Practices and policies of clinical exome sequencing providers: analysis and implications

Abstract

Exome and whole genome sequencing (ES/WGS) offer potential advantages over traditional approaches to diagnostic genetic testing. Consequently, use of ES/WGS in clinical settings is rapidly becoming commonplace. Yet there are myriad moral, ethical, and perhaps legal implications attached to the use of ES and health care professionals and institutions will need to consider these implications in the context of the varied practices and policies of ES service providers. We developed "core elements" of content and procedures for informed consent, data sharing, and results management and a quantitative scale to assess the extent to which research protocols met the standards established by these core elements. We then used these tools to evaluate the practices and policies of each of the 6 U.S. CLIA-certified labs offering clinical ES. Approaches toward informed consent, data sharing, and results return vary widely among ES providers as do the overall potential merits and disadvantages of each, and more importantly, the balance between the two.

Figure 1. Distribution of scores for core elements assessed (A,C,D) and readability of informed consent documents (B)

Each ES provider is represented by a symbol of a different shape: hexagon: Ambry; circle: ARUP; star: Baylor; pentagon: Emory; square: GeneDx; triangle: UCLA.

Figure 2. Principal component (PC) analysis summarizing variation in core elements among six clinical ES providers

Forty-four percent of the variance in the scores of core elements assessed for informed consent, data sharing and return of results is explained by PC1, and thirty-two percent of the variance is explained by PC2.