Evidence map›Paper›PMID 39666202›Full record

SynthesisJournal of neurology2024

Attrition and discontinuation in amyotrophic lateral sclerosis clinical trials: a meta-analysis.

Ruben P A van Eijk, Floris T van Loon, Jordi W J van Unnik, Daphne N Weemering, Georgios Seitidis, Dimitris Mavridis, Leonard H van den Berg, Stavros Nikolakopoulos

Abstract readMeta-AnalysisSystematic Review
PubMed Publisher
In one paragraph

Synthesis in Journal of neurology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Trial
  2. Article
  3. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Ruben P A van EijkDepartment of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands. r.p.a.vaneijk-2@umcutrecht.nl.ORCID http://orcid.org/0000-0002-7132-5967
Floris T van LoonDepartment of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands.ORCID http://orcid.org/0009-0007-4871-2567
Jordi W J van UnnikDepartment of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands.ORCID http://orcid.org/0000-0002-3238-6740
Daphne N WeemeringDepartment of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands.ORCID http://orcid.org/0009-0005-4182-3294
Georgios SeitidisDepartment of Psychology, University of Ioannina, Ioannina, Greece.ORCID http://orcid.org/0000-0003-0856-1892
Dimitris MavridisDepartment of Primary Education, School of Education, University of Ioannina, Ioannina, Greece.ORCID http://orcid.org/0000-0003-1041-4592
Leonard H van den BergDepartment of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands.ORCID http://orcid.org/0000-0002-5203-9674
Stavros NikolakopoulosBiostatistics and Research Support, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.ORCID http://orcid.org/0000-0002-9769-3725

Funding

Stichting ALS Nederland EVIDENCE
6 · The paper itself

Abstract

objectivesAttrition due to adverse events and disease progression impacts the integrity and generalizability of clinical trials. The aim of this study is to provide evidence-based estimates of attrition for clinical trials in amyotrophic lateral sclerosis (ALS), and identify study-related predictors, through a comprehensive systematic review and meta-analysis.

methodsWe systematically reviewed the literature to identify all randomized, placebo-controlled clinical trials in ALS and determined the number of patients who discontinued the study per randomized arm. Subsequently, we meta-analyzed attrition rates across studies, evaluated the difference between study arms, and explored the impact of study-level characteristics. Finally, a meta-regression model predicting study discontinuation for future clinical trials was translated into a web application.

resultsIn total, 60 randomized placebo-controlled clinical trials were included in the meta-analysis, randomizing 14,493 patients with ALS. Attrition varied significantly between studies, ranging from 3.1% to 75.7% of all randomized patients, with a pooled effect of 32.0% (90% prediction interval 6.1% to 66.3%). Attrition was similar between the intervention and placebo arm (odds ratio 1.08, 95% CI 0.89 to 1.31, p = 0.43). The follow-up duration was identified as the sole study-level predictor (0.032, 95% CI 0.026 to 0.039, p < 0.001), resulting in predicted attrition of 19.3% for 6-month, 36.4% for 12-month, and 55.6% for 18-month clinical trials.

conclusionsALS clinical trials encounter high attrition, which increases with the follow-up duration. These findings underscore the need to refine our strategies to manage attrition, preserving the integrity and generalizability of ALS clinical trials.

Indexed as

Amyotrophic Lateral SclerosisRandomized Controlled Trials as TopicHumansPatient DropoutsALSAttritionClinical trialsMeta-analysisTreatment discontinuation

Identifiers

PMID39666202

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.