Delivering high quality care to patients depends on having accurate test results whose clinical implications are understood. While these requirements apply throughout medicine, the question of how best to ensure the quality of genetic tests used in clinical care, in particular, has vexed scientists and regulators alike for roughly two decades. Numerous federal advisory committees, expert scientific bodies, and professional societies have weighed in on the issue, proposed a variety of approaches, and identified a number of governmental and non-governmental entities to regulate the quality of single-gene tests. Over time, the understanding and clinical use of genetic tests have increased dramatically, but challenges in ensuring patients get accurate results whose clinical impact is understood are not yet solved. One need only look at discrepant results from different laboratories and the number of variants of uncertain significance to see the enormity of the current challenges.
As difficult as the issues attending single-gene tests are, genomic tests — which make possible the examination of multiple variants across one genome that can be analyzed individually or in combination to inform patient care — present a whole new level of complexity. An ongoing challenge for genomic tests, including those using next-generation or genome sequencing technology (NGS), is determining when the results of such testing are of sufficient quality to inform clinical decision-making. Indeed, simply gaining consensus on the meaning and appropriate parameters of “quality” in this context — let alone on which entities should be responsible for serving as quality gatekeepers — is difficult.
This article seeks both to identify the key components of quality in the NGS context and to evaluate the extent to which existing federal regulatory “checkpoints” for NGS test quality are sufficient to ensure the quality of genomic data and interpretation intended for use in diagnosis and treatment of patients. As part of this analysis, we will also identify the role of professional organizations, which have an important part to play in driving quality that is explored in greater length in a companion piece to this article. This article does not provide a general overview of state regulatory efforts to ensure quality or the potentially practice-informing impact of state liability rules even though these sources of law are often quite important. It does, however, briefly note interactions between New York State's laboratory regulations and the federal Clinical Laboratory Improvement Amendments (CLIA) and Food and Drug Administration (FDA) regulatory frameworks. Our focus here is on clinical testing. Later work can address the questions of ensuring quality in direct-to-consumer genetic testing and return of research results, even while we acknowledge that clinicians increasingly are being faced with requests to interpret and act upon genetic information originating from both of these contexts.