Patrick Vermersch1, Vittorio Martinelli2, Claudia Pfleger3, Peter Rieckmann4, Lucia Alonso-Magdalena5, Andrew Galazka6, Fernando Dangond7, Lawrence Phillips8. 1. Department of Neurology, CHU Lille, LIRIC-INSERM U995, FHU Imminent, University of Lille, Lille, France. 2. Neurological Division, San Raffaele Hospital, Milan, Italy. 3. Department of Neurology, Aalborg Universitets Hospital, Aalborg, Denmark. 4. Department of Neurology, Hospital for Nervous Diseases Medical Park Loipl, Loipl-Bischofswiesen, Germany; Department of Neurology, University of Erlangen, Erlangen, Germany. 5. Neurology Department, Skåne University Hospital, Malmö, Sweden. 6. Global Medical Excellence, Merck, Aubonne, Switzerland. 7. Global Clinical Development, Neurology, EMD Serono, Inc, Billerica, Massachusetts, USA. 8. Department of Management, London School of Economics and Political Science, London, United Kingdom. Electronic address: larry_phillips@msn.com.
Abstract
PURPOSE: We applied Multi-Criteria Decision Analysis (MCDA) methods in a structured benefit-risk assessment of cladribine and newer approved disease-modifying drugs (DMDs) for patients with relapsing-remitting multiple sclerosis (RRMS). METHODS: Decision conferencing with clinical neurologists as decision makers was used to create an MCDA model that incorporated available evidence on DMDs for RRMS and clinical judgments about the relevance of the evidence. Benefit-risk assessments were conducted for DMDs in both patients with RRMS and patients with RRMS with high disease activity (HDA; defined as ≥2 relapses in the previous year). Treatment options included cladribine and recently approved DMDs available in European Union countries at the time of assessment (December 2015): alemtuzumab, dimethyl fumarate, fingolimod, natalizumab, and teriflunomide. To account for the relative importance of DMD effects, scores for the MCDA model were weighted to ensure that the most clinically important attributes carried more weight in the final benefit-risk calculation. The neurologists weighted different efficacy and safety profile attributes without any reference to individual DMDs to disassociate the assessment of weights with any specific DMD. The neurologists did not do direct comparisons between DMDs. FINDINGS: The highest overall weighted preference value for the RRMS model was for dimethyl fumarate (63) followed closely by cladribine (62). For patients with RRMS and HDA, cladribine had the highest overall weighted preference value (76), followed by alemtuzumab (62) and natalizumab (61). The benefit-risk balance of cladribine in patients with RRMS and specifically patients with RRMS who exhibited HDA characterized by high relapse activity (≥2 relapses in the previous year) was more favorable than the other DMDs included in the model. IMPLICATIONS: The balance of high efficacy and the safety profile makes cladribine an important treatment option to consider, both in patients with RRMS and patients with HDA. Regular, single-country meetings could be organized to explore how differences in cultural values (scores and weights) and updated input data might affect the usefulness of MCDA in different, real-world, dynamic clinical settings.
PURPOSE: We applied Multi-Criteria Decision Analysis (MCDA) methods in a structured benefit-risk assessment of cladribine and newer approved disease-modifying drugs (DMDs) for patients with relapsing-remitting multiple sclerosis (RRMS). METHODS: Decision conferencing with clinical neurologists as decision makers was used to create an MCDA model that incorporated available evidence on DMDs for RRMS and clinical judgments about the relevance of the evidence. Benefit-risk assessments were conducted for DMDs in both patients with RRMS and patients with RRMS with high disease activity (HDA; defined as ≥2 relapses in the previous year). Treatment options included cladribine and recently approved DMDs available in European Union countries at the time of assessment (December 2015): alemtuzumab, dimethyl fumarate, fingolimod, natalizumab, and teriflunomide. To account for the relative importance of DMD effects, scores for the MCDA model were weighted to ensure that the most clinically important attributes carried more weight in the final benefit-risk calculation. The neurologists weighted different efficacy and safety profile attributes without any reference to individual DMDs to disassociate the assessment of weights with any specific DMD. The neurologists did not do direct comparisons between DMDs. FINDINGS: The highest overall weighted preference value for the RRMS model was for dimethyl fumarate (63) followed closely by cladribine (62). For patients with RRMS and HDA, cladribine had the highest overall weighted preference value (76), followed by alemtuzumab (62) and natalizumab (61). The benefit-risk balance of cladribine in patients with RRMS and specifically patients with RRMS who exhibited HDA characterized by high relapse activity (≥2 relapses in the previous year) was more favorable than the other DMDs included in the model. IMPLICATIONS: The balance of high efficacy and the safety profile makes cladribine an important treatment option to consider, both in patients with RRMS and patients with HDA. Regular, single-country meetings could be organized to explore how differences in cultural values (scores and weights) and updated input data might affect the usefulness of MCDA in different, real-world, dynamic clinical settings.
Authors: Anne Katrin Schlag; David S Baldwin; Michael Barnes; Steve Bazire; Rachel Coathup; H Valerie Curran; Rupert McShane; Lawrence D Phillips; Ilina Singh; David J Nutt Journal: J Psychopharmacol Date: 2020-06-10 Impact factor: 4.153
Authors: Isa Ahmed AlSharoqi; Mohamed Aljumah; Saeed Bohlega; Cavit Boz; Abdelkader Daif; Salam El-Koussa; Jihad Inshasi; Murat Kurtuncu; Thomas Müller; Chris Retief; Mohammad Ali Sahraian; Vahid Shaygannejad; Ilham Slassi; Karim Taha; Magd Zakaria; Per Soelberg Sørensen Journal: Neurol Ther Date: 2020-04-15
Authors: David J Nutt; Lawrence D Phillips; Michael P Barnes; Brigitta Brander; Helen Valerie Curran; Alan Fayaz; David P Finn; Tina Horsted; Julie Moltke; Chloe Sakal; Haggai Sharon; Saoirse E O'Sullivan; Tim Williams; Gregor Zorn; Anne K Schlag Journal: Cannabis Cannabinoid Res Date: 2021-03-17