JMIR Publications

ABSTRACT

Background:

Population genomic screening (PGS) offers great promise in identifying the 1-2% of the population that carries a pathogenic variant that puts them at elevated risk for serious, yet manageable genetic conditions such as Hereditary Breast and Ovarian Cancer Syndrome, Lynch Syndrome, and Familial Hypercholesterolemia.1-5 Rapidly decreasing sequencing costs, endorsement of PGS by national bodies, and attention to precision medicine applications have accelerated the spread of PGS programs.6,7 To date, no clear guidelines or strategies exist to support the equitable implementation of PGS. Contextual factors, including program-level procedures, organizational structure, and characteristics of the patient population, influence implementation of these large-scale PGS initiatives. Research by our team and others has identified factors impacting the implementation of PGS, including engagement of key stakeholders and champions, implementation of PGS as a research program or clinical service, and availability of genetic counseling services.8-11 Given the anticipated growth of PGS programs, practice-based research is needed to better understand these and other factors to inform equitable implementation of PGS programs.11 In its report, the Genomics and Population Health Action Collaborative emphasized the importance of engaging diverse populations in PGS, including racial and ethnic minority groups, people living in rural communities, and those with lower education or income.12-14 Diverse populations are at risk of being left behind in the implementation of PGS if efforts are not oriented to explicitly address health equity in genomics.15 Current PGS implementation inequities limit the ability for genomics-based research and genetics services to capture genetic diversity from a broad range of populations to support the development of effective precision prevention strategies and therapies for individuals of all backgrounds.13,14,16,17 Implementation science contains tools to integrate health equity and genomic medicine to ensure implementation of PGS does not exacerbate inequities. To help facilitate growth of PGS programs and enhance recruitment and retention of representative populations into genomic initiatives, we propose to identify best practices for PGS implementation and develop and test a freely available, online, multicomponent implementation guide (FOCUS toolkit). Our project’s specific aims are as follows: 1) Describe differences in processes, barriers, and facilitators to equitable implementation across sites at various stages of PGS implementation, 2) Develop and package implementation strategies into the FOCUS toolkit to support the equitable implementation of PGS programs, 3) Evaluate the impact of the FOCUS toolkit on improving implementation of PGS in diverse populations and settings using a hybrid stepped wedge cluster randomized trial. This project will establish a gold standard approach for equitably integrating PGS and offer the field generalizable methods and knowledge about PGS implementation. In this paper we describe the planned approach for achieving these aims and highlight how this approach is intended to advance the goal of implementing equitable PGS programs that improve population health.

Objective:

With a focus on health equity and stakeholder engagement, the FOCUS toolkit will establish a standardized approach to scaling PGS programs across diverse populations and settings, ensuring genomics benefits are accessible to all.

Methods:

