerations in clinical research. Value of Insight Consulting [Commissioned by Association of Clinical Research Organizations]. 2009 July 21. Available from: http://www.acrohealth.org/globalization-white-paper.html

Harris, Gardener. Concern over foreign trials for drugs sold in U.S. The New York Times. 2010 Jun 21. Available from: http://www.nytimes.com/2010/06/22/health/research/22trial.html

ICH. Guideline for good clinical practice. International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). 1996 Jun 10. E6(R1). Available from: http://www.ich.org/LOB/media/MEDIA482.pdf

Malani, Anup and Tomas J. Philipson. Push for more trials may hurt patients. The Washington Examiner. 2010 Jul 21. Available from: http://www.washingtonexaminer.com/opinion/columns/Push-for-more-clinical-trials-may-hurt-patients-1002114-98875969.html

Office of the Inspector General, HHS. Challenges to FDA’s ability to monitor and inspect foreign clinical trials. Department of Health and Human Services (US); 2010 Jun. 50 p. Report No.: OEI-01-08-00510. Available from: http://oig.hhs.gov/oei/reports/oei-01-08-00510.pdf

Ogrosky, Kirk and Arnold & Porter. Heightened scrutiny of foreign clinical trials. Arnold & Porter, LLP. 2010 Jul 12. Available from: http://www.arnoldporter.com/resources/documents/Advisory-Heightened_Scrutiny_of_Foreign_Clinical_Trials_071210.pdf

Other Research Ethics News

Jonathan D. Moreno. One Small Step for Embryonic Stem Cells: FDA approves first clinical trial for stem cell treatment. Science Progress. August 4, 2010.

Janet Moore. U is closer to a campuswide policy on business conflicts of interest. Star Tribune [Minneapolis-St. Paul, Minnesota]. August 4, 2010.

Elizabeth Cooney. Industry-funded drug trials more likely to report positive results, study finds. White Coat Notes. [The Boston Globe]. August 2, 2010.

Yojana Sharma. Conference agrees global science ethics code. SciDevNet. July 28, 2010.

Columbia Professor accused of research misconduct/fraud. GhanaWeb. July 21, 2010.

Benedict Carey. Studies halted at brain lab over impure injections. The New York Times. July 16, 2010.

Kathy D. Miller. Is mandatory biopsy in clinical trials justifiable? Medscape Today. July 13, 2010.

Gardiner Harris. Diabetes drug maker hid test data, files indicate. The New York Times. July 12, 2010.

David Glenn. Inside the Risky World of Drug-Trial ‘Guinea Pigs’. The Chronicle of Higher Education. July 11, 2010.

Meredith Wadman. Institute of Medicine weighs in on the ethics of post-market drug trials (Subtext: Avandia). The Great Beyond. July 9, 2010.

Measuring Coercion: Research Ethics in the Academic Literature

When do incentives to participate in research become coercive? The answer to this question may seem to be entirely subjective; that is, each individual faces a unique list of motivators and pressures when confronted with the informed consent process. We are all vulnerable to coercion in different ways and to differing degrees. However, a standardized scale might be useful in measuring the extent to which human subjects feel coerced. With such a scale, a researcher might know when “yes” actually means “no.”

In their recent paper, Measuring coercion to participate in research within a doubly vulnerable population … , Karen Leggett Dugosh, David S. Festinger, Jason R. Croft and Douglas B. Marlowe report the creation and testing of this tool. According to the authors, the Coercion Assessment Scale (CAS) is only the second coercion scale developed for use with human subjects. (A longer list of coercion scales have been developed for use in non-research settings.) The authors developed and tested the instrument to survey the feelings of coercion among “criminally involved substance abusers.” The 84 human subjects were facing or serving sentences in a misdemeanor drug court in Wilmington, Delaware. They were, therefore, “doubly vulnerable”–substance abusers and criminally “involved.” In other words, the subjects were in medical, financial, and legal circumstances that made them into easy targets for coercive pressures to consent to research.

