Methodological quality of clinical practice guidelines for genetic testing in children: A systematic assessment using the appraisal of guidelines for research and evaluation II instrument

Genetic testing of children is faced with numerous problems. High-quality clinical practice guidelines (CPGs) are needed to ensure its safe, and appropriate use. This study aimed to systematically identify the current CPGs for genetic testing in children, and to assess the methodological quality of these CPGs. We searched 6 databases, 3 guideline clearinghouses, and 9 web sites of relevant academic agencies from inception to February 2019. CPGs focused on genetic testing in children were included. Four reviewers independently appraised the quality of the eligible CPGs using the appraisal of guidelines for research, and evaluation (AGREE) II instrument. Seventeen CPGs meeting our inclusion criteria were included. Among them, 16 CPGs were focused on the genetic diagnosis/evaluation of diseases, while only 1 CPG was focused on pharmacogenetics. The median domain scores from highest to lowest were: scope and purpose 80.56% (range: 56.95%–87.50%), clarity of presentation 72.22% (range: 45.83%–88.89%), stakeholder involvement 45.83% (range: 27.78%–55.56%), applicability 31.25% (range: 19.79%–54.17%), rigor of development 21.88%, (range: 13.02%–71.88%), and editorial independence 18.75% (range: 0%–83.33%). According to the overall quality, 6 (35%) CPGs were “not recommended,” 8 (47%) CPGs were “recommended with modifications,” and only 3 (18%) CPGs were “recommended.” The clinical topics of the “recommended” CPGs were warfarin, familial Mediterranean fever, and pediatric pulmonary arterial hypertension. The quality of CPGs for genetic testing in children was generally low, and variable across different CPGs and different AGREE II domains. In future guideline development, more attention should be paid to the aspects of stakeholder involvement, rigor of development, applicability, and editorial independence. Not only will guideline users benefit from our results when determining whether to adopt related CPGs to guide genetic testing in children, but guideline developers could also take into account our results to improve the quality of future CPGs.