Reducing Variability in Endpoint Adjudication Outcomes
Too often, endpoint adjudication planning is the last bit of a clinical trial to be organized, at times even after the trial has begun. This should not happen. In today’s event-driven trials, the choice of endpoints and how the endpoint adjudication process is managed can have a major impact on the success of the trial.
As we know, endpoint adjudication is the process by which an independent, blinded expert committee reviews clinical events that occur during the trial. When a quality, systematic and standardized clinical event committee (CEC) process is incorporated into a clinical trial, it can enhance the validity of trial results.
Endpoint adjudication is used when the outcomes of interest are made up of clinical events. When a clinical event occurs in a trial, the onsite investigator will have an opinion as to what type of event the patient has had. However, if you were to ask a different doctor for an opinion about what the event was, a different answer might be obtained. Opinions though are not clinically valid outcomes. By relying solely on investigator-assignation of outcome events in a clinical trial, there is risk of introducing a significant degree of variability into the results.
There are multiple reasons for the variability in reporting between physicians:
- Differences in medical training.
- Geographical differences in the management of disease and availability of diagnostic tests.
- Differences in healthcare systems.
- Bias, as often the investigator is also the treating physician.
In multi-center and multi-country studies, this effect may be amplified as myriad opinions and backgrounds get absorbed into the trial.
A centralized and standardized adjudication process reduces such variability in adjudication outcomes by limiting the number of individuals tasked with classifying the potential endpoint events and by ensuring that those individuals have special expertise in the relevant clinical area(s) of interest. This enhances consistency and improves the accuracy of results.
Endpoint adjudication can be used to assess both efficacy outcomes such as myocardial infarction and safety outcomes such as the occurrence of angioedema. Centralized endpoint adjudication should improve the reliability of outcomes data, so it is particularly useful when events of interest are more subjective, e.g. hospitalization for heart failure or when sub-categorization of endpoints is needed, for example a sub-type of myocardial infarction or stroke.
There are increasing regulatory requirements for centralized adjudication. For example, for several years such centralized adjudication has been mandated in trials examining the CV safety of new treatments for type 2 diabetes mellitus. In addition to adjudication of events, the endpoint committee can also be used to help identify events. They may recognize potential new events in source documentation and flag these. In addition, CECs can be used to review serious adverse events for unreported potential endpoint events and thus ensure that this process is done independently of the sponsor.
If we better streamline and automate endpoint adjudication events, trials and their investigators can make the best decisions possible about the future progress of the clinical trial.