The DOI matches its Crossref record; 38 of the 40 references it cites were found in a registry or an index; none of the 36 sources its claims cite is checked for support yet.
Alzheimer’s disease drug development pipeline: 2021
Open accessAbstract
Introduction: The number of individuals worldwide with Alzheimer's disease (AD) is growing at a rapid rate. New treatments are urgently needed. We review the current pipeline of drugs in clinical trials for the treatment of AD. Methods: We interrogated ClinicalTrials.gov, the federal registry of clinical trials to identify drugs in trials. Results: There are 126 agents in 152 trials assessing new therapies for AD: 28 treatments in Phase 3 trials, 74 in Phase 2, and 24 in Phase 1. The majority of drugs in trials (82.5%) target the underlying biology of AD with the intent of disease modification; 10.3% are putative cognitive enhancing agents; and 7.1% are drugs being developed to reduce neuropsychiatric symptoms. Discussion: This pipeline analysis shows that target biological processes are more diversified, biomarkers are more regularly used, and repurposed agents are being explored to determine their utility for the treatment of AD.
Overview
AI snapshot
Written from the paper’s full text.
TL;DR
This annual pipeline review identified 126 agents in 152 ongoing Alzheimer’s disease clinical trials as of January 5, 2021, with most agents intended as disease-modifying therapies. The pipeline showed continued target diversification, frequent biomarker use in later-phase disease-modifying trials, and substantial participant burden.
Key findings
- There were 126 agents in 152 trials: 28 agents in 41 Phase 3 trials, 74 agents in 87 Phase 2 trials, and 24 agents in 24 Phase 1 trials.
- Disease-modifying therapies made up 104 agents (82.5%); 13 (10.3%) were cognitive enhancers and 9 (7.1%) targeted neuropsychiatric/behavioral symptoms.
- Repurposed agents numbered 50, or 39.6% of candidate agents; they were more likely to have academic medical center/NIH sponsors (59%) than industry sponsors (16%).
- Currently active trials required 38,826 participants, contributing 2,540,014 participant-weeks; biopharma sponsored 49% of all trials, academic centers/NIH 29%, public–private partnerships 14%, and others 7%.
Methods
- The authors interrogated ClinicalTrials.gov as of January 5, 2021, including Phase 1, 2, and 3 trials listed as recruiting, active but not recruiting, enrolling by invitation, or not yet recruiting.
- They excluded completed, terminated, suspended, unknown, or withdrawn trials, non-pharmacologic therapeutic approaches, and biomarker trials; stem cell therapies were included.
- Agents were classified by mechanism using the Common Alzheimer’s Disease Research Ontology (CADRO), and trials were categorized as disease-modifying, cognitive-enhancing, or neuropsychiatric-symptom treatments based on trial features and stated intent.
Limitations
- The paper states that ClinicalTrials.gov includes the majority of AD agents in trials, making the review “comprehensive but not exhaustive”; Phase 1 trials conducted outside the United States may be under-represented.
- The authors state that not all trial descriptions on ClinicalTrials.gov note whether biomarkers are included, and they recognize that definitions of “disease-modifying” versus “symptomatic” are arbitrary.
- Evident from the design: this is a registry-based descriptive analysis without efficacy outcomes, and it excludes completed, terminated, suspended, unknown, or withdrawn trials, so it does not assess whether agents work.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
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Verification
Claims the paper makes
119 Own result · 29 Not checked yet · 17 Own interpretation · 16 No basis given · 4 Own method
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Of the DMTs 16 (15.4%) have amyloid and 11 (10.6%) have tau as the primary target or as one of several potential effects.”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Overview
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“There were five Phase 3 prevention trials enrolling cognitively normal participants known to be at risk for AD (preclinical AD).”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Phase 3
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“There are 10 repurposed agents in Phase 3 trials.”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Phase 3
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“13 (10.3%) agents in trials target cognitive enhancement”
- Also stated in: § Results · hedged
“10.3% are putative cognitive enhancing agents”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Overview
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § Results · hedged
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“There were 126 agents in 152 trials of treatments for AD (as of the index date of January 5, 2021).”
- Also stated in: § Results · plain
“There are 126 agents in 152 trials assessing new therapies for AD”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Overview
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § Results · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“All four of the biological therapies and one of the small molecules—four monoclonal antibodies and one receptor for advanced glycation end products (RAGE) antagonist—have amyloid as the primary or one of several targets (29.4% of DMTs).”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Phase 3
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“9 (7.1%) are intended to treat neuropsychiatric and behavioral symptoms”
- Also stated in: § Results · plain
“7.1% are drugs being developed to reduce neuropsychiatric symptoms”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Overview
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § Results · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“74 agents are in 87 Phase 2 trials”
- Also stated in: § Results · plain
“74 in Phase 2”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Overview
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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- Also stated in: § Results · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In Phase 3 there are 28 agents in 41 trials”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Phase 3
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“DMTs are the most common agents being studied (104; 82.5% of the total number of agents in trial)”
- Also stated in: § Results · plain
“The majority of drugs in trials (82.5%) target the underlying biology of AD with the intent of disease modification”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Overview
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § Results · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Twenty‐eight agents are in 41 Phase 3 trials”
- Also stated in: § Results · plain
“28 treatments in Phase 3 trials”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Overview
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § Results · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Four (23.5%) of the DMT agents in Phase 3 are repurposed agents approved for use in another indication.”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Phase 3
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Of the DMTs 16 (15.4%) have amyloid and 11 (10.6%) have tau as the primary target or as one of several potential effects.”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Overview
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“24 agents are in 24 Phase 1 trials”
- Also stated in: § Results · plain
“24 in Phase 1”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Overview
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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- Also stated in: § Results · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“were on average 145 weeks in duration”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Phase 2
plainn = 104- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Twenty‐six of the Phase 2 DMT agents are repurposed after approval for use in another indication.”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Phase 2
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“one cognitive enhancing agent”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Phase 1
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“were on average 197 weeks in duration”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Phase 2
plainn = 147- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Repurposed agents comprise 41.6% (N = 10) of the Phase 1 pipeline.”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Phase 1
plainn = 10- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“There are six trials in Phase 2 involving cell therapies (see Table 4).”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Phase 2
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Of Phase 1 candidates, there are 23 potential DMTs”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Phase 1
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“one trial was for mild‐to‐moderate AD or healthy participants”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Phase 2
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“and 121 weeks for recruitment”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Phase 2
plainn = 147- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Phase 2 trials for agents targeting behavioral symptoms included 104 participants”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Phase 2
plainn = 104- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“including an average of 8 weeks of treatments”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Phase 2
plainn = 104- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“including an average of 52 weeks of treatment”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Phase 2
plainn = 147- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Phase 2 trials for cognitive‐enhancing agents included an average of 117 participants”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Phase 2
plainn = 117- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thirty (40.5%) of the Phase 2 agents are repurposed from other indications.”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Phase 2
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“More than 38,000 participants are required for currently registered trials; cumulatively they will contribute more than 2.5 million participant‐weeks in trials.”
