Development and pilot implementation of guidelines for culturally tailored research recruitment materials for African Americans and Latinos.

BACKGROUND: Previous studies support cultural tailoring of recruitment materials as a strategy to promote the enrollment of minoritized groups in clinical trials. However, there is a lack of guidance for research teams to create culturally tailored materials, potentially contributing to low recruitment rates of minoritized groups. We describe the development and pilot testing of recruitment material guidelines used to culturally tailor clinical trial recruitment materials targeting African Americans and Latinos. METHODS: The guideline development team consisted of investigators, research staff, and community leaders and members experienced in the recruitment and community engagement of minoritized groups. The recruitment material guidelines were developed using the literature, focus groups with African Americans and Latinos, the teams' research experience, and guidance from a community advisory board. To assess the effectiveness of the guidelines, a pilot study was conducted comparing advertisement click-through rates and enrollment outcomes between two institutions differing in use of culturally tailored versus non-tailored Facebook banner ads for the "Aspirin Dosing: A Patient-centric Trial Assessing Benefits and Long-Term Effectiveness" (ADAPTABLE) study. RESULTS: Five themes emerged from focus groups: (1) employ diversity and inclusion in recruitment efforts; (2) access multiple recruitment channels to increase reach and possible participation; (3) increase your "footwork"; (4) personalize outreach and recruitment to specific groups' beliefs and values; (5) align recruitment messaging with language preferences and motivations for study participation; and (6) specify incentives for participation. Guidelines were: 1) be inclusive; 2) use all forms of media; 3) take a personalized approach; 4) align recruitment messaging with motivations for study participation; 5) specify incentives; and 6) get out into the community. Additional guidelines were developed addressing specific considerations for images and language when targeting African American and Latino populations. Pilot study results demonstrated that clicks per impression ratio (0.47 clicks per impression vs. 0.03 clicks per impression) and the percentage of African American enrollment were significantly higher when using tailored compared to non-tailored ads (12.8% vs. 8.3%, respectively). CONCLUSION: The recruitment material guidelines offer practical recommendations to reach diverse populations for clinical trial participation more effectively. Our preliminary data supports use of these guidelines as a strategy to enhance recruitment of minoritized groups into clinical research studies.

Determinants of stage at diagnosis of HPV-related cancer including area deprivation and clinical factors.

BACKGROUND: Collecting social determinants of health in electronic health records is time-consuming. Meanwhile, an Area Deprivation Index (ADI) aggregates sociodemographic information from census data. The objective of this study was to ascertain whether ADI is associated with stage of human papillomavirus (HPV)-related cancer at diagnosis. METHODS: We tested for the association between the stage of HPV-related cancer presentation and ADI as well as the association between stage and the value of each census-based measure using ordered logistic regression, adjusting for age, race and sex. RESULTS: Among 3247 cases of HPV-related cancers presenting to an urban academic medical center, the average age at diagnosis was 57. The average stage at diagnosis was Surveillance, Epidemiology and End Results Stage 3. In the study population, 43% of patients were female and 87% were white. In this study population, there was no association between stage of HPV-related cancer presentation and either aggregate or individual census variables. CONCLUSIONS: These results may reflect insufficient sample size, a lack of socio-demographic diversity in our population, or suggest that simplifying social determinants of health into a single geocoded index is not a reliable surrogate for assessing a patient's risk for HPV-related cancer.

Design and implementation of a massive open online course on enhancing the recruitment of minorities in clinical trials - Faster Together.

