Why Core Lab Research Is Superior in Drug Approval Trials
By Joseph Pierro, chief medical officer of Biomedical Systems.
People with chronic health conditions and diseases rely on physicians and their local medical teams to perform clinical assessments and provide the medicine they need.
However, clinical researchers and study sponsors who evaluate such medicines often cannot rely solely on the results produced by physicians at local clinical institutions to support their study endpoints. Local clinics often follow their own protocols that differ from the study protocols and use assessment criteria or modifications different from other clinical sites. This can create variability or discrepancies in drug response interpretations, which may complicate the understanding of clinical study results.
Oncology studies, for instance, require levels of qualification and measurements that local clinical reviewers may not be able to provide. Therefore, study sponsors turn to core laboratories to perform assessments using a limited number of subtherapeutic specialists who review electrocardiograms, clinical images, pathology specimens, and other study data. Experts at a core laboratory standardize the assessment rules or criteria for all involved reviewers to ensure that results contain less variability, and this provides more accurate interpretations throughout the clinical trials.
Complications With Clinical Interpretations
During a clinical trial, using local clinical assessments to track drug response data poses several obstacles to researchers and the study’s sponsors. One common complication is reviewer bias. General physicians at local clinical sites might let personal knowledge of a study participant’s medical history influence how they interpret that participant’s imaging results. In a core laboratory setting, however, the research interpretations are based solely on radiographic or imaging details, which eliminates the potential bias of local reviewers.
Another obstacle is that many clinical institutions may not have dedicated experts with the right skills to accurately perform the assessment. In the case of oncology studies, it is rare for a clinical site to have a formal oncologic imaging department or a team of radiologists skilled in all oncology response assessments, including the appropriate modifications to use in clinical research studies. Typically, studies do not include dedicated radiologists; therefore, assessments and study reads have to be performed within the normal department workload by any general physician who is available at the time.
Because of the heavy workload and everyday demands most clinical institutions face, separate physicians may have to perform study reads. If readers and their colleagues differently apply the response criteria, such as selecting and tracking the development of target lesions, then the interpretations may vary, which can lead to inaccurate drug response determinations.
Unfortunately, such variability is often unavoidable when you rely on local clinical site interpretations, which makes a dedicated core laboratory even more important to a clinical trial’s success.
Higher-Quality Data Through Core Lab Research
The level of rigor and standardization that core labs apply to clinical research studies is far more extensive than the subjective interpretation requirements needed for clinical treatment. For example, Response Evaluation Criteria in Solid Tumors 1.1 is a set of published rules that define how to determine cancer patients’ responses to treatment. The rules are usually followed closely in oncologic research studies but are rarely used by physicians in local clinical interpretations.
Standard regulations and guidelines, like RECIST 1.1, are vital to protecting the integrity of clinical trial results. They ensure that every reviewer, regardless of location and background, follows the same interpretation guidelines set forth by the core laboratory. In oncology trials, this standardization makes it simpler to record images at each study visit with correct target and non-target responses clearly identified and appropriately measured.
Besides standardizing a study’s interpretation requirements, core laboratories also make it easier for remote readers to share and collaborate over their findings. Researchers at the core lab can implement software that allows readers to create interactive reporting and tracking for better communication, consistency, and compliance with the response assessment criteria. The software allows the core lab to quickly communicate modifications to the response criteria so local evaluators will be made instantly aware of the changes. It also enables measurement of reviewer performance throughout the study to determine when reviewers should be retrained or replaced.
In general, local evaluations and interpretations are excellent for clinical care and patient treatment requirements but are generally not adequate for determining response endpoints for clinical trials upon which drug approval will be based. Food and Drug Administration approval has provided a series of guidances, and as the studies grow more complex, standardizing response criteria and assessments becomes more vital for minimizing variability and maximizing success.
Joseph Pierro is chief medical officer of Biomedical Systems, a premier global provider of centralized diagnostic services. He has served in global senior level positions within the pharmaceutical industry and as a medical reviewer at the FDA Center for Drug Evaluation and Research. His thorough understanding of regulatory submission requirements and outstanding track record of success with regulatory approvals and responses to regulatory authorities make him an asset to Biomedical Systems’ Scientific Affairs team.