§ Alzheimer's disease drug development pipeline: 2021 > METHODS > HIGHLIGHTS
plainn = 38,000- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In Phase 2 there are 74 agents in 87 trials”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Phase 2
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“were on average 103 weeks in duration”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Phase 2
plainn = 117- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Phase 1 has 24 agents in 24 trials (Figure 1, Table 3).”
- Also stated in: § Phase 1 · plain
“Twenty‐four agents in 24 Phase 1 clinical trials currently ongoing as of January 5, 2021 according to ClinicalTrials.gov.”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Phase 1
What the sources say
- Not checked yetcites ClinicalTrials.gov
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § Phase 1 · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“All types of trials took between two and three times longer to recruit patients to the trial than to assess the effects of the treatment during the exposure period.”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Phase 2
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“one trial included patients with mild, moderate, or severe AD”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Phase 2
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The time required for recruitment of the patient population typically exceeded the treatment period by up to two‐ to five‐fold.”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Phase 3
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Phase 2 trials for DMTs included an average of 147 participants in each trial”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Phase 2
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Two thirds of Phase 3 trials took longer to complete than originally planned as recorded on ClinicalTrials.gov.”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Phase 3
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“one trial included preclinical patients and patients with prodromal/mild AD”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Phase 2
plainn = 2- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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In the paper
“Of Phase 2 trials 78.6% took longer to complete than originally planned as recorded on ClinicalTrials.gov.”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Phase 2
What the sources say
- Not checked yetcites ClinicalTrials.gov
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“49 trials involved patients with prodromal or prodromal/mild AD dementia”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Phase 2
plainn = 49- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“30 were trials for mild‐to‐moderate AD”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Phase 2
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Seventy‐four agents in 87 Phase 2 clinical trials currently ongoing as of January 5, 2021 according to ClinicalTrials.gov.”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Phase 2
What the sources say
- Not checked yetcites ClinicalTrials.gov
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“including an average of 31 weeks of treatment”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Phase 2
plainn = 117- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Of Phase 3 DMT trials, 15 (63%) use biomarkers as supportive outcomes.”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Biomarkers
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Two (3%) of the Phase 2 DMT trials used tau PET as an entry criterion, two (3%) used either CSF amyloid or CSF tau, and one (1%) used either amyloid PET or CSF tau.”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Biomarkers
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“synaptic plasticity/neuroprotection (two agents; 8.7%)”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Phase 1
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In Phase 2, 11 (14%) DMT trials used amyloid PET as an entry criterion, nine (12%) used CSF amyloid, and 11 (14%) used either amyloid PET or CSF amyloid.”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Biomarkers
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“circadian rhythm (one agent; 4.3%)”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Phase 1
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“neurogenesis (one agent; 4.3%)”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Phase 1
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The AD drug development pipeline comprises 126 agents in 152 trials (Figure 1).”
§ Alzheimer's disease drug development pipeline: 2021 > DISCUSSION
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“One hundred four putative DMTs are being assessed (17 in Phase 3, 64 in Phase 2, 23 in Phase 1).”
§ Alzheimer's disease drug development pipeline: 2021 > DISCUSSION
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“North America participates in 75% of all trials registered on ClinicalTrials.gov.”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Global distribution of trials
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“inflammation (five agents; 21.7%)”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Phase 1
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Of the 24 Phase 3 DMT trials, four trials (17%) used amyloid positron emission tomography (PET) as an entry criterion, one (4%) used cerebrospinal fluid (CSF) amyloid, and six (25%) used either amyloid PET or CSF‐amyloid.”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Biomarkers
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Two (3%) of the Phase 2 DMT trials used tau PET as an entry criterion, two (3%) used either CSF amyloid or CSF tau, and one (1%) used either amyloid PET or CSF tau.”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Biomarkers
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Phase 2 trials are more often conducted in North America (60%) only and involve North America in 80%.”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Global distribution of trials
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Phase 1 trials have an average duration of 127 weeks (recruitment and treatment period) and include a mean of 43 participants in each trial.”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Phase 1
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“cell death (one agent; 4.3%)”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Phase 1
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“and no agents targeting behavioral symptoms”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Phase 1
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Of the 24 Phase 3 DMT trials, four trials (17%) used amyloid positron emission tomography (PET) as an entry criterion, one (4%) used cerebrospinal fluid (CSF) amyloid, and six (25%) used either amyloid PET or CSF‐amyloid.”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Biomarkers
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Across all trials, 49% are sponsored by the biopharma industry, 29% by academic medical centers (usually with funding from NIH), 14% are public–private partnerships, and 7% by others.”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Trial sponsors
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“epigenetic regulators (two agents; 8.7%)”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Phase 1
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In Phase 2, nine DMT trials (12%) have biomarkers as primary outcomes and 29 (38%) have biomarkers as supportive outcomes.”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Biomarkers
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Three (13%) of the Phase 3 DMT trials include tau PET imaging as an outcome and nine (12%) of Phase 2 DMT trials include tau PET imaging as an outcome.”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Biomarkers
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Forty (53%) of the Phase 2 trials did not require biomarker confirmation for study entry.”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Biomarkers
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Three (13%) of the Phase 3 DMT trials include tau PET imaging as an outcome and nine (12%) of Phase 2 DMT trials include tau PET imaging as an outcome.”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Biomarkers
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thirty‐seven percent of Phase 3 trials involve North American only and 71% included North America and non–North American countries.”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Global distribution of trials
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thirteen (54%) of the Phase 3 trials did not use biomarkers for study entry.”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Biomarkers
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“growth factors and hormones (two agents; 8.7%)”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Phase 1
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“There are 17 DMT small molecules”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Phase 1
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“metabolism and bioenergetics (one agent; 4.3%)”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Phase 1
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In Phase 2, 11 (14%) DMT trials used amyloid PET as an entry criterion, nine (12%) used CSF amyloid, and 11 (14%) used either amyloid PET or CSF amyloid.”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Biomarkers
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“There are three trials in Phase 1 involving stem cell therapies (Table 4).”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Phase 1
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“proteostasis (two agents; 8.7%)”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Phase 1
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“There is one trial in Phase 3 of a cognitive enhancer trial that requires CSF amyloid or CSF tau for entry.”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Biomarkers
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Phase 2 trials are more often conducted in North America (60%) only and involve North America in 80%.”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Global distribution of trials
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“DMTs represent 83% of the pipeline of agents.”