BACKGROUND: Racial and ethnic minorities are often underrepresented in clinical trials, threatening the generalizability of trial results. Several factors may contribute to underrepresentation of minorities in clinical trials, including lack of training for researchers and staff on the importance of diversity in clinical trials and effective strategies for recruiting and retaining minority populations. METHODS: Applying community engaged research principles, we developed a massive open online course (MOOC) to help research team members develop knowledge and skills to enhance the recruitment of minorities in clinical trials. A transdisciplinary working group, consisting of clinical researchers, community engagement specialists, minority clinical trial recruitment and retention educators and specialists, and knowledge management information scientists, was formed to develop an evidence-based curriculum. Feedback from the Recruitment Innovation Center Community Advisory Board was incorporated to help finalize the curriculum. The course was implemented in Coursera, an online learning platform offering MOOCs. A bootstrap paired sample t-test was used to compare pre- and post-assessments of knowledge, attitudes, and intentions as it relates to minority recruitment. RESULTS: The final course, entitled Faster Together, was divided into eight 1-h modules. Each module included video presentations, reading assignments, and quizzes. After 10 months, 382 individuals enrolled in the course, 105 participants completed the pre-test, and 14 participants completed the post-test. Participants' knowledge scores were higher with an increase in the mean number of correct answers from 15.4 (95% CI:12.1-18.7) on the pre-test to 18.7 (95% CI:17.42-20.2) on the post-test. All post-test respondents (n = 14) indicated that the course improved their professional knowledge, and 71.4% of respondents indicated that they were very likely to make changes to their recruitment practices. CONCLUSIONS: Faster Together, a massive open online course, is an acceptable, accessible approach to educating research teams on minority recruitment in clinical trials. Preliminary evidence indicates the course increased knowledge on how to recruit minorities into clinical trials and could promote change in their recruitment practices.

Determinants of Trustworthiness to Conduct Medical Research: Findings from Focus Groups Conducted with Racially and Ethnically Diverse Adults.

BACKGROUND: Potential research participants, particularly those from racial and ethnic groups underrepresented in medical research, often decide to participate based on how they judge people, places, and study protocols as trustworthy. And yet, few studies have explored notions of trustworthiness or determinants of trustworthiness from the perspective of potential medical research participants. OBJECTIVE: This paper describes how racially and ethnically diverse potential medical research participants conceptualize what makes researchers, research settings, and research protocols seem trustworthy. DESIGN: Using a criterion sampling strategy, we recruited African American, Latinx, and White adults for participation in focus groups conducted at a community center servings the Latinx community and at a health clinic that primarily serves the African American community. PARTICIPANTS: A total of 57 African American, Latinx, and White adults APPROACH: We conducted seven focus groups that explored perceptions and determinants of research, trust, privacy, confidentiality, and research participation. We used a phenomenological thematic analytic approach to explore the determinants of trustworthiness to conduct medical research. RESULTS: In our effort to identify the factors that affect potential research participants' perspectives on the trustworthiness of medical research, we found three themes: Who is trustworthy to conduct medical research? What influences perceptions of trustworthiness in medical research? And what institutions or settings are trustworthy to conduct medical research? CONCLUSIONS: These findings highlight that one's willingness to participate in research is driven in part by their perception of the trustworthiness of researchers, research institutions, and the information they are given about potential research opportunities. There are important and modifiable determinants of trustworthiness that may facilitate minority participation in research. We found that research, researchers, and research institutions each have things that can be done to increase trustworthiness and minority participation in research.

Trans-ethnic Meta-analysis and Functional Annotation Illuminates the Genetic Architecture of Fasting Glucose and Insulin.

Knowledge of the genetic basis of the type 2 diabetes (T2D)-related quantitative traits fasting glucose (FG) and insulin (FI) in African ancestry (AA) individuals has been limited. In non-diabetic subjects of AA (n = 20,209) and European ancestry (EA; n = 57,292), we performed trans-ethnic (AA+EA) fine-mapping of 54 established EA FG or FI loci with detailed functional annotation, assessed their relevance in AA individuals, and sought previously undescribed loci through trans-ethnic (AA+EA) meta-analysis. We narrowed credible sets of variants driving association signals for 22/54 EA-associated loci; 18/22 credible sets overlapped with active islet-specific enhancers or transcription factor (TF) binding sites, and 21/22 contained at least one TF motif. Of the 54 EA-associated loci, 23 were shared between EA and AA. Replication with an additional 10,096 AA individuals identified two previously undescribed FI loci, chrX FAM133A (rs213676) and chr5 PELO (rs6450057). Trans-ethnic analyses with regulatory annotation illuminate the genetic architecture of glycemic traits and suggest gene regulation as a target to advance precision medicine for T2D. Our approach to utilize state-of-the-art functional annotation and implement trans-ethnic association analysis for discovery and fine-mapping offers a framework for further follow-up and characterization of GWAS signals of complex trait loci.

