TY - JOUR
T1 - Using the ALSFRS-R in multicentre clinical trials for amyotrophic lateral sclerosis
T2 - potential limitations in current standard operating procedures
AU - Bakers, Jaap N E
AU - de Jongh, Adriaan D
AU - Bunte, Tommy M
AU - Kendall, Lindsay
AU - Han, Steve S
AU - Epstein, Noam
AU - Lavrov, Arseniy
AU - Beelen, Anita
AU - Visser-Meily, Johanna M A
AU - van den Berg, Leonard H
AU - van Eijk, Ruben P A
N1 - Funding Information:
This study was funded by the Netherlands ALS foundation The authors acknowledge the ALS patients who participated in the dexpramipexole and ozanezumab trials, and their contribution to the search for a cure for ALS. We would also like to thank Biogen and GlaxoSmithKline for sharing their clinical research data.
Publisher Copyright:
© 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
PY - 2022/10/2
Y1 - 2022/10/2
N2 - Objective: Uniform data collection is fundamental for multicentre clinical trials. We aim to determine the variability, between ALS trial centers, in the prevalence of unexpected or implausible improvements in the revised ALS functional rating scale (ALSFRS-R) score, and its associations with individual patient and item characteristics.Methods: We used data from two multicentre studies to estimate the prevalence of an unexpected increase or implausible improvement in the ALSFRS-R score, defined as an increase of 5 points or more between two consecutive, monthly visits. For each patient with a 5-point or more increase, we evaluated the individual contribution of each ALSFRS-R item.Results: Longitudinal ALSFRS-R scores, originating from 114 trial centers enrolling a total of 1,240 patients, were analyzed. A 5-point or more increase in ALSFRS-R total score was found in 151 (12.2%) patients, with prevalence per study center ranging from 0% to 83%. Bulbar onset, faster disease progression at enrollment, and a lower ALSFRS-R score at baseline were associated with a sudden 5-point or more increase in the ALSFRS-R total score. ALSFRS-R items 2 (saliva), 9 (stairs), 10 (dyspnea), and 11 (orthopnea) were the primary drivers when a 5-point or more increase occurred.Conclusions: Sudden 5-point or more increases in ALSFRS-R total scores between two consecutive visits are relatively common. These sudden increases were not found to occur with equal frequency in trial centers; which underscores the need for amending existing standard operating procedures toward a universal version and monitoring of data quality during the study, in multicentre research.
AB - Objective: Uniform data collection is fundamental for multicentre clinical trials. We aim to determine the variability, between ALS trial centers, in the prevalence of unexpected or implausible improvements in the revised ALS functional rating scale (ALSFRS-R) score, and its associations with individual patient and item characteristics.Methods: We used data from two multicentre studies to estimate the prevalence of an unexpected increase or implausible improvement in the ALSFRS-R score, defined as an increase of 5 points or more between two consecutive, monthly visits. For each patient with a 5-point or more increase, we evaluated the individual contribution of each ALSFRS-R item.Results: Longitudinal ALSFRS-R scores, originating from 114 trial centers enrolling a total of 1,240 patients, were analyzed. A 5-point or more increase in ALSFRS-R total score was found in 151 (12.2%) patients, with prevalence per study center ranging from 0% to 83%. Bulbar onset, faster disease progression at enrollment, and a lower ALSFRS-R score at baseline were associated with a sudden 5-point or more increase in the ALSFRS-R total score. ALSFRS-R items 2 (saliva), 9 (stairs), 10 (dyspnea), and 11 (orthopnea) were the primary drivers when a 5-point or more increase occurred.Conclusions: Sudden 5-point or more increases in ALSFRS-R total scores between two consecutive visits are relatively common. These sudden increases were not found to occur with equal frequency in trial centers; which underscores the need for amending existing standard operating procedures toward a universal version and monitoring of data quality during the study, in multicentre research.
KW - ALSFRS-R
KW - Amyotrophic lateral sclerosis
KW - clinical trials
KW - standard operating procedures
UR - http://www.scopus.com/inward/record.url?scp=85121840028&partnerID=8YFLogxK
U2 - 10.1080/21678421.2021.2016838
DO - 10.1080/21678421.2021.2016838
M3 - Article
C2 - 34949141
SN - 2167-8421
VL - 23
SP - 500
EP - 507
JO - Amyotrophic Lateral Sclerosis & Frontotemporal Degeneration
JF - Amyotrophic Lateral Sclerosis & Frontotemporal Degeneration
IS - 7-8
ER -