GRADE evidence to decision framework in genomics guidelines: systematic review & appraisal

Abstract Background Transparent development of clinical practice guidelines (CPGs) is important for genomic medicine, as this field promises to partially challenge the traditional hierarchies of evidence. The GRADE Evidence to Decision (EtD) framework has recently emerged as a transparent and rigorous tool to produce recommendations. Our aim was to survey the genomic CPGs that used the GRADE EtD and appraise the applicability of its criteria and the quality of produced CPGs. Methods We systematically searched PubMed, Scopus, Web of Science and the gray literature till 2023 for relevant CPGs. From each eligible CPG, we extracted the reporting of the GRADE EtD criteria: benefits, harms, resource use, cost-effectiveness, acceptability, feasibility, equity and values. The quality of the CPGs were appraised across various domains using the (AGREE) II instrument. Results Among 1,144 records, 15 CPGs met inclusion criteria between 2018 and 2023, comprising 66 recommendations. Reporting of GRADE EtD criteria varied. Benefits, harms and their balance were addressed in approximately half of the recommendations 48% and 52% respectively. Feasibility, acceptability and values were also 52%, 47% and 40% respectively, resource use 39%, cost-effectiveness 23%. Equity was addressed in 36% of the recommendations. Quality appraisal of the CPGs also varied, domains were reported as follows: scope and purpose, clarity of presentation, editorial independence 86%, 85% and 84% respectively, rigor of development 77%, stakeholder involvement 72%, while applicability was 59%. Conclusions GRADE EtD is applied heterogeneously in genomic medicine CPGs, with difficulty in applying all of its criteria, including benefits and harms. Quality varied across domains with applicability of the CPGs less demonstrated. Key messages • Transparent approaches are needed in developing CPGs for genomic medicine. • Current genomic CPGs fail to address crucial aspects for producing recommendations, including benefits and harms.