Perhaps one should not be surprised, therefore, that the CAS revealed that many of the 84 subjects felt inappropriately coerced. In addition to the 12 people reporting feeling that they “could not say no to entering the study,” 33% “entered the study mainly for financial reasons,” 51% thought “the judge would like it,” and 51% believed “the study would help” their court case. Running parallel to the evaluation of the CAS, the authors were also studying the impact of research intermediaries in their efforts to improve the consent process and decrease coercive motivators. Lamentably, the effort failed to demonstrate statistically significant improvements in the subjects’ feelings of coercion.

The authors have laid the ground work for a very useful tool. They have also opened the door for ethicists to take a careful look at how prisoners (and other “criminally involved” subjects) are protected from research related harms. Although fraught with ethical complications, medical research within this very vulnerable population is essential to improving health outcomes and social rehabilitation. Although a “coercion assessment scale” will not resolve all the ethical complications of conducting research with prisoners (and others in-and-out of the criminal justice system), it could become a very useful indicator, a tool for uncovering coercion that might otherwise go unreported.

Reference

Dugosh KL, Festinger DS, Croft JR, Marlowe DB. Measuring coercion to participate in research within a doubly vulnerable population: initial development of the coercion assessment scale. J Empir Res Hum Res Ethics. 2010 Mar;5(1):93-102. PubMed PMID: 20235867.

Relalted Literature and Links

Advisory Commission on Human Radiation Experiments. Chapter 9 — Prisoners: A Captive Research Population. DOE Openness: Human Radiation Experiments.

Bioethics | Prisoners as Human Subjects. The University of Texas Health Science Center at Tyler.

Festinger DS, Marlowe DB, Dugosh KL, et al. Higher magnitude cash payments improve research follow-up rates without increasing drug use or perceived coercion. Drug Alcohol Depend. 2008 Jul 1;96(1-2):128-35. Epub 2008 Apr 18. PubMed PMID: 18395365

Gostin, Lawrence O., Cori Vanchieri, and Andrew MacPherson Pope; IOM Committee on Ethical Considerations for Revisions to DHHS Regulations for Protection of Prisoners Involved in Research. Ethical Considerations for Research Involving Prisoners. Washington, D.C.: National Academies Press, 2007.

Lerner BH. Subjects or objects? Prisoners and human experimentation. N Engl J Med. 2007 May 3;356(18):1806-7. PubMed PMID: 17476006.

Moser DJ, Arndt S, Kanz JE, et al. Coercion and informed consent in research involving prisoners. Compr Psychiatry. 2004 Jan-Feb;45(1):1-9. PubMed PMID: 14671730.

National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, U.S. Reports and recommendations: research involving prisoners. 1976. Available from: https://scholarworks.iupui.edu/handle/1805/565

Office of Extramural Research, NIH. Research Involving Vulnerable Populations.

Office for Human Research Protections, HHS. OHRP Guidance on the Involvement of Prisoners in Research.

Stone, T.H. Prisoners as human subjects: clinical research reference guide. 2004. [PDF – 844 KB]

Wyman BP. Biomedical and behavioral research on juvenile inmates: uninformed choices and coerced participation. J Law Health. 2000-2001;15(1):77-104. PubMed PMID: 11930505.

Other Recent Research Ethics Articles: PubMed – April 2010 | PubMed – May 2010

— J.O.

A Minimal Genome, A Giant Step? Research Ethics in the News

In late May the J. Craig Venter Institute (JCVI) announced the creation of the “First Self-Replicating, Synthetic Bacterial Cell.” (The research team’s report was published simultaneously: Gibson DG, …, Venter JC. Creation of a Bacterial Cell Controlled by a Chemically Synthesized Genome. Science. 2010 May 20. PubMed PMID: 20488990.) With $40 million and over a decade of work, the team produced the synthetic cell by piecing together a replica of a bacterial genome (Mycoplasma mycoides) and transplanting this DNA “software” into a cell from a related bacteria (Mycoplasma capricolum). When the cell began to replicate the information from its “synthetic genome,” the JCVI declared success.

