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A National Spinal Muscular Atrophy Registry for Real-World Evidence

  • Victoria L. Hodgkinson (a1), Maryam Oskoui (a2) (a3), Joshua Lounsberry (a1), Saïd M’Dahoma (a1), Emily Butler (a1), Craig Campbell (a4), Alex MacKenzie (a5), Hugh J. McMillan (a5), Louise Simard (a6), Jiri Vajsar (a7), Bernard Brais (a3), Kristine M. Chapman (a8), Nicolas Chrestian (a9), Meghan Crone (a10), Peter Dobrowolski (a11), Susan Dojeiji (a12), James J. Dowling (a7), Nicolas Dupré (a13), Angela Genge (a3) (a14), Hernan Gonorazky (a7), Simona Hasal (a10), Aaron Izenberg (a15), Wendy Johnston (a11), Edward Leung (a16), Hanns Lochmüller (a5) (a17), Jean K. Mah (a1) (a18), Alier Marerro (a19), Rami Massie (a3), Laura McAdam (a20), Anna McCormick (a5), Michel Melanson (a21), Michelle M. Mezei (a8), Cam-Tu E. Nguyen (a22), Colleen O’Connell (a23) (a24), Erin K. O’Ferrall (a3) (a14), Gerald Pfeffer (a1), Cecile Phan (a11), Stephanie Plamondon (a1), Chantal Poulin (a2) (a3), Xavier Rodrigue (a13), Kerri L. Schellenberg (a25), Kathy Selby (a26), Jordan Sheriko (a27), Christen Shoesmith (a28), Garth Smith (a29), Monique Taillon (a23) (a24), Sean Taylor, Jodi Warman Chardon (a5) (a17), Scott Worley (a23) (a24) and Lawrence Korngut (a1)...

Abstract:

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.

RÉSUMÉ :

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.

Copyright

This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited.

Corresponding author

Correspondences to: Lawrence Korngut, MD, MSc, FRCPC, Department of Clinical Neurosciences, University of Calgary, Hotchkiss Brain Institute, 480060, 4th Floor Administration, Clinical Neurosciences, South Health Campus, 4448 Front Street SE, Calgary, AB T3M 1M4, Canada. Phone: (403) 956-2464. Fax: (403) 956-2992. Email: lawrence.korngut@albertahealthservices.ca

Footnotes

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These authors share first authorship.

Footnotes

References

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A National Spinal Muscular Atrophy Registry for Real-World Evidence

  • Victoria L. Hodgkinson (a1), Maryam Oskoui (a2) (a3), Joshua Lounsberry (a1), Saïd M’Dahoma (a1), Emily Butler (a1), Craig Campbell (a4), Alex MacKenzie (a5), Hugh J. McMillan (a5), Louise Simard (a6), Jiri Vajsar (a7), Bernard Brais (a3), Kristine M. Chapman (a8), Nicolas Chrestian (a9), Meghan Crone (a10), Peter Dobrowolski (a11), Susan Dojeiji (a12), James J. Dowling (a7), Nicolas Dupré (a13), Angela Genge (a3) (a14), Hernan Gonorazky (a7), Simona Hasal (a10), Aaron Izenberg (a15), Wendy Johnston (a11), Edward Leung (a16), Hanns Lochmüller (a5) (a17), Jean K. Mah (a1) (a18), Alier Marerro (a19), Rami Massie (a3), Laura McAdam (a20), Anna McCormick (a5), Michel Melanson (a21), Michelle M. Mezei (a8), Cam-Tu E. Nguyen (a22), Colleen O’Connell (a23) (a24), Erin K. O’Ferrall (a3) (a14), Gerald Pfeffer (a1), Cecile Phan (a11), Stephanie Plamondon (a1), Chantal Poulin (a2) (a3), Xavier Rodrigue (a13), Kerri L. Schellenberg (a25), Kathy Selby (a26), Jordan Sheriko (a27), Christen Shoesmith (a28), Garth Smith (a29), Monique Taillon (a23) (a24), Sean Taylor, Jodi Warman Chardon (a5) (a17), Scott Worley (a23) (a24) and Lawrence Korngut (a1)...

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