Misdiagnosis of amyotrophic lateral sclerosis in clinical practice in Europe and the USA: a patient chart review and physician survey

Abstract

Objective

Delays in amyotrophic lateral sclerosis (ALS) diagnosis can result in compromised disease management and unnecessary costs. We examined the extent of ALS misdiagnosis in the US and Europe.

Methods

Data were collected via the Adelphi ALS Disease Specific Programme™, a cross-sectional survey of physicians and a medical chart review of their consulting patients with ALS in France, Germany, Italy, Spain, the UK (EU5), and the US. Between July 2020 and March 2021, eligible physicians (primary speciality neurology, active involvement in managing patients with ALS) abstracted data from patients (≥18 years old) with confirmed ALS.

Results

Overall, 138 physicians completed the survey (EU5 107, US 31), with data reviewed from 795 patient medical charts (EU5 568, US 227); 278 (35.0%) patients (EU5 183 [32.2%], US 95 [41.9%]) had received ≥1 initial misdiagnosis based on symptoms later attributed to ALS. Mean (SD) time from symptom onset to first healthcare professional consultation was 3.8 (5.2) months (EU5 4.3 [4.8] months, US 2.6 [5.8] months). Mean (SD) time from symptom onset to ALS diagnosis was 8.2 (12.5) months (EU5 9.6 [14.0] months, US 5.0 [6.8] months) and increased to 10.4 (17.9) for patients with a misdiagnosis (compared with 6.9 [7.2] for patients with no misdiagnosis). Physician-identified barriers to timely ALS diagnosis included the similarity of symptoms to other conditions and delayed referral to neurologists.

Conclusions

Misdiagnosis of ALS is frequent, with a protracted diagnostic pathway. Targeted education of patients and physicians about signs and symptoms and benefits of prompt referral to multidisciplinary care are needed.

Keywords:

• ALS
• barriers
• diagnosis
• real-world data
• symptoms

Subject Classification Code:

• Epidemiology
• neuropathology
• pathology

Acknowledgments

The authors thank Rosalind Carney, DPhil, and Esther Race, PhD, of Ogilvy Health, London, UK, for medical writing support. The authors thank Margarita Lens, MSci, CMPP, of UCB Pharma, Slough, UK, for publication coordination.

Consent

The Disease Specific Programme was conducted in accordance with the European Pharmaceutical Market Research Association (EphMRA) Code of Conduct. The study protocol (reference number AG8802) was submitted to the Western Institutional Review Board, which provided an ethics waiver, as it was determined that ethics approval was not required for this study. All data were collected following procedures with ethics committee approval, and data were fully de-identified prior to receipt by Adelphi Real World. The respondents provided informed consent for the use of their anonymized and aggregated data for research and publication in scientific journals. All data, i.e., methodology, materials, data and data analysis, that support the findings of this survey are the intellectual property of Adelphi Real World. As such no administrative permissions were required to access and use the data.

Disclosure of interest

Namita Goyal has received research support from Amylyx, Alexion, Anelixis, Annexon, BrainStorm Cell Therapeutics, Calico, Cytokinetics, Fulcrum Therapeutics, Healey Pharma, Kezar, MediciNova, Mitsubishi Tanabe Pharma, Octapharma, Orphazyme, PTC and Transposon. Dr Goyal has served on Advisory Boards for Abcuro, Alexion, Amylyx, Annexon, argenx, AstraZeneca, CSL Behring, Fulcrum Therapeutics, Kezar, Mitsubishi Tanabe Pharma, Sanofi Genzyme and UCB. In relation to these activities, she has received travel reimbursement and honoraria. She has also served on the speaker’s bureau for argenx and CSL.

Kerina Bonar, Natasa Savic, and Raphaëlle Beau Lejdstrom are employees of UCB Pharma.

Jack Wright and Jennifer Mellor are employees of Adelphi Real World.

Christopher McDermott is an employee of the University of Sheffield and is supported by the NIHR Biomedical Research Center Sheffield and an NIHR Research Professorship award.

Data availability statement

All data, i.e., methodology, materials, data and data analysis, that support the findings of this survey are the intellectual property of Adelphi Real World. All requests for access should be addressed directly to Jennifer Mellor at [email protected].

Additional information

Funding

UCB Pharma is one of the multiple subscribers to the Adelphi ALS Disease Specific Programme™. Medical writing support, provided by Ogilvy Health UK, was funded by UCB Pharma.