Evaluation of Clinical Validity and Clinical Utility of Actionable Molecular Diagnostic Tests in Adult Oncology

While molecular diagnostics offer tremendous promise for improving health and offsetting costs in the oncology setting, the benefits and harms of testing are often not well known in terms that are meaningful to stakeholders. Tests are often presumed to offer clinical benefits, and may even be taken up into clinical practice based on that assumption.  Yet, systematic reviews have noted the lack of sufficient evidence for many of these molecular diagnostic tests, and called for more and higher quality studies to demonstrate analytic and clinical validity as well as clinical utility. Although the calls for better evidence are frequent, there is considerable debate about how much evidence is needed and how it can be generated in an efficient and timely way.

The purpose of this effectiveness guidance document (EGD) is to close this gap between the presumed benefits of tests undergoing technology assessments and the information needs of payers, clinicians and patients. We accomplish this by providing specific recommendations for designing studies to evaluate the clinical validity and utility of “actionable” MDx tests, meaning those tests intended to guide clinical decision-making for patients with a known diagnosis of cancer.

The EGD is designed to create a common framework for evidence, so that:

1. test developers and researchers can anticipate reimbursement and clinical evidence expectations and plan studies appropriately, and
2. payers and technology assessors can use the same standards for evaluating study results

In this way, if used consistently, the EGD will bring greater clarity and predictability regarding the evidence requirements of post-regulatory stakeholders.

In addition to developing methodological recommendations, the EGD also offers position statements to acknowledge current barriers to evidence generation that go beyond better study designs and involve factors such as alignment of incentives, education, and the need for ongoing research collaborations. These statements reflect the aspirations of the EGD project team and highlight key areas that need ongoing innovation for the field to realize the full potential of better evidence to support the clinical integration of MDx tests in oncology.

The EGD recommendations were created through an iterative process that incorporated the perspectives of major stakeholder groups, including researchers, clinicians, payers, industry, guideline developers and patient advocates. This stakeholder-driven process for developing the EGD provides an opportunity for input from potential EGD users and others who have a direct interest in how evidence is created and evaluated for actionable MDx tests in clinical oncology. This collaborative multi-stakeholder process is essential not only for acceptance by researchers and test developers, but also to enhance the prospect that MDx tests evaluated by these standards (and receiving a positive assessment) will be used appropriately and reimbursed.

The project team recognizes that MDx tests, as well as evaluation methodologies for clinical validity and clinical utility, will continue to advance following the publication of this document. For this reason, we expect to revisit and update these recommendations periodically in light of new technical developments. We welcome feedback from all stakeholders regarding this version of the EGD; all comments received will be reviewed and considered for inclusion in future versions of this document.

To submit feedback, please visit our website and use the email form provided on the Contact page.

Workgroups and Meetings

CMTP convened a workshop titled “Methodological Guidance for Molecular Diagnostics Research in Oncology” on May 23rd, 2012 to discuss the EGD recommendations with representatives from the life sciences industry as well as private and public payers. The presentations from this meeting are available here: Methodological Guidance for Molecular Diagnostics Research in Oncology Workshop Slides (pdf) (622.65 kB)

CMTP and the Institute of Medicine co-sponsored a public workshop titled “Evidence for Clinical Utility of Molecular Diagnostics in Oncology” on May 24th, 2012 in Washington DC to discuss the key evidence gaps and methodological issues surrounding this topic with all the relevant stakeholder groups.

Meeting information can be found here.

Support

Documents

Evaluation of Clinical Validity and Clinical Utility of Actionable Molecular Diagnostic Tests in Adult Oncology (pdf) (1.8 MB)

For more information, contact Pat Deverka.