Observational Study

. 2020 Nov;47(6):810-815.

doi: 10.1017/cjn.2020.111. Epub 2020 Jun 4.

A National Spinal Muscular Atrophy Registry for Real-World Evidence

Victoria L Hodgkinson^#¹, Maryam Oskoui^#^{2

3}, Joshua Lounsberry¹, Saïd M'Dahoma¹, Emily Butler¹, Craig Campbell⁴, Alex MacKenzie⁵, Hugh J McMillan⁵, Louise Simard⁶, Jiri Vajsar⁷, Bernard Brais³, Kristine M Chapman⁸, Nicolas Chrestian⁹, Meghan Crone¹⁰, Peter Dobrowolski¹¹, Susan Dojeiji¹², James J Dowling⁷, Nicolas Dupré¹³, Angela Genge^{3

14}, Hernan Gonorazky⁷, Simona Hasal¹⁰, Aaron Izenberg¹⁵, Wendy Johnston¹¹, Edward Leung¹⁶, Hanns Lochmüller^{5

17}, Jean K Mah^{1

18}, Alier Marerro¹⁹, Rami Massie³, Laura McAdam²⁰, Anna McCormick⁵, Michel Melanson²¹, Michelle M Mezei⁸, Cam-Tu E Nguyen²², Colleen O'Connell^{23

24}, Erin K O'Ferrall^{3

14}, Gerald Pfeffer¹, Cecile Phan¹¹, Stephanie Plamondon¹, Chantal Poulin^{2

3}, Xavier Rodrigue¹³, Kerri L Schellenberg²⁵, Kathy Selby²⁶, Jordan Sheriko²⁷, Christen Shoesmith²⁸, Garth Smith²⁹, Monique Taillon^{23

24}, Sean Taylor, Jodi Warman Chardon^{5

17}, Scott Worley^{23

24}, Lawrence Korngut¹

Affiliations

¹ Department of Clinical Neurosciences and Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada.
² Department of Pediatrics, McGill University, Montréal, QC, Canada.
³ Department of Neurology and Neurosurgery and of Pathology, McGill University, Montréal, QC, Canada.
⁴ Department of Pediatrics, Children's Health Research Institute, University of Western Ontario, London, ON, Canada.
⁵ Department of Pediatrics, Children's Hospital of Eastern Ontario, University of Ottawa, Ottawa, ON, Canada.
⁶ Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, MB, Canada.
⁷ Division of Neurology, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.
⁸ Division of Neurology, Department of Medicine, Vancouver General Hospital, University of British Columbia, Vancouver, BC, Canada.
⁹ CHUL Centre Mère-Enfant-Soleil, Laval University, Québec City, QC, Canada.
¹⁰ Department of Pediatrics, Kinsmen Child Centre, University of Saskatchewan, Saskatoon, SK, Canada.
¹¹ Division of Neurology, University of Alberta, Edmonton, AB, Canada.
¹² Division of Physical Medicine and Rehabilitation, Department of Medicine, University of Ottawa, Ottawa, ON, Canada.
¹³ Department of Medicine, Laval University, and CHU de Québec-UL, Québec City, QC, Canada.
¹⁴ Montreal Neurological Institute and Hospital, Montreal, QC, Canada.
¹⁵ Division of Neurology, Department of Medicine, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada.
¹⁶ Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, MB, Canada.
¹⁷ Department of Medicine, The Ottawa Hospital and Brain and Mind Research Institute, University of Ottawa, Ottawa, ON, Canada.
¹⁸ Department of Pediatrics, University of Calgary, Calgary, AB, Canada.
¹⁹ CHU Dr. Georges-L-Dumont, and CFNMB, Université de Sherbrooke, Moncton, NB, Canada.
²⁰ Department of Pediatrics, Holland Bloorview Kids Rehabilitation Hospital, Bloorview Research Institute, University of Toronto, Toronto, ON, Canada.
²¹ Department of Physical Medicine and Rehabilitation, Queen's University, Kingston, ON, Canada.
²² CHU Sainte-Justine, Université de Montréal, Montréal, QC, Canada.
²³ Stan Cassidy Centre for Rehabilitation, Fredericton, NB, Canada.
²⁴ Faculty of Medicine, Dalhousie University, Halifax, NS, Canada.
²⁵ Division of Neurology, Department of Medicine, University of Saskatchewan, Saskatoon, SK, Canada.
²⁶ Division of Neurology, Department of Pediatrics, BC Children's Hospital, University of Vancouver, Vancouver, BC, Canada.
²⁷ Division of Neurology, Department of Pediatrics, Dalhousie University, Halifax, NS, Canada.
²⁸ Division of Neurology and Clinical Neurological Sciences, London Health Sciences Centre, University of Western Ontario, London, ON, Canada.
²⁹ Department of Pediatrics, KidsInclusive Centre for Child & Youth Development, Hotel Dieu Hospital, Queen's University, Kingston, ON, Canada.