Overall Study Design and Conceptual Model We will use an implementation mapping (IM) approach to complete the FOCUS project (Figure 1).Once an organization has made the decision to implement an evidence-based intervention (e.g., PGS), use of IM supports the integration of this program in real-world settings.18 IM is a structured framework involving five steps that incorporates theory, empirical evidence, and diverse perspectives with the target population to iteratively guide decision making at each step.18 We incorporate a health equity focus in genomic medicine as described by the NHGRI in 2019 throughout all components of the IM process, the global applicability of genomic knowledge, fair and even access to genomic services such as testing and counseling, and unbiased implementation of genomic medicine.15 Consolidated Framework for Implementation Research integrated with the Health Equity Implementation Framework (CFIR/HE) The Consolidated Framework for Implementation Research (CFIR) integrated with health equity (HE) helps create a robust approach for advancing equitable implementation. CFIR/HE includes multilevel determinants of implementation and factors that inform differences in individuals’ access to health services, including key factors at the patient, provider, and system levels.19,20 When combined with CFIR, the HE framework, which focuses on identifying and addressing structural and systemic barriers that perpetuate health disparities, supports a nuanced understanding of determinants of implementation. The CFIR/HE framework will be used to guide Task 1 of IM. Reach, Effectiveness, Adoption, Implementation, Maintenance framework for Health Equity (RE-AIM/HE) The RE-AIM/HE framework emphasizes the five dimensions of reach, effectiveness, adoption, implementation, and maintenance to evaluate implementation across diverse settings. Integration of HE adds and explicit focus on identifying and addressing health disparities by incorporating structural, cultural, and systematic factors that influence equitable implementation, which can help inform the evaluation and impact of new programs such as PGS across diverse populations and settings.21,22 The RE-AIM/HE framework will be used to guide Task 5 of IM. PGS Sites We will work with two distinct sets of PGS sites: FOCUS Design Sites and FOCUS Test Sites. The FOCUS Design Sites will be part of Aim 1, which will involve identification and synthesis of evidence about the implementation processes, barriers, and facilitators for PGS implementation. We will include 10 diverse organizations that can speak to experiences across implementation stages: exploration, preparation, implementation, sustinment.23 We will also work with FOCUS Test Sites to rigorously evaluate the FOCUS toolkit for improving the implementation of PGS. These sites will also be at various stages of implementation. We plan to include 12 organizations as FOCUS Test Sites.23,24 Implementation Mapping (IM) Advisory Panel Stakeholder engagement is a critical part of implementation mapping (IM) to ensure an equity-focused approach to the project and will support all aspects of this work. Thus, we have organized an Advisory Panel of 13 individuals consisting of public health agency members, community members, patient groups, a private population screening company, primary care, and clinical stakeholders that will be engaged throughout each Aim. The group will meet on a quarterly basis and support the study team in prioritizing, designing, and conducting research throughout the duration of the project. Study Aim 1: Describe differences in processes, barriers, and facilitators to equitable implementation across sites at various stages of PGS implementation The first Aim of the FOCUS study is aligned with IM Task 1. We will conduct a qualitative needs assessment among ten PGS programs (i.e. FOCUS Design Sites) at various implementation stages (exploration, preparation, implementation, and sustainment) guided by CFIR/HE.19,20 Emerging Sites are defined as institutions in the planning and development stages of PGS program implementation. Implementing Sites are defined as institutions that have begun conducting screenings and are building out their programs. Sustaining Sites are defined as sites that have been implementing their PGS program for over a year. These 10 sites will be enrolling either clinical or research PGS cohorts.22,25 The CFIR/HE framework will be used to create an interview guide to identify barriers and facilitators of implementing PGS. The needs assessment will be conducted via interview(s) of implementation team members (ITM), PGS patients (PAT), and laboratory sites. Participants will be assigned a study identification number and all identifying data elements (e.g., name, dates) will be removed. The questions asked during the interviews have been adapted from CFIR and agreed upon by the FOCUS study team and the IM Advisory Panel. Interview questions will be specific to the participants (e.g., IMP, PAT, laboratory sites). As interviews are completed, we will begin extracting qualitative data from the transcripts and audio/visual recordings, via Microsoft Teams for analysis. We will use rapid qualitative data analysis methods to code interviews for each site.26,27 We will complete Transcript Summaries for each interview that match interview question responses to CFIR/HE domains and sub-domains. These Transcript Summaries will be utilized in two subsequent qualitative data analysis steps – Process Mapping and Data Matrix Heat Mapping - that have been described by Salvati et al.28 Briefly, process maps will visually detail the PGS implementation process and workflow described by each team member during their interview. Upon completion of all interviews at the respective site, we will conduct member