A taxonomy of impacts on clinical and translational research from community stakeholder engagement.

BACKGROUND: Community engagement is increasingly recognized as a valuable tool in clinical and translational research; however, the impact of engagement is not fully understood. No standard nomenclature yet exists to clearly define how research changes when community stakeholders are engaged across the research spectrum. This severely limits our ability to assess the value of community engagement in research. To address this gap, we developed a taxonomy for characterizing and classifying changes in research due to community engagement. METHODS: Using an iterative process, we (a) identified areas of potential impact associated with community engagement from author experience, (b) categorized these in taxonomic bins based on research stages, (c) conducted semi-structured interviews with researchers and community stakeholders, (d) validated the codebook in a sample dataset and (e) refined the taxonomy based on the validation. Community stakeholders were involved in every step of the process including as members of the primary study team. RESULTS: The final taxonomy catalogues changes into eleven domains corresponding to research phases. Each domain includes 2-4 dimensions depicting concepts within the domain's scope and, within each dimension, 2-10 elements labelling activities through which community engagement could change research. CONCLUSIONS: Community engagement has great potential to enhance clinical and translational research. This taxonomy provides a common vocabulary and framework for understanding the impact of community engagement and suggests metrics for assessing the value of community engagement in research.

Penetrance of Hemochromatosis in HFE Genotypes Resulting in p.Cys282Tyr and p.[Cys282Tyr];[His63Asp] in the eMERGE Network.

Hereditary hemochromatosis (HH) is a common autosomal-recessive disorder associated with pathogenic HFE variants, most commonly those resulting in p.Cys282Tyr and p.His63Asp. Recommendations on returning incidental findings of HFE variants in individuals undergoing genome-scale sequencing should be informed by penetrance estimates of HH in unselected samples. We used the eMERGE Network, a multicenter cohort with genotype data linked to electronic medical records, to estimate the diagnostic rate and clinical penetrance of HH in 98 individuals homozygous for the variant coding for HFE p.Cys282Tyr and 397 compound heterozygotes with variants resulting in p.[His63Asp];[Cys282Tyr]. The diagnostic rate of HH in males was 24.4% for p.Cys282Tyr homozygotes and 3.5% for compound heterozygotes (p < 0.001); in females, it was 14.0% for p.Cys282Tyr homozygotes and 2.3% for compound heterozygotes (p < 0.001). Only males showed differences across genotypes in transferrin saturation levels (100% of homozygotes versus 37.5% of compound heterozygotes with transferrin saturation > 50%; p = 0.003), serum ferritin levels (77.8% versus 33.3% with serum ferritin > 300 ng/ml; p = 0.006), and diabetes (44.7% versus 28.0%; p = 0.03). No differences were found in the prevalence of heart disease, arthritis, or liver disease, except for the rate of liver biopsy (10.9% versus 1.8% [p = 0.013] in males; 9.1% versus 2% [p = 0.035] in females). Given the higher rate of HH diagnosis than in prior studies, the high penetrance of iron overload, and the frequency of at-risk genotypes, in addition to other suggested actionable adult-onset genetic conditions, opportunistic screening should be considered for p.[Cys282Tyr];[Cys282Tyr] individuals with existing genomic data.

A Multilevel Approach to Stakeholder Engagement in the Formulation of a Clinical Data Research Network.

