ArticleNeuro-degenerative diseases2012
Validity, significance, strengths, limitations, and evidentiary value of real-world clinical data for combination therapy in Alzheimer's disease: comparison of efficacy and effectiveness studies.
Article in Neuro-degenerative diseases, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 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
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.
- Withdrawal or continuation of cholinesterase inhibitors or memantine or both, in people with dementia.The Cochrane database of systematic reviews · 2021Pooled it
- Memantine ER Maintains Patient Response in Moderate to Severe Alzheimer's Disease: Post Hoc Analyses From a Randomized, Controlled, Clinical Trial of Patients Treated With Cholinesterase Inhibitors.Alzheimer disease and associated disordersTrial
- Generating real-world evidence in Alzheimer's disease: Considerations for establishing a core dataset.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Meaningful benefits: a framework to assess disease-modifying therapies in preclinical and early Alzheimer's disease.Alzheimer's research & therapy · 2022Review
- Practical recommendations for timely, accurate diagnosis of symptomatic Alzheimer's disease (MCI and dementia) in primary care: a review and synthesis.Journal of internal medicine · 2021Review
- FDA position statement "Early Alzheimer's disease: Developing drugs for treatment, Guidance for Industry".Alzheimer's & dementia (New York, N. Y.) · 2019Review
- Insights into globalization: comparison of patient characteristics and disease progression among geographic regions in a multinational Alzheimer's disease clinical program.Alzheimer's research & therapy · 2018Article
- Withdrawal of Antidementia Drugs in Older People: Who, When and How?Drugs & aging · 2016Review
- The Use of Cholinesterase Inhibitors Across All Stages of Alzheimer's Disease.Drugs & aging · 2015Review
- Cumulative, additive benefits of memantine-donepezil combination over component monotherapies in moderate to severe Alzheimer's dementia: a pooled area under the curve analysis.Alzheimer's research & therapy · 2015Article
- Article
- Efficacy of memantine, donepezil, or their association in moderate-severe Alzheimer's disease: a review of clinical trials.TheScientificWorldJournal · 2013Review
- Memantine in patients with Alzheimer's disease receiving donepezil: new analyses of efficacy and safety for combination therapy.Alzheimer's research & therapy · 2013Article
- Neuropsychological test performance and cognitive reserve in healthy aging and the Alzheimer's disease spectrum: a theoretically driven factor analysis.Journal of the International Neuropsychological Society : JINS · 2012Article
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
backgroundRandomized controlled efficacy trials (RCTs), the scientific gold standard, are required for regulatory approval of Alzheimer's disease (AD) interventions, yet provide limited information regarding real-world therapeutic effectiveness.
objectiveTo compare the nature of evidence regarding the combination of approved AD treatments from RCTs versus long-term observational controlled studies (LTOCs).
methodsComparisons of strengths, limitations, and evidence level for monotherapy [cholinesterase inhibitor (ChEI) or memantine] and combination therapy (ChEI + memantine) in RCTs versus LTOCs.
resultsRCTs examined highly selected populations over months. LTOCs collected data across multiple AD stages in large populations over many years. RCTs and LTOCs show similar patterns favoring combination over monotherapy over placebo/no treatment. Long-term combination therapy compared to monotherapy reduced cognitive and functional decline and delayed time to nursing home admission. Persistent treatment was associated with slower decline. While LTOCs used control groups, adjusted for multiple covariates, had higher external validity, and favorable ethical, practical and cost considerations, their limitations included potential selection bias due to lack of placebo comparisons and randomization.
conclusionsNaturalistic LTOCs provide complementary long-term level II evidence to complement level I evidence from short-term RCTs regarding therapeutic effectiveness in AD that may otherwise be unobtainable. A coordinated strategy/consortium to pool LTOC data from multiple centers to estimate long-term comparative effectiveness, risks/benefits, and costs of AD treatments is needed.
Indexed as
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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.