The Honorable Sylvia M. Burwell
Secretary of Health and Human Services
200 Independence Avenue, S.W.
Washington, D.C. 20201
Dear Ms. Burwell:
On behalf of the Secretary’s Advisory Committee on Human Research Protections (SACHRP), I respectfully submit for your consideration comments relevant to the Department of Health and Human Services (HHS) human subjects protection regulations at 45 CFR part 46. These comments were passed by SACHRP at their October 2014 meeting.
Recommendations from the Subcommittee on Harmonization
On October 28, 2009, SACHRP approved a recommendation establishing a Subcommittee on Harmonization (SOH). SACHRP’s charge to this subcommittee was to identify and prioritize areas in which regulations and/or guidelines for human subjects research adopted by various agencies or offices within HHS would benefit from harmonization, consistency, clarity, simplification and/or coordination. The Subcommittee will develop recommendations for consideration and possible adoption by SACHRP, to harmonize and simplify these guidelines and regulations. The goal of this subcommittee effort is to reduce unnecessary burdens on research efforts, thus resulting in better allocation of research resources and promoting the safety and welfare of human subjects.
On October 29, 2014, SACHRP passed the attached commentary on the FDA Draft Guidance, “Informed Consent Information Sheet; Guidance for IRBs, Clinical Investigators, and Sponsors,” released July 15, 2014, docket number FDA-2006-D-0031. See attachment A.
“For another example of the risks involved in CRTs, consider a study of community-based study to address the recognized problem of post-partum hemorrhage in rural Indonesia. One hundred villages will be randomized to either be provided with misoprostol, an inexpensive drug to treat post-partum hemorrhage, or have no access as a matter of local standard of care. In the active arm of the study, pregnant women will be asked to consent to participate in the research, and will receive tablets of misoprostol in a small baggy with directions on use presented in pictures. After they have their children, the women in the active arm will be interviewed to see if they had postpartum bleeding and used the misoprostol. In the control arm of the study, pregnant women will be identified by professional surveyors, but there is no intervention in their care and they will not be asked to provide consent. After they have their children, the women’s level of postpartum bleeding will be determined by professional surveyors. In the active arm, the women face the risks of misoprostol, particularly if they take it while still pregnant prior to the birth of the infant. In the control arm, the women face the risks of untreated postpartum bleeding as they would have if the research did not exist. This illustrates that there can be above minimal risk in CRTs.”
After SACHRP discussion on October 30, 2014, the latter part of the paragraph was revised to read as follows:
"The arm of this study involves greater than minimal risk. In the control arm, the women face the risks of untreated postpartum bleeding as they would have if the research did not exist. However, this risk is no different from the risk they would have experienced were they not subjects in the study. Applying the “but for” test indicates that research risk to subjects in the control arm is not greater than minimal."
On behalf of SACHRP, I would like to thank you for your consideration of this report. The committee, the Subpart A Subcommittee and the Subcommittee on Harmonization have been actively working in pursuit of their charges, and we look forward to continuing this work to enhance human subjects protections for the benefit of all Americans.
Jeffrey R. Botkin, M.D.
Chair, Secretary’s Advisory Committee
on Human Research Protections (SACHRP)
cc: Jerry Menikoff, M.D., J.D., Executive Secretary, SACHRP
Julia Gorey, J.D., Executive Director, SACHRP
University of Utah
Salt Lake City, Utah
James Anderson, Ph.D.
University of Nebraska
Albert J. Allen, M.D., PhD.
Eli Lilly & Co.
Gary Chadwick, PharmD., MPH,University of Rochester
Rochester, New York
Diana T. Chingos, M.S., M.F.A.
Noreen Fraser Foundation
Thomas Eissenberg, Ph.D.
Virginia Commonwealth University
Holly Fernandez-Lynch, J.D., M.Bioetichs
Petrie-Flom Center for Health Law Policy, Biotechnology and Bioethics
Harvard Law School
Owen Garrick, M.D., M.B.A.
Bridge Clinical Research
Pilar Ossorio, J.D.
University of Wisconsin Law School
Reed E. Pyeritz, M.D., Ph.D.
William Smilow Professor of Medicine and Professor of Genetics
Leonard Davis Institute of Health
Economics Perelman School of Medicine
University of Pennsylvania
Stephen Rosenfeld, M.D., M.B.A.Quorum Review IRB
Jerry Menikoff, M.D., J.D.
Julia Gorey, J.D.