for the IRB/IEC4 Records that the IRB/IEC is expected to maintain
In addition, the chapter will highlight some of the areas where IRB/IECs have not adhered to these expectations. Such information should be useful as the risk assessment for a trial is prepared.
8.3 Responsibilities of the IRB/IEC
The IRB/IEC first and foremost is responsible for safeguarding the rights, safety, and well‐being of the human subjects participating in the trial. If a trial involves a population that is considered vulnerable, e.g. children, then the IRB/IEC must apply an even more rigorous approach to their review and assessment of documents, people, processes, and places.
8.3.1 Documents
All the critical and essential documents which define the clinical trial are provided to the IRB/IEC for assessment and approval. That includes the Protocol, Informed Consent Form, Investigator’s Brochure, subject recruitment materials such as advertisements, and the investigator’s qualifications. Their conclusions about the acceptability of the investigational plan and the supporting materials are determinative when it comes to starting the trial. Absent their approval the trial cannot proceed. The IRB/IEC must provide their approval/favorable opinion. The IRB/IEC can require modifications to any of the essential documents as well as disapproving a study. In addition, their review must be ongoing which usually means annually but can differ if the IRB/IEC so decides. Vulnerable populations such as children call for the IRB/IEC to be even more attentive to details such as the circumstances under which the subject’s consent is obtained and who may give consent on behalf of the subject. Compensation for participation in a trial is permitted in some form by most regulatory authorities. However, the method and monetary value of compensation associated with payment often calls for close review to ensure that subjects are not coerced or enticed in a manner which violates ethical standards. And it is not just the amount of a payment that could be problematic but also any claims related to the effect that the investigational product may have on the disease or injury being treated.
8.4 Composition, Functions, and Operations
Membership or makeup of the IRB/IEC as described in the guideline focuses on two aspects. A minimum number of members is set at five with one having a nonscientific background and one being independent of the institution or trial site. The investigator and sponsor must not have a voting representative on the IRB/IEC but can provide information about the trial as part of the IRB/IEC evaluation process. Outside experts can be invited to participate in the information gathering process if needed. The exact number of members and their credentials may be controlled by regulation or law for the country or region where the trial is to be conducted and those requirements must be followed.
The IRB/IEC should have written procedures (SOPs) in place to direct its operations. There should be written records of all meetings including decisions. Meeting minutes should list the members present and whether a quorum was achieved. The number of members constituting a quorum will be defined in an SOP.
8.5 Procedures
SOPs are a key part of meeting ICH E6(R2) across the board and the IRB expectations are no exception. The IRB/IEC’s role in ensuring that ethical practices and policies are built into every trial is documented in part by having written procedures and records documenting that those procedures were followed. The procedures that are expected to be in writing include:
Determining the composition such as qualifications for members and under what authority the IRB/IEC is established.
How scheduling will be handled. This might include timing, notification procedures, and how members will be notified.
How the Committee will conduct initial and ongoing reviews of trials.
Criteria for ongoing review of trials.
Special procedures such as expedited review
Specifications that apply to every trial such as: not enrolling subjects until a written approval for the trial is given; deviations from an approved protocol cannot be made without IRB/IEC approval; items that must be reported to the IRB in a timely manner such as protocol changes, changes which might increase subject risk, adverse experiences that are unexpected or serious, and new information.
The IRB/IECs timeline for reporting decisions on approvals as well as reasons for decisions and any criteria for appeals of decisions.
8.6 Records
The IRB/IEC should maintain all records for a retention period of 3 years. That is a minimum timeframe listed in some regulations. The retention period may vary. In the United States the retention period for IRB records is 3 years [1] after completion of the research however in the European Union the archiving requirement is for 25 years [2] after the end of the clinical trial.
8.7 Noncompliance by IRB/IECs – Areas of Risk
IRB/IECs are generally regarded and viewed as professional organizations established by government legislation or within the structure of academic medical institutions where clinical trial research may be centered. There are however commercial or independent IRB/IECs that operate globally which have found a niche in the business of clinical trial conduct. The independent IRBs have become a substantive presence in the review of clinical trials and the ethics of using a commercial or paid entity to conduct a review that is intended to determine if there are among other things any ethical concerns about a clinical trial plan may seem a dichotomy. However independent IRB/IECs have been around for some time and offer a sense of continuity to the review process especially when there are multiple trial sites involved as with large phase III trials.
Irrespective of whether the IRB/IEC is independent or affiliated with the institution where the trial is occurring inspections of IRB/IECs have shown noncompliance in a variety of areas. Many of the deficiencies might be described as administrative but the primary role of the IRB/IEC is in a way just that – Administrative. A list of the types of deficiencies follows and it should provide a basis for deciding whether to add any risk assessment regarding the IRB/IEC review process for a given trial.
Inadequate meeting minutes
Inadequate membership rosters
Inadequate initial and continuing review of research
Inadequate written procedures for prompt reporting of noncompliance, suspension, or termination
Quorum issues
Failure to promptly report noncompliance, suspension/termination of a site
It is useful to point out that from a practical standpoint IRB/IECs have established administrative control mechanisms due to the detailed requirements and record keeping that they must adhere to. This administrative staff is not the IRB/IEC per se but they (the staff) often know the details of the regulatory requirements better than the IRB members themselves. While not foolproof, having such organizational units overseeing and directing the IRB’s functional activities can and does prevent noncompliance.
The US FDA publishes data from their inspections of the IRB/IECs that register with them. The items listed above are compiled from the inspections that the US FDA conducts and reported in FDA’s
