Systematic review of outcomes in studies of reproductive genetic carrier screening: Towards development of a core outcome set

Abstract

Current practice recommendations support the widespread implementation of reproductive genetic carrier screening (RGCS). These consensus-based recommendations highlight a research gap, with findings from current studies being insufficient to meet the standard required for more rigorous evidence-based recommendations. This systematic review assessed methodological aspects of studies on RGCS to inform the need for a core outcome set. Methods: We conducted a systematic search to identify peer-reviewed published studies offering population-based RGCS. Study designs, outcomes, and measurement methods were extracted. A narrative synthesis was conducting using an existing outcome taxonomy and criteria used in the evaluation of genetic screening programs as frameworks. Results: Sixty-five publications were included. We extracted 120 outcomes representing 24 outcome domains. Heterogeneity in outcome selection, measurement methods and time points of assessment was extensive. Quality appraisal raised concerns for bias. We found that reported outcomes had limited applicability to criteria used to evaluate genetic screening programs. Conclusion: Despite a large body of literature, diverse approaches to research have limited the conclusions that can be cumulatively drawn from this body of evidence. Consensus regarding meaningful outcomes for evaluation of RGCS would be a valuable first step in working towards evidence-based practice recommendations, supporting the development of a core outcome set.

Outcomes of Importance to Patients in Reproductive Genetic Carrier Screening: A Qualitative Study to Inform a Core Outcome Set

“…In total, 55 unique outcomes were identified across the 15 interviews. Thirty-seven of these outcomes overlapped with outcomes identified from our previous sequential systematic reviews of quantitative studies [ 4 ] ( n = 8), qualitative studies [ 5 ] ( n = 13), or both ( n = 16); and 18 were new outcomes.…”

“…Outcome domains, hereafter referred to as CODECS domains, were previously defined during data analysis for our sequential systematic review [ 4 , 5 ]. Definition of the domain and grouping of outcomes were developed iteratively by ER and AC and taken to the study management group (CJ, AM, TNJ) for final review and consensus.…”

“…We used a deductive approach to map the outcomes to an existing taxonomy previously developed for this study (available in Supplementary Material ), and to an overarching taxonomy defined by the COMET initiative [ 22 ]. This analysis resulted in a list of outcomes that were elicited from patients, grouped into outcome domains, which was directly comparable to outcome domains reported in a previous sequential systematic review [ 4 , 5 ]. Outcomes were collated to determine a final long list that would be included in the consensus process for development of a COS and assessed for outcomes that were uniquely identified by patients in this study.…”

“…We developed an interview schedule that engaged participants in a discussion about their experience and allowed them to conceptualise outcomes that were appropriate to capture it. The interview guide was informed by our sequential systematic review [ 4 , 5 ] and developed iteratively with two patient representatives (available in Supplementary Material ). The interview guide was broken into four sections, becoming increasingly specific as the interview progressed ( Figure 1 ): Narrative exploration—participants were asked open questions about their uptake of RGCS and prompted to tell the story of their experience.…”

“…Current consensus-derived practice guidelines recommend that RGCS is offered to all women planning a pregnancy or in their first trimester [ 1 , 2 , 3 ]. In a previous sequential systematic review of quantitative and qualitative studies on RGCS, we highlighted the heterogeneity of research to date and identified a need for standardised outcome reporting to inform evidence-based practice recommendations that can draw on a robust underlying literature [ 4 , 5 ].…”