The Quorum Review: Institutional Edition Letter from the CEO

How can we help each research site initiate clinical trials as effectively as possible? A recent article by researchers at Duke University1 concludes that U.S. researchers face impediments from many sources, including:

Aging regulations

Broad risk management by trial sponsors

Layers of oversight by institutions

Health system incentives that do not favor research

The researchers describe the current clinical trials process as “unsustainably burdensome, threatening to deprive patients and health-care providers of new therapies and new evidence to guide the use of existing treatments.” As this article makes clear, there is no easy fix to streamline the clinical trials process. Even so, here at Quorum Review we will continue to do our small part – to provide ethics review carefully, promptly, accurately and courteously. To help you with your mission, we’ve enclosed several articles regarding the ethics review of proposed clinical research. Please contact us if we can be of additional assistance.

Sincerely, Cami Gearhart, CEO Quorum Review IRB

1 Kramer, Smith & Califf, Impediments to Clinical Research in the United States, Clinical Pharmacology & Therapeutics (February 2012), http://www.nature.com/clpt/journal/v91/n3/full/clpt2011341a.html

February 24, 2012 | Volume 2, Issue 1

New Draft Guidance on “Exculpatory Language” from FDA and OHRP

On August 19, 2011, OHRP and FDA issued a joint Draft Guidance document: “Guidance on Exculpatory Language in Informed Consent.” When finalized, the Guidance will replace guidance on this topic from both OHRP2 and FDA3. The Draft Guidance provides an updated interpretation of the regulatory restriction on “exculpatory language” in informed consent documents.4 The Draft Guidance specifically addresses the issue of a subject’s rights with respect to a biospecimen provided for research purposes, stating: “a subject’s waiver of any rights…with respect to a biospecimen…would not be exculpatory.” This conclusion is based on two factors: (1) the practice of not compensating research subjects who provide biospecimens for research purposes, and (2) the absence of federal or state laws or policies that recognize a legal right to compensation if a subject has voluntarily signed an informed consent form stating they would not be paid for biospecimens. The position is a departure from previous guidance documents, which will be replaced when this Draft Guidance is finalized. The 1998 Frequently Asked Questions Guidance from FDA advised that it was acceptable “for [a] consent to say that specimens are to be used for research purposes” but not to say that they were donated because “the word ‘donation’ implies abandonment of rights to the property [and] 21 CFR 50.20 prohibits requiring subjects to waive or appear to waive any rights as a condition for participation in the study.”5 The 1996 Guidance from OHRP took the same position with respect to sample ownership, providing the following examples of “exculpatory” language: By agreeing to this use, you should understand that you will give up all claim to personal benefit from commercial or other use of these substances. I voluntarily and freely donate any and all blood, urine, and tissue samples to the U.S. Government and hereby relinquish all right, title, and

interest to said items. By consent to participate in this research, I give up any property rights I may have in bodily fluids or tissue samples obtained in the course of the

research.6

In contrast with the position taken in the previous guidance documents, the Draft Guidance provides several examples of “acceptable language” as follows: By agreeing to this use, you are giving up all claims to any money obtained by the researchers from commercial or other use of these specimens. I voluntarily and freely donate any and all blood, urine, and tissue samples to the [name of research institution] and hereby relinquish all property

rights, title, and interest I may have in those samples. By consenting to participate in this research, I give up any property rights I may have in bodily fluids or tissue samples collected during this

research.7

Quorum Review’s practice, based on the existing guidance, has been to modify language that explicitly or implicitly indicated subjects were “donating” samples or otherwise giving up ownership rights with respect to samples. Given the updated interpretation of “exculpatory language”, Quorum Review anticipates making a change to our policies. Quorum Review will not make a formal change until the Final Guidance is issued; however, please feel free to contact us with questions about consent language addressing sample ownership in the interim. Questions can be addressed to your study manager or sent to our Site Support Team at sitesupport@quorumreview.com.