OBJECTIVES: To ensure meaningful engagement of stakeholders (patients, clinicians, and communities) in developing the Mid-South Clinical Data Research Network (MS-CDRN), we implemented a comprehensive, multilevel approach: (1) identify barriers to involving stakeholders in governance, network design, and implementation; (2) engage stakeholders in priority setting and research topic generation; (3) develop strategies to fully integrate stakeholders in CDRN governance and oversight; and (4) solicit guidance on patient-centered tools and strategies for recruiting research participants. METHODS: We engaged stakeholders: (1) as integral research team members; (2) on oversight and advisory committees; (3) as consultants (using Community Engagement Studios); and (4) through interviews and surveys. We recruited stakeholders from community health centers, churches, barbershops, health fairs, a volunteer registry, and a patient portal. We prioritized recruitment from populations often underrepresented in research. RESULTS: During the first 18 months, we engaged 5670 stakeholders in developing the MS-CDRN. These were research team members and on governance committees (N=10), consultants (N=58), survey respondents (N=5543), and interviewees (N=59). Stakeholders identified important barriers and facilitators to engagement, developed stakeholder-informed policies, provided feedback on priority topics and research questions, and developed an intake process for data requests and interventional studies that included reviewing for appropriate patient-centeredness, patient engagement, and dissemination. DISCUSSION: Multilevel stakeholder engagement is a novel systematic approach to developing a meaningful patient-centered and patient-engaged research program. This approach allows ongoing input from highly engaged stakeholders while leveraging focused input from larger, more diverse groups to enhance the patient-centeredness of research and increase relevance to broader audiences.

Conducting a large, multi-site survey about patients' views on broad consent: challenges and solutions.

BACKGROUND: As biobanks play an increasing role in the genomic research that will lead to precision medicine, input from diverse and large populations of patients in a variety of health care settings will be important in order to successfully carry out such studies. One important topic is participants' views towards consent and data sharing, especially since the 2011 Advanced Notice of Proposed Rulemaking (ANPRM), and subsequently the 2015 Notice of Proposed Rulemaking (NPRM) were issued by the Department of Health and Human Services (HHS) and Office of Science and Technology Policy (OSTP). These notices required that participants consent to research uses of their de-identified tissue samples and most clinical data, and allowing such consent be obtained in a one-time, open-ended or "broad" fashion. Conducting a survey across multiple sites provides clear advantages to either a single site survey or using a large online database, and is a potentially powerful way of understanding the views of diverse populations on this topic. METHODS: A workgroup of the Electronic Medical Records and Genomics (eMERGE) Network, a national consortium of 9 sites (13 separate institutions, 11 clinical centers) supported by the National Human Genome Research Institute (NHGRI) that combines DNA biorepositories with electronic medical record (EMR) systems for large-scale genetic research, conducted a survey to understand patients' views on consent, sample and data sharing for future research, biobank governance, data protection, and return of research results. RESULTS: Working across 9 sites to design and conduct a national survey presented challenges in organization, meeting human subjects guidelines at each institution, and survey development and implementation. The challenges were met through a committee structure to address each aspect of the project with representatives from all sites. Each committee's output was integrated into the overall survey plan. A number of site-specific issues were successfully managed allowing the survey to be developed and implemented uniformly across 11 clinical centers. CONCLUSIONS: Conducting a survey across a number of institutions with different cultures and practices is a methodological and logistical challenge. With a clear infrastructure, collaborative attitudes, excellent lines of communication, and the right expertise, this can be accomplished successfully.

Association of Arrhythmia-Related Genetic Variants With Phenotypes Documented in Electronic Medical Records.

