Committed stakeholders chart a course for future molecular diagnostic quality assurance

May 2016

 “Getting the right diagnosis is a key aspect of health care: It provides an explanation of a patient’s health problem and informs subsequent health care decisions … improving the diagnostic process is not only possible, but also represents a moral, professional, and public health imperative.” 

Note: The following concept note was finalized at the end of 2015 based on inputs from the SPOT/Dx Working Group (details below). Tapestry is pleased to share the concept note publically as a historical document reflecting the initial design of a diagnostic quality assurance pilot that was subsequently launched by a subset of SPOT/Dx stakeholders in March 2016. The final design of the pilot has evolved since this original concept note. Further details on the pilot’s scope, execution, and progress will be published throughout 2016.  

The development of new molecular techniques and the identification of new biomarkers are dramatically increasing the scope and value of molecular diagnostics. With this acceleration comes a need for greater system-wide assurance that the correct patients are selected for targeted cancer therapies regardless of the particular lab or diagnostic test employed in their care. This need has become more acute with the interest and expansion of personalized medicine as demonstrated by the President’s Precision Medicine Initiative. In service to this, the US Food and Drug Administration (FDA) has noted the need to consider novel ways to optimize regulations of Next Generation Sequencing (NGS) tests for human genomes with the end goal of developing a “flexible, adaptive regulatory approach that ensures that patients receive accurate and meaningful results, while accommodating innovation in test development.” There is cross-stakeholder agreement that identifying and implementing consensus reference standards and quality assurance measures to address this issue in a sustainable manner would offer significant benefit to the field of molecular pathology and the healthcare system as a whole.

The Sustainable Predictive Oncology Therapeutics and Diagnostics (SPOT/Dx) Working Group recently announced the development of a Quality Assurance Pilot for Companion Diagnostics. The multistakeholder-initiated effort will test a process to improve molecular companion diagnostic quality and consistency. To do this, the SPOT/Dx Working Group has designed an approach focusing on the creation and adoption of platform-agnostic (commutable) consensus performance standards set by the specifications of a companion diagnostic (CDx) and targeted drug in phase 3 of development (pre-market process). The goal is to equip labs with traceable quality standards materials and specifications (including preanalytic and analytic components) in the pre-market phase that will subsequently enable them to demonstrate equivalent levels of molecular diagnostic performance. Labs will be able to demonstrate their ability to accurately discriminate at the clinical decision point for a given product regardless of whether they are using an FDA-approved in vitro companion diagnostic (IVD) or a laboratory-developed test (LDT). Simply put, the intention is to ensure that regardless of the CDx used, that diagnostic would identify the appropriate patient population for the associated targeted therapy.

Appreciating the oncology community’s commitment to using molecular diagnostics while also concerned about the widespread variability in the accuracy of results gleaned from their use, SPOT/Dx participants asked, “What can we do to ensure that different measurement procedures for new biomarkers will give comparable and appropriate results?”  The solution? A proposed process to support the “search for diagnostic truth.”  As a molecular pathologist noted, “We want to focus on getting to a diagnostic truth for any particular molecular diagnostic given to any particular patient. If we can develop a set of quality standards materials that are platform agnostic, make them available to all of the laboratories out there, and ask ‘are you getting diagnostic truth?’ then we have achieved our goal.”

The pilot will include participation of key stakeholders impacted by molecular diagnostics quality including patient advocates, clinicians (pathologists and oncologists), payers, regulators, drug and diagnostic developers, and labs. The proof of concept pilot is initially oncology-focused with a potential candidate CDx that will be a two gene (multiple variant) NGS panel proposed by Amgen and Illumina. The intention is to start deliberately with a small scale in this pilot.   The pilot will involve a limited number of laboratories on a voluntary basis to test and evaluate this approach.