Medidata Blog
Making Therapies Safer with Clinical Trial Adjudication
Good drug and device safety is the bedrock of good clinical development, and that means keeping a meticulous catalogue of clinical events. To know whether your therapy or treatment works as intended, you must know with absolute precision how large numbers of individual patients respond to it. But how do you decide with certainty whether a patient in a clinical trial for, say, a new diabetes treatment has suffered from heart failure—or not?
You might think the answer to this question would be straightforward. But when it comes to interpreting even the most common of clinical endpoints, there is some grey area.1 In fact, a number of studies have documented that disagreement between investigators in the interpretation of clinical endpoint data can run as high as 10%.2 At that rate, the clinical outcomes for one out of every ten patients in your clinical trial could be a question mark.
Some clinical endpoints are more difficult to assess than others. The range of interpretations varies most when endpoints are subjective, complex, or image-based. For example, pain and fatigue are highly subjective endpoints. Cardiovascular events are especially challenging because they often require the evaluation of multiple data points. To detect heart failure, for instance, an investigator might need to examine the results of an EKG, an echocardiogram, a chest x-ray, and a blood test.3
Among image-based tests, neurological scans are some of the most difficult to decipher because the areas of the brain that light up on an fMRI can correspond to a number of different brain functions. Genetic testing is another challenge to interpret because a negative result is often inconclusive. Also notoriously difficult to assess in a standardized way: incidence of infection or disease; disease severity and progression; and determination of cause of death.4
Today, standard clinical endpoint definitions have been drawn up for many routine medical events. But even standard definitions do not resolve all disagreements. Differences in medical training, geographical variation in disease management, and the availability of diagnostic tests will always create differences of opinion. Bias can also derail assessments, as the head investigator on a clinical trial is often the treating physician and may have preconceived ideas about the patient’s health and care.5 Large multi-country and multi-center studies present the greatest risk, as the highest numbers of medical opinions come into play.
Inconsistency in the data can have serious consequences,6 throwing the validity of drug safety evaluations into question and delaying or interfering with regulatory approval.7 Delays are costly—each extra month on a trial can cost a drugmaker hundreds of thousands of dollars and deny patients lifesaving treatments.8
The Rise of Clinical Endpoints Committees
To wade through all of the noise in the data, many clinical research organizations are increasingly relying on Clinical Endpoints Committees (CEC), also known as Endpoint Adjudication Committees (EAC). These teams of expert clinicians are tasked with providing independent, blinded evaluation of suspected clinical events reported by site investigators.
Today, a long list of therapeutic categories actually require9 the use of CECs to secure U.S. Food and Drug Administration (FDA) or European Medicines Agency (EMA) approval for drugs and devices, including therapies for cardiovascular conditions, nephrology, endocrinology, gastroenterology, infectious diseases, oncology, pediatrics, and respiratory medicine. Where CECs are not mandated, they are often recommended for regulatory approval. Indeed, the use of CECs has been included in guidance from the FDA, the Pharmaceuticals and Medical Devices Agency (PMDA), and the EMA.10
But CECs create their own cost and compliance challenges. For instance, some small and mid-sized research organizations still rely on outmoded, laborious methods such as paper, spreadsheets, and fax to collect and redact patient documents for privacy, route these documents to the right physician experts for adjudication, collect their decisions, and make the requisite adjustments to their clinical trials. Large research groups use technology to help streamline this process, which is far more efficient and cost effective.
Ultimately, there are no shortcuts when it comes to drug and device safety. By far the best—and safest—solutions to CEC management are at the cutting edge: cloud-based platforms that are integrated with electronic data capture (EDC) systems, such as Medidata Adjudicate. The best of the best offer single sign-on, flexible workflows, self-configuration, and real-time data.
To educate yourself about the rise of CECs and the kinds of technology and workflows best equipped to manage them, please enjoy Medidata’s white paper on the subject!
Learn more about Medidata Adjudicate.
1 Claes Held, “When do we need clinical endpoint adjudication in clinical trials?” Ups J Med Sci. January 2019; 124(1): 42–45.
2 Nolen T, Dimmick B, Ostrosky-Zeichner L, et al. “A web-based endpoint adjudication system (WebEAS) for interim analyses in clinical trials.” Clin Trials. 2009;6(1):60–6.; Mahaffey K, Harrington R, Akkerhuis M, et al. “Disagreements between central clinical events committee and site investigator assessments of myocardial infarction end-points in an international clinical trial: review of the PURSUIT study.” Curr Control Trials Cardiovasc Med. 2001;2:187–94.
3 Nazario, Brunilda. (2021, June 8). “How Do I Get a Diagnosis of Heart Failure?” WebMD. https://www.webmd.com/heart-disease/heart-failure/heart-failure-diagnosis
4 Tracy L. Nolen, “A web-based endpoint adjudication system (WebEAS) for interim analyses in clinical trials,” Clin Trials. February 2009; 6(1): 60–66.
5 Pardeep Jhund, “Adjudication in Clinical Trials: A primer,” Journal for Clinical Studies, March 4, 2019, Vol. 11, Issue 1.
6 Scott R. Evans, “Fundamentals of Clinical Trial Design,” J Exp Stroke Transl Med. 2010 January 1; 3(1): 19–27.
7 “Which clinical trials need a Clinical Endpoint Adjudication Committee,” George Clinical, January 8, 2017: https://www.georgeclinical.com/resources/research/clinical-trials-need-clinical-endpoint-adjudication-committee
8 “Clinical trials and their patients: The rising costs and how to stem the loss,” Pharmafile, March 11, 2016: http://www.pharmafile.com/news/511225/clinical-trials-and-their-patients-rising-costs-and-how-stem-loss
9 Pardeep Jhund, “Adjudication in Clinical Trials: A primer,” Journal for Clinical Studies, March 4, 2019, Vol.11, Issue 1.
10 “CECs: What Are They and Why Does Your Trial Need One?,” Premier Research, June 27, 2017. https://premier-research.com/perspectives-clinical-endpoint-committees-trial-needs-one/