Understanding stakeholder perspectives, preferences and experiences on the return of individual pharmacogenomic research results

Abstract

Globally, the return of results from genomic analyses including pharmacogenomics research has been approached with several debates in the past decades. Despite research participants’ high demand for individual genomic and pharmacogenomic research results, there is little consensus on whether results should be returned at all in research setting and if so, what kinds of results, how they should be returned, and under what circumstances should results be returned. This study aimed to analyse stakeholder perspectives, experiences, and preferences to develop an institutional procedural guidance for the return of individual pharmacogenomic research results to people living with HIV. We carried out three sub studies at Makerere University College of Health Sciences and affiliated HIV research institutions located on Mulago Hill. In sub-study I, a convergent parallel mixed methods study was conducted where 225 participants were enrolled in a survey and 30 of them participated in deliberative focus group discussions (dFGDs). Qualitative data were analysed using thematic analysis method. Quantitative data were analysed using a Poisson model and a multinomial logistic regression model to determine the factors influencing the primary outcome (preferences for either all results, partial results or none of the results) and secondary outcome (preference for either the active role, collaborative role or passive role) respectively. In Sub-study II, an exploratory descriptive qualitative study was conducted with 12 REC members, 12 researchers and 30 CAB members to analyse the stakeholder perspectives and ethical considerations on how individual results should be safely returned to people living with HIV. The data were analysed using thematic analysis. In sub-study III, a modified ADAPTE process methodology was employed to develop an institutional procedural guidance for the return of individual pharmacogenomic research results in three phases. These included the set-up phase, adaptation phase, and finalization phase. We utilized the findings from sub-study I and II in the adaptation phase to develop the first draft of the procedural guidance. We also utilized the feedback from the panelists and potential end-users to develop the second and final draft of the procedural guidance. Sub-study I: For the primary outcome; the majority (98%) participants wanted to receive individual primary pharmacogenomics research results. Factors that significantly influenced preference for all results were antiretroviral experience for than five years (PR: 1.69, p=0.001), attending the IDI clinic from more than five years (PR: 1.19, p=0.045), and religion (PR: 0.76, p=0.036). Reasons for the desire to receive results were reciprocity for valuable time and effort, preparing for future eventualities, and the right to health information. For the secondary outcome; most participants 55.2% (122/221) preferred the collaborative role, 30.3% (67/221) preferred the active role, and 14.5% (32/221) preferred the passive role. Factors that significantly influenced preference for an active role compared with a collaborative role were marital status (OR: 0.282, p=0.013), research experience (OR: 4.37, p=0.028), and religion (OR: 2.346, p=0.041). The reasons proffered for the active role included prior experience with antiretroviral treatment and increased exposure to research activities. Sub-study II: The prominent themes from the interviews and deliberative focus group discussions included stakeholder’s attitudes, ethical and social implications, perceived challenges and recommendations to the process of returning individual results. Additionally, five themes emerged regarding the key considerations for a safe return of individual results. These included, (i) defining the nature of research results to return to participants; (ii) obtaining informed consent and preparing research participants to receive their individual results; (iii) opinion on how to communicate results to participants, (iv) community engagement strategies for promoting understanding of pharmacogenomic results; (v) perceived roles of stakeholders in promoting participants’ understanding and utilization of pharmacogenomic research results. Sub-study III: The institutional procedural guidance comprised of three main phases, which include pre-study phase (protocol development phase), the feedback of individual results phase, and the post-feedback of individual results phase. In each phase, several key considerations have been described to guide researchers on how individual results can be safely returned to participants. This study provides insights into stakeholder perspectives, preferences, and experiences on whether and how individual pharmacogenomic research results should be returned to PLHIV safely. These insights contribute to the national and international debates on whether and how genomic and genetic results should be returned to participants. Of interest, all stakeholders agree that individual results provide an opportunity to improve participants’ quality of life and uphold the principle of autonomy. However, there is a need for caution when returning such results, especially the incidental findings whose implications do not only affect an individual but might extend to their families and communities. We recommend further research to explore the feasibility of using various culturally appropriate strategies to enhance participants’ understanding of pharmacogenomic research information and the implications of these results.