THE ALLIANCE FOR HUMAN RESEARCH PROTECTION (AHRP)
142 West End Ave, Suite 28P
New York, NY 10023

September 4, 2002

Michael Carome, MD
Associate Director for Regulatory Affairs
Office for Human Research Protections
The Tower Building
1101 Wootton Parkway, Suite 200
Rockville, Maryland 20852

Re: Acute Respiratory Distress Syndrome Network (ARDSNet) Study Entitled "Prospective, Randomized, Multicenter Trial of 12 ml/kg vs. 6 ml/kg Tidal Volume Positive Pressure Ventilation and Lisofylline vs. Placebo for Treatment of Acute Lung Injury and Acute Respiratory Distress Syndrome"

Dear Dr. Carome,

Thank you for your considered response to our July 29 letter to the director of the Office of Human Research Protection.

We are astonished to learn that OHRP found that all 12 major research institutions involved in this multi-site trial had violated Federal protections (45 CFR 46.117):

(a) "in all cases OHRP found that the informed consent documents approved by the institutional review boards (IRBs) for the research failed to describe adequately the reasonably foreseeable risks and discomforts of the research."

(b) "for nearly all subjects, informed consent was obtained from another individual on behalf of the subject."

Title 45 of the Code of Federal Regulations Part 46, section 101 states that compliance with these Federal regulations permit either Federal or State laws or regulations to "provide additional protections for human subjects" but not fewer:

(e) "Compliance with this policy requires compliance with pertinent Federal laws or regulations which provide additional protections for human subjects."

(f) "This policy does not affect any State or local laws or regulations which may otherwise be applicable and which provide additional protections for human subjects."

Since OHRP is responsible for enforcing Federal laws/ regulations that protect the rights and welfare of human subjects, we are frankly puzzled by the following statement– inasmuch as it contradicts Federal regulatory protection requirements:

"When an institution interprets its applicable State law as authorizing an individual to consent on behalf of a prospective subject to the subject’s participation in the procedure(s) involved in the research and has a reasonable basis for this interpretation, OHRP accepts this interpretation as meeting the requirements of HHS regulations at 45 CFR 46.102(c)." (underline added)

45 CFR 46.102(c) defines "Legally authorized representative" as "an individual or judicial or other body authorized under applicable law to consent on behalf of a prospective subject·" Thus, surrogates who provided consent for the human subjects in the ARDS experiment were not "legally authorized" unless a "judicial or other body authorized" them to give surrogate consent for research.

The "interpretation" offered by the University of California, San Francisco (UCSF) – and possibly by the other 11 research institutions referenced in your letter – would allow local institutions to circumvent the requirement for judicial review and legal authorization for surrogate consent to human research. OHRP is not legally authorized to encourage circumvention of judicial review, nor is the agency on firm moral ground if it accepts every local institution’s self-serving "interpretation" as correct when the effect is to reduce rather than provide additional protections for human subjects to those afforded under 45 CFR 46.

Under California law research conducted at an institution with a General Assurance from DHHS must comply with federal regulations. Indeed, University counsel at the University of California, Los Angeles (UCLA) recognized the fallacy of UCSF’s unsupportable "interpretation" – which did not comply with either Federal regulations or California law. A moratorium was announced by UCLA’s Vice-Chancellor on all research conducted with proxy consent stating:

“University Counsel informed our IRB that surrogate or proxy informed consent for human subjects research is inconsistent with California law." http://www.oprs.ucla.edu/human/NewsLetters/041602.htm

UCSF is part of the same University of California system as UCLA.

Given that research institutions have a vested interest in the "interpretations" they formulate, OHRP’s acceptance of such self-serving "interpretations" may well be tantamount to accepting the "interpretation" of an entity with a fairly obvious conflict of interest and stake in obtaining the permission to proceed entailed in its artfully contrived "interpretation" of state law.

The fact is that 12 major research institutions conducted an experiment on most of 861 incapacitated patients without legally valid informed consent. Instead of addressing that major systemic breakdown, OHRP is engaging in superficial analysis and accommodation of any local institution’s interpretation – rather than enforcing Federal protections for human subjects. If OHRP is not there to monitor and enforce Federal research protections, then who is?

Sincerely,

Vera Hassner Sharav
President
The Alliance for Human Research Protection

John H. Noble, Jr. Ph.D.
Board of Directors member
The Alliance for Human Research Protection

Cc: Tommy Thompson
Eve Slater, MD
Michael Mangano OIG