The strongest foundation for successful widespread marketing of any diagnostic is evidence of clinical utility. Clinical validation—determining a test’s ability to diagnose a health condition or predict risk of clinical outcomes—may fail to convince physicians and especially healthcare payers to accept a new diagnostic. Failure to gain payer acceptance may even result in business failure for the developer. This was the unfortunate result for Predictive Biosciences and its non-invasive, urinebased diagnostic for bladder cancer. Predictive’s CertNDx test for urothelial cancer utilized protein biomarkers and molecular DNA analysis to stratify patients based on likelihood of cancer and disease progression and potentially offered substantial advantages, especially for patients, over cystoscopy, the standard invasive diagnostic procedure for bladder cancer.
The Chasm Between Test Result and Healthcare Outcome
Because early diagnostics development focuses on analytic and clinical validation, developers may postpone steps required to lay the groundwork for demonstrating clinical utility. In addition, many diagnostics developers have historically found it easy to assume that a diagnostic with clear advantages over previous generations or invasive medical procedures will gain acceptance based on intrinsic merit. However, for regulators, healthcare payers and many physicians, the method of choice for demonstrating clinical utility is the randomized clinical trial (RCT). What diagnostics developers may fail to consider in planning a trial to demonstrate clinical utility is the complex sequence of activities that are necessary to transform the result of their new test into an improved health outcome.
Each step on the path from test result to health outcome may become a point of failure for a clinical utility study. For this reason, optimizing a study to demonstrate clinical utility requires attention to every potential point of failure between the diagnostic and the health outcome.
Provisions for reducing variability in physician decision-making and increasing patient compliance with recommended treatments have the potential to increase the likelihood of successfully demonstrating clinical utility.
The following tips for establishing clinical utility of molecular diagnostics studies address a variety of issues with particular attention to the requirements of conducting RCTs to provide evidence of changes in treatment decisions and health outcomes. These tips will assist developers of molecular diagnostics in bridging the chasm between test result and improved healthcare outcome and successfully demonstrating clinical utility.