§ Alzheimer's disease drug development pipeline: 2021 > DISCUSSION
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“tau (one agent; 4.3% of Phase 1 DMTs)”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Phase 1
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In Phase 2, 11 (14%) DMT trials used amyloid PET as an entry criterion, nine (12%) used CSF amyloid, and 11 (14%) used either amyloid PET or CSF amyloid.”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Biomarkers
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“vascular factors (two agents; 8.7%)”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Phase 1
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Of the 24 Phase 3 DMT trials, four trials (17%) used amyloid positron emission tomography (PET) as an entry criterion, one (4%) used cerebrospinal fluid (CSF) amyloid, and six (25%) used either amyloid PET or CSF‐amyloid.”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Biomarkers
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Phase 1 trials have an average duration of 127 weeks (recruitment and treatment period) and include a mean of 43 participants in each trial.”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Phase 1
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This allows calculation of the total number of participant‐weeks across all active trials and shows that there are 2,540,014 participant weeks of time devoted to clinical trials.”
- Also stated in: § SUMMARY · plain
“Participants are making a remarkable contribution of 2,540,014 participant‐weeks to support AD drug development, making a major contribution to treatment development efforts.”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Trial participants
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § SUMMARY · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In Phase 2, nine DMT trials (12%) have biomarkers as primary outcomes and 29 (38%) have biomarkers as supportive outcomes.”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Biomarkers
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“none of the small molecules and only one of the biologics in Phase I has amyloid reduction as the major mechanism attributed to the agent (4.3% of DMTs).”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Phase 1
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“and six DMT biologics being assessed in Phase 1”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Phase 1
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thirty‐seven percent of Phase 3 trials involve North American only and 71% included North America and non–North American countries.”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Global distribution of trials
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In Phase 2, 47% of trials are sponsored by the biopharma industry, 31% by academic medical centers (with NIH funding), 15% are public–private partnerships, and 7% by others.”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Trial sponsors
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Across all currently active trials, the total number of participants needed is 38,826.”
- Also stated in: § DISCUSSION · plain
“Participants required for currently active trials total 38,826; when calculated in terms of participant‐weeks in trials (Table 7), the total number in all ongoing trials is 2,540,014.”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Trial participants
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § DISCUSSION · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In Phase 3, 61% of trials are sponsored by the biopharma industry, 20% by academic medical centers (with funding from NIH), 12% are public–private partnerships, and 7% by others.”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Trial sponsors
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“none of the small molecules and only one of the biologics in Phase I has amyloid reduction as the major mechanism attributed to the agent (4.3% of DMTs).”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Phase 1
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Two (3%) of the Phase 2 DMT trials used tau PET as an entry criterion, two (3%) used either CSF amyloid or CSF tau, and one (1%) used either amyloid PET or CSF tau.”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Biomarkers
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“There are nine trials of cell therapies in AD (Table 4), one oligonucleotide targeting tau expression, and several epigenetic modulators.”
§ Alzheimer's disease drug development pipeline: 2021 > DISCUSSION
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Three senolytics in current AD trials are metformin, rapamycin, and dasatinib plus quercetin; these therapies have shown benefit in non‐clinical models of aging and AD. 39 , 40 , 41”
§ Alzheimer's disease drug development pipeline: 2021 > DISCUSSION
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“There are five prevention trials in Phase 3 and two prevention trials in Phase 2; the number of prevention trials in Phase 3 has remained constant over the past 6 years, while the number of Phase 2 prevention trials has varied (0 to 4).”
§ Alzheimer's disease drug development pipeline: 2021 > DISCUSSION
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Senolytic therapies directed at removing senescent cells are included in the AD pipeline.”
§ Alzheimer's disease drug development pipeline: 2021 > DISCUSSION
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“There are five prevention trials in Phase 3 and two prevention trials in Phase 2; the number of prevention trials in Phase 3 has remained constant over the past 6 years, while the number of Phase 2 prevention trials has varied (0 to 4).”
§ Alzheimer's disease drug development pipeline: 2021 > DISCUSSION
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Amyloid and tau protein are important targets; inflammation, synaptic plasticity, neuroprotection, and bioenergetics/metabolism account for most of the rest of the current pipeline of agents.”
§ Alzheimer's disease drug development pipeline: 2021 > DISCUSSION
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The 126 agents in the pipeline compares to 121 in the pipeline in 2020; 13 with one less agent in Phase 3, nine additional agents in Phase 2, and three less agents in Phase 1.”
- Also stated in: § SUMMARY · plain
“There are slightly more agents in the AD pipeline in 2021 compared to 2020.”
§ Alzheimer's disease drug development pipeline: 2021 > DISCUSSION
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § SUMMARY · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Amyloid and tau protein are important targets; inflammation, synaptic plasticity, neuroprotection, and bioenergetics/metabolism account for most of the rest of the current pipeline of agents.”
