A qualitative study among guideline developers revealed challenges and strategies for rare disease guideline development

Journal of Clinical Epidemiology, vol. 189, pp. 112045

Abstract

OBJECTIVES: Clinical practice guideline (CPG) development for rare diseases is challenging due to scarce evidence, small expert groups, limited resources, and heterogeneity and complexity of conditions. Critical appraisals of existing rare disease CPGs reveal variable methodological quality. We aimed to gather the experiences of rare disease guideline developers to identify methodological challenges and strategies and eventually inform methodological guidance for rare disease CPGs. STUDY DESIGN AND SETTING: We conducted semistructured interviews with 15 guideline developers from ten countries and diverse medical fields with hands-on experience in rare disease CPG development. Data were analyzed through a combined deductive and inductive approach following the structure of the GIN-McMaster Guideline Development Checklist. RESULTS: Small rare disease expert groups, while highly dedicated, faced significant risks related to conflicts of interest, limited methodological expertise, resource constraints, and challenges in achieving interest-holder representation. Guideline developers adopted pragmatic approaches to utilize scarce and very low-certainty direct evidence and supplement it with indirect and expert-based evidence, registry data, and mechanistic reasoning. The Grading of Recommendations Assessment, Development and Evaluation methodology was valued for providing transparency, structure, and consistency, but some considered it not feasible in rare disease contexts. Topics beyond the GIN-McMaster Guideline Development Checklist included deciding whether to develop a CPG or another type of quality document and supporting the broader knowledge cycle. CONCLUSION: We gained insight into the most salient methodological issues and identified a need for further guidance and method development to improve guideline development processes for rare diseases.

Authors 9

1. Mirthe J Klein Haneveld

   Emma Kinderziekenhuis · Amsterdam Public Health · Hôpital Robert-Debré · Amsterdam University Medical Centers · ERN ITHACA · Amsterdam Reproduction Development · University of Amsterdam

   Affiliation as printed

   Amsterdam UMC, University of Amsterdam, Emma Children's Hospital, Amsterdam Reproduction & Development, Amsterdam Public Health, Meibergdreef 9, PO Box 22660, Amsterdam 1100 DD, The Netherlands; European Reference Network on Rare Congenital Malformations and Rare Intellectual Disability ERN-ITHACA, Clinical Genetics Department, Robert Debré University Hospital, 48 Boulevard Serurier, Paris 75935, France. Electronic address: m.j.kleinhaneveld@amsterdamumc.nl

2. Willemijn F. E. Irvine

   Erasmus MC - Sophia Children’s Hospital

   Affiliation as printed

   Department of Pediatric Surgery, Erasmus MC Sophia Children's Hospital, P.O. Box 2060, Rotterdam 3000 CB, The Netherlands; Department of Evidence Based Medicine and Methodology, Qualicura Healthcare Support Agency, Mauritssingel 8, Breda, The Netherlands

3. Martina Cornelia Cornel

   Amsterdam Public Health · Amsterdam University Medical Centers · Amsterdam Reproduction Development · Vrije Universiteit Amsterdam

   Affiliation as printed

   Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Human Genetics, Amsterdam Reproduction & Development, Amsterdam Public Health, De Boelelaan 1117, PO Box 7057, Amsterdam 1007 MB, The Netherlands

4. Federico Germini

   Thrombosis and Atherosclerosis Research Institute · IRCCS Humanitas Research Hospital · McMaster University

   Affiliation as printed

   Clinical Epidemiology and Research Center, IRCCS Humanitas Research Hospital, Via Manzoni 56 Rozzano, Milan 20089, Italy; Department of Medicine, Division of Hematology & Thromboembolism, Thrombosis and Atherosclerosis Research Institute (TaARI), McMaster University, 237 Barton Street East, Hamilton, Ontario, Canada

5. Miranda W. Langendam

   Amsterdam Public Health · Amsterdam University Medical Centers · University of Amsterdam

   Affiliation as printed

   Amsterdam UMC, University of Amsterdam, Epidemiology and Data Science, Meibergdreef 9, PO Box 22660, Amsterdam 1100 DD, The Netherlands; Amsterdam Public Health Research Institute, Methodology Program, Meibergdreef 9, PO Box 22660, Amsterdam 1100 DD, The Netherlands

6. Holger Jens Schünemann

   IRCCS Humanitas Research Hospital

   Affiliation as printed

   Clinical Epidemiology and Research Center, IRCCS Humanitas Research Hospital, Via Manzoni 56 Rozzano, Milan 20089, Italy

7. Johanna H. van der Lee

   University Medical Center Utrecht

   Affiliation as printed

   Knowledge Institute of the Dutch Association of Medical Specialists, Mercatorlaan 1200, PO Box 3320, Utrecht 3502 GH, The Netherlands

   Knowledge Institute of the Dutch Association of Medical Specialists, Mercatorlaan 1200, PO Box 3320, 3502 GH, Utrecht, The Netherlands

8. Agnies M. van Eeghen

   Emma Kinderziekenhuis · Amsterdam Public Health · Hôpital Robert-Debré · Amsterdam University Medical Centers · 's Heeren Loo · ERN ITHACA · Amsterdam Reproduction Development · University of Amsterdam

   Affiliation as printed

   Amsterdam UMC, University of Amsterdam, Emma Children's Hospital, Amsterdam Reproduction & Development, Amsterdam Public Health, Meibergdreef 9, PO Box 22660, Amsterdam 1100 DD, The Netherlands; European Reference Network on Rare Congenital Malformations and Rare Intellectual Disability ERN-ITHACA, Clinical Genetics Department, Robert Debré University Hospital, 48 Boulevard Serurier, Paris 75935, France; Advisium, 's Heeren Loo Zorggroep, Berkenweg 11, Amersfoort 2818 LA, The Netherlands

9. Charlotte M. W. Gaasterland Aachen Department of Clinical Epidemiology

   Leiden University Medical Center

   Affiliation as printed

   Department of Clinical Epidemiology, Leiden University Medical Center, Postbus 9600, Leiden 2300 RC, The Netherlands