Clinical Development Expert Committees are all part of a system that helps to ensure the conduct of trials that produce valid, reliable and credible results. In its revised guidance on the “Use of Data Monitoring Committees in Clinical Trials” (see previous blogpost here) the FDA recognizes the important role played by other oversight groups and reviews the responsibilities assigned among IRBs, clinical trial Steering Committees, Endpoint Adjudication Committees, Entities reviewing Safety Reporting, and finally Adaptation Committees. A good opportunity to take a closer look at these important clinical development expert committees.
Clinical trials are regulated in many ways and fall under several regulations. The declaration of Helsinki and subsequent Good Clinical Practice rules have set the framework of modern days clinical development that guarantees the safety of participants and generates solid data about medicines for human use.
Pharmaceutical companies have been diligently following these and other regulations, which in principle should be sufficient. However, over the past decades, experience has revealed the need for several types of clinical development expert committees to leverage disease expertise, detect safety signals and further guarantee the absence of bias in the interpretation of study results.
Let’s have a look at the committees which, besides DMCs, may have or share responsibility for aspects of clinical trial monitoring and oversight in the context of the revised guidance on the “Use of Data Monitoring Committees in Clinical Trials”.
Ethics Committees (EC) / Institutional Review Boards (IRBs): A cornerstone feature of Good Clinical Practice regulation the Ethics Committees (EC) and Institutional Review Boards (IRB) whether local or central have the obligation and the privilege to review all clinical research protocols and assess the measures that safeguard the safety of all participants. In particular, EC/IRBs review the informed consent forms (ICF) that inform participants of the potential risks and foreseen benefits of the study and make sure that the language is understandable to all without excessive technical or ambiguous terms. By definition, EC/IRBs communicate only with the principal investigators (PI) who submit the documents to them and do not interact directly with study sponsors. Their composition may vary as defined by the institution to which they are attached but typically include at least one lay person.
Clinical Trial Steering Committees (SC): Even though sponsor companies usually have a good knowledge of the disease in study, cutting edge expertise can only come from clinicians who see patients every day. Many of these also have clinical research knowledge. Setting up a Steering Committee to help design and monitor the conduct of the study may not be mandatory in any respect but is definitely a wise decision the importance of which may only become apparent much later, when results and design may be challenged by regulators. Steering Committee members can be investigators in the study. They are usually interested in the drug in development and are usually associated as authors of the subsequent publication of the results. A SC Charter is necessary to set the rules for the committee and proper contracts should be signed in respect of Fair Market Value (FMV) rules to avoid criticism of conflict of interest.
Endpoint Assessment/Adjudication Committees: This is one of the most commonly used clinical development expert committees. Depending on the nature of the disease and the design of the study, certain clinical events, either adverse or related to the study endpoints may need to be adjudicated by external experts to avoid investigator bias. The need for a CEC may arise from open-label design, complex assessments, image interpretations and other features. The CEC members may be involved in the study but provisions must be made in the charter to avoid them adjudicating their own patients. FMV-compliant contracts must be established before the study start and delays in contract signature must be anticipated to avoid impact on the study timelines.
Patient selection committees are a subcategory of the above clinical development expert committee, indicated when enrollment of patients depends on very specific criteria which are difficult to assess even by investigators. Clearing the patient for enrolment is then delegated to an independent expert or experts. These can be investigators in the study.
Entities Reviewing Safety Data: These clinical development expert committees are usually specialized in one type of adverse events such as liver events; cardiac events and so on. The committee may oversee a group of studies and is usually focused on the level of a particular compound or drug class to be able to group similar events and detect class effects. Such committees may be operational for long periods, possibly as long as development of a compound is still ongoing.
Adaptation Committees (AC): Adaptive design has become popular over the past twenty years, especially in cancer studies and other cases where it may be beneficial to permanently adjust the design in light of interim results. Whether blinded or not, sponsors may benefit from the advice of external experts who can monitor study results on an ongoing basis and provide valuable input on the adaptation opportunities.
Ethical offers robust, user-friendly and reliable platforms for clinical development expert committees management, allowing to standardize process, manage meetings and authorizations, and document the decisions in a GxP-compliant way. Our platforms help save time for both the study team and committee members and support the overall trial quality. Please contact us for more information.
