October 26

OHRP Response to AHRP re: Surrogate Consent to Research

OHRP Response to AHRP re: Surrogate Consent to Research

Office of the Secretary
Department of Health & Human Services
Office of Public Health and Science

Office for Human Research Protections
Rockville, Maryland

E-mail: mcarome@osophs.dhhs.gov

August 28, 2002

Vera Hassner Sharav
President, The Alliance for Human Research Protection

John H. Noble, Jr., Ph.D.
Board Member, The Alliance for Human Research Protection


OHRP Investigation of experimental treatment for Acute Respiratory Distress Syndrome. ARDSNet studies: ARMA, FACCT, and ALVEOLI (Fax from OHRP to ARDSNet)

AHRP Letter of complaint to Dr. Greg Koski, OHRP. Re: ethical violations in multi-center respiratory distress experiment.

Other ARDS links on Ethical Violations page

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 Ms. Sharav and Dr. Noble:

The Office for Human Research Protections (OHRP) has received your July 29, 2002 letter regarding the above-referenced multicenter clinical trial sponsored by the National Heart, Lung, and Blood Institute (NHLBI).

Please be aware that because the coordinating site for the ARDSNet clinical trials is Massachusetts General Hospital, Dr. Greg Koski is formally recused from all deliberations related to this matter. As a result, I respectfully request that you direct all future inquiries regarding this matter to my attention.

Regarding your concerns and questions related to the study design and informed consent process for the above-referenced clinical trial, OHRP provides the following responses:

(1) You expressed concern about the scientific design of the research. OHRP has already begun an evaluation of this concern. This evaluation is ongoing.

(2) You expressed concern in your letter that the University of California, San Francisco (UCSF), one of the study sites for the trial, may have failed to comply with the informed consent requirement of 45 CFR Part 46 by allowing individuals to consent on behalf of another individual to participation in the research procedures.

Department of Health and Human Services (HHS) regulations for the protection of human subjects at 45 CFR 46.116 stipulate that no investigator may involve a human being in research covered by the HHS regulations unless the investigator has obtained the legally effective informed consent of the subject or the subject’s legally authorized representative. HHS regulations at 45 CFR 46.102(c) define legally authorized representative as an individual or judicial or other body authorized under applicable law to consent on behalf of a prospective subject to the subject’s participation in the procedure(s) involved in the research. Thus, under 45 CFR 46.102(c), the determination of who may be a legally authorized representative is a matter of state or local law.

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). In reviewing this matter, OHRP found that there was a reasonable basis at that time for UCSF’s interpretation that these individuals were legally authorized representatives. OHRP acknowledges that different institutions in the same state may have different interpretations of state law, but believes this is a matter for the State to resolve.

Therefore, OHRP does not intend to pursue further an evaluation of this matter at this time. If you have ongoing concerns that UCSF is violating California State law, OHRP recommends that you contact appropriate State authorities.

(3) You asked whether OHRP evaluated the informed consent process at other sites that participated in the clinical trial.

OHRP conducted a compliance oversight evaluation of the 12 major sites participating in this clinical trial. OHRP’s determination letters documenting the outcomes of these evaluations can be viewed at the OHRP website at the following URLs:
























In reviewing the above letters, you will note that 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. You will also see that for nearly all subjects, informed consent was obtained from another individual on behalf of the subject. In reviewing this matter for most of the institutions, OHRP found that the institution presented a reasonable basis under applicable state law for the institution’s interpretation that these individuals were legally authorized representatives. For two institutions, OHRP’s investigation remains open.

(4) You asked several questions about the role of the Data and Safety Monitoring Board, criteria for stopping the trial early, and other collateral research in which the subject may have been involved in. The study protocol addresses many of these issues and can be viewed on the ARDSNet website at http://hedwig.mgh.harvard.edu/ardsnet/vent-prot.pdf.

(5) You asked whether Medicaid or Medicare charged for hospital services for this clinical trial. As this issue is not relevant to its jurisdiction, OHRP is unable to pursue an evaluation of this matter.

OHRP appreciates your concern about the protection of human research subjects. Please feel free to contact me if you have additional questions or wish to provide additional information.


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

Telephone: 301-402-5567
FAX: 301-402-2071


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