IMPORTANCE: Large-scale DNA sequencing identifies incidental rare variants in established Mendelian disease genes, but the frequency of related clinical phenotypes in unselected patient populations is not well established. Phenotype data from electronic medical records (EMRs) may provide a resource to assess the clinical relevance of rare variants. OBJECTIVE: To determine the clinical phenotypes from EMRs for individuals with variants designated as pathogenic by expert review in arrhythmia susceptibility genes. DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study included 2022 individuals recruited for nonantiarrhythmic drug exposure phenotypes from October 5, 2012, to September 30, 2013, for the Electronic Medical Records and Genomics Network Pharmacogenomics project from 7 US academic medical centers. Variants in SCN5A and KCNH2, disease genes for long QT and Brugada syndromes, were assessed for potential pathogenicity by 3 laboratories with ion channel expertise and by comparison with the ClinVar database. Relevant phenotypes were determined from EMRs, with data available from 2002 (or earlier for some sites) through September 10, 2014. EXPOSURES: One or more variants designated as pathogenic in SCN5A or KCNH2. MAIN OUTCOMES AND MEASURES: Arrhythmia or electrocardiographic (ECG) phenotypes defined by International Classification of Diseases, Ninth Revision (ICD-9) codes, ECG data, and manual EMR review. RESULTS: Among 2022 study participants (median age, 61 years [interquartile range, 56-65 years]; 1118 [55%] female; 1491 [74%] white), a total of 122 rare (minor allele frequency <0.5%) nonsynonymous and splice-site variants in 2 arrhythmia susceptibility genes were identified in 223 individuals (11% of the study cohort). Forty-two variants in 63 participants were designated potentially pathogenic by at least 1 laboratory or ClinVar, with low concordance across laboratories (Cohen κ = 0.26). An ICD-9 code for arrhythmia was found in 11 of 63 (17%) variant carriers vs 264 of 1959 (13%) of those without variants (difference, +4%; 95% CI, -5% to +13%; P = .35). In the 1270 (63%) with ECGs, corrected QT intervals were not different in variant carriers vs those without (median, 429 vs 439 milliseconds; difference, -10 milliseconds; 95% CI, -16 to +3 milliseconds; P = .17). After manual review, 22 of 63 participants (35%) with designated variants had any ECG or arrhythmia phenotype, and only 2 had corrected QT interval longer than 500 milliseconds. CONCLUSIONS AND RELEVANCE: Among laboratories experienced in genetic testing for cardiac arrhythmia disorders, there was low concordance in designating SCN5A and KCNH2 variants as pathogenic. In an unselected population, the putatively pathogenic genetic variants were not associated with an abnormal phenotype. These findings raise questions about the implications of notifying patients of incidental genetic findings.

Differences between health and ethical vegetarians. Strength of conviction, nutrition knowledge, dietary restriction, and duration of adherence.

Little research has been published concerning the differences between health oriented and ethically oriented vegetarians. The present study compared differences in conviction, nutrition knowledge, dietary restriction, and duration of adherence to vegetarianism between the two groups. Subjects completed an online survey and were grouped by original reason for becoming vegetarian (n=292, 58 health, 234 ethical), and current reason for remaining vegetarian (n=281, 49 health, 232 ethical). Whether grouped by current or original motivation, ethical vegetarians scored higher on the conviction instrument than health vegetarians and exhibited somewhat greater dietary restriction (significant when grouped by current motivation) and had been vegetarian for longer (significant when grouped by original motivation). Nutrition knowledge did not differ between the two groups. The results suggest that ethical vegetarians could experience stronger feelings of conviction and consume fewer animal products than health vegetarians, and may remain vegetarian longer. More research is necessary to understand how vegetarians' eating behaviors are influenced by their motivational profiles.

Assessing patient-level knowledge of precision medicine in a community health center setting.

As precision medicine approaches are implemented, cancer treatment decisions have come to require comprehension of genetic tests and their role in risk stratification and treatment options. Acceptance and implementation of precision medicine requires patient understanding of numeracy, genetic literacy, health literacy, and medical trust. Implementing precision medicine in a US federally qualified community health center (FQCHC) setting has received little attention. Using a mixed-methods approach, we sought to identify patient-level factors influencing the understanding of cancer risk and precision medicine among FQCHC patients. We enrolled 26 English-speaking adults aged 40-79 years. Participants enrolled in focus groups and completed surveys to assess patient-level understanding of precision medicine, numeracy, and health literacy. The majority of participants were female (77%) and self-identified as African American (89%). Approximately one-third reported having a high school degree or less. While health literacy was generally high, 42% felt that genes or genetics had little impact on health and most (69%) reported little familiarity with precision medicine. Many participants reported that trust in their providers was extremely or very important when receiving genetic tests. Numeracy levels were moderate, with nearly half reporting some discomfort working with fractions and 38% finding numerical information only occasionally useful. Findings suggest that patients may lack familiarity with precision medicine concepts relevant for understanding cancer treatment decisions. Future educational efforts may help bridge the gap in patient understanding and facilitate equitable opportunities for precision medicine for all patients, including those seeking care from community health centers.