checking among these interviewees to reconcile discrepancies or omissions in the process maps. This will allow us to create a final aggregate process map for each site. Site-level data matrix heat maps will be generated through an iterative process that involves mapping interview data to each of the CFIR/HE factors within a spreadsheet and then color coding each construct to represent the extent to which it serves as a facilitator or barrier for PGS implementation at that site. Site-level heat maps will then be consolidated and combined to allow for cross-site comparisons and the identification of patterns of factors that are similar and different across sites. Study Aim 2: Develop and package implementation strategies into the FOCUS toolkit to support the equitable implementation of PGS programs The second Aim of the FOCUS study is to develop the FOCUS toolkit consisting of equity-focused implementation strategies, materials, and protocols for implementing and improving PGS programs. This Aim will cover IM Tasks 2-4. First, we will identify outcomes and objectives by working with the IM Advisory Panel to prioritize the facilitators, barriers, and inefficiencies identified in IM Task 1 by importance, health equity relevance, and changeability. This will allow us to identify outcomes (i.e., what needs to be added or changed to improve PGS implementation) and objectives (i.e., how we will address the identified outcomes) (IM Task 2). We will work with the IM Advisory Panel during Aim 2 to select evidence-based strategies to address the facilitators, barriers, and inefficiencies of PGS implementation (e.g., information chunking, guided practice, etc.). Using the CFIR-ERIC matching tool (IM Task 3),29 which aligns ERIC strategies with CFIR factors identified in Task 1. This will allow us to identify appropriate implementation strategies for each priority implementation need,30 including the need for equity in access to and quality of PGS. The study team will host a feedback session with the IM Advisory Panel on these potential methods and strategies at the conclusion of Task 3 and integrate feedback from the panel based on this session. Ultimately we will draft implementation strategy protocols and develop materials to package our implementation strategies into the online FOCUS Toolkit for PGS (IM Task 4). Once the FOCUS toolkit draft has been developed, we will host a feedback session with the IM Advisory panel to capture and integrate recommendations. Finally, we will use a human centered design approach to prototype and refine the FOCUS toolkit with our FOCUS design sites.731 Engaging program champions and implementation team members from the eight FOCUS design sites, we will conduct a live rapid prototyping and iterating session (non-statistical approaches) to refine our proposed protocols and materials. Validated measures will be used to assess acceptability, appropriateness, and feasibility of using the FOCUS toolkit.32,33 Through these live sessions we will collect feedback until we have reached consensus among the IM Advisory Panel of the planned FOCUS toolkit materials. We will prioritize strategies that were common across PGS sites and that aim to achieve equity in PGS participation and implementation. Study Aim 3: Evaluate the impact of the FOCUS toolkit on improving implementation of PGS in diverse populations and settings using a hybrid stepped wedge cluster randomized trial The final Aim of the FOCUS study is to evaluate the impact of the FOCUS toolkit on Reach, Effectiveness, Implementation, Adoption, Maintenance (RE-AIM), and HE outcomes for PGS in 12 FOCUS Test Sites with diverse populations and settings. The Stepped-Wedge Cluster Randomized Trial design to evaluate the utility of the FOCUS toolkit for improving outcomes among the 12 FOCSU test sites).21 This approach will allow us to assess improvements in RE-AIM/HE outcomes among sites at varying stages of implementation: exploration, preparation, implementation, and sustainment. Because sites in the exploration phase will not have begun implementing PGS prior to using the FOCUS toolkit (no baseline/pre-FOCUS toolkit data about the PGS program), they will be randomized 1:1 to either control (no FOCUS toolkit) or intervention (FOCUS toolkit) conditions using a parallel design. The eight existing sites will be actively implementing or sustaining their PGS programs (have baseline/pre-FOCUS toolkit data) and will be randomized 1:1 to one of four possible time steps every three months for a 21-month implementation period (steps at 3, 6, 9, and 12 months) (Figure 2). This hybrid stepped wedge cluster randomized trial design is a pragmatic approach that will allow us to simultaneously assess RE-AIM/HE outcomes across a representative and generalizable sample of PGS sites with varying amounts of baseline program implementation data and assessment of correlates of post-toolkit use outcomes.34-36 Quantitative data about RE-AIM/HE outcomes will be collected using three tools: 1) PGS Program Data Collection Form, 2) Stakeholder Surveys, and 3) Toolkit Tracking Data (Table 1). The PGS Program Data Collection Form will be completed monthly by each site using a REDCap (Research Electronic Data Capture) form designed by the study team. The form will assess metrics related to the implementation outcomes of Reach, Effectiveness, and Adoption. Reach, or how well the PGS site recruits the intended audience, will be measured by the total number of people recruited to participate in the PGS program.37 Effectiveness will be assessed based on how well the PGS program is achieving its intended public health outcome of identifying individuals with pathogenic variants in genes associated with Tier 1 conditions. Our primary measure of Effectiveness is the proportion of eligible individuals