Evidence map›Paper›PMID 35342092›Full record

ReviewJournal of Alzheimer's disease : JAD2022

Alzheimer's Disease: Key Insights from Two Decades of Clinical Trial Failures.

C Kwon Kim, Yin Rui Lee, Lynnett Ong, Michael Gold, Amir Kalali, Joydeep Sarkar

Abstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Journal of Alzheimer's disease : JAD, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 135 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
135citing papers in PubMed, 1 pooled it
–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

135 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  5. Enhancing early Alzheimer's disease clinical trials through prognostic score covariate adjustment.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
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  17. Digital seed amplification assay for TDP-43 aggregate quantification in CSF.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
  18. Review
  19. Article
  20. Article

75 more citing papers are in PubMed but not listed here.

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

6 authors.

C Kwon KimHolmusk, New York, NY, USA.
Yin Rui LeeHolmusk, New York, NY, USA.
Lynnett OngHolmusk, New York, NY, USA.
Michael GoldNeuroscience Development, AbbVie, North Chicago, IL, USA.
Amir KalaliChairman, CNS Summit, San Diego, CA, USA.
Joydeep SarkarHolmusk, New York, NY, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Given the acknowledged lack of success in Alzheimer's disease (AD) drug development over the past two decades, the objective of this review was to derive key insights from the myriad failures to inform future drug development. A systematic and exhaustive review was performed on all failed AD compounds for dementia (interventional phase II and III clinical trials from ClinicalTrials.gov) from 2004 to the present. Starting with the initial ∼2,700 AD clinical trials, ∼550 trials met our initial criteria, from which 98 unique phase II and III compounds with various mechanisms of action met our criteria of a failed compound. The two recent reported phase III successes of aducanumab and oligomannate are very encouraging; however, we are awaiting real-world validation of their effectiveness. These two successes against the 98 failures gives a 2.0% phase II and III success rate since 2003, when the previous novel compound was approved. Potential contributing methodological factors for the clinical trial failures were categorized into 1) insufficient evidence to initiate the pivotal trials, and 2) pivotal trial design shortcomings. Our evaluation found that rational drug development principles were not always followed for AD therapeutics development, and the question remains whether some of the failed compounds may have shown efficacy if the principles were better adhered to. Several recommendations are made for future AD therapeutic development. The whole database of the 98 failed compounds is presented in the Supplementary Material.

Indexed as

Alzheimer DiseaseHumansAlzheimer’s diseaseamyloidbiomarkersclinical trialdementiadrug development

Identifiers

PMID35342092
PMCPMC9198803

What OpenQuestion holds

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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 OpenQuestion graph.