Marcello Moccia1, Pietro Annovazzi2, Maria Chiara Buscarinu3, Massimiliano Calabrese4, Paola Cavalla5, Cinzia Cordioli6, Massimiliano Di Filippo7, Diana Ferraro8, Alberto Gajofatto4, Antonio Gallo9, Roberta Lanzillo10, Alice Laroni11, Lorena Lorefice12, Simona Mallucchi13, Viviana Nociti14, Damiano Paolicelli15, Federica Pinardi16, Luca Prosperini17, Marta Radaelli18, Paolo Ragonese19, Valentina Tomassini20, Carla Tortorella17, Eleonora Cocco12, Claudio Gasperini17, Claudio Solaro21. 1. MS Clinical Care and Research Centre, Department of Neuroscience, Federico II University of Naples, Italy. Electronic address: marcello.moccia@unina.it. 2. MS Centre, ASST Valle Olona, Gallarate Hospital, Varese, Italy. 3. Department of Neurosciences, Mental Health and Sensory Organs, Sapienza University, Rome, Italy. 4. Department of Neuroscience, Biomedicine and Movement, University of Verona, Italy. 5. MS Center, Department of Neurosciences and Mental Health, AOU City of Health & Science University Hospital, Turin, Italy. 6. Multiple Sclerosis Center, ASST Spedali Civili di Brescia, Brescia, Italy. 7. Neurology Unit, Medicine Department, University of Perugia, Italy. 8. Department of Biomedical, Metabolic and Neurosciences, University of Modena and Reggio Emilia, Italy. 9. Department of Advanced Medical and Surgical Sciences, University of Campania "L. Vanvitelli", Naples, Italy. 10. MS Clinical Care and Research Centre, Department of Neuroscience, Federico II University of Naples, Italy. 11. Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health and Center of Excellence for Biomedical Research (CEBR), University of Genova, Italy; IRCCS Ospedale Policlinico San Martino, Genoa, Italy. 12. Department of Medical Sciences and Public Health, University of Cagliari, Italy. 13. Multiple Sclerosis Centre, San Luigi Gonzaga Hospital, Orbassano, Turin, Italy. 14. Multiple Sclerosis Center, Fondazione Policlinico Universitario 'A. Gemelli' IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy. 15. Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari, Italy. 16. UOSI Multiple Sclerosis Rehabilitation, IRCCS, Bologna, Italy. 17. Department of Neurosciences, Ospedale San Camillo Forlanini, Rome, Italy. 18. Department of Neurology, San Raffaele Hospital, Milan, Italy. 19. Department of Biomedicine Neurosciences and advanced Diagnostic (BiND), University of Palermo, Italy. 20. Institute for Biomedical Technologies (ITAB), Department of Neurosciences, Imaging and Clinical Sciences, University of Chieti-Pescara "G. d'Annunzio", Chieti, Italy; MS Centre, Neurology Unit, SS. Annunziata University Hospital, Chieti, Italy; Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University School of Medicine, United Kingdom. 21. Rehabilitation Department, Mons. L. Novarese, Moncrivello, Vercelli, Italy.