Association of genetically-predicted placental gene expression with adult blood pressure traits.

OBJECTIVE: Blood pressure is a complex, polygenic trait, and the need to identify prehypertensive risks and new gene targets for blood pressure control therapies or prevention continues. We hypothesize a developmental origins model of blood pressure traits through the life course where the placenta is a conduit mediating genomic and nongenomic transmission of disease risk. Genetic control of placental gene expression has recently been described through expression quantitative trait loci (eQTL) studies which have identified associations with childhood phenotypes. METHODS: We conducted a transcriptome-wide gene expression analysis estimating the predicted gene expression of placental tissue in adult individuals with genome-wide association study (GWAS) blood pressure summary statistics. We constructed predicted expression models of 15 154 genes from reference placenta eQTL data and investigated whether genetically-predicted gene expression in placental tissue is associated with blood pressure traits using published GWAS summary statistics. Functional annotation of significant genes was generated using FUMA. RESULTS: We identified 18, 9, and 21 genes where predicted expression in placenta was significantly associated with systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure (PP), respectively. There were 14 gene-tissue associations (13 unique genes) significant only in placenta. CONCLUSIONS: In this meta-analysis using S-PrediXcan and GWAS summary statistics, the predicted expression in placenta of 48 genes was statistically significantly associated with blood pressure traits. Notable findings included the association of FGFR1 expression with increased SBP and PP. This evidence of gene expression variation in placenta preceding the onset of adult blood pressure phenotypes is an example of extreme preclinical biological changes which may benefit from intervention.

Development and Validation of the Perceptions of Research Trustworthiness Scale to Measure Trust Among Minoritized Racial and Ethnic Groups in Biomedical Research in the US.

Importance: Historically, trust in biomedical research has been lower among minoritized racial and ethnic groups who are underrepresented in and excluded from research, with the same groups experiencing worse health outcomes. Unfortunately, instruments that measure trust may not capture components of trust relevant to minoritized racial and ethnic groups. Objective: To develop and validate a scale to measure trust in biomedical research among minoritized racial and ethnic groups. Design, Setting, and Participants: This cross-sectional, community-based survey study compared trust and distrust in biomedical research among Black, Latino, and White subgroups in the US using the Perceptions of Research Trustworthiness (PoRT) scale. The scale was developed between March 22, 2016, and September 19, 2018, as part of this study, and its structure, reliability, and validity were examined during pilot (n = 381) and validation (n = 532) phases between February 4, 2019, and July 27, 2021. Convenience samples of adult participants (aged ≥18 years) were recruited locally (Nashville, Tennessee, and San Antonio, Texas) and nationally through the ResearchMatch and Cint online platforms. Main Outcomes and Measures: Overall and individual item Trust and Distrust subscale scores were compared. Overall Trust and Distrust scores were compared by race and ethnicity using a Kruskal-Wallis H test and individual item scores were compared using independent samples t test. Results: Of the 532 participants in the scale validation study, 144 (27.1%) were Black, 90 (16.9%) were Latino, and 282 (53.0%) were White. Participants had a median age of 43 years (range, 18-90 years), 352 (66.2%) were women, and 198 (37.2%) had educational attainment levels less than a college degree. Factor analysis of the 18-item PoRT scale revealed a 2-factor structure with two 9-item PoRT subscales (Trust and Distrust), which demonstrated high internal consistency (Cronbach α = 0.72 and 0.87, respectively). Mean (SD) Trust subscale scores were lower among Black (34.33 [2.02]) and Latino (34.55 [1.97]) participants compared with White participants (36.32 [1.81]; P < .001). Mean (SD) Distrust subscale scores were higher among Black (21.0 [2.15]) and Latino (20.53 [2.21]) participants compared with White participants (18.4 [2.03]; P < .001). Individual item results showed that Black and Latino participants were less trusting and more distrusting than White individuals on items related to risks, harms, secrecy, confidentiality, and privacy. Conclusions and Relevance: These findings suggest that the PoRT scale incorporates trust and trustworthiness concepts relevant among Black and Latino individuals and may allow more precise assessment of trust in research among these groups.

