SynthesisBMC neurology2016
A review of clinical trial designs used to detect a disease-modifying effect of drug therapy in Alzheimer's disease and Parkinson's disease.
Synthesis in BMC neurology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled 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.
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.
Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 48 citations in OpenAlex.
- Systematic Review Looking at the Use of Technology to Measure Free-Living Symptom and Activity Outcomes in Parkinson's Disease in the Home or a Home-like Environment.Journal of Parkinson's disease · 2020Pooled it
- Improved Parkinsons disease motor score in a single-arm open-label trial of febuxostat and inosine.Medicine · 2020Trial
- Training gains and transfer effects after mnemonic strategy training in mild cognitive impairment: A fMRI study.International journal of psychophysiology : official journal of the International Organization of Psychophysiology · 2020Trial
- Delayed-Start Analyses in the Phase 3 Solanezumab EXPEDITION3 Study in Mild Alzheimer's Disease.The journal of prevention of Alzheimer's disease · 2018Trial
- Phase IIb Study of Intranasal Glutathione in Parkinson's Disease.Journal of Parkinson's disease · 2017Trial
- What should convince a clinician of disease modification in Alzheimer's disease clinical trials?Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- The patient-centric development of an inclusive multi-arm multi-stage trial for Parkinson's disease.Brain communications · 2026Article
- The Search for Disease Modification in Parkinson's Disease-A Review of the Literature.Life (Basel, Switzerland) · 2025Review
- Improving recruitment and retention of people with Parkinson's disease to clinical studies: A scoping review.Journal of Parkinson's disease · 2025Article
- Transforming Alzheimer's Treatment: Unveiling New Potential with Drug Repurposing Strategies.Current medicinal chemistry · 2025Review
- GLP-1 receptor agonists in Alzheimer's and Parkinson's disease: endocrine pathways, clinical evidence, and future directions.Frontiers in endocrinology · 2025Review
- Constructing the Framework for Disease Modification in Pulmonary Arterial Hypertension.American journal of respiratory and critical care medicine · 2024Article
- Patient and Public Involvement and Engagement in the Development of a Platform Clinical Trial for Parkinson's Disease: An Evaluation Protocol.Journal of Parkinson's disease · 2024Article
- Advancing precision medicine therapeutics for Parkinson's utilizing a shared quantitative systems pharmacology model and framework.Frontiers in systems biology · 2024Article
- Investigating trial design variability in trials of disease-modifying therapies in Parkinson's disease: a scoping review protocol.BMJ open · 2023Article
- Development of iPSC-based clinical trial selection platform for patients with ultrarare diseases.Science advances · 2022Article
- The emerging postural instability phenotype in idiopathic Parkinson disease.NPJ Parkinson's disease · 2022Article
- Safety, pharmacokinetics and pharmacodynamics of SBT-020 in patients with early stage Huntington's disease, a 2-part study.British journal of clinical pharmacology · 2021Article
- Targeting for Success: Demonstrating Proof-of-Concept with Mechanistic Early Phase Clinical Pharmacology Studies for Disease-Modification in Neurodegenerative Disorders.International journal of molecular sciences · 2021Review
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundDisease-modification clinical trials in neurodegenerative disorders have struggled to separate symptomatic effects of putative agents from disease-modification. In response, a variety of clinical trial designs have been developed. A systematic review was undertaken to examine which trial designs have been used in Alzheimer's disease (AD) and Parkinson's disease (PD) to detect disease-modifying, as opposed to symptomatic, drug effects. In addition we aimed to identify novel clinical trial designs used in the past or planned for use in the future. We aimed to critique whether the methods used would have identified true disease-modification.
methodsMEDLINE, Embase and CENTRAL (1980-2015) were searched to identify papers meriting review in full. ClinicalTrials.gov was searched to identify unpublished or planned randomised controlled trials (RCTs). We included RCTs in PD or AD which aimed to demonstrate the disease-modifying properties of drug therapy and differentiate that benefit from any symptomatic effect.
results128 RCTs were finally included: 84 in AD (59 published, 25 unpublished); 44 in PD (36 published, 8 unpublished). A variety of clinical trial designs were applied including long-term follow-up, wash-in and wash-out analyses, randomised delayed-start, the use of time-to-event outcome measures and surrogate disease progression biomarkers. Deficiencies in each of these design strategies, the quantity of missing data in included RCTs and the methods used to deal with missing data, meant that none of the included studies convincingly demonstrated disease-modification. No truly novel clinical trial designs were identified.
conclusionWe currently believe that the best clinical trial design available to demonstrate disease-modification is a long-term follow-up study, in which an examination is made for sustained divergence in outcome measures between treatment arms over the study period.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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 OpenQuestion graph.