Clinical and Regulatory Aspects of Companion Diagnostic Development in Oncology

Abstract

Nearly 20 years have passed since the US Food and Drug Administration (FDA) approved the first companion diagnostic and today this type of assay governs the use of 21 different anticancer drugs. The regulators deem these assays essential for the safe and effective use of a corresponding therapeutic product. The companion diagnostic assays are important both during the drug development process as well as essential treatment decision tools after the approval of the drugs.

Twenty Years with Personalized Medicine: Past, Present, and Future of Individualized Pharmacotherapy

“…These biomarkers are used to identify patients who are likely to experience a favorable outcome of pharmacotherapy and thereby enable individualization and avoid inappropriate and often expensive treatments. The regulatory terms for these predictive biomarker assays are companion or complementary diagnostics, often developed in parallel to the drugs they are meant to guide using the drug‐diagnostic codevelopment model .…”

“…Because of the increasing role of companion diagnostics in drug development and in clinical practice, especially within oncology and hematology, new guidelines and legislation have been issued in recent years in a number of countries and regions, such as Australian, Canada, the EU, Japan, and the U.S. . In 2014, an official definition of a companion diagnostic was published in a guideline issued by the FDA stating that it is an in vitro diagnostic assay that provides information that is essential for the safe and effective use of a corresponding therapeutic product .…”

“…The drug‐diagnostic codevelopment model has had major impact on drug development in the past 20 years. Only a few years back, the traditional path in drug development would have involved phase I–III clinical trials including a large number of patients using an all‐comers design . In the drug‐diagnostic codevelopment model the assumption is that specific molecular characteristics need to be present for the drug to be effective.…”

“…Therefore, the traditional drug development model, with its phase I–III clinical trials, seems to be replaced gradually by a more innovative and adaptive development process . What we currently experience within oncology may be regarded as a kind of “disruption” of the traditional drug development model .…”

Current postgraduate training programs and online courses in precision medicine

“…Such molecular assays determine variations in the sequence, structure or expression of that person's DNA, RNA or protein (i.e. biomarkers) and serve as predictive markers of response to treatment [7]. For cancers such as advanced/metastatic melanoma and nonsmall cell lung cancer, targeted therapies have replaced standard-of-care chemotherapy regimens as front-line treatments for patients with defined molecular aberrations in their tumors, resulting in reduced toxicities and more manageable side-effects [8,9].…”