What will be the scientific and social impact of this research? Both researchers and ethicists appear to be of two minds: the synthetic cell is big news, but maybe not worth the “hype” everyone is more than willing to supply. For example, while announcing JCVI’s discovery with great fanfare (suggesting solutions for the flu vaccine, greenhouse gas, and even the BP oil spill), Venter insists in The Wall Street Journal that this is not the creation of life ex nihilo. In fact, he refers us to Arthur Kornberg’s work in 1967 to make a copy of a virus. Perhaps the history lesson is meant to reassure the public; although considered by President Johnson to be “a very spectacular breakthrough,” Kornberg’s work was completed over forty years ago and, while the effort did have a scientific impact, we’re not overrun with zombies … yet.

Ethicists responded similarly: part “hype”, part reassurance. Arthur Caplan (in January 2009) reminded us that ethicists have been thinking and writing about the risks and benefits of synthetic biology for a long time. In fact, Caplan was one of the authors on paper published in 1999: Cho MK, Magnus D, Caplan AL, McGee D. Policy forum: genetics. Ethical considerations in synthesizing a minimal genome. Science. 1999 Dec 10;286(5447):2087, 2089-90. PubMed PMID: 10617419. Caplan echoes these reassuring sentiments in his recent Breaking Bioethics commentary: “The regulatory, social and legal challenges can be solved.” He, nevertheless, insists that grander issues might now be at stake:  “The real fallout from the Venter group’s achievement is subtle but more powerful. The scientists are chipping away at the view that there is something unique and unknowable about life itself. From this day forward, we know that the right chemical messages, presented in the right order and put in the right chemical context, can produce life.”

Julian Savulescu, quoted at BBC News, also looked at both sides of the coin. According to Savulescu the risks and benefits of synthetic biology are “in the far future,” but also “unparalleled”: “If this research goes in one direction Dr Venter may get the Nobel prize, but if it goes in another direction there will be no Nobel prizes to give because there will be no people to give them.”

On the very day of Venter’s press release, President Obama sent a letter to Amy Gutmann, the director of the recently formed Presidential Commission for the Study of Bioethical Issues. The Commission now has six months to complete “a study of the implications of this scientific milestone.” Reporting to the Science and Technology Advisor, Dr. John P. Holdren, the Commission will also develop recommendations for how the Federal government should anticipate and respond to similar scientific developments. Erik Parens, writing for the Hastings Center’s Bioethics Forum wonders if the new commission’s focus on “practical” questions will limit its ability to address the larger philosophical implications of synthetic biology. Although not responding directly to Parens, Jonathan Moreno takes a quick look at one of these big philosophical questions at Science Progress. Not unlike Venter’s reference to Kornberg, Moreno remembers early investigations of the idea that scientists are overstepping natural boundaries and “playing God.” By producing “an organic substance from non-organic matter,” chemist Friedrich Wohler crossed a “natural” boundary in 1828. This was a big deal for chemistry and for the philosophy of science. While Moreno, it seems, believes the ethical issues and philosophical questions are not insurmountable, he graciously opens the debate to a variety of voices: “Whatever challenge it may pose to our contemporary assumptions, it would be foolish to reject wisdom from any source in helping us decide where the path should lead, divine ones included.”

Readers looking for a thorough introduction to ethical issues of synthetic biology may wish to begin with:

Michele S. Garfinkel, Drew Endy, Gerald L. Epstein, and Robert M. Friedman, “Synthetic Biology,” in From Birth to Death and Bench to Clinic: The Hastings Center Bioethics Briefing Book for Journalists, Policymakers, and Campaigns, ed. Mary Crowley (Garrison, NY: The Hastings Center, 2008), 163-168.