§ Alzheimer's disease drug development pipeline: 2021 > DISCUSSION
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“There has been no trend toward shortening recruitment times over the past 5 years despite expanded efforts to improve recruitment.”
§ Alzheimer's disease drug development pipeline: 2021 > DISCUSSION
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Repurposed agents rarely progress to Phase 3; the Phase 2 trials of these drugs produce invaluable data on molecules that can be reengineered to have better intellectual property protection, pathways, and processes that may be promising therapeutic targets, and effects on biomarkers or novel clinical outcomes.”
§ Alzheimer's disease drug development pipeline: 2021 > DISCUSSION
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Trials are being conducted in preclinical, prodromal, and AD dementia populations in an effort to prevent, delay the onset, slow the progression, or improve the cognitive and behavioral symptoms of AD.”
§ Alzheimer's disease drug development pipeline: 2021 > SUMMARY
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“There are nine trials of cell therapies in AD (Table 4), one oligonucleotide targeting tau expression, and several epigenetic modulators.”
§ Alzheimer's disease drug development pipeline: 2021 > DISCUSSION
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“There are nine trials of cell therapies in AD (Table 4), one oligonucleotide targeting tau expression, and several epigenetic modulators.”
§ Alzheimer's disease drug development pipeline: 2021 > DISCUSSION
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Biomarkers are rarely used for diagnostic confirmation in trials for cognitive enhancing agents or drugs targeting neuropsychiatric symptoms.”
§ Alzheimer's disease drug development pipeline: 2021 > DISCUSSION
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“The average length of time required for recruitment of participants exceeds the duration of the treatment period in nearly all trials.”
§ Alzheimer's disease drug development pipeline: 2021 > DISCUSSION
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This pipeline analysis shows that target biological processes are more diversified, biomarkers are more regularly used, and repurposed agents are being explored to determine their utility for the treatment of AD.”
§ Alzheimer's disease drug development pipeline: 2021 > Abstract > Discussion
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Repurposed agents play an important role in the pipeline, especially in Phase 2 trials.”
§ Alzheimer's disease drug development pipeline: 2021 > METHODS > RESEARCH IN CONTEXT
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This pipeline analysis shows that target biological processes are more diversified, biomarkers are more regularly used, and repurposed agents are being explored to determine their utility for the treatment of AD.”
§ Alzheimer's disease drug development pipeline: 2021 > Abstract > Discussion
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“ClinicalTrials.gov includes the majority of agents currently in clinical trials for AD”
§ Alzheimer's disease drug development pipeline: 2021 > METHODS
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This pipeline analysis shows that target biological processes are more diversified, biomarkers are more regularly used, and repurposed agents are being explored to determine their utility for the treatment of AD.”
§ Alzheimer's disease drug development pipeline: 2021 > Abstract > Discussion
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Understanding of the continuum of AD from preclinical stages to severe dementia is reflected in broadening of the trial populations to include preclinical AD, prodromal AD, and AD dementia.”
§ Alzheimer's disease drug development pipeline: 2021 > METHODS > RESEARCH IN CONTEXT
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Most drugs in trials aim to achieve disease modification by targeting the underlying biological processes of Alzheimer's disease (AD).”
§ Alzheimer's disease drug development pipeline: 2021 > METHODS > RESEARCH IN CONTEXT
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“comparisons show that only a few agents registered in the European Union Clinical Trial Register, for example, are not found on ClinicalTrials.gov.”
§ Alzheimer's disease drug development pipeline: 2021 > METHODS
What the sources say
- Not checked yetcites [18] Bauzon J, Lee G, Cummings J. Repurposed agents in the Alzheimer's disease drug development pipeline. Alzheimer's Res Ther. 2020; 12: 98. 32807237 PMC7433208 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Five of the approved agents are DMTs involving neurodegeneration—2 for neuromyelitis optica, 1 for multiple sclerosis, 1 for Duchenne muscular dystrophy, and 1 for spinal muscular atrophy.”
§ Alzheimer's disease drug development pipeline: 2021 > DISCUSSION
What the sources say
- Not checked yetcites [21] Food and Drug Administration. Advancing Health Through Innovation: New Drug Therapy Approvals 2020. US Food and Drug Administration. Silver Spring, MD. 2020.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“There were no new therapies for AD.”
§ Alzheimer's disease drug development pipeline: 2021 > DISCUSSION
What the sources say
- Not checked yetcites [21] Food and Drug Administration. Advancing Health Through Innovation: New Drug Therapy Approvals 2020. US Food and Drug Administration. Silver Spring, MD. 2020.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Thirty‐six percent of the CNS approvals were for DMTs, suggesting that DMT‐related targets, biomarkers, and trial designs are progressing.”
