Background & Objective

1. Decisionmaking for rare diseases: developing evidence-based clinical practice guidelines for growth hormone therapy in Prader-WilliSyndrome using the EVIDEM framework MichèleTony MSc,1,2,3MireilleM. GoetghebeurPhD,2,3,4HananeKhoury PhD,3Monika Wagner PhD,3Renaldo Battista MD, ScD,1,4 Cheri L. Deal PhD, MD4,5 1Health Administration, Medical Faculty, University of Montreal, Montréal, Québec, Canada; 2EVIDEM Collaboration, Dorval, Québec, Canada; 3BioMedCom Consultants inc., Dorval, Québec, Canada; 4Research Center, CHU-Sainte-Justine and 5Department of Pediatrics, Medical Faculty, University of Montreal, Montréal, Québec, Canada • Background & Objective • Clinical Practice Guidelines (CPGs) are meant to “assist practitioner and patient decisions about appropriate healthcare for specific clinical circumstances”.1 To be more consistent and efficient, the process to generate them needs to be systematic in its assessment of evidence and in the development of questions and recommendations.2-4 • The Appraisal of Guidelines Research & Evaluation (AGREE) Collaboration provides an instrument to “appraise the quality of the process and reporting of CPGs development”.5,6 • The EVIDEM framework is a systematic approach to synthesize and consider evidence by decision criteria.7,8 It could provide a consistent structure to organize evidence and facilitate CPGs development, in agreement with the recommendations of the AGREE collaboration. • Prader-Willi syndrome (PWS) is a rare and complex multisystem disorder, with serious long-term consequences. Use and coverage of growth hormone (GH) in patients with PWS vary widely across Canada and there is a need to clarify its benefits. • Objective: To test a pragmatic framework (EVIDEM) to facilitate systematic development of evidence-based CPGs for the use of GH in patients with PWS. • Collaborative Web Site • A collaborative web site was built to facilitate the CPGs process including: • Access to evidence and CPGs questions structured in a consistent systematic manner • Interactive online validation by international experts (about 50 clinicians and other experts) of: synthesized data; quality assessments of evidence; and CPGs questions • Reflection by CPGs working groups on assigned questions prior to the workshop • Involvement of all CPGs workshop participants prior to the consensus workshop • To facilitate knowledge transfer, validated synthesized data on GH for PWS and by-criteria CPGs process (CPGs module) will be made publicly available, hosted by the EVIDEM collaborative registry under a Creative Common license.10 • Results • CPGs Module • Based on the analysis of the literature and feedback from experts, CPGs questions reflecting current issues in management of patients PWS were developed and organized using the adapted EVIDEM framework (Intervention & Overview, MCDA Core Model and Contextual Tool). • This framework structure and questions identified will be used to structure the program of the workshop and to assign questions to CPGs working groups. • Clinical Aspects • Intervention Overview • MCDA Core Model • MCDA Core Model (continued) • Resource Allocation and Ethical Aspects • Overview • MCDA Core Model (continued) • Contextual Tool • Discussion and Conclusion • CPGs questions elicitation and organization was facilitated by the EVIDEM framework, providing a pragmatic means to ensure systematic consideration of evidence for a wide range of criteria and associated issues. • By clearly revealing current knowledge and gaps, the framework will facilitate developing evidence-based CPGs and identifying research needed for continued improvement of management of patient with PWS. • Using the EVIDEM framework, a by-criteria HTA model, to develop CPGs is expected to facilitate alignment of clinical and policy decisionmaking and ultimately optimize resource allocation and healthcare system sustainability. • Methodology • An extensive literature review was performed to identify available evidence on GH for PWS for each criterion of the EVIDEM framework covering disease impact, therapeutic context, treatment outcomes (efficacy/effectiveness, safety, patient-reported outcomes), type of benefits and economic impact (MCDA Core Model) as well as ethical and contextual considerations (Contextual Tool). • Given the complexity of the efficacy outcomes measures reported, the efficacy criterion was subdivided into sub-criteria for each type of outcome measured including growth, body composition, exercise tolerance, metabolic effects, bone health, cardiovascular health, psychomotor development and behavioral outcomes. • Data was organized in evidence tables and synthesized; level and strength of evidence were assessed using respectively the Centre for Evidence-Based Medicine (CEBM) levels of evidence9 and EVIDEM data quality assessment instruments. • To support the development of CPGs, in which, clinical aspects are the primary focus, the framework was adapted into a CPGs module and used to elicit questions for CPGs development; an interactive web information system was developed to facilitate the CPGs process. • Key Steps for Development of CPGs Using EVIDEM CPGs Module Acknowledgments We would like to acknowledge the contributions of the members of the CPGs workshop organizing committee who participated in this study. This workshop is sponsored by the Growth Hormone Research Society and a complementary grant from the Foundation for Prader-Willi Research. Internal sources of support were provided by BioMedCom Consultants. Inc. References 1. Committee to Advise the Public Health Service on Clinical Practice Guidelines Institute of Medicine, Institute of Medicine. Field MJ, Lohr KN, editors. Clinical practice guidelines: directions for a new program. Washington, D.C.: National Academy Press; 1990. 2. Woolf SH, Grol R, Hutchinson A, Eccles M, Grimshaw J. Clinical guidelines: potential benefits, limitations, and harms of clinical guidelines. BMJ. 1999;318(7182):527-30. 3. Shekelle PG, Woolf SH, Eccles M, Grimshaw J. Developing clinical guidelines. West J Med. 1999;170(6):348-51. 4. Oxman AD, Fretheim A, Schunemann HJ. Improving the use of research evidence in guideline development: introduction. Health Res Policy Syst. 2006;4:12. 5. Brouwers MC, Kho ME, Browman GP, Burgers JS, Cluzeau F, Feder G, et al. AGREE II: advancing guideline development, reporting, and evaluation in health care. Prev Med. 2010;51(5):421-4. 6. AGREE Collaboration. Development and validation of an international appraisal instrument for assessing the quality of clinical practice guidelines: the AGREE project. QualSaf Health Care. 2003;12(1):18-23. 7. Goetghebeur MM, Wagner M, Khoury H, Levitt RJ, Erickson LJ, Rindress D. Evidence and Value: Impact on DEcisionMaking - the EVIDEM framework and potential applications. BMC Health Serv Res. 2008;8(1):270. 8. Goetghebeur MM, Wagner M, Khoury H, Rindress D, Gregoire JP, Deal C. Combining multicriteria decision analysis, ethics and health technology assessment: applying the EVIDEM decisionmaking framework to growth hormone for Turner syndrome patients. Cost EffResourAlloc. 2010;8(1):4. 9. Centre for Evidence Based Medicine. CEBM levels of evidence version #2. On Centre for Evidence Based Medicine website. Available from: http://www.cebm.net/index.aspx?o=5653.10. 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