Factors influencing precision medicine knowledge and attitudes.

Precision medicine holds great promise for improving health and reducing health disparities that can be most fully realized by advancing diversity and inclusion in research participants. Without engaging underrepresented groups, precision medicine could not only fail to achieve its promise but also further exacerbate the health disparities already burdening the most vulnerable. Yet underrepresentation by people of non-European ancestry continues in precision medicine research and there are disparities across racial groups in the uptake of precision medicine applications and services. Studies have explored possible explanations for population differences in precision medicine participation, but full appreciation of the factors involved is still developing. To better inform the potential for addressing health disparities through PM, we assessed the relationship of precision medicine knowledge and trust in biomedical research with sociodemographic variables. Using a series of linear regression models applied to survey data collected in a diverse sample, we analyzed variation in both precision medicine knowledge and trust in biomedical research with socioeconomic factors as a way to understand the range of precision medicine knowledge (PMK) in a broadly representative group and its relationship to trust in research and demographic characteristics. Our results demonstrate that identifying as Black, while significantly PMK, explains only 1.5% of the PMK variance in unadjusted models and 7% of overall variance in models adjusted for meaningful covariates such as age, marital status, employment, and education. We also found a positive association between PMK and trust in biomedical research. These results indicate that race is a factor affecting PMK, even after accounting for differences in sociodemographic variables. Additional work is needed, however, to identify other factors contributing to variation in PMK as we work to increase diversity and inclusion in precision medicine applications.

Patient Stories Can Make a Difference in Patient-Centered Research Design.

Amid increasing interest in improving the patient-centeredness of research, new forms of engagement are emerging that enable researchers to get input from community members on research goals, methods, and implementation. This input often includes stories, which are useful for understanding lived experiences of illness and encounters with health care organizations, and for locating these experiences within larger meta-narratives of specific communities. We analyzed the stories in transcripts of 13 Community Engagement Studios and identified 4 major functions that the stories served in the sessions. Major functions included: (1) establishing mutual understanding, (2) adding expansion and depth, (3) characterizing abstract concepts, and (4) providing context for experience, with the latter being the most frequent. We assert that stories can serve to better communicate the complex contexts of patient experiences, helping to align research priorities and research design with community interests, leading to more patient-centered innovations in clinical practice.

Heritability and genome-wide association study of benign prostatic hyperplasia (BPH) in the eMERGE network.

Benign prostatic hyperplasia (BPH) results in a significant public health burden due to the morbidity caused by the disease and many of the available remedies. As much as 70% of men over 70 will develop BPH. Few studies have been conducted to discover the genetic determinants of BPH risk. Understanding the biological basis for this condition may provide necessary insight for development of novel pharmaceutical therapies or risk prediction. We have evaluated SNP-based heritability of BPH in two cohorts and conducted a genome-wide association study (GWAS) of BPH risk using 2,656 cases and 7,763 controls identified from the Electronic Medical Records and Genomics (eMERGE) network. SNP-based heritability estimates suggest that roughly 60% of the phenotypic variation in BPH is accounted for by genetic factors. We used logistic regression to model BPH risk as a function of principal components of ancestry, age, and imputed genotype data, with meta-analysis performed using METAL. The top result was on chromosome 22 in SYN3 at rs2710383 (p-value = 4.6 × 10-7; Odds Ratio = 0.69, 95% confidence interval = 0.55-0.83). Other suggestive signals were near genes GLGC, UNCA13, SORCS1 and between BTBD3 and SPTLC3. We also evaluated genetically-predicted gene expression in prostate tissue. The most significant result was with increasing predicted expression of ETV4 (chr17; p-value = 0.0015). Overexpression of this gene has been associated with poor prognosis in prostate cancer. In conclusion, although there were no genome-wide significant variants identified for BPH susceptibility, we present evidence supporting the heritability of this phenotype, have identified suggestive signals, and evaluated the association between BPH and genetically-predicted gene expression in prostate.