§ Alzheimer's disease drug development pipeline: 2021 > DISCUSSION
What the sources say
- Not checked yetcites [21] Food and Drug Administration. Advancing Health Through Innovation: New Drug Therapy Approvals 2020. US Food and Drug Administration. Silver Spring, MD. 2020.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Eleven of the approved treatments addressed central nervous system (CNS) diseases. 21”
§ Alzheimer's disease drug development pipeline: 2021 > DISCUSSION
What the sources say
- Not checked yetcites [21] Food and Drug Administration. Advancing Health Through Innovation: New Drug Therapy Approvals 2020. US Food and Drug Administration. Silver Spring, MD. 2020.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“A toolkit of biomarkers relevant to trials of senolytics suggests measures relevant to peripheral effects of treatment that may be useful in some AD trials. 42”
§ Alzheimer's disease drug development pipeline: 2021 > DISCUSSION
What the sources say
- Not checked yetcites [42] Justice JN, Ferrucci L, Newman AB, et al. A framework for selection of blood‐based biomarkers for geroscience‐guided clinical trials: report from the TAME. Biomarkers Workgroup Geroscience. 2018; 40: 419‐ 436. 30151729 PMC6294728 source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Plasma p‐tau‐181 and plasma p‐tau 217 are elevated as AD advances and may be useful in trials to assess impact on tau pathology of trial participants. 28 , 29”
§ Alzheimer's disease drug development pipeline: 2021 > DISCUSSION
What the sources say
- Not checked yetcites [28] Moscoso A, Grothe MJ, Ashton NJ, et al. Time course of phosphorylated‐tau181 in blood across the Alzheimer's disease spectrum. Brain. 2020; 144: 325‐ 339. PMC7880671 33257949 source
- Not checked yetcites [29] Palmqvist S, Janelidze S, Quiroz YT, et al. Discriminative accuracy of plasma phospho‐tau217 for Alzheimer's disease vs other neurodegenerative disorders. JAMA. 2020; 324: 772‐ 781. 32722745 PMC7388060 source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Lack of diagnostic precision in these trials may contribute to commonly observed challenges including robust placebo responses and failure of placebo groups to decline. 24 , 25”
§ Alzheimer's disease drug development pipeline: 2021 > DISCUSSION
What the sources say
- Not checked yetcites [24] Lang F, Mo Y, Sabbagh M, et al. Intepirdine as adjunctive therapy to donepezil for mild‐to‐moderate Alzheimer's disease: a randomized, placebo‐controlled, phase 3 clinical trial (MINDSET). Alzheimer's Dement TRCI. 2021. In Press. PMC8165732 34095437 source
- Not checked yetcites [25] Rosenberg PB, Drye LT, Porsteinsson AP, et al. Change in agitation in Alzheimer's disease in the placebo arm of a nine‐week controlled trial. Int Psychogeriatr. 2015; 27: 2059‐ 2067. 26305876 PMC4669064 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Plasma NfL, a measure of neuronal degeneration, is increasingly elevated as AD progresses. 30”
§ Alzheimer's disease drug development pipeline: 2021 > DISCUSSION
What the sources say
- Not checked yetcites [30] Mattsson N, Cullen NC, Andreasson U, Zetterberg H, Blennow K. Association between longitudinal plasma neurofilament light and neurodegeneration in patients with Alzheimer's disease. JAMA Neurol. 2019; 76: 791‐ 799. 31009028 PMC6583067 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Technologies have advanced to facilitate trials of gene therapy in AD and trials are anticipated in the pipeline. 35”
§ Alzheimer's disease drug development pipeline: 2021 > DISCUSSION
What the sources say
- Not checked yetcites [35] Sudhakar V, Richardson RM. Gene therapy for neurodegenerative diseases. Neurotherapeutics. 2019; 16: 166‐ 175. 30542906 PMC6361055 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Plasma amyloid beta protein (Aβ) 42/40 correlates highly with amyloid PET 27 and is commercially available for clinical application (PrecivityAD).”
§ Alzheimer's disease drug development pipeline: 2021 > DISCUSSION
What the sources say
- Not checked yetcites [27] Schindler SE, Bollinger JG, Ovod V, et al. High‐precision plasma beta‐amyloid 42/40 predicts current and future brain amyloidosis. Neurology. 2019; 93: e1647‐ e59. 31371569 PMC6946467 source
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Plasma amyloid beta protein (Aβ) 42/40 correlates highly with amyloid PET 27 and is commercially available for clinical application (PrecivityAD).”
§ Alzheimer's disease drug development pipeline: 2021 > DISCUSSION
What the sources say
- Not checked yetcites [27] Schindler SE, Bollinger JG, Ovod V, et al. High‐precision plasma beta‐amyloid 42/40 predicts current and future brain amyloidosis. Neurology. 2019; 93: e1647‐ e59. 31371569 PMC6946467 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“A continuing challenge to trial conduct is the slow rate of recruitment.”
§ Alzheimer's disease drug development pipeline: 2021 > DISCUSSION
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“There is an increasing diversity of targets and corresponding therapeutic mechanisms of drugs in the AD pipeline.”
§ Alzheimer's disease drug development pipeline: 2021 > SUMMARY
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Therapeutic concepts related to the larger universe of diseases of aging are beginning to influence the AD pipeline.”
§ Alzheimer's disease drug development pipeline: 2021 > DISCUSSION
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“With these measures it is possible to characterize all of the ATN framework elements using peripheral markers.”
§ Alzheimer's disease drug development pipeline: 2021 > DISCUSSION
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Plasma p‐tau‐181 and plasma p‐tau 217 are elevated as AD advances and may be useful in trials to assess impact on tau pathology of trial participants. 28 , 29”
§ Alzheimer's disease drug development pipeline: 2021 > DISCUSSION
What the sources say
- Not checked yetcites [28] Moscoso A, Grothe MJ, Ashton NJ, et al. Time course of phosphorylated‐tau181 in blood across the Alzheimer's disease spectrum. Brain. 2020; 144: 325‐ 339. PMC7880671 33257949 source
- Not checked yetcites [29] Palmqvist S, Janelidze S, Quiroz YT, et al. Discriminative accuracy of plasma phospho‐tau217 for Alzheimer's disease vs other neurodegenerative disorders. JAMA. 2020; 324: 772‐ 781. 32722745 PMC7388060 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“This large number is a marked underestimate of total weeks because it does not include weeks spent in screening prior to randomization or weeks contributed by participants who are excluded during the screening period.”