2 Exculpatory Language in Informed Consent, OHRP (November 15, 1996). 3 Question 52, Institutional Review Boards Frequently Asked Questions—Information Sheet Guidance for Institutional Review Boards and Clinical Investigators, FDA (1998). 4 45 CFR 45.116 and 21 CFR 50.20 state: “No informed consent, whether oral or written, may include any exculpatory language through which the subject or the representative is made to waive or appear to waive any of the subject’s legal rights, or releases or appears to release the investigator, the sponsor, the institution, or its agents from liability for negligence.” 5 Question 52, Institutional Review Boards Frequently Asked Questions—Information Sheet Guidance for Institutional Review Boards and Clinical Investigators, FDA (1998). 6 Exculpatory Language in Informed Consent, OHRP (November 15, 1996). 7 Draft Guidance, Guidance on Exculpatory Language in Informed Consent, DHHS (August 19, 2011).

February 24, 2012 | Volume 2, Issue 1

The Importance of Addressing Local Research Context

An important consideration for the IRB is commonly referred to as the “local research context.” Local research context may include community attitudes towards research, the literacy rate, subject recruitment, or other community factors, such as: geographic, socioeconomic, gender, cultural, and moral backgrounds of the proposed human subject population.

In January, 2010, the Office for Human Research Protections (OHRP) withdrew two policy documents suggesting that OHRP favored local IRB review over review by a non-local IRB.8 OHRP has clarified that it no longer holds this position.9 Although OHRP’s policy has shifted, the reviewing IRB, whether local or central, still must obtain appropriate knowledge of the local research context.

The OHRP policy memorandum “IRB Knowledge of Local Research Context” outlines the necessary information an IRB should obtain as follows:

the anticipated scope of the institution's research activities the types of subject populations likely to be involved the size and complexity of the institution institutional commitments and regulations applicable law standards of professional conduct and practice method for equitable selection of subjects method for protection of privacy of subjects

8 (Archived) OPRR Policy Memorandum, Local Institutional Review Board (IRB) of Multicenter Clinical Trials Sponsored by the Division of Aids (DAIDS) Nat’l Institute of Allergy and Infectious Diseases (NIAID), Sept.13,’93,, http://www.hhs.gov/ohrp/archive/humansubjects/guidance/hsdcsep93.htm (Archived) OPRR Policy Memorandum, Local IRB Review of Multicenter Clinical Trials, Nov.9, ‘92, 93-01, http://www.hhs.gov/ohrp/humansubjects/guidance/hsdc93-01.htm.

9 OHRP April 30, 2010 Response, Use of a Central Institutional Review Board, http://www.hhs.gov/ohrp/policy/Correspondence/mcdeavitt20100430letter.html

method for maintenance of confidentiality of data language(s) understood by prospective subjects method for minimizing the possibility of coercion or undue

influence in seeking consent, and, safeguards to protect the rights and welfare of vulnerable

subjects10

The OHRP memorandum includes a number of methods by which an IRB may obtain necessary information, including personal knowledge of the research context by one or more IRB members, consultants, and an exchange of information between the IRB and the research site.

Quorum Review IRB recognizes the importance of the local research context for institutions. We have incorporated a number of steps within our standard process to obtain knowledge about the research context in your community. Quorum solicits information about the local population, site privacy and confidentiality practices, and local laws and requirements from investigators on our required submission forms. In addition, Quorum maintains information about unique local requirements related to research, such as state law, or institution-specific requirements. Quorum’s IRB members come from a variety of backgrounds, professions, and geographic regions. If needed, our specialty consultants are available to field questions for the IRB members regarding specific scientific and local context issues.

For further information or to obtain a copy of Quorum’s Institutional Start-Up Package, please contact Quorum’s Business Development Team at busdev@quorumreview.com.

10 OPRR Policy Memorandum, IRB Knowledge of Local Research Context, August 27, 1998 (updated 2000), http://www.hhs.gov/ohrp/policy/local.html