Individuals participating in biobanks and other large research projects are increasingly asked to provide broad consent for open-ended research use and widespread sharing of their biosamples and data. We assessed willingness to participate in a biobank using different consent and data sharing models, hypothesizing that willingness would be higher under more restrictive scenarios. Perceived benefits, concerns, and information needs were also assessed. In this experimental survey, individuals from 11 US healthcare systems in the Electronic Medical Records and Genomics (eMERGE) Network were randomly allocated to one of three hypothetical scenarios: tiered consent and controlled data sharing; broad consent and controlled data sharing; or broad consent and open data sharing. Of 82,328 eligible individuals, exactly 13,000 (15.8%) completed the survey. Overall, 66% (95% CI: 63%-69%) of population-weighted respondents stated they would be willing to participate in a biobank; willingness and attitudes did not differ between respondents in the three scenarios. Willingness to participate was associated with self-identified white race, higher educational attainment, lower religiosity, perceiving more research benefits, fewer concerns, and fewer information needs. Most (86%, CI: 84%-87%) participants would want to know what would happen if a researcher misused their health information; fewer (51%, CI: 47%-55%) would worry about their privacy. The concern that the use of broad consent and open data sharing could adversely affect participant recruitment is not supported by these findings. Addressing potential participants' concerns and information needs and building trust and relationships with communities may increase acceptance of broad consent and wide data sharing in biobank research.

Genetic variation can affect drug response in multiple ways, though it remains unclear how rare genetic variants affect drug response. The electronic Medical Records and Genomics (eMERGE) Network, collaborating with the Pharmacogenomics Research Network, began eMERGE-PGx, a targeted sequencing study to assess genetic variation in 82 pharmacogenes critical for implementation of “precision medicine.” The February 2015 eMERGE-PGx data release includes sequence-derived data from ~5000 clinical subjects. We present the variant frequency spectrum categorized by variant type, ancestry, and predicted function. We found 95.12% of genes have variants with a scaled CADD score above 20, and 96.19% of all samples had one or more Clinical Pharmacogenetics Implementation Consortium Level A actionable variants. These data highlight the distribution and scope of genetic variation in relevant pharmacogenes, identifying challenges associated with implementing clinical sequencing for drug treatment at a broader level, underscoring the importance for multifaceted research in the execution of precision medicine.

Family history of colorectal cancer (CRC) is a known risk factor for CRC, and encompasses both genetic and shared environmental risk. We conducted a systematic review to estimate the impact of family history on the natural history of CRC and adherence to screening. We found high heterogeneity in family history definitions, the most common definition being one or more first-degree relatives. The prevalence of family history may be lower than commonly cited 10%, and confirms evidence for increasing levels of risk associated with increasing family history burden. There is evidence for higher prevalence of adenomas and of multiple adenomas in people with family history of CRC, but no evidence for differential adenoma location or adenoma progression by family history. Limited data on the natural history of CRC by family history suggests a differential age or stage at cancer diagnosis and mixed evidence on tumor location. Adherence to recommended colonoscopy screening was higher in people with family history of CRC. Stratification based on polygenic and/or multifactorial risk assessment may mature to the point of displacing family history-based approaches, but for the foreseeable future family history may remain a valuable clinical tool for identifying individuals at increased risk of CRC.

BACKGROUND AND OBJECTIVES: Physicians have a major influence on parental vaccine decisions. We tested a physician-targeted communication intervention designed to (1) reduce vaccine hesitancy in mothers of infants seen by trained physicians and (2) increase physician confidence in communicating about vaccines. METHODS:We conducted a community-based, clinic-level, 2-arm cluster randomized trial in Washington State. Intervention clinics received physician-targeted communications training. We enrolled mothers of healthy newborns from these clinics at the hospital of birth. Mothers and physicians were surveyed at baseline and 6 months. The primary outcome was maternal vaccine hesitancy measured by Parental Attitudes on Childhood Vaccines score; secondary outcome was physician self-efficacy in communicating with parents by using 3 vaccine communication domains. RESULTS:We enrolled 56 clinics and 347 mothers. We conducted intervention trainings at 30 clinics, reaching 67% of eligible physicians; 26 clinics were randomized to the control group. Maternal vaccine hesitancy at baseline and follow-up changed from 9.8% to 7.5% in the intervention group and 12.6% to 8.0% in the control group. At baseline, groups were similar on all variables except maternal race and ethnicity. The intervention had no detectable effect on maternal vaccine hesitancy (adjusted odds ratio 1.22, 95% confidence interval 0.47-2.68). At follow-up, physician self-efficacy in communicating with parents was not significantly different between intervention and control groups.CONCLUSIONS: This physician-targeted communication intervention did not reduce maternal vaccine hesitancy or improve physician self-efficacy. Research is needed to identify physician communication strategies effective at reducing parental vaccine hesitancy in the primary care setting.

The eMERGE Consortium* , * The advancement of precision medicine requires new methods to coordinate and deliver genetic data from heterogeneous sources to physicians and patients. The eMERGE III Network enrolled >25,000 participants from biobank and prospective cohorts of predominantly healthy individuals for clinical genetic testing to determine clinically actionable findings. The network developed protocols linking together the 11 participant collection sites and 2 clinical genetic testing laboratories. DNA capture panels targeting 109 genes were used for testing of DNA and sample collection, data generation, interpretation, reporting, delivery, and storage were each harmonized. A compliant and secure network enabled ongoing review and reconciliation of clinical interpretations, while maintaining communication and data sharing between clinicians and investigators. A total of 202 individuals had positive diagnostic findings relevant to the indication for testing and 1,294 had additional/secondary findings of medical significance deemed to be returnable, establishing data return rates for other testing endeavors. This study accomplished integration of structured genomic results into multiple electronic health record (EHR) systems, setting the stage for clinical decision support to enable genomic medicine. Further, the established processes enable different sequencing sites to harmonize technical and interpretive aspects of sequencing tests, a critical achievement toward global standardization of genomic testing. The eMERGE protocols and tools are available for widespread dissemination.