§ Alzheimer's disease drug development pipeline: 2021 > DISCUSSION
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- It may state two separate claims as one. 44
- The quote only partly states this claim. 1
- Probably not a substantial claim. 16
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“There is one Phase 3 trial enrolling both preclinical patients and patients with MCI to mild AD dementia (DIAN‐TU trial); 13 trials in patients with prodromal AD/MCI or prodromal/mild AD dementia; 11 trials of patients with mild to moderate AD; and 11 trials of patients with mild‐to‐severe AD (most of the neuropsychiatric agents).”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Phase 3
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The mean treatment exposure period was 154 weeks for prevention trials, 87 weeks for prodromal AD or prodromal AD/mild AD dementia trials, and 31 weeks for mild‐to‐moderate AD dementia trials.”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Phase 3
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Two of these trials are assessing monoclonal antibodies (solanezumab, gantenerumab), there is one vaccine trial (CAD106), and two trials of small molecules (icosapent ethyl and a combination of losartan, amlodipine, and atorvastatin).”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Phase 3
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Phase 3 trials included a mean of 619 participants per trial and a total of 25,373 participants were needed for enrollment.”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Phase 3
plainn = 25,373- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Other CADRO mechanisms represented among Phase 3 DMT therapies include tau (one agent; 5.9% of Phase 3 DMTs), inflammation/infection (two agents; 11.8%), oxidative stress (two agents; 11.8%), metabolism and bioenergetics (two agents; 11.8%), vascular factors (one agent; 5.9%), synaptic plasticity/neuroprotection (three agents; 17.6%), and gut–brain axis (one agent; 5.9%).”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Phase 3
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Across all phases, DMTs comprise 31 (29.8%) biological therapies and 73 (70.2%) small‐molecule drugs.”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Overview
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“There are 50 repurposed agents in the pipeline—39.6% of the candidate agents.”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Overview
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“There are 11 (39.3%) symptomatic agents in Phase 3: six (21.4%) cognitive enhancers and five (17.9%) targeting behavioral symptoms.”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Phase 3
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Among the 17 DMTs there are four biological therapies and 13 oral agents/small molecule therapies.”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Phase 3
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Since the 2020 review, seven Phase 3 trials have been completed or terminated and there are five new agents in this phase.”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Phase 3
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Considering DMTs only, there are 17 in Phase 3, 64 in Phase 2, 23 in Phase 1.”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Overview
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Two Phase 2 trials are prevention trials involving participants with preclinical AD (assessing crenezumab and levetiracetam)”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Phase 2
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Across all trials, biopharmaceutical companies sponsor 49% of trials and collaborate in another 14% of trials sponsored by public–private partnerships.”
§ Alzheimer's disease drug development pipeline: 2021 > METHODS > HIGHLIGHTS
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Of Phase 2 candidate treatments, there are 64 potential DMTs, six cognitive enhancing agents, and four drugs targeting behavioral symptoms.”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Phase 2
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Since the 2020 review, 16 trials have been completed or terminated and there are 22 new agents in the Phase 2 pipeline.”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Phase 2
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Among DMTs in Phase 2 there are 21 biologics and 43 small molecules.”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Phase 2
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Using the CADRO approach, four of the small molecules and seven of the biologics in Phase 2 have amyloid reduction as one of the mechanisms (17.2% of DMTs).”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Phase 2
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Other CADRO mechanisms represented among Phase 2 DMT therapies include tau (nine agents; 14.1% of Phase 2 DMTs), inflammation/infection/immunity (12 agents; 18.8%), transmitter systems and receptors (two agents; 3.1%), oxidative stress (one agent; 1.6%), cell death (2 agents; 3.1%), proteostasis (four agents; 6.3%), metabolism and bioenergetics (four agents; 6.3%), vascular factors (three agents;”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Phase 2
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one. The quote only partly states this claim.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Trial participants make an enormous contribution to clinical trials (calculated to be ≈2.5 million participant‐weeks for currently ongoing trials)”
§ Alzheimer's disease drug development pipeline: 2021 > METHODS > RESEARCH IN CONTEXT
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Repurposed agents are more likely to have academic medical centers/NIH sponsors (59%) and less likely to have industry sponsors (16%; Table 5).”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Trial sponsors
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Across all phases, 54% of trials are conducted in North America only, 25% are conducted only outside North America, and 21% are conducted with both North American and non–North American sites.”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Global distribution of trials
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Of these, 25,373 are in Phase 3 trials; 12,414 in Phase 2 trials; and 1039 in Phase 1 trials.”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Trial participants
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“There are 28 agents in Phase 3, 74 in Phase 2, and 24 in Phase 1.”
§ Alzheimer's disease drug development pipeline: 2021 > DISCUSSION
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“There are five prevention trials in Phase 3 and two prevention trials in Phase 2; the number of prevention trials in Phase 3 has remained constant over the past 6 years, while the number of Phase 2 prevention trials has varied (0 to 4).”
§ Alzheimer's disease drug development pipeline: 2021 > DISCUSSION
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Phase 2 has both more agents in trials and a greater diversity of targets than other phases; this may reflect a more diversified approach to treatment targets in Phase 2 or a reduction of targets in Phase 3 because of the lack of success in Phase 2 outcomes.”
§ Alzheimer's disease drug development pipeline: 2021 > DISCUSSION
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The 126 agents in the pipeline compares to 121 in the pipeline in 2020; 13 with one less agent in Phase 3, nine additional agents in Phase 2, and three less agents in Phase 1.”
§ Alzheimer's disease drug development pipeline: 2021 > DISCUSSION
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Although sponsors plan for slow recruitment, 66.7% of Phase 3 trials and 78.6% of Phase 2 trials took longer to complete than originally anticipated as recorded on ClinicalTrials.gov.”
§ Alzheimer's disease drug development pipeline: 2021 > DISCUSSION
plain- Asserted: passes — The authors put it forward as true.
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- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“There are 13 cognitive enhancers and nine drugs targeting neuropsychiatric symptoms in the pipeline.”
§ Alzheimer's disease drug development pipeline: 2021 > DISCUSSION
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Since the 2020 pipeline, 7 trials in Phase 3, 18 trials in Phase 2, and 9 trials in Phase 1 have been either completed, terminated, suspended, or the status is unknown.”
§ Alzheimer's disease drug development pipeline: 2021 > DISCUSSION
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Repurposed agents are more common in trials in Phase 2 and more likely to be in trials sponsored by NIH/academic medical centers (Table 5).”
§ Alzheimer's disease drug development pipeline: 2021 > DISCUSSION
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Phase 1 trials are often conducted outside of the United States, may not be registered on ClinicalTrials.gov, and may be under‐represented in our analysis.”
§ Alzheimer's disease drug development pipeline: 2021 > METHODS
hedgedconditional- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“AD has preclinical, prodromal, and dementia phases”
§ Alzheimer's disease drug development pipeline: 2021 > METHODS > HIGHLIGHTS
What the sources say
- Not checked yetcites [20] Dubois B, Feldman HH, Jacova C, et al. Advancing research diagnostic criteria for Alzheimer's disease: the IWG‐2 criteria. Lancet Neurol. 2014; 13: 614‐ 629. 24849862 source
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“The reporting of results of clinical trials is required, but trial sponsors are less adherent to this expectation.”
