Evaluator Training and Reliability for SMA Global Nusinersen Trials1

Overview

Journal J Neuromuscul Dis

Publisher Sage Publications

Specialty Neurology

Date 2018 Jun 6

PMID 29865090

Citations 21

Authors

Allan M Glanzman

Elena S Mazzone

Sally Dunaway Young

Richard Gee

Kristy Rose

Anna Mayhew

Leslie Nelson

Chris Yun

Katie Alexander

Basil T Darras

Zarazuela Zolkipli-Cunningham

Gihan Tennekoon

John W Day

Richard S Finkel

Eugenio Mercuri

Darryl C De Vivo

Ron Baldwin

Kathie M Bishop

Jacqueline Montes

Affiliations

Soon will be listed here.

Abstract

Background: Training methodology was established to optimize reliability of outcome measures in the nusinersen clinical trials. The Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND), Hammersmith Functional Motor Scale Expanded (HFMSE), and Revised Upper Limb (RULM) were primary or secondary outcomes.

Methods: Video review, quarterly conference calls, and item scoring checks supported evaluator competence. Baseline and screening along with video review established intra and inter-rater reliability.

Results: Inter and intra-rater reliability were both excellent. Intraclass correlation coefficients (ICC) ranged between 0.906-0.994 across initial training meetings and 0.824-0.996 across annual retraining meetings. This was similar for CHOP INTEND (ICC = 0.824-0.951), HFMSE (ICC = 0.981-0.996), and RULM (ICC = 0.966-0.990). Intra-rater reliability for the CHOP INTEND, HFMSE, and RULM were ICC = 0.895 (95% CI: 0.852-0.926; n = 116), ICC = 0.959 (95% CI: 0.942-0.971; n = 125), and ICC = 0.948 (95% CI: 0.927-0.963; n = 126) respectively.

Conclusions: Rigorous evaluator training ensures reliability of assessment of subjects with spinal muscular atrophy (SMA) in multicenter international trials.

Citing Articles

Calculation of the Minimal Clinically Important Difference in Upper and Lower Limb Motor Assessment in Spinal Muscular Atrophy.

Hara T, Miyazaki Y, Shimizu-Motohashi Y, Nishida D, Kamimura A, Takeuchi M Prog Rehabil Med. 2025; 10():20250001.

PMID: 39781427 PMC: 11704608. DOI: 10.2490/prm.20250001.

Long-term natural history in type II and III spinal muscular atrophy: a 4-year international study on the Hammersmith Functional Motor Scale Expanded.

Coratti G, Bovis F, Pera M, Civitello M, Rohwer A, Salmin F Eur J Neurol. 2024; 31(12):e16517.

PMID: 39392101 PMC: 11555017. DOI: 10.1111/ene.16517.

Smartphone-Based Assessment of Mobility and Manual Dexterity in Adult People with Spinal Muscular Atrophy.

Arteaga-Bracho E, Cosne G, Kanzler C, Karatsidis A, Mazza C, Penalver-Andres J J Neuromuscul Dis. 2024; 11(5):1049-1065.

PMID: 38995798 PMC: 11380318. DOI: 10.3233/JND-240004.

Determining minimal clinically important differences in the Hammersmith Functional Motor Scale Expanded for untreated spinal muscular atrophy patients: An international study.

Coratti G, Bovis F, Pera M, Scoto M, Montes J, Pasternak A Eur J Neurol. 2024; 31(8):e16309.

PMID: 38656662 PMC: 11236020. DOI: 10.1111/ene.16309.

Disease Trajectories in the Revised Hammersmith Scale in a Cohort of Untreated Patients with Spinal Muscular Atrophy types 2 and 3.

Wolfe A, Stimpson G, Ramsey D, Coratti G, Dunaway Young S, Mayhew A J Neuromuscul Dis. 2024; 11(3):665-677.

PMID: 38427497 PMC: 11091622. DOI: 10.3233/JND-230211.

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