Continuing Review

To satisfy 45 CFR 46.111 both initial and continuing review, the IRB review must consider risk, potential benefits, consent and safeguards for human subjects. All IRB members must receive the protocol summary and a status report on the progress of the research that includes the following:

• "The number of subjects accrued;
• A summary of adverse events and any unanticipated problems involving risks to subjects or others and any withdrawal of subjects from the research or complaints about the research since the last IRB review;
• A summary of any relevant recent literature, interim findings, and amendments or modifications to the research since the last review;
• DSMB report or any relevant multi-center trial reports (if appropriate),
• Any other relevant information, especially information about risks associated with the research;
• A copy of the current informed consent document and any newly proposed consent document.
• Review of the consent by the IRB "should ensure the following:
  • The currently approved or proposed consent document is still accurate and complete;
  • Any significant new findings that may relate to the subject's willingness to continue participation are provided to the subject in accordance with HHS regulations at 45 CFR 46.116(b)(5)." (b) Additional elements of informed consent. When appropriate, one or more of the following elements of information shall also be provided to each subject: (5) A statement that significant new findings developed during the course of the research which may relate to the subject's willingness to continue participation will be provided to the subject;
  • The administrator passes along to the primary reviewer a copy of the "complete protocol including any modifications previously approved by the IRB." And any IRB member can "have access to the complete protocol and relevant IRB minutes prior to the convened IRB meeting."
  • This guidance about the complete protocol also applies to expedited review of continuing reviews

Special considerations must be made by the IRB for a Continuing Review of Multi-Center Trials Monitored by a Data Safety Monitoring Board (DSMB), Data Monitoring Committee (DMC), Other Similar Body, or Sponsor. Multi-Center trials present challenges to investigators preparing continuing reviews when providing information about study-wide adverse events, interim findings, and recent literature that may be relevant to the research. OHRP notes this challenge and recognizes that multi-center trials generally have DSMB, DMC or other oversight bodies. When this is the case, the NH IRB "may rely on a current statement from the DSMB or sponsor indicating that it has reviewed study-wide adverse events, interim findings, and any recent literature that may be relevant to the research, in lieu of requiring that this information be submitted directly to the IRB." However, local activities and information must still be reported to the NH IRB.

Specific language definitions for multi-center trials/studies:

• The criteria "no subjects have been enrolled" is recognized by OHRP to mean "no subjects have ever been enrolled at a particular site,"
• "No additional risks have been identified" is recognized by OHRP "to mean that neither the investigator nor the IRB at a particular site has identified any additional risks from any site or other relevant source."

The "IRB must conduct continuing review of research at intervals appropriate to the degree of risk, but not less frequently than once per year." The review date is the date of the IRB meeting EXCEPT:

• When a 30-day review prior to the termination date is used;
• For deferred new protocols the termination date is the date of the LAST IRB meeting that reviewed and approved the study.
• If minor modifications are requested, the renewal date is set for new studies based on the date of the original IRB meeting date, regardless of the length of time taken to complete the minor revisions required.

A grace period is not allowed by the regulations. The following must occur then there is a lapse of continuing review:

• Research must stop, "unless the IRB finds that it is in the best interests of individual subjects to continue participating in the research interventions or interactions."
• No enrollment of new subjects can occur

The committee shall have, at a minimum, 7 members with varying backgrounds to promote complete and adequate review of research activities. The committee shall be sufficiently qualified through the experience, expertise, and diversity of its members to promote respect for its advice and counsel in protecting human subjects in research and safeguarding the privacy and confidentiality of medical records information that is used for the purposes of research. The committee shall include at least one member whose primary area of expertise is scientific and one member whose primary area of expertise is non-scientific. The committee shall include at least 2 members who are not otherwise affiliated with the department and who are not part of the immediate family of a person who is affiliated with the department. The committee shall include at least 2 members who are consumers or family members of consumers. No member of the committee shall participate in initial or continuing review of any research project in which the member has a conflicting interest, except to provide information requested by the committee.

When an approved research project is completed, the investigator must promptly notify the IRB and file with the IRB a cumulative "final report" which includes the information listed above for continuing review of protocols for the entire research project period.

Please note that studies that previously qualified for expedited review can change to require full board review depending on the increase risk.