Evidence of clinical utility: an unmet need in molecular diagnostics for patients with cancer.

This article defines and describes best practices for the academic and business community to generate evidence of clinical utility for cancer molecular diagnostic assays. Beyond analytical and clinical validation, successful demonstration of clinical utility involves developing sufficient evidence to demonstrate that a diagnostic test results in an improvement in patient outcomes. This discussion is complementary to theoretical frameworks described in previously published guidance and literature reports by the U.S. Food and Drug Administration, Centers for Disease Control and Prevention, Institute of Medicine, and Center for Medical Technology Policy, among others. These reports are comprehensive and specifically clarify appropriate clinical use, adoption, and payer reimbursement for assay manufacturers, as well as Clinical Laboratory Improvement Amendments-certified laboratories, including those that develop assays (laboratory developed tests). Practical criteria and steps for establishing clinical utility are crucial to subsequent decisions for reimbursement without which high-performing molecular diagnostics will have limited availability to patients with cancer and fail to translate scientific advances into high-quality and cost-effective cancer care. See all articles in this CCR Focus section, "The Precision Medicine Conundrum: Approaches to Companion Diagnostic Co-development."

FDA perspective on companion diagnostics: an evolving paradigm.

Therapeutic products are now being developed that target particular molecular lesions found in various types of cancers. The ability to correctly identify patients whose cancers have targetable lesions generally depends on a well-validated diagnostic test. Development and use of diagnostic tests together with therapies in clinical trials yields the information necessary to make a regulatory determination that both products are safe and effective, likely have clinical utility when used together, and reach the market for patient benefit. This model, called co-development, has been developed relatively recently, and is being put to use in numerous cancer therapeutic development programs. The U.S. Food and Drug Administration (FDA) has articulated a policy that requires the coapproval of a diagnostic with a therapeutic product when the diagnostic is essential to the safe and effective use of the therapeutic product. At the same time, FDA has implemented a number of processes to manage the model without slowing the approval of the co-developed products. New diagnostic technologies, together with a rapid uptick in interest in targeted drugs, will challenge the still-evolving regulatory paradigm, but will likely result in some simplified approaches presenting new challenges in determining safety and effectiveness, but all with the promise of greater benefit to patients with cancer. See all articles in this CCR Focus section, "The Precision Medicine Conundrum: Approaches to Companion Diagnostic Co-development."

Biospecimen reporting for improved study quality (BRISQ).

Human biospecimens are subjected to collection, processing, and storage that can significantly alter their molecular composition and consistency. These biospecimen preanalytical factors, in turn, influence experimental outcomes and the ability to reproduce scientific results. Currently, the extent and type of information specific to the biospecimen preanalytical conditions reported in scientific publications and regulatory submissions varies widely. To improve the quality of research that uses human tissues, it is crucial that information on the handling of biospecimens be reported in a thorough, accurate, and standardized manner. The Biospecimen Reporting for Improved Study Quality (BRISQ) recommendations outlined herein are intended to apply to any study in which human biospecimens are used. The purpose of reporting these details is to supply others, from researchers to regulators, with more consistent and standardized information to better evaluate, interpret, compare, and reproduce the experimental results. The BRISQ guidelines are proposed as an important and timely resource tool to strengthen communication and publications on biospecimen-related research and to help reassure patient contributors and the advocacy community that their contributions are valued and respected.