Producing Cochrane reviews with multi-stakeholder synergic involvement. An experience with treatments for multiple sclerosis
2Cochrane Review Group Multiple Sclerosis and Rare Diseases of the CNS. IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna. Department of Epidemiology, Lazio Health Regional Service, Rome, Italy
3Cochrane Review Group Multiple Sclerosis and Rare Diseases of the CNS. IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna. Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milano, Italy
4Department of Biomedical Sciences, Humanitas University, Milan. Michael G. DeGroote Cochrane Canada Centre & McMaster GRADE Centre, McMaster University, Hamilton, ON, Italy, Canada
5Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada
6Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
7Faculty of Medicine and Health Sciences, University of East Anglia, Norwich, Norfolk, UK
8Department of Research and Clinical Development, Scientific Directorate, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy
9Department of Neuroscience, Multiple Sclerosis Center - Neurology Unit, S.Maria delle Croci Hospital, AUSL Romagna, Ravenna, Italy. Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy
10Department of Medical and Surgical Sciences for Children and Adults, Unit of Statistical and Methodological support, University-Hospital of Modena and Reggio Emilia, Modena, Italy
11WHO Collaborating Centre in Evidence-Based Research Synthesis and Guideline Development. Direzione Generale Cura della Persona, Salute e Welfare. Area Governo del Farmaco e dei Dispositivi Medici. Settore Assistenza Ospedaliera. Bologna, Italy
12Multiple Sclerosis International Federation, London, UK
Background: Involvement of key stakeholders and evidence users in the planning and development of systematic reviews (SRs) improve their overall quality and usefulness, facilitate uptake and reduce health inequities. Synergy among entities influencing or making decisions in health is important to avoid conflict, duplication of efforts and resource waste.
Objectives: To present an example of harmonization in decision-making on disease-modifying treatments (DMTs) for multiple sclerosis (MS) involving the Cochrane Review Group for MS and Rare Diseases of the CNS (CRGMS), the World Health Organization (WHO) Collaborating Centre on Evidence Synthesis and Guideline Production of Bologna, Italy (WHOCC) and the MS International Federation (MSIF), a nonprofit organisation.
Methods: The CRGMS produced four SRs, two with pairwise and two with network meta-analysis (NMA), including 30 DMTs for MS. The SRs served as the evidence base for clinical practice recommendations developed according to the GRADE methodology by two international multi-stakeholder guideline panels (MSIF Off-Label Treatments panel, MOLT and MSIF Essential Medicines Panel, MEMP) appointed by MSIF. A productive interaction between the CRGMS and both guideline panels at the SRs planning and development stage helped to identify outcomes that are meaningful for persons with MS and clinicians. Imprecision in the NMA estimates was assessed within a fully contextualised approach where thresholds between different magnitudes of effect were set by means of health state utility values, determined through scoping reviews and guideline panel judgement. The WHOCC contributed to the evidence base for domains on cost and resource use of the GRADE Evidence-to-Decision framework.
Results: An application for the inclusion of the first-ever DMTs for the treatment of MS in the 23rd WHO Model List of Essential Medicines (EML) was submitted by MSIF and the WHOCC, based on the evidence base that informed rigorously developed recommendations by two highly representative multi-stakeholder panels on the use of labelled and off-label DMTs.
Conclusions: Involvement of key stakeholders in the planning and development stages of Cochrane reviews of intervention, together with mutual collaboration among different actors in the ecosystem of health decision-making, may facilitate Cochrane becoming a knowledge translation-oriented organization.