Review after Clinical Investigation Approval

Status: Draft

Date: January 2010

Target Audience:

IRBs, clinical investigators, and drug sponsors

Laws and Regulations: 

Developing and executing procedures for continuing review of clinical studies- 21 CFR 56.108(a)(1) and 56.115 (a)(2)

Background:

An institutional review board (IRB) is a diverse group of people who possess the qualifications and background to review and decide whether or not a clinical study can begin. IRB review helps protect clinical study participants. IRBs can disapprove proposed clinical study activities or ask that they be modified before subsequent approval. Even after IRB approval, clinical studies require ongoing review, generally by a different IRB.

Rationale:

IRBs must follow  developing and executing procedures for continuing review of clinical studies. IRBs can use this guidance to develop and execute procedures for ongoing review. The guidance is also helpful for clinical investigators and drug sponsors because both parties submit information to the IRB.

Summary:

The guidance describes suggested topic areas and actions, so IRBs can develop a procedure for how often the IRB will meet and the communication parameters between the IRB and clinical investigator. The guidance also describes when a clinical study is eligible for expedited review, one that requires less IRB votes for approval, and when a clinical study may be suspended or terminated.

Recommendations:

  1. The procedure should describe how an IRB reviews the appropriate documents and discusses topics pertaining to the risk-benefit ratio. IRB decisions must be communicated in writing and the clinical investigator be afforded the opportunity to respond. Each meeting should be carefully documented (eg, minutes, meeting agenda, and votes) and filed, as the FDA has the right to inspect such records.
  2. IRBs must review an ongoing clinical study at least once per year. Meeting frequency depends on the most recent study status. More risks means more frequent reviews.
  3. Each IRB review should involve a risk assessment, which evaluates the potential risks a participant may encounter during the clinical study and whether those risks are acceptable in comparison to the benefits (21 CFR 56.111). IRBs review safety-related summary documents for results that impact the risk/benefit ratio, which can affect the IRB’s decision to approve continuation of a clinical study.
  4. IRBs should verify that the informed consent documents are correct and contain the necessary material that constitute informed consent as described in 21 CFR 50.25.
  5. IRBs review local issues or business-related items that can affect the safety of clinical study participants. For example, a site that has a lot of personnel turnover may disrupt the quality of a clinical study.
  6. IRBs evaluate how well the clinical study adheres to the protocol, a document that describes how the clinical study will be conducted. If changes are needed, the investigator must justify that such changes will not increase the risks to participants. An IRB can stop approval if the study does not follow the IRB-approved plan and/or if participants are at risk for serious harm (21 CFR 56.113).

Impact:

The clinical investigator and sponsor will know when to prepare and submit clinical study-related documents for IRB review and avoid disruptions (eg, missing an IRB meeting, not submitting documents ahead of time) when such information is described in a procedure.

For more information on this issue, contact the Kulkarni Law Firm.