Eliciting preferences on secondary findings: the Preferences Instrument for Genomic Secondary Results.

PURPOSE: Eliciting and understanding patient and research participant preferences regarding return of secondary test results are key aspects of genomic medicine. A valid instrument should be easily understood without extensive pretest counseling while still faithfully eliciting patients' preferences. METHODS: We conducted focus groups with 110 adults to understand patient perspectives on secondary genomic findings and the role that preferences should play. We then developed and refined a draft instrument and used it to elicit preferences from parents participating in a genomic sequencing study in children with intellectual disabilities. RESULTS: Patients preferred filtering of secondary genomic results to avoid information overload and to avoid learning what the future holds, among other reasons. Patients preferred to make autonomous choices about which categories of results to receive and to have their choices applied automatically before results are returned to them and their clinicians. The Preferences Instrument for Genomic Secondary Results (PIGSR) is designed to be completed by patients or research participants without assistance and to guide bioinformatic analysis of genomic raw data. Most participants wanted to receive all secondary results, but a significant minority indicated other preferences. CONCLUSIONS: Our novel instrument-PIGSR-should be useful in a wide variety of clinical and research settings.Genet Med 19 3, 337-344.

Mapping the incidentalome: estimating incidental findings generated through clinical pharmacogenomics testing.

PURPOSE: Greater clinical validity and economic feasibility are driving the more widespread use of multiplex genetic technologies in routine clinical care, especially for applications in pharmacogenomics. Empirical data on the numbers and types of incidental findings generated through such testing are needed to develop policies and practices related to their clinical use. Of particular importance are disparities in findings relevant to different ancestry groups. METHODS: The Pharmacogenomic Resource for Enhanced Decisions in Care and Treatment Resource, or PREDICT, is an institutional program to implement prospective clinical genotyping of 34 pharmacogenomic-related genes to guide drug selection and dosing. We curated 5,566 journal articles to quantify and characterize the incidental, non-pharmacogenomic genotype-phenotype associations that could be generated through this clinical genotyping project. RESULTS: We identified 372 putative incidental genotype-phenotype associations that might be revealed in patients undergoing clinical genotyping for pharmacogenomic purposes. Of these, 287 associations were supported by at least one study demonstrating an odds ratio ≥2.0 or ≤0.5. Numbers of potentially relevant findings varied widely by ancestry group. CONCLUSION: Rigorous clinical policies for the clinical management of incidental findings are needed because the sheer number of significant findings could prove overwhelming to health-care institutions, providers, and patients.