The Synthetic Biology Project, established at the Woodrow Wilson International Center for Scholars and partnering with both The Hastings Center and the JCVI, also provides many resources on the subject, including:

Erik Parens, Josephine Johnston, and Jacob Moses. Ethical issues in synthetic biology: an overview of the debates. Synbio 3; 2009 June. [PDF – 585 KB]

For an international perspective, visit SYNBIOSAFE, a project funded by a grant from the European Commission. Browse four years of related links and publications on the site, or begin with this review, commissioned by the Biotechnology and Biological Sciences Research Council:

Andrew Balmer and Paul Martin. Synthetic biology: social and ethical challenges. May 2008. [PDF – 493 KB]

Related News Links

Sharon Schmickle. Genetic research: What are the risks of terrorism or accidents? MinnPost. June 1, 2010.
Natalie Angier. Peering over the fortress that is the mighty cell. The New York Times. May 31, 2010.
Scientist: ‘We didn’t create life from scratch’. CNN Health. May 21, 2010.
Life after the synthetic cell. Nature. 2010 May 27;465(7297):422-4. [PDF – 220 KB]
Michele Norris and David Rejeski. The ethics of creating synthetic life. All Things Considered. NPR. May 20, 2010.
Jonathan D. Moreno. Synthetic Biology Grows Up. Science Progress. May 20, 2010.

Other Research Ethics News

John Fauber. Doctors’ role in drug studies criticized. Journal Sentinel. May 30, 2010.
Harold Varmus. Ten years on–the human genome and medicine. N Engl J Med. 2010 May 27;362(21):2028-9.
Sarah Boseley. Andrew Wakefield case highlights the importance of ethics in science. Guardian. May 24, 2010.
Marie Woolf. NHS uses babies’ blood for secret database. The Times. May 23, 2010.
NIH. Financial Conflict of Interest Notice of Proposed Rule Making. NIH News. May 20, 2010.
Aaron S. Kesselheim, David M. Studdert, Michelle M. Mello. Whistle-blowers’ experiences in fraud litigation against pharmaceutical companies. N Engl J Med. 2010 May 13;362(19):1832-9.
U.S. group urges FDA to halt Glaxo’s Avandia trial. Reuters. May 11, 2010.
Eric M. Meslin. Problem solvers: what to expect from our new bioethics commission. Science Progress. May 7, 2010.
Sean Philpott and Udo Schuklenk. A study that should not have been done. Bioethics Forum. May 5, 2010.
Marcia Angell. Big pharma, bad medicine. Boston Review. May/June 2010.

– J.O.

Broad Consent Comes Up Short in Arizona: Research Ethics in the News

Members of the Havasupai tribe, a small tribe from the Grand Canyon, were angered to discover that their blood samples were being used for research studies beyond the original scope or perceived intent of the project. In other words, the tribe thought it had consented to diabetes research, but found that researchers were also studying schizophrenia and the tribe’s ethnic origins. Over 200 members of the tribe completed a consent form that included an indication that the blood samples could be used to “study the causes of behavioral/medical disorders.” (See: Amy Harmon. Indian wins fight to limit research of its DNA. The New York Times. April 21, 2010. ) Such a clause is certainly broad enough to include research on schizophrenia; research on genetic origins seems less appropriate.

The dust has settled a bit since the Arizona State University Board of Regents agreed to a legal settlement with the Havasupai tribe. (For an overview of the legal issues, see Katherine Drabiak-Syed’s “Havasupai Tribe and Arizona State University Settlement Agreement: ASU to Return the Blood Samples” at PredictER News.) In hindsight, ASU probably wishes it had implemented a more robust outreach and collaboration effort with the tribe. Including Havasupai representatives on a communications team or community advisory board might have helped. Perhaps the tribe would have cautioned the university against culturally sensitive research, including studies on mental illness and genetic origins. Perhaps the tribe would have agreed to research on topics in addition to diabetes.

