In clinical research the twin responsibilities of medical care and research each have standards which must be met simultaneously. Knowing what those standards are is especially important when a patient is faced with a life-threatening problem which might respond to an experimental treatment.

For this reason, the Office of Research Development has prepared the following summary:

REVIEW OF RESEARCH PROTOCOLS AND THE USE OF INVESTIGATIONAL NEW DRUGS AND DEVICES

Research involving human subjects is governed by a common federal rule : 45 CFR PART 46 Protection of Human Subjects . Most federal agencies subscribe to the common rule, including the Department of Health and Human Services (DHHS). The Scientific Committees of Cook County Bureau facilities report to DHHS by way of a Multiple Project Assurance, and therefore follow the standard federal regulations.

The Food and Drug Administration concurs with this standard policy, but has not adopted it in its entirety. For FDA-regulated trials, another set of regulations (21 CFR 50 & 21 CFR 56) apply. For this reason, some aspects of review and approval of protocols involving human subjects may have different requirements imposed by DHHS and FDA.

When both FDA and DHHS have jurisdiction, both sets of requirements must be met. At Cook County Bureau entities, many research protocols do fall under both sets of requirements. In this summary the standard federal requirements are discussed first, followed by a description of circumstances in which the FDA rules apply.

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REVIEW OF RESEARCH PROTOCOLS INVOLVING HUMAN SUBJECTS

Any research involving human subjects must be reviewed by the Institutional Review Board (IRB). At Cook County facilities the IRB is called the Scientific Committee. Two levels of review are possible: Full review and expedited review. In addition, in some limited cases research may qualify for an exemption from IRB review, as described below.

A Full Board Review is a review of proposed research at a convened meeting at which a majority of the Scientific Committee is present, including at least one member whose primary concerns are in nonscientific areas. For the research to be approved, it must receive the approval of the majority of members present at the meeting.

An Expedited Review is a review of the proposed research by the IRB chair or a designated voting member, or group of voting members, rather than by the entire IRB. Federal rules permit expedited review for certain kinds of research involving no more than minimal risk and for minor changes in approved research.

A risk is minimal where the probability and magnitude of harm or discomfort anticipated in the proposed research are not greater, in and of themselves, than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests. For instance, the risk of drawing a small amount of blood from a healthy individual for research purposes is no greater than the risk of doing so as part of a routine physical examination.

This is clearly not the case when a physician wishes to treat a patient for a life-threatening condition with an experimental drug. Nor is it usually the case in when an investigators wants a quick IRB approval of a protocol because an eligible patient has been identified. An expedited review can only be used if the risk is minimal.

For emergency treatment, the appropriate route to approval is an Emergency IND or "emergency drug request", not expedited review.

For a quick turn around review of a protocol requiring full review, there is no recourse except to complete your application to the IRB as soon as you know you will carry out the trial. Delay in completing paperwork is not a good reason to rush deliberations about research which carries potential risks to subjects.

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CIRCUMSTANCES ALLOWING EXPEDITED REVIEW are outlined here.

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EXEMPTION FROM REVIEW

In some limited cases, research may be exempted from IRB review. Examples include research which involves observation of adults in public places; record reviews, case reports and historical surveys using preexisting data; and surveys, questionnaires and structured interviews involving adults.

Circumstances in which an exemption from review may be allowed can be found here.

Note that exemptions from review are not allowed for research on some populations, including jail detainees, prisoners, pregnant women, fetuses, nor are they allowed for survey and interview research with minors.

If a research project seems to fall into one of the exempt categories, the research investigator must receive confirmation of the project's exempt status from the Chair of the Scientific Committee. A one-page form is provided for this purpose.

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USE OF INVESTIGATIONAL DRUGS OR DEVICES OUTSIDE CONTROLLED CLINICAL TRIALS

The Food and Drug Administration recognizes that treatment decisions may be made outside of research considerations. Physicians retain the authority to provide emergency medical care to their patients without prior IRB approval. In these cases, physicians must meet FDA requirements to use investigational articles for emergency purposes.

An Emergency Drug Request allows the use of an investigational article without prior IRB approval in emergency situations. These are defined as life-threatening situations in which no standard acceptable treatment is available and there is not sufficient time to obtain IRB approval for use. The investigator is required to obtain informed consent from the patient, interim approval from the IRB Chair, and to report the emergency drug use to the IRB within 5 working days. Any subsequent use of the investigational item is subject to IRB review.

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Note that patients treated under an Emergency Drug Request may not be entered as subjects in a research project or clinical trial
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In addition to emergency drug requests, clinicians may use investigational new drugs for treatment purposes outside controlled clinical trials under several circumstances, as explained in the Guidelines for Research Investigators. Note that all these uses require prior IRB review and the patient's informed consent.

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RESEARCH ON EMERGENCY TREATMENTS

All the mechanisms for using investigational drugs outside a trial, or alternatively, for speeding approval of a minimal risk proposal, assume that the patient -- or a patient's representative empowered to give consent -- is fully aware of the experimental nature of the treatment or study and is able to give informed consent. What about research on emergency treatments that must be applied when the patient is incapacitated and an appropriate representative cannot be reached? In this situation, federal regulations allow for a waiver of consent under very circumscribed conditions. Currently this type of waiver is not being applied in County affiliates pending clarification of State laws. For a more complete discussion of this topic, see Waiver of Consent in Emergency Research.

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See Also:
The Belmont Report
45 CFR PART 46 Protection of Human Subjects
Bureau Guidelines for Investigators
Bureau Multiple Project Assurance