§ Alzheimer's disease drug development pipeline: 2021 > METHODS
What the sources say
- Not checked yetcites [17] DeVito NJ, Bacon S, Goldacre B. Compliance with legal requirement to report clinical trial results on clinicaltrials.gov: a cohort study. Lancet. 2020; 395: 361‐ 369. 31958402 source
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“There are 126 agents in clinical trials in 2021; the total number of treatments in trials is similar in 2021 and 2020.”
§ Alzheimer's disease drug development pipeline: 2021 > METHODS > RESEARCH IN CONTEXT
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“The United States has more clinical trials than any other country”
§ Alzheimer's disease drug development pipeline: 2021 > METHODS
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Studies of ClinicalTrials.gov suggest that compliance with the common rule is high.”
§ Alzheimer's disease drug development pipeline: 2021 > METHODS
What the sources say
- Not checked yetcites [15] Lassman SM, Shopshear OM, Jazic I, Ulrich J, Francer J. Clinical trial transparency: a reassessment of industry compliance with clinical trial registration and reporting requirements in the United States. BMJ Open. 2017; 7: e015110. PMC5623439 28942418
- Not checked yetcites [16] Phillips AT, Desai NR, Krumholz HM, Zou CX, Miller JE, Ross JS. Association of the FDA Amendment Act with trial registration, publication, and outcome reporting. Trials. 2017; 18: 333. 28720112 PMC5516301
hedged- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“The Common Alzheimer's Disease Research Ontology (CADRO) provides a means of classifying targets for drug development relevant to AD.”
§ Alzheimer's disease drug development pipeline: 2021 > INTRODUCTION
What the sources say
- Not checked yetcites [5] International Alzheimer's and Related Dementia Research Portfolio; Accessed January 4, 2021; https://iadrp.nia.nih.gov/about/cadro
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“this review is therefore comprehensive but not exhaustive”
§ Alzheimer's disease drug development pipeline: 2021 > METHODS
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
- Rests on an assumption: Phase 1 trials are often conducted outside of the United States, may not be registered on ClinicalTrials.gov, and may be under-represented in this analysis.
- Rests on an assumption: ClinicalTrials.gov includes the majority of agents currently in clinical trials for Alzheimer's disease.
In the paper
“In 2020, the FDA approved 53 new drugs across all therapeutic categories.”
§ Alzheimer's disease drug development pipeline: 2021 > DISCUSSION
What the sources say
- Not checked yetcites [21] Food and Drug Administration. Advancing Health Through Innovation: New Drug Therapy Approvals 2020. US Food and Drug Administration. Silver Spring, MD. 2020.
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“This sum does not include time devoted to screening prior to randomization or the number of participant‐weeks consumed in screen fails of individuals who do not progress to randomization.”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Trial participants
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Some Phase 1 trials conducted outside the United States may not be registered on ClinicalTrials.gov and may have gone undetected in this review.”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Global distribution of trials
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thirty‐six percent of the CNS approvals were for DMTs, suggesting that DMT‐related targets, biomarkers, and trial designs are progressing.”
§ Alzheimer's disease drug development pipeline: 2021 > DISCUSSION
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Phase 2 has both more agents in trials and a greater diversity of targets than other phases; this may reflect a more diversified approach to treatment targets in Phase 2 or a reduction of targets in Phase 3 because of the lack of success in Phase 2 outcomes.”
§ Alzheimer's disease drug development pipeline: 2021 > DISCUSSION
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Stem cell interventions may promote nerve cell regeneration, adding a dimension to therapeutic response beyond the slowing of cognitive decline targeted by DMTs in current trials. 36 , 37”
§ Alzheimer's disease drug development pipeline: 2021 > DISCUSSION
What the sources say
- Not checked yetcites [36] Vasic V, Barth K, Schmidt MHH. Neurodegeneration and neuro‐regeneration‐Alzheimer's disease and stem cell therapy. Int J Mol Sci. 2019: 20. PMC6747457 31480448
- Not checked yetcites [37] Han F, Bi J, Qiao L, Arancio O. Stem cell therapy for Alzheimer's disease. Adv Exp Med Biol. 2020; 1266: 39‐ 55. 33105494
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Cell senescence occurs throughout the lifespan but plays a larger role with aging and is postulated to contribute to many diseases of aging including vascular disease, arthritis, and neurodegeneration. 38”
§ Alzheimer's disease drug development pipeline: 2021 > DISCUSSION
What the sources say
- Not checked yetcites [38] Childs BG, Gluscevic M, Baker DJ, et al. Senescent cells: an emerging target for diseases of ageing. Nat Rev Drug Discov. 2017; 16: 718‐ 735. 28729727 PMC5942225 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“This reflects the increased focus of biopharmaceutical companies on late‐stage development and outsourcing larger portions of the early‐stage drug development enterprise. 31”
§ Alzheimer's disease drug development pipeline: 2021 > DISCUSSION
What the sources say
- Not checked yetcites [31] Dierks RML, Bruyere O, Reginster JY. Critical analysis of valuation and strategical orientation of merger and acquisition deals in the pharmaceutical industry. Expert Rev Pharmacoecon Outcomes Res. 2018; 18: 147‐ 160. 29243501
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
In the paper
“The COVID‐19 pandemic further exacerbated recruitment struggles with many clinics suspending research at least temporarily, delaying visits during this time, and experiencing attrition due to SARS‐CoV‐2 infections in patients and family members or an unwillingness to attend medical facilities. 33”
§ Alzheimer's disease drug development pipeline: 2021 > DISCUSSION
What the sources say
- Not checked yetcites [33] Ousset PJ, Vellas B. Viewpoint: impact of the Covid‐19 outbreak on the clinical and research activities of memory clinics: an Alzheimer's disease center facing the Covid‐19 crisis. J Prev Alzheimer's Dis. 2020; 7: 197‐ 198. 32463074 PMC7147199
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“There are at least an equivalent number of weeks contributed by research partners, doubling the total participant‐partner weeks to 5,080,028 weeks.”
