Patient priorities for fulfilling the principle of respect in research: findings from a modified Delphi study.

BACKGROUND: Standard interpretations of the ethical principle of respect for persons have not incorporated the views and values of patients, especially patients from groups underrepresented in research. This limits the ability of research ethics scholarship, guidance, and oversight to support inclusive, patient-centered research. This study aimed to identify the practical approaches that patients in community-based settings value most for conveying respect in genomics research. METHODS: We conducted a 3-round, web-based survey using the modified Delphi technique to identify areas of agreement among English-speaking patients at primary care clinics in Washington State and Idaho who had a personal or family history of cancer. In Round 1, respondents rated the importance of 17 items, identified in prior qualitative work, for feeling respected. In Round 2, respondents re-rated each item after reviewing overall group ratings. In Round 3, respondents ranked a subset of the 8 most highly rated items. We calculated each item's mean and median rankings in Round 3 to identify which approaches were most important for feeling respected in research. RESULTS: Forty-one patients consented to the survey, 21 (51%) completed Round 1, and 18 (86% of Round 1) completed each of Rounds 2 and 3. Two sets of rankings were excluded from analysis as speed of response suggested they had not completed the Round 3 ranking task. Respondents prioritized provision of study information to support decision-making (mean ranking 2.6 out of 8; median ranking 1.5) and interactions with research staff characterized by kindness, patience, and a lack of judgment (mean ranking 2.8; median ranking 2) as the most important approaches for conveying respect. CONCLUSIONS: Informed consent and interpersonal interactions are key ways that research participants experience respect. These can be supported by other approaches to respecting participants, especially when consent and/or direct interactions are infeasible. Future work should continue to engage with patients in community-based settings to identify best practices for research without consent and examine unique perspectives across clinical and demographic groups in different types of research.

Motivations and concerns of patients considering participation in an implementation study of a hereditary cancer risk assessment program in diverse primary care settings.

PURPOSE: Understanding the motivations and concerns of patients from diverse populations regarding participation in implementation research provides the needed evidence about how to design and conduct studies for facilitating access to genetics services. Within a hereditary cancer screening study assessing a multifaceted intervention, we examined primary care patients' motivations and concerns about participation. METHODS: We surveyed and interviewed study participants after they enrolled, surveyed those who did not complete enrollment, and used descriptive qualitative and quantitative methods to identify motivations and concerns regarding participation. RESULTS: Survey respondents' most common motivations included a desire to learn about their future risk (81%), receiving information that may help family (58%), and a desire to advance research (34%). Interviews revealed 3 additional important factors: affordability of testing, convenience of participation, and clinical relationships supporting research decision-making. Survey data of those who declined enrollment showed that the reasons for declining included concerns about privacy (38%), burdens of the research (19%), and their fear of not being able to cope with the genetic information (19%). CONCLUSION: Understanding the facilitating factors and concerns that contribute to decisions about research may reveal ways to improve equity in access to care and research that could lead to greater uptake of genomic medicine across diverse primary care patient populations.

Literacy-adapted, electronic family history assessment for genetics referral in primary care: patient user insights from qualitative interviews.

BACKGROUND: Risk assessment for hereditary cancer syndromes is recommended in primary care, but family history is rarely collected in enough detail to facilitate risk assessment and referral - a roadblock that disproportionately impacts individuals with healthcare access barriers. We sought to qualitatively assess a literacy-adapted, electronic patient-facing family history tool developed for use in diverse, underserved patient populations recruited in the Cancer Health Assessments Reaching Many (CHARM) Study. METHODS: Interview participants were recruited from a subpopulation of CHARM participants who experienced barriers to tool use in terms of spending a longer time to complete the tool, having incomplete attempts, and/or providing inaccurate family history in comparison to a genetic counselor-collected standard. We conducted semi-structured interviews with participants about barriers and facilitators to tool use and overall tool acceptability; interviews were recorded and professionally transcribed. Transcripts were coded based on a codebook developed using inductive techniques, and coded excerpts were reviewed to identify overarching themes related to barriers and facilitators to family history self-assessment and acceptability of the study tool. RESULTS: Interviewees endorsed the tool as easy to navigate and understand. However, they described barriers related to family history information, literacy and language, and certain tool functions. Participants offered concrete, easy-to-implement solutions to each barrier. Despite experience barriers to use of the tool, most participants indicated that electronic family history self-assessment was acceptable or preferable in comparison to clinician-collected family history. CONCLUSIONS: Even for participants who experienced barriers to tool use, family history self-assessment was considered an acceptable alternative to clinician-collected family history. Barriers experienced could be overcome with minor adaptations to the current family history tool. TRIAL REGISTRATION: This study is a sub-study of the Cancer Health Assessments Reaching Many (CHARM) trial, ClinicalTrials.gov, NCT03426878. Registered 8 February 2018.

Integrating stakeholder feedback in translational genomics research: an ethnographic analysis of a study protocol's evolution.