In any case, it is probable that ongoing Havasupai participation in the governance of the genetic research on their samples would have preserved the tribe’s trust in the research process. As it turns out, research without community trust can be very expensive. After spending $1.7 million in legal fees on the case, the Board of Regents agreed to settle the dispute by paying $700,000 to the tribe for their troubles. ASU also agreed to return the blood samples and, as Harmon reports, to “provide other forms of assistance.” In the long run, the loss of trust may be the most damaging outcome of this dispute between ASU and the Havasupai tribe. Arizona is the home of 22 tribes and ASU is proud of its partnerships with American Indiana Tribes. Following the dispute with the Havasupai, other tribes may be wary of future research projects. Given that the dispute was reported widely, the loss of tribal trust in researchers may impact the progress of research in other states as well. In fact, Rob Capriccioso of Indian Country Today reported that tribal officials “nationwide” had already condemned the conduct of the principle investigator. With this in mind, Rob Rosette, a lawyer for the Havasupai tribe, comments on the future impact of the settlement:  “A precedent was set. Researchers will now know that if they do this kind of research without informed consent, they are going to get in big trouble for it, costing themselves time and money. Exploiting these people was just not worth it.”

Related:

Rex Dalton. Native American Research Lawsuit Settled. The Great Beyond [Nature blog]. April 22, 2010.
Michael Kiefer. Havasupai Tribe ends regents lawsuit with burial. The Arizona Republic. April 22, 2010.
The Havasupai Case: Research Without Patient Consent. Who Owns Your Body? [2007]

Other Research Ethics News

Derek Parker. His little piggies may save lives: Paul Tan. The Australian. May 1, 2010.

Kounteya Sinha. ‘Cervical cancer vaccine trial guidelines not followed’. The Times of India. April 29, 2010.

Rob Stein. 13 additional stem cell lines eligible for federal funding, NIH says. The Washington Post. April 28, 2010.

Nancy Walton. The Thalidomide tragedy: reminding us why research ethics oversight is here to stay. The Research Ethics Blog. April 27, 2010.

Clinical trials hindered by red tape: MDs. CBC News. April 26, 2010.

Evan Binns. St. Louis doctors get $2.5 million from Pfizer, Lilly, Glaxo, Merck. St. Louis Business Journal. April 23, 2010.

AP. Doctor Groups Set New Policy to Curb Industry Sway. The New York Times. April 21, 2010.

Katherine Hobson. Medical Groups Sign on to Tough Ethics Rules. WSJ Health Blog. April 21, 2010.

Wagdy Sawahel. New centre to document bioethics in the Arab world. SciDevNet. April 9, 2010.

Amy Davis. PRIM&R joins the University of Pittsburgh in “Building Trust Between Minorities and Researchers”. Ampersand. April 6, 2010.

— J.O.

Obama Fills The Presidential Commision for the Study of Bioethical Issues: Research Ethics in the News

The White House announced the remaining members of the The Presidential Commission for the Study of Bioethical Issues on April 7, 2010 [press release – PDF]. The new members are:

Lonnie Ali, M.B.A
Anita L. Allen, J.D., Ph.D.
Barbara F. Atkinson, M.D.
Nita A. Farahany, J.D., Ph.D.
Alexander G. Garza, M.D.
Christine Grady, R.N., Ph.D.
Stephen L. Hauser, M.D.
Raju S. Kucherlapati, Ph.D.
Nelson Lee Michael, M.D., Ph.D.
Daniel Sulmasy, M.D., Ph.D.

President Obama appointed the Commission’s Chair (Amy Gutmann, Ph.D.) and Vice Chair (James W. Wagner, Ph.D.) in November 2009 (press release). According to Executive Order 13521 [PDF], the Commission’s members serve two year terms without compensation. The new Commission “works with the goal of identifying and promoting policies and practices that ensure scientific research, health care delivery, and technological innovation are conducted in an ethically responsible manner.” Prior Presidents convened similar commissions. In 2001, President Bush created the President’s Council on Bioethics which replaced President Clinton’s National Bioethics Advisory Commission, created in 1996. A list of former commissions and their publications is provided on the Bioethics.gov website.