Abstract
BACKGROUND: Worldwide multiple sclerosis (MS) centers have coordinated their efforts to use data acquired in clinical practice for real-world observational studies. In this retrospective study, we aim to harmonize outcome measures, and to evaluate their heterogeneity within the Rising Italian Researchers in MS (RIReMS) study group. METHODS: RIReMS members filled in a structured questionnaire evaluating the use of different outcome measures in clinical practice. Thereafter, thirty-four already-published papers from RIReMS centers were used for heterogeneity analyses, using the DerSimonian and Laird random-effects method to compute the between-study variance (τ2). RESULTS: Based on questionnaire results, we defined basic modules for diagnosis and follow-up, consisting of outcome measures recorded by all participating centers at the time of diagnosis, and, then, at least annually; we also defined more detailed/optional modules, with outcome measures recorded less frequently and/or in the presence of specific clinical indications. Looking at heterogeneity, we found 5-year variance in age at onset (ES=27.34; 95%CI=26.18, 28.49; p<0.01; τ2=4.76), and 7% in female percent (ES=66.42; 95%CI=63.08, 69.76; p<0.01; τ2=7.15). EDSS variance was 0.2 in studies including patients with average age <36.1 years (ES=1.96; 95%CI=1.69, 2.24; p<0.01; τ2=0.19), or from 36.8 to 41.1 years (ES=2.70; 95%CI=2.39, 3.01; p<0.01; τ2=0.18), but increased to 3 in studies including patients aged >41.4 years (ES=4.37; 95%CI=3.40, 5.35; p<0.01; τ2=2.96). The lowest variance of relapse rate was found in studies with follow-up duration ≤2 years (ES=9.07; 95%CI=5.21, 12.93; p = 0.02; τ2=5.53), whilst the lowest variance in EDSS progression was found in studies with follow-up duration >2 years (ES=5.41; 95%CI=3.22, 7.60; p = 0.02; τ2=1.00). DISCUSSION: We suggest common sets of biomarkers to be acquired in clinical practice, that can be used for research purposes. Also, we provide researchers with specific indications for improving inclusion criteria and data analysis, ultimately allowing data harmonization and high-quality collaborative studies.
BACKGROUND: Worldwide multiple sclerosis (MS) centers have coordinated their efforts to use data acquired in clinical practice for real-world observational studies. In this retrospective study, we aim to harmonize outcome measures, and to evaluate their heterogeneity within the Rising Italian Researchers in MS (RIReMS) study group. METHODS: RIReMS members filled in a structured questionnaire evaluating the use of different outcome measures in clinical practice. Thereafter, thirty-four already-published papers from RIReMS centers were used for heterogeneity analyses, using the DerSimonian and Laird random-effects method to compute the between-study variance (τ2). RESULTS: Based on questionnaire results, we defined basic modules for diagnosis and follow-up, consisting of outcome measures recorded by all participating centers at the time of diagnosis, and, then, at least annually; we also defined more detailed/optional modules, with outcome measures recorded less frequently and/or in the presence of specific clinical indications. Looking at heterogeneity, we found 5-year variance in age at onset (ES=27.34; 95%CI=26.18, 28.49; p<0.01; τ2=4.76), and 7% in female percent (ES=66.42; 95%CI=63.08, 69.76; p<0.01; τ2=7.15). EDSS variance was 0.2 in studies including patients with average age <36.1 years (ES=1.96; 95%CI=1.69, 2.24; p<0.01; τ2=0.19), or from 36.8 to 41.1 years (ES=2.70; 95%CI=2.39, 3.01; p<0.01; τ2=0.18), but increased to 3 in studies including patients aged >41.4 years (ES=4.37; 95%CI=3.40, 5.35; p<0.01; τ2=2.96). The lowest variance of relapse rate was found in studies with follow-up duration ≤2 years (ES=9.07; 95%CI=5.21, 12.93; p = 0.02; τ2=5.53), whilst the lowest variance in EDSS progression was found in studies with follow-up duration >2 years (ES=5.41; 95%CI=3.22, 7.60; p = 0.02; τ2=1.00). DISCUSSION: We suggest common sets of biomarkers to be acquired in clinical practice, that can be used for research purposes. Also, we provide researchers with specific indications for improving inclusion criteria and data analysis, ultimately allowing data harmonization and high-quality collaborative studies.
Authors: Ferrán Catalá-López; Jane A Driver; Matthew J Page; Brian Hutton; Manuel Ridao; Clara Berrozpe-Villabona; Adolfo Alonso-Arroyo; Cristina A Fraga-Medín; Enrique Bernal-Delgado; Alfonso Valencia; Rafael Tabarés-Seisdedos Journal: BMJ Open Date: 2022-04-29 Impact factor: 3.006