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Jerry Menikoff, M.D., J.D.
Office for Human Research Protections
Department of Health and Human Services
1101 Wootton Parkway
Suite 200
Rockville, MD  20852

RE: HHS-OPHS -2011-0005, Advance notice of proposed rulemaking, Human Subjects Research Protections

Dear Dr. Menikoff:

The National Coalition for Cancer Survivorship (NCCS), representing cancer survivors nationwide, supports the revision of the regulations governing human subjects research (the Common Rule).   NCCS commends the Department of Health and Human Services (HHS) for initiating the review of the Common Rule, as this reformulation may address inefficiencies in the review of cancer research that affect  the initiation and completion of clinical trials to develop new therapies, studies related to survivorship issues, and investigations that utilize the resources in biorepositories and databases. 

We are pleased to offer the comments below in response to questions posed in the advance notice of proposed rulemaking (ANPRM), and we will also participate in the formal rulemaking process that   follows.

Streamlining IRB Review of Multi-Site Studies

NCCS and other cancer advocacy organizations have for many years advocated the utilization of central institutional review boards (IRBs) for multi-site cancer clinical trials.  We have supported the establishment of central IRBs at the National Cancer Institute (NCI) for the review of certain adult cancer clinical studies and pediatric cancer studies, but we never expected that the NCI central IRBs would be an adequate solution to problems of review of multi-site research without changes in the interpretation of the Common Rule or revisions to the language of the Rule.

We recommend that revisions of the Common Rule establish central IRB review as a requirement – and not simply an option -- for multi-site research.  This requirement must be accompanied by a clarification of Common Rule provisions so that the local institution will not be held responsible for regulatory noncomplicance by the central IRB or other IRB of record.    Only the combination of a requirement for central IRB review and certainty about the responsibilities of the IRB of record will break the cycle of review in which the IRBs at all participating institutions in a multi-site study review and edit the research protocol and consent documents and as a result trigger re-review of the trial by IRBs at all other institutions in the trial.

This seemingly endless cycle of review has led to intolerable delays in initiation of clinical trials.  Although the reviews by IRBs at each institution may be intended to protect research participants, they are ultimately disrespectful of research participants because such reviews waste participants’ time commitment to trial enrollment and squander research opportunities. 

HHS has identified the opportunity to make a meaningful difference in the manner in which multi-institutional research is evaluated and approved by IRBs, and we urge the Department to move ahead decisively and aggressively with a central IRB review mandate.

Consent for Biospecimens and Information

We endorse the recommendation of the ANPRM that individual consent would be required for future research uses of biospecimens and individual health information.  HHS cites the inability to de-identify biospecimens or information as a significant motivation and justification for requiring consent for future research uses.  We do not dispute the conclusions of HHS regarding the difficulties associated with de-identification but believe the more important principle is giving individuals control over their specimens and health information.  Past experience suggesting that most individuals will consent to future research uses will likely be confirmed going forward, although we doubt that consent will be granted by all.

The ANPRM recommends that consent related to biospecimens and information be granted through a “standard, brief consent form allowing for broad, future consent.”  We think that there will be great opportunity for IRBs to make revisions to a broad consent form so that the scope of future research might be limited.   If this happens, the value of biospecimens for research purposes could be restricted.  We urge the Department to set standards for the future research consent form, including sample language, in anticipation of and to bar action by IRBs to modify the future research consent form.

The determination of HHS that consent for biospecimen research should be applied prospectively is appropriate, but this decision will have implications in terms of institutional burden to store and manage biospecimens and develop procedures permitting future research utilizing stored biospecimens.  The challenge will relate to distinguishing those samples that are considered de-identified and for which individual consent was not obtained, those samples for which consent was granted, and those samples whose owners refused consent or placed limits on future research uses.  Information technology improvements may help institutions meet this management responsibility, but the responsibility and resulting burden cannot be dismissed.

Harmonization of the Common Rule and HIPAA Requirements for Future Research Use of Biospecimens

To realize the potential research benefits resulting from broad consent for future research uses of biospecimens, the Health insurance Portability and Accountability Act (HIPAA) standards for authorization for future research uses must also be revised.  If HHS provides specific guidance about the language of future research consent forms, as we recommend, the same definitions of future research uses should be incorporated in HIPAA authorization forms.  These steps would achieve harmonization of Common Rule consent requirements and HIPAA authorization requirements at least on the matter of future research uses of biospecimens. 

We commend HHS for soliciting public input regarding the ANPRM related to the Common Rule.  We are pleased to offer comments early in the regulatory process and will also offer comments when the proposed rule is published.