Related

Andrew Plemmons Pratt. Practical Science. Science Progress. April 8, 2010.
Jere Odell. Obama stops The President’s Council on Bioethics: Research Ethics in the News. Indiana Bioethics. June 24, 2009.

Other Research Ethics News

Robin Erb. In blood debate, new consent effort aims to open research doors. Detroit Free Press. April 8, 2010.

Lisbeth Fog. Tensions remain over biological access protocol. SciDevNet. April 2, 2010.

Ann E. Mills and Patti M. Tereskerz. The Uncertain Future of Gene Patents. Bioethics Forum. April 1, 2010.

Duff Wilson. Pfizer gives details on payments to doctors. The New York Times. March 31, 2010.

Donna Dickenson. Bioethics à la Française: the new French bioethics laws. BioNews. March 29, 2010.

Steve E. Nissen. Setting the RECORD Straight. JAMA. 2010;303(12):1194-1195.

Carla K. Johnson. Top US psychiatrist calls for ethics cleanup. [AP] Google News. March 23, 2010.

Gerd Antes. The new CONSORT statement. BMJ 2010;340:c1432. | doi:10.1136/bmj.c1432

Jocelyn Kaiser. Should NIH-Funded Researchers Be Required to Publicly Reveal Conflicts? ScienceInsider. March 16, 2010.

Jonathan D. Moreno. Red Tape Around Stem Cells? Science Progress. March 16, 2010.

— J.O.

Peer-Driven Recruitment: Research Ethics in the Academic Literature

In peer-driven recruitment (PDR) research subjects recruit new subjects. These subjects, in turn, may recruit additional subjects. In some cases, the process may repeat for successive waves. Often, subjects are paid or given other incentives to recruit their peers. As an approach to recruitment, PDR can be a very effective tool—some difficult to reach populations (examples might include: sex workers, immigrants, abuse victims, and others) are more likely to participate in a research study when engaged by a “peer.” However, when subjects are recruited by their peers, researchers should be aware of potential ethical problems. For example, if peers are “driven” by money to recruit new subjects from their social networks, they may be tempted to take shortcuts when acquiring consent and conducting other responsible research practices. At the same time, one’s peers (perhaps, particularly when from a tight social network) are not always the best people to entrust with confidential information. Privacy prefers anonymity.

In their recent paper, “Community members as recruiters of human subjects: ethical considerations,” Simon and Mosavel explore these issues and provide an account of a variant version of PDR (Am J Bioeth. 2010 Mar;10(3):3-11. PubMed PMID: 20229402). The authors identify four ethical concerns worth consideration prior to employing peers in subject recruitment: 1) PDR without comprehensive community engagement in the research project can devalue the role of community participation; 2) as “insiders,” peer recruiters may inadvertently bias the sample; 3) maintaining privacy and confidentiality in intimate communities; and 4) “the potential for exploitation of peer recruiters and/or their social networks, particularly in cases where peer recruiters are compensated on a per-capita basis.”

Simon and Mosavel offer what they consider to be a variant version of PDR which (although not without its challenges) is less susceptible to ethical difficulties. In a “resource-poor community” near Cape Town, South Africa, the authors conducted a study of the health knowledge and attitudes of women regarding cervical cancer. With a pre-existing, intensive community engagement program in place, the project hired “community members” to work as research staff. Seven, bilingual women were hired from the neighborhood and received training which included sessions addressing the ethical conduct of research. These new research staff members helped to troubleshoot the study design, revised and translated the informed consent forms, consented subjects, and conducted the research interviews in the subjects’ homes.
Some staff members were emotionally distressed following interviews with women living with illness or in unhealthy environments. To develop stress-related coping strategies, the team met with a trained psychologist, kept diaries, and (when appropriate) distributed a list of local support services to interviewees. Over the three year lifecycle of the research, only one staff member left. When the project was complete, some staff members received help from the PIs in finding new employment opportunities.