Enrichment sampling for a multi-site patient survey using electronic health records and census data.

Objective: We describe a stratified sampling design that combines electronic health records (EHRs) and United States Census (USC) data to construct the sampling frame and an algorithm to enrich the sample with individuals belonging to rarer strata. Materials and Methods: This design was developed for a multi-site survey that sought to examine patient concerns about and barriers to participating in research studies, especially among under-studied populations (eg, minorities, low educational attainment). We defined sampling strata by cross-tabulating several socio-demographic variables obtained from EHR and augmented with census-block-level USC data. We oversampled rarer and historically underrepresented subpopulations. Results: The sampling strategy, which included USC-supplemented EHR data, led to a far more diverse sample than would have been expected under random sampling (eg, 3-, 8-, 7-, and 12-fold increase in African Americans, Asians, Hispanics and those with less than a high school degree, respectively). We observed that our EHR data tended to misclassify minority races more often than majority races, and that non-majority races, Latino ethnicity, younger adult age, lower education, and urban/suburban living were each associated with lower response rates to the mailed surveys. Discussion: We observed substantial enrichment from rarer subpopulations. The magnitude of the enrichment depends on the accuracy of the variables that define the sampling strata and the overall response rate. Conclusion: EHR and USC data may be used to define sampling strata that in turn may be used to enrich the final study sample. This design may be of particular interest for studies of rarer and understudied populations.

Development and validation of the Person-Centeredness of Research Scale.

AIM: Person-centeredness shifts the focus of healthcare and research to the needs and priorities of patients and communities, and may improve health outcomes. There are no instruments available, however, with which we can assess the degree to which research is indeed person-centered. Our aim was to develop and validate a quantitative instrument to rate person-centeredness of research. MATERIALS & METHODS: Scale development and validation entailed a multistep approach that led to the seven-item Person Centeredness of Research Scale (PCoR Scale) that uses a 5-point Likert rating scale. The scale was validated using ratings of the Patient-Centered Outcomes Research Institute-funded research abstracts or abstracts submitted to a translational science meeting. RESULTS: Psychometric properties of the PCoR Scale showed high internal consistency (α = 0.96). All seven items were highly correlated with the total score (rs range from 0.63 to 0.90). An exploratory factor analysis demonstrated that all of the items loaded on a single factor, explaining 80% of the variance. The Patient-Centered Outcomes Research Institute-funded research abstracts had a mean PCoR Scale score of 6.52 (±8.01) that was significantly higher than the abstracts submitted to the translational science meeting (-2.56 (±9.18); t = 8.09; p < 0.0001). Inter-rater reliability in the validation of the revised instrument was high (Intraclass Correlation Coefficient [ICC](group1) = 0.89; ICC(group2) = 0.95). CONCLUSION: This brief, quantitative rating scale is the first to assess the main constructs that describe person-centeredness of research products. The PCoR Scale can be used to assess person-centeredness in research products; for example, by funders evaluating proposals, data networks evaluating data requests or researchers evaluating their research designs.

A case study evaluating the portability of an executable computable phenotype algorithm across multiple institutions and electronic health record environments.

Electronic health record (EHR) algorithms for defining patient cohorts are commonly shared as free-text descriptions that require human intervention both to interpret and implement. We developed the Phenotype Execution and Modeling Architecture (PhEMA, http://projectphema.org) to author and execute standardized computable phenotype algorithms. With PhEMA, we converted an algorithm for benign prostatic hyperplasia, developed for the electronic Medical Records and Genomics network (eMERGE), into a standards-based computable format. Eight sites (7 within eMERGE) received the computable algorithm, and 6 successfully executed it against local data warehouses and/or i2b2 instances. Blinded random chart review of cases selected by the computable algorithm shows PPV ≥90%, and 3 out of 5 sites had >90% overlap of selected cases when comparing the computable algorithm to their original eMERGE implementation. This case study demonstrates potential use of PhEMA computable representations to automate phenotyping across different EHR systems, but also highlights some ongoing challenges.