Abstract
The development of genomic tests is one of the most significant technological advances in medical testing in recent decades. As these tests become increasingly available, so does the need for a pragmatic framework to evaluate the evidence base and evidence gaps in order to facilitate informed decision-making. In this article we describe such a framework that can provide a common language and benchmarks for different stakeholders of genomic testing. Each stakeholder can use this framework to specify their respective thresholds for decision-making, depending on their perspective and particular needs. This framework is applicable across a broad range of test applications and can be helpful in the application and communication of a regulatory science for genomic testing. Our framework builds upon existing work and incorporates principles familiar to researchers involved in medical testing (both diagnostic and prognostic) generally, as well as those involved in genomic testing. This framework is organized around six phases in the development of genomic tests beginning with marker identification and ending with population impact, and highlights the important knowledge gaps that need to be filled in establishing the clinical relevance of a test. Our framework focuses on the clinical appropriateness of the four main dimensions of test research questions (population/setting, intervention/index test, comparators/reference test, and outcomes) rather than prescribing a hierarchy of study designs that should be used to address each phase.
Highlights
The development of genetic and genomic tests is one of the most significant technological advances in medical testing in recent decades
This environment has created a number of issues to determining the most appropriate point in time to adopt a new test in clinical practice which cannot be determined solely by availability, marketing, or regulatory approval
Despite the importance of medical testing in patient management, the profit margins for the development of new tests are often low, compared to new pharmaceuticals, so there may be little incentive for diagnostic test developers to support clinical testing beyond that required for regulatory approval [2]
Summary
The development of genetic and genomic tests is one of the most significant technological advances in medical testing in recent decades. The majority of these frameworks are phased or tiered models that make a distinction between categories of evidence that address technical efficacy (analytic validity), diagnostic accuracy (clinical validity), and patient outcome efficacy (clinical utility) [19] None of these diagnostic or prognostic models have been universally adopted by regulatory science agencies, health systems, or professional groups as the standard for the evaluating the evidence needed to inform decision-making around test regulatory approval, clinical use, reimbursement or guidelines implementation. Our proposed framework could help unify perspectives and shared understanding in the same way that the four phases of drug development allow a clearly understood benchmarking process for approval and usage of new pharmaceuticals If this framework were incorporated into the FDA's developing “evidence-based regulatory science” approach, regulatory agencies could be explicit on what an appropriate level of evidence (taking into consideration different populations, comparator tests, and outcomes) might be for a given assay and what constitutes a similar enough (vs new/different) assay. If our effort reflects a useful synthesis of existing frameworking efforts to date, it may allow more consistency in definitions for terms and concepts going forward and provide a platform for future collaborative efforts
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