Although Simon and Mosavel’s account of a community engaged research project in Cape Town, South Africa is certainly a memorable and instructive narrative, and although their review of the ethical issues inherent in PDR is informative, the article struggles to bring these topics together. The research team hired in Cape Town may have been from the “community,” but they were not “peers”—as staff they were not subjects, nor were they “driven” by incentives to recruit new subjects. This variant of PDR is not “peer,” not “driven” and not really “recruitment.” Nevertheless, Simon and Mosavel’s recommendations are worth considering for future PDR projects and other forms of community-based research employment: ethical training, ongoing support, and the anticipation challenges related to researcher/subject proximity.

Reference:

Simon C, Mosavel M. Community members as recruiters of human subjects: ethical considerations. Am J Bioeth. 2010 Mar;10(3):3-11. PubMed PMID: 20229402.

Open Peer Review Commentaries on Simon and Mosavel:

Landy DC, Sharp RR. Examining the potential for exploitation by local intermediaries. Am J Bioeth. 2010 Mar;10(3):12-3. PubMed PMID: 20229405.
Phillips T. Protecting the subject: PDR and the potential for compromised consent. Am J Bioeth. 2010 Mar;10(3):14-5. PubMed PMID: 20229406.
Fry CL. Ethical implications of peer-driven recruitment: guidelines from public health research. Am J Bioeth. 2010 Mar;10(3):16-7. PubMed PMID: 20229407.
Bean S, Silva DS. Betwixt & between: peer recruiter proximity in community-based research. Am J Bioeth. 2010 Mar;10(3):18-9. PubMed PMID:20229408.
Anderson EE. The role of community-based organizations in the recruitment of human subjects: ethical considerations. Am J Bioeth. 2010 Mar;10(3):20-1. PubMed PMID: 20229409.
Constantine M. Disentangling methodologies: the ethics of traditional sampling methodologies, community-based participatory research, and respondent-driven sampling. Am J Bioeth. 2010 Mar;10(3):22-4. PubMed PMID: 20229410.
Molyneux S, Kamuya D, Marsh V. Community members employed on research projects face crucial, often under-recognized, ethical dilemmas. Am J Bioeth. 2010 Mar;10(3):24-6. PubMed PMID: 20229411.
Simon C, Mosavel M. Response to open peer commentaries on “community members as recruiters of human subjects: ethical considerations”. Am J Bioeth. 2010 Mar;10(3):W1-3. PubMed PMID: 20229401.

Related Links and Literature:

Respondent Driven Sampling [Cornell]
DeJong J, Mahfoud Z, Khoury D, et al. Ethical considerations in HIV/AIDS biobehavioral surveys that use respondent-driven sampling: illustrations from Lebanon. Am J Public Health. 2009 Sep;99(9):1562-7. PubMed PMID: 19608961.
Semaan S, Santibanez S, Garfein RS, et al. Ethical and regulatory considerations in HIV prevention studies employing respondent-driven sampling. Int J Drug Policy. 2009 Jan;20(1):14-27. PubMed PMID: 18243679.
Scott G. “They got their program, and I got mine”: a cautionary tale concerning the ethical implications of using respondent-driven sampling to study injection drug users. Int J Drug Policy. 2008 Feb;19(1):42-51. PubMed PMID: 18226516.
Tiffany JS. Respondent-driven sampling in participatory research contexts: participant-driven recruitment. J Urban Health. 2006 Nov;83(6 Suppl):i113-24. PubMed PMID: 16933100.
Brace-Govan J. Issues in snowball sampling: the lawyer, the model and ethics. Qualitative Research Journal. 2004;4(1):52-60. informit.com.au

Other Recent Research Ethics Articles

– J.O.