^# Contributed equally.

PMID: 32493524
PMCID: PMC7656664
DOI: 10.1017/cjn.2020.111

Observational Study

A National Spinal Muscular Atrophy Registry for Real-World Evidence

Victoria L Hodgkinson et al. Can J Neurol Sci. 2020 Nov.

. 2020 Nov;47(6):810-815.

doi: 10.1017/cjn.2020.111. Epub 2020 Jun 4.

Authors

Affiliations

¹ Department of Clinical Neurosciences and Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada.
² Department of Pediatrics, McGill University, Montréal, QC, Canada.
³ Department of Neurology and Neurosurgery and of Pathology, McGill University, Montréal, QC, Canada.
⁴ Department of Pediatrics, Children's Health Research Institute, University of Western Ontario, London, ON, Canada.
⁵ Department of Pediatrics, Children's Hospital of Eastern Ontario, University of Ottawa, Ottawa, ON, Canada.
⁶ Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, MB, Canada.
⁷ Division of Neurology, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.
⁸ Division of Neurology, Department of Medicine, Vancouver General Hospital, University of British Columbia, Vancouver, BC, Canada.
⁹ CHUL Centre Mère-Enfant-Soleil, Laval University, Québec City, QC, Canada.
¹⁰ Department of Pediatrics, Kinsmen Child Centre, University of Saskatchewan, Saskatoon, SK, Canada.
¹¹ Division of Neurology, University of Alberta, Edmonton, AB, Canada.
¹² Division of Physical Medicine and Rehabilitation, Department of Medicine, University of Ottawa, Ottawa, ON, Canada.
¹³ Department of Medicine, Laval University, and CHU de Québec-UL, Québec City, QC, Canada.
¹⁴ Montreal Neurological Institute and Hospital, Montreal, QC, Canada.
¹⁵ Division of Neurology, Department of Medicine, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada.
¹⁶ Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, MB, Canada.
¹⁷ Department of Medicine, The Ottawa Hospital and Brain and Mind Research Institute, University of Ottawa, Ottawa, ON, Canada.
¹⁸ Department of Pediatrics, University of Calgary, Calgary, AB, Canada.
¹⁹ CHU Dr. Georges-L-Dumont, and CFNMB, Université de Sherbrooke, Moncton, NB, Canada.
²⁰ Department of Pediatrics, Holland Bloorview Kids Rehabilitation Hospital, Bloorview Research Institute, University of Toronto, Toronto, ON, Canada.
²¹ Department of Physical Medicine and Rehabilitation, Queen's University, Kingston, ON, Canada.
²² CHU Sainte-Justine, Université de Montréal, Montréal, QC, Canada.
²³ Stan Cassidy Centre for Rehabilitation, Fredericton, NB, Canada.
²⁴ Faculty of Medicine, Dalhousie University, Halifax, NS, Canada.
²⁵ Division of Neurology, Department of Medicine, University of Saskatchewan, Saskatoon, SK, Canada.
²⁶ Division of Neurology, Department of Pediatrics, BC Children's Hospital, University of Vancouver, Vancouver, BC, Canada.
²⁷ Division of Neurology, Department of Pediatrics, Dalhousie University, Halifax, NS, Canada.
²⁸ Division of Neurology and Clinical Neurological Sciences, London Health Sciences Centre, University of Western Ontario, London, ON, Canada.
²⁹ Department of Pediatrics, KidsInclusive Centre for Child & Youth Development, Hotel Dieu Hospital, Queen's University, Kingston, ON, Canada.

^# Contributed equally.

PMID: 32493524
PMCID: PMC7656664
DOI: 10.1017/cjn.2020.111

Abstract
in English, French

Background: Spinal muscular atrophy (SMA) is a devastating rare disease that affects individuals regardless of ethnicity, gender, and age. The first-approved disease-modifying therapy for SMA, nusinursen, was approved by Health Canada, as well as by American and European regulatory agencies following positive clinical trial outcomes. The trials were conducted in a narrow pediatric population defined by age, severity, and genotype. Broad approval of therapy necessitates close follow-up of potential rare adverse events and effectiveness in the larger real-world population.

Methods: The Canadian Neuromuscular Disease Registry (CNDR) undertook an iterative multi-stakeholder process to expand the existing SMA dataset to capture items relevant to patient outcomes in a post-marketing environment. The CNDR SMA expanded registry is a longitudinal, prospective, observational study of patients with SMA in Canada designed to evaluate the safety and effectiveness of novel therapies and provide practical information unattainable in trials.