PURPOSE: This study describes challenges faced while incorporating sometimes conflicting stakeholder feedback into study design and development of patient-facing materials for a translational genomics study aiming to reduce health disparities among diverse populations. METHODS: We conducted an ethnographic analysis of study documents including summaries of patient advisory committee meetings and interviews, reflective field notes written by study team members, and correspondence with our institutional review board (IRB). Through this analysis, we identified cross-cutting challenges for incorporating stakeholder feedback into development of our recruitment, risk assessment, and informed consent processes and materials. RESULTS: Our analysis revealed three key challenges: (1) balancing precision and simplicity in the design of study materials, (2) providing clinical care within the research context, and (3) emphasizing potential study benefits versus risks and limitations. CONCLUSIONS: While involving patient stakeholders in study design and materials development can increase inclusivity and responsiveness to patient needs, patient feedback may conflict with that of content area experts on the research team and IRBs who are tasked with overseeing the research. Our analysis highlights the need for further empirical research about ethical challenges when incorporating patient feedback into study design, and for dialogue with genomic researchers and IRB representatives about these issues.

Demonstrating 'respect for persons' in clinical research: findings from qualitative interviews with diverse genomics research participants.

The ethical principle of 'respect for persons' in clinical research has traditionally focused on protecting individuals' autonomy rights, but respect for participants also includes broader, although less well understood, ethical obligations to regard individuals' rights, needs, interests and feelings. However, there is little empirical evidence about how to effectively convey respect to potential and current participants. To fill this gap, we conducted exploratory, qualitative interviews with participants in a clinical genomics implementation study. We interviewed 40 participants in English (n=30) or Spanish (n=10) about their experiences with respect in the study and perceptions of how researchers in a hypothetical observational study could convey respect or a lack thereof. Most interviewees were female (93%), identified as Hispanic/Latino(a) (43%) or non-Hispanic white (38%), reported annual household income under US$60 000 (70%) and did not have a Bachelor's degree (65%); 30% had limited health literacy. We identified four key domains for demonstrating respect: (1) personal study team interactions, with an emphasis on empathy, appreciation and non-judgment; (2) study communication processes, including following up and sharing results with participants; (3) inclusion, particularly ensuring materials are understandable and procedures are accessible; and (4) consent and authorisation, including providing a neutral informed consent and keeping promises regarding privacy protections. While the experience of respect is inherently subjective, these findings highlight four key domains that may meaningfully demonstrate respect to potential and current research participants. Further empirical and normative work is needed to substantiate these domains and evaluate how best to incorporate them into the practice of research.

Reexamining the categorical exclusion of pediatric participants from controlled human infection trials.

Controlled human infection (CHI) models have been developed for numerous pathogens in order to better understand disease processes and accelerate drug and vaccine testing. In the past, some researchers conducted highly controversial CHIs with vulnerable populations, including children. Ethical frameworks for CHIs now recommend vulnerable populations be excluded because they cannot consent to high risk research. In this paper we argue that CHI studies span a wide spectrum of benefit and risk, and that some CHI studies may involve minimal risk. The categorical exclusion of children from CHIs therefore departs from the standard approach to evaluating research risks, as international regulations and ethical guidance for pediatric research generally permit non-beneficial research with low risks. The paradigm in research ethics has also shifted from focusing on protecting vulnerable participants to recognizing that inclusion can be important as a matter of justice, providing new reasons to question this default exclusion of children from CHIs. Recognizing that pediatric CHIs can raise complex ethical issues and are easy to sensationalize in ways that may threaten the public's trust in research and sponsor institutions, we conclude by describing additional complexities that must be addressed before pediatric CHIs beyond licensed vaccine studies might be ethically acceptable.

Development of the Better Research Interactions for Every Family (BRIEF) intervention to support recruitment for neonatal clinical trials: an intervention mapping guided approach.

BACKGROUND: Recruitment for neonatal clinical trials can be particularly challenging. Low enrollment rates bias the research population and decrease generalizability of findings. We identified a critical need for an intervention to improve how researchers recruit for neonatal clinical trials. Working within the US neonatal research context, we developed the Better Research Interactions for Every Family (BRIEF) Intervention, which had two overarching goals: to improve the recruitment experience for all parents, focusing on minoritized populations, and to increase participation, focusing on decreasing disparities in research participation. METHODS: We used intervention mapping (IM) to guide all steps of intervention development. IM is a planning framework that provides a systematic process and detailed protocol for step-by-step decision-making for intervention development, implementation, and evaluation. RESULTS: We performed IM's six steps. In step 1, we convened two stakeholder groups, a parent panel and an expert panel, who provided guidance through development of all BRIEF components. Through a recent systematic review, empirical data collected by our team, and consultations with the panels, we identified key determinants (barriers and facilitators) of low enrollment rates and research team members as change agents. In step 2, we iteratively refined our list of key factors to include and linked determinants of behavior changes to these performance objectives. In step 3, we chose three theories (social cognitive theory, theory of information processing, and the trans-theoretical model), methods from identified practical applications suitable for the population (research team members) and the context (busy research NICU teams). In step 4, we developed and refined the intervention components, including self-guided pre-work and a single in-person session. In step 5, we identified the Darbepoetin plus slow-release intravenous iron trial as our partner study in which to pilot BRIEF. In step 6, we developed a multi-stage evaluation plan that included five distinct levels of outcomes. CONCLUSIONS: This manuscript shares our rationale and processes for the creation of a research team member-facing intervention aiming to improve recruitment processes for neonatal clinical trials. Our approach can inform those aiming to improve recruitment for neonatal clinical trials and those who may be considering use of IM within similar contexts.