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Race/Ethnicity and the Pharmacogenetics of Reported Suicidality With Efavirenz Among Clinical Trials Participants.

ABSTRACT: Background:We examined associations between suicidality and genotypes that predict plasma efavirenz exposure among AIDS Clinical Trials Group study participants in the United States. Methods:Four clinical trials randomly assigned treatment-naive participants to efavirenz-containing regimens; suicidality was defined as reported suicidal ideation or attempted or completed suicide. Genotypes that predict plasma efavirenz exposure were defined by CYP2B6 and CYP2A6 polymorphisms. Associations were evaluated with weighted Cox proportional hazards models stratified by race/ethnicity. Additional analyses adjusted for genetic ancestry and selected covariates. Results:Among 1833 participants, suicidality was documented in 41 in exposed analyses, and 34 in on-treatment analyses. In unadjusted analyses based on 12 genotype levels, suicidality increased per level in exposed (hazard ratio, 1.11; 95% confidence interval, .96-1.27) and on-treatment 1.16; 1.01-1.34) analyses. In the on-treatment analysis, the association was strongest among white but nearly null among black participants. Considering 3 metabolizer levels (extensive, intermediate and slow), slow metabolizers were at increased risk. Results were similar after baseline covariate-adjustment for genetic ancestry, sex, age, weight, injection drug use history, and psychiatric history or recent psychoactive medication. Conclusions:Genotypes that predict higher plasma efavirenz exposure were associated with increased risk of suicidality. Strength of association varied by race/ethnicity.

SUBMITTER: Mollan KR

PROVIDER: S-EPMC5853681 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Race/Ethnicity and the Pharmacogenetics of Reported Suicidality With Efavirenz Among Clinical Trials Participants.

Mollan Katie R KR Tierney Camlin C Hellwege Jacklyn N JN Eron Joseph J JJ Hudgens Michael G MG Gulick Roy M RM Haubrich Richard R Sax Paul E PE Campbell Thomas B TB Daar Eric S ES Robertson Kevin R KR Ventura Diana D Ma Qing Q Edwards Digna R Velez DRV Haas David W DW

The Journal of infectious diseases 20170901 5

<h4>Background</h4>We examined associations between suicidality and genotypes that predict plasma efavirenz exposure among AIDS Clinical Trials Group study participants in the United States.<h4>Methods</h4>Four clinical trials randomly assigned treatment-naive participants to efavirenz-containing regimens; suicidality was defined as reported suicidal ideation or attempted or completed suicide. Genotypes that predict plasma efavirenz exposure were defined by CYP2B6 and CYP2A6 polymorphisms. Assoc ...[more]

PMID: 28931220

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Project description:BackgroundSystemic progress in improving trial representation is uncertain, and previous analyses of minority trial participation have been limited to small cohorts with limited exploration of driving factors.MethodsWe analyzed detailed trial records from all US clinical trials registered in ClinicalTrials.gov from March 2000 to March 2020. Minority enrollment was compared to 2010 US Census demographic estimates using Wilcoxon test. We utilized logistic regression and generalized linear regression with a logit link to assess the association of possible drivers (including trials' funding source, size, phase, and design) with trials' disclosure of and amount of minority enrollment respectively.FindingsAmong 20,692 US-based trials with reported results (representing ~4·76 million enrollees), only 43% (8,871/20,692) reported any race/ethnicity data. The majority of enrollees were White (median 79·7%; interquartile range [IQR] 61·9-90·0%), followed by Black (10·0%; IQR 2·5-23·5%), Hispanic/Latino (6·0%; IQR 0·43-15·4%), Asian (1·0%; IQR 0·0-4·1%), and American Indian (0·0%; IQR 0·0-0·2%). Median combined enrollment of minority race/ethnicity groups (Black, Hispanic/Latino, Asian, American Indian, Other/Multi) was below census estimates (27·6%) (p<0·001) however increased at an annual rate of 1·7%. Industry and Academic funding were negatively associated with race/ethnicity reporting (Industry adjusted odds ratio [aOR]: 0·42, 95% confidence interval [CI]: 0·38 to 0·46, p<0.0001; Academic aOR: 0·45, CI: 0·41 to 0·50, p<0.0001). Industry also had a negative association with the proportion of minority ethnicity enrollees (aOR: 0·69, CI: 0·60 to 0·79) compared to US Government-funded trials.InterpretationOver the past two decades, the majority of US trials in ClinicalTrials.gov do not report race/ethnicity enrollment data, and minorities are underrepresented in trials with modest improvement over time.FundingStanford Medical Scholars Research Funding, the National Heart, Lung, and Blood Institute, NIH (1K01HL144607) and the American Heart Association/Robert Wood Johnson Medical Faculty Development Program.

Project description:ImportanceRepresentativeness of populations within neonatal clinical trials is crucial to moving the field forward. Although racial and ethnic disparities in research inclusion are well documented in other fields, they are poorly described within neonatology.ObjectiveTo describe the race and ethnicity of infants included in a sample of recent US neonatal clinical trials and the variability in this reporting.Evidence reviewA systematic search of US neonatal clinical trials entered into Cochrane CENTRAL 2017 to 2021 was conducted. Two individuals performed inclusion determination, data extraction, and quality assessment independently with discrepancies adjudicated by consensus.FindingsOf 120 studies with 14 479 participants that met the inclusion criteria, 75 (62.5%) included any participant race or ethnicity data. In the studies that reported race and ethnicity, the median (IQR) percentage of participants of each background were 0% (0%-1%) Asian, 26% (9%-42%) Black, 3% (0%-12%) Hispanic, 0% (0%-0%) Indigenous (eg, Alaska Native, American Indian, and Native Hawaiian), 0% (0%-0%) multiple races, 57% (30%-68%) White, and 7% (1%-21%) other race or ethnicity. Asian, Black, Hispanic, and Indigenous participants were underrepresented, while White participants were overrepresented compared with a reference sample of the US clinical neonatal intensive care unit (NICU) population from the Vermont Oxford Network. Many participants were labeled as other race or ethnicity without adequate description. There was substantial variability in terms and methods of reporting race and ethnicity data. Geographic representation was heavily skewed toward the Northeast, with nearly one-quarter of states unrepresented.Conclusions and relevanceThese findings suggest that neonatal research may perpetuate inequities by underrepresenting Asian, Black, Hispanic, and Indigenous neonates in clinical trials. Studies varied in documentation of race and ethnicity, and there was regional variation in the sites included. Based on these findings, funders and clinical trialists are advised to consider a 3-point targeted approach to address these issues: prioritize identifying ways to increase diversity in neonatal clinical trial participation, agree on a standardized method to report race and ethnicity among neonatal clinical trial participants, and prioritize the inclusion of participants from all regions of the US in neonatal clinical trials.

Dataset Information

Race/Ethnicity and the Pharmacogenetics of Reported Suicidality With Efavirenz Among Clinical Trials Participants.

Publications

Race/Ethnicity and the Pharmacogenetics of Reported Suicidality With Efavirenz Among Clinical Trials Participants.

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