tested. We will also evaluate rate of positive findings (number of positive results returned/number tested). Adoption will be assessed based on the number of providers who participate in the PGS program at each site out of the total number of providers eligible to participate at the site. The Stakeholder Surveys will be distributed to implementation stakeholders at each site prior to beginning to use the PGS toolkit, three months after starting to use the toolkit, and at the conclusion of using the toolkit. These will capture data to assess RE-AIM/HE outcomes of Implementation and Maintenance. Implementation assessment will include acceptability, appropriateness, and feasibility of PGS. These will be captured using the Acceptability of Intervention Measure, Intervention Appropriateness Measure, and Feasibility of Intervention Measure, where the Intervention is defined as PGS.33 To assess Maintenance, we will ask stakeholders to complete the Program Sustainability Assessment Tool to rate the PGS program on the presence of elements associated with long-term sustainability. We will also capture fidelity to the FOCUS toolkit through the Toolkit Tracking Data, which will include website metrics of 1) FOCUS test sites’ registered users and 2) the number of times the FOCUS toolkit was opened and number of pages or components of the toolkit are visited. Our primary research question is: Does the use of the FOCUS toolkit improve PGS implementation and effectiveness. RE-AIM/HE outcomes among the eight existing sites (i.e., implementation and sustainment sites) that are actively implementing or sustaining PGS using generalized mixed effects regression models (GLMM).38 The primary temporal variable for the analysis of RE-AIM/HE outcomes is the time step; all participants enrolled during a given time step will be retained in that step regardless of study completion date. Statistical analysis will be based on the principle of intention to treat. The step at which a participant was enrolled in the PGS program will be used as the treatment indicator. At the participant level, a mixed effects logistic regression model will be used to estimate the impact of sites’ use of the FOCUS toolkit strategies on the likelihood of participants returning for sample collection. Fixed effects of study time will be included in the model to adjust for secular temporal events throughout the study and random site effects included to account for correlation of participants within site over time. Participant-level baseline data will be assessed for association with study outcomes and when significant, included in adjusted models. Between-site sample size imbalance may impact the study power and estimation bias, thus initial models will be fit using Fay and Graubard bias corrected sandwich variance estimator.39,40 Period-specific recruitment totals will be assessed at the site level utilizing a gaussian distribution with an identity link. We will use GLMM to assess the impact of the FOCUS toolkit among the four emerging sites that are part of the parallel design (FOCUS toolkit use vs no FOCUS toolkit use). In addition to addressing primary study outcomes, models including post-intervention data from all sites will be assessed to determine if newly emerging PGS sites differ across outcomes as compared to existing sites. Generalized linear mixed effects regression will be assessed with an indicator of site implementation stage to assess post-intervention RE-AIM/HE outcomes. All RE-AIM/HE outcomes will also be assessed qualitatively through in-depth Stakeholder Interviews conducted with five implementation stakeholders (e.g., program champion (n=1), genetic counselor (n=1), organizational leadership (n=1), and implementation teams (n=2)) per site (n=60) at the conclusion of the implementation period. Reach will include questions to understand whether all populations are equitably reached, who is not reached, and how the FOCUS toolkit supports better reach among diverse populations. Effectiveness will focus on whether program impact is equitable across groups, whether sample collection and findings are different across sociodemographics. Adoption will be assessed by asking about the uptake of PGS among clinicians and other key stakeholders within their setting. Implementation will be assessed by asking how PGS has been implemented, facilitators and barriers to implementation, and ways that the FOCUS toolkit helped the site overcome these barriers. To assess Maintenance, we will ask stakeholders about the ways they plan to sustain the PGS program long-term and plans for institutionalization of the FOCUS toolkit.41 A summary will be created immediately following each interview. These summaries will allow for high-level analysis during data collection, facilitate initial codebook development and reduce the number of new codes requiring re-coding during data analysis. Coding will be conducted using an a priori codebook guided by the RE-AIM/HE and CFIR (for contextual factors that are described as impacting RE-AIM/HE outcomes. After initial review of this codebook, new codes will be added to the other relevant sections of the transcript text not fitting a priori codes. A team-based approach will be used to refine the codebook with discrepancies resolved by the study team. All coding will occur in MaxQDA and completed by two coders. Qualitative and quantitative results will be reviewed together, and triangulation of data will occur using a rapid analytic coding matrix.42-44 This will allow us to better understand how the PGS programs have changed over time and to what extent the FOCUS toolkit was adapted and/or used in accordance with the protocol.

Results:

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Conclusions:

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