Results: The consensus expanded dataset includes items that address therapy effectiveness and safety and is collected in a multicenter, prospective, observational study, including SMA patients regardless of therapeutic status. The expanded dataset is aligned with global datasets to facilitate collaboration. Additionally, consensus dataset development aimed to standardize appropriate outcome measures across the network and broader Canadian community. Prospective outcome studies, data use, and analyses are independent of the funding partner.

Conclusion: Prospective outcome data collected will provide results on safety and effectiveness in a post-therapy approval era. These data are essential to inform improvements in care and access to therapy for all SMA patients.

Un registre national des cas d’amyotrophie spinale en vue d’obtenir des données probantes basées sur l’expérience des patients.

Contexte :: L’amyotrophie spinale (AS) est une maladie rare et dévastatrice qui affecte les individus indépendamment de leur origine ethnique, de leur sexe et de leur âge. Le premier traitement modificateur de cette maladie, le nusinursen, a été approuvé par Santé Canada ainsi que par des agences réglementaires américaines et européennes à la suite de résultats encourageants obtenus dans le cadre d’essais cliniques. Ces derniers ont été effectués sur une population restreinte de jeunes patients recrutés en fonction de leur âge, de la gravité de leur AS et de leur génotype. On le sait, l’approbation à plus grande échelle d’un traitement nécessite un suivi étroit de ses rares et potentiels effets indésirables et de son efficacité au sein d’une population réelle beaucoup plus importante.

Méthodes :: À cet égard, le Canadian Neuromuscular Disease Registry (CNDR) a entrepris, avec diverses parties prenantes, une démarche itérative visant à élargir l’ensemble des données actuelles au sujet de l’AS, et ce, afin de saisir les aspects se rapportant de façon pertinente à l’évolution de l’état de santé des patients dans un contexte de vigilance post-marketing d’un traitement. De fait, ce registre élargi du CNDR au sujet de l’AS repose sur une étude observationnelle longitudinale et prospective de patients canadiens atteints de l’AS. Cette étude a été conçue pour évaluer la sécurité et l’efficacité des nouveaux traitements et fournir des renseignements pratiques impossibles à obtenir dans le cadre d’essais cliniques.

Résultats :: De façon consensuelle, ces données élargies ont inclus des aspects tenant compte de l’efficacité du traitement et de sa sécurité. Elles ont été collectées lors d’une étude menée dans plusieurs établissements de santé au sujet de patients atteints d’AS, et ce, quel que soit le niveau de soins qui leur étaient prodigués. Ces données élargies étaient aussi conformes à l’ensemble des données obtenues précédemment afin de faciliter la collaboration. De plus, cette approche consensuelle dans l’élaboration d’un ensemble de données a pour objectif de standardiser de manière appropriée les instruments de mesure de l’évolution de l’état de santé des patients dans ce réseau et plus largement au Canada. Enfin, soulignons que tant les études prospectives portant sur l’évolution de l’état de santé des patients, l’utilisation des données que les analyses effectuées sont demeurées indépendantes du bailleur de fonds.

Conclusion :: Ces données prospectives quant à l’évolution de l’état de santé des patients atteints d’AS offriront, en lien avec le nusinursen, des résultats en matière de sécurité et d’efficacité dans un contexte de suivi « post-approbation » des traitements. Ces données sont également essentielles pour en savoir davantage à propos des améliorations aux soins et de l’accès aux traitements pour tous les patients.

Keywords: Rare disease; Real-world evidence; Registry; Spinal muscular atrophy.

