Q: What are some of the key considerations for reducing bias and maximizing regulatory potential when designing a study?
A: Certain design features and methods can be incorporated into a clinical trial to minimize bias and increase precision and accuracy of potentially subjective observer-dependent assessments. Prior to patient enrollment, efforts to encourage uniform interpretation of endpoint data among assessors and minimize assessment variability across the study should be incorporated in as part of the study design. One such effort is the blinding of patient data. At WCC, we recommend using a central (external) review committee to avoid bias stemming from the sponsor or study monitor’s familiarity with particular patients, which can influence endpoint assessments.
Q: What types of trials can benefit from using an endpoint assessment and adjudication committee (EAC)?
A: Still relatively novel, EACs are so far most prevalent in oncology trials, although the FDA’s push toward more robust and definitive datasets for regulatory approval means that they will become important to all therapeutic areas in the future. For demonstrating clinical benefit in oncology drug trials, overall survival (OS) is still the endpoint gold standard. However, FDA approval takes longer for these kinds of studies than when based on studies using other accepted primary efficacy endpoints, such as time to progression (TTP) or objective response rate (ORR), which are often used as surrogates for OS in patients with solid tumors. These tumor assessment endpoints are less expensive and much more time-effective than OS, and are therefore an attractive alternative for demonstrating efficacy. Because they are based on subjective evaluations (i.e. clinical or radiological observations), however, they are also less objective than OS and must be used in accordance with strict quality control measures to ensure validity. When a complicated definition of efficacy like this is required, an EAC can be instrumental in providing a more complete method for determining total tumor and drug effect, as well as reducing physician bias and overcoming some of the limitations inherent to imaging that may make precise diagnosis difficult.
Q. Who usually takes part in the EAC?
A: For oncology trials, the EAC is defined by the oncologist(s), who utilizes data beyond radiology images, including clinical data, pathology results, and other physical measurements (i.e. skin lesions for melanoma, etc.) to more holistically determine the disease status of the patient. Specifically, board-certified oncologists are required, but it is also often of value to have radiology and pathology representation on the committee. All members must be trained under an EAC chair to minimize variability among assessments and determine the different roles each clinical specialist plays in them.
At WCC, we have a solid understanding of these committees’ regulatory and technology requirements, as well as an understanding of the process needed to make them successful. For sponsors looking to further enhance surrogate imaging endpoints by incorporating a more holistic evaluation of effect important to the FDA, we offer services specifically designed to manage this process.
Dr. Walovitch joined WCC in January 2009 as chief medical officer. As president of WCC, Dr. Walovitch provides medical leadership for the entire organization. Additionally, he is responsible for directing the operations, regulatory, sales, and marketing activities and plays a vital role in defining the strategic vision of the company.
Prior to joining WCC, he served as the senior vice president of clinical research at Acusphere, Inc., vice president of preclinical and clinical research at Epix Medical, and held various positions as research pharmacologist and project clinician in the Imaging Agent Group at the DuPont Merck Pharmaceutical Company. He completed his postdoctoral fellowship at the National Institute on Drug Abuse’s Addiction Research Center in the Neurochemistry section. Walovitch has a doctorate in pharmacology from the University of Illinois Medical Center and a bachelor’s degree in biology from the University of Illinois. He is an author of more than 100 peer-reviewed publications, mostly in the field of medical imaging.