PubMed Disclaimer

Conflict of interest statement

Dr. VLH reports personal fees from Biogen, Roche, Sarepta outside the submitted work. Dr. MO reports grants from Fonds de Recherche Sante du Québec, grants from Kids Brain Health Network, grants from Canadian Institutes of Health Research, grants from SickKids Foundation, grants from Cerebral Palsy Alliance Research Foundation, other from Ionis, other from Biogen, other from Roche, other from Cytokinetics, personal fees and non-financial support from American Academy of Neurology, grants from Fondation du Grand Defi Pierre Lavoie, outside the submitted work. Mr. JL reports personal fees from Biogen Canada Limited, outside the submitted work. Ms. EB has nothing to disclose. Dr. SMD has nothing to disclose. Dr. CC reports grants, personal fees, and other from Biogen, during the conduct of the study; grants, personal fees, and other from PTC Therapeutics, other from Acceleron, AMO, Catabasis, Pfizer, Sarepta, Wave, BMS, Scholar Rock, and Roche, outside the submitted work. Dr. AM reports grants from Biogen, outside the submitted work. Dr. HJM has nothing to disclose. Dr. JV has nothing to disclose. Dr. BB has nothing to disclose. Dr. KMC has nothing to disclose. Dr NC received financial support to prepare review courses about SMA for neurologists, physical therapists, and pediatricians. Dr. MC reports personal fees from Biogen, outside the submitted work. Dr. PD has nothing to disclose. Dr. SD has nothing to disclose. Dr. JJD has nothing to disclose. Dr. ND has nothing to disclose. Dr. AG reports grants from Biogen, Sanofi-Genzyme, CSL Behring, MTPA, AL-S Pharma, AB Sciences, Novartis, Wave Life Sciences, Argenx, Alexion, Avexis, Ackea, Cytokinetics, Hoffman-La Roche, outside the submitted work. Dr. HG reports personal fees from Biogen. Dr. SH has nothing to disclose. Dr. AI has nothing to disclose. Dr. WJ reports personal fees from MT Pharma Canada, other from Cytokinetics, other from Biogen, other from Orion, other from Mallinkrodt, other from Apellis, other from Alexion, other from AB Science, outside the submitted work. Dr. EL has nothing to disclose. Dr. HL reports grants and personal fees from AMO Pharma, Biogen, Desitin, GW Pharma, Pfizer, PTC Therapeutics, Roche, Santhera, Sarepta, Satellos, Ultragenyx, outside the submitted work. Dr. JKM has nothing to disclose. Dr. AM has nothing to disclose. Dr. RM has nothing to disclose. Dr. LM reports other from Italfarmaco, outside the submitted work. Dr. AM has nothing to disclose. Dr. MM has nothing to disclose. Dr. MMM reports personal fees from Genzyme, Alnylam, Pfizer, Akcea, CSL Behring, outside the submitted work. Dr. C-TEN reports other from Pfizer, other from Catabasis, outside the submitted work. Dr. COC reports personal fees from MT Pharma, grants and personal fees from Canopy Growth, personal fees from IPSEN, grants from Cytokinetics, grants from Mallincrodtk, grants from Orion, personal fees from Shoppers Drug Mart, outside the submitted work. Dr. EKOF reports personal fees from PTC Therapeutics nmDMD Advisory Board, grants from Sanofi Genzyme, grants from Acceleron, from SAnofi Genzyme, grants from Grifols, during the conduct of the study. Dr. CP has nothing to disclose. Dr. GP has nothing to disclose. Dr. SP reports other from Biogen, outside the submitted work. Dr. CP has nothing to disclose. Dr. XR has nothing to disclose. Dr. KLS has nothing to disclose. Dr. KS reports grants from Biogen/IONIS, personal fees from Biogen, outside the submitted work. Dr. JS reports personal fees from Biogen, outside the submitted work. Dr. Simard has nothing to disclose. Dr. CS reports other from Biogen, outside the submitted work. Dr. GS reports personal fees from Shire Pharmaceuticals, personal fees from Purdue Pharmaceuticals, personal fees from Janssen Pharmaceuticals, outside the submitted work. Dr. MT reports grants from Allergan, personal fees from Biogen outside the submitted work. Dr. ST has nothing to disclose. Dr. JWC has nothing to disclose. Dr. SW reports personal fees from Cytokinetics, outside the submitted work. Dr. LK reports grants from Biogen, during the conduct of the study; grants from Sanofi Genzyme, Cytokinetics, personal fees from Alexion, Novartis, Mitsubishi Tanabe, Sarepta, Biogen, CSL Behring, outside the submitted work.

References

1. Verhaart IEC, Robertson A, Leary R, et al. A multi-source approach to determine SMA incidence and research ready population. J Neurol. 2017;264(7):1465–73. - PMC - PubMed
1. Arnold ES, Fischbeck KH. Spinal muscular atrophy. Handb Clin Neurol. 2018;148:591–601. - PubMed
1. Oskoui M, Levy G, Garland CJ, et al. The changing natural history of spinal muscular atrophy type 1. Neurology. 2007;69(20):1931–6. - PubMed
1. Mercuri E, Bertini E, Iannaccone ST. Childhood spinal muscular atrophy: controversies and challenges. Lancet Neurol. 2012;11(5):443–52. - PubMed
1. Parente V, Corti S. Advances in spinal muscular atrophy therapeutics. Ther Adv Neurol Disord. 2018;11:1756285618754501. - PMC - PubMed

Publication types

Actions
Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions

LinkOut - more resources

Full Text Sources
Medical
- ClinicalTrials.gov
- MedlinePlus Health Information

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

A National Spinal Muscular Atrophy Registry for Real-World Evidence

Affiliations

A National Spinal Muscular Atrophy Registry for Real-World Evidence

Authors

Affiliations

Abstract
in English, French

Conflict of interest statement

References

Publication types

MeSH terms

LinkOut - more resources

Full Text Sources

Medical

Abstract in English, French

Conflict of interest statement

References

Publication types

MeSH terms

LinkOut - more resources

Full Text Sources

Medical

Abstract
in English, French