§ Alzheimer's disease drug development pipeline: 2021 > DISCUSSION
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
- Rests on an assumption: Research partners contribute at least an equivalent number of weeks as trial participants.
None of the sources cited for this claim have been checked yet.
In the paper
“Three senolytics in current AD trials are metformin, rapamycin, and dasatinib plus quercetin; these therapies have shown benefit in non‐clinical models of aging and AD. 39 , 40 , 41”
§ Alzheimer's disease drug development pipeline: 2021 > DISCUSSION
What the sources say
- Not checked yetcites [39] Zhu Y, Tchkonia T, Pirtskhalava T, et al. The Achilles' heel of senescent cells: from transcriptome to senolytic drugs. Aging Cell. 2015; 14: 644‐ 658. 25754370 PMC4531078 source
- Not checked yetcites [40] Farr SA, Roesler E, Niehoff ML, Roby DA, McKee A, Morley JE. Metformin improves learning and memory in the SAMP8 mouse model of Alzheimer's disease. J Alzheimers Dis. 2019; 68: 1699‐ 1710. 30958364
- Not checked yetcites [41] Partridge L, Fuentealba M, Kennedy BK. The quest to slow ageing through drug discovery. Nat Rev Drug Discov. 2020; 19: 513‐ 532. 32467649 source
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Biomarkers play an increasing role in drug development and use the amyloid (A), tau (T), neurodegeneration (N)—A/T/N—biomarker framework. 22 , 23”
§ Alzheimer's disease drug development pipeline: 2021 > DISCUSSION
What the sources say
- Not checked yetcites [22] Cummings J. The role of biomarkers in Alzheimer's disease drug development. Adv Exp Med Biol. 2019; 1118: 29‐ 61. 30747416 PMC6750734
- Not checked yetcites [23] Jack CR Jr, Bennett DA, Blennow K, et al. NIA‐AA research framework: toward a biological definition of Alzheimer's disease. Alzheimer's Dement. 2018; 14: 535‐ 562. 29653606 PMC5958625 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Many questions remain unresolved concerning the relationship of cellular senescence and neurodegeneration/AD; 43 trials of senolytics will provide key insights into the value of these agents as treatments for AD and late‐life cognitive decline.”
§ Alzheimer's disease drug development pipeline: 2021 > DISCUSSION
What the sources say
- Not checked yetcites [43] Saez‐Atienzar S, Masliah E. Cellular senescence and Alzheimer disease: the egg and the chicken scenario. Nat Rev Neurosci. 2020; 21: 433‐ 444. 32601397 PMC12548380 source
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Global trials allow diversified participant exposures and improved understanding of effects of ethnicity, standard of care, body size, nutrition, and educational level on trial outcomes.”
§ Alzheimer's disease drug development pipeline: 2021 > DISCUSSION
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These observations identify a gap in the trial system that requires remedy to accelerate trials and drug development.”
§ Alzheimer's disease drug development pipeline: 2021 > DISCUSSION
plain- Asserted: passes — The authors put it forward as true.
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- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence.
The paper relies on this without support.
Phase 1 trials are often conducted outside of the United States, may not be registered on ClinicalTrials.gov, and may be under-represented in this analysis.
“Phase 1 trials are often conducted outside of the United States, may not be registered on ClinicalTrials.gov, and may be under‐represented in our analysis.”
The paper relies on this without support.
ClinicalTrials.gov includes the majority of agents currently in clinical trials for Alzheimer's disease.
“ClinicalTrials.gov includes the majority of agents currently in clinical trials for AD”
The paper relies on this without support.
Information on completed, terminated, suspended, unknown, or withdrawn trials and reasons for their current status are often not publicly revealed.
“We did not include trials listed as completed, terminated, suspended, unknown, or withdrawn as information on these trials and reasons for their current status are often not publicly revealed.”
The paper relies on this without support.
The features of trials (clinical outcomes, trial duration, use of biomarkers, number of participants) can determine whether a trial was attempting to demonstrate disease modification or symptomatic benefit.
“We used the features of the trials (e.g., clinical outcomes, trial duration, use of biomarkers, number of participants) to determine whether a trial was attempting to demonstrate disease medication or symptomatic benefit.”
The paper relies on this without support.
The available literature can identify a dominant mechanism of action for agents with multiple mechanisms of action.
“Some agents have more than one mechanism of action and, in these cases, we noted both mechanisms and depended on the available literature to identify a dominant mechanism.”
The paper relies on this without support.
The trials registered on ClinicalTrials.gov as of January 5, 2021 are representative of the AD drug development pipeline.
“Table 6 shows the biomarkers used as entry criteria or as outcome measures in current Phase 2 and Phase 3 AD clinical trials of DMTs as described on ClinicalTrials.gov; not all trial descriptions on the website note if biomarkers are included in the trial.”
The paper relies on this without support.
Research partners contribute at least an equivalent number of weeks as trial participants.
“There are at least an equivalent number of weeks contributed by research partners, doubling the total participant‐partner weeks to 5,080,028 weeks.”
The paper relies on this without support.
ClinicalTrials.gov is a US trial registry and most trials conducted by sponsors anywhere in the world are registered on ClinicalTrials.gov.
“This is, in part, a reflection of the fact that ClinicalTrials.gov is a US trial registry (although note that most trials conducted by sponsors anywhere in the world are registered on ClinicalTrials.gov).”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“The most recent list of studies was provided by the 2024 AD drug development pipeline, which includes 164 trials (of which 127 are exploring possible treatments or medicines).”
From Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease (2024) · cites this paper as [182]
In the citing paper
“Of these trials, 41% look into disease-modifying small molecule medications, 34% look into biological agents that change disease, and the remaining trials focus on treatments that improve cognitive function or address neuropsychiatric symptoms linked to ADs [68,70,71,182,183,184].”
From Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease (2024) · cites this paper as [182]
In the citing paper
“Another molecule in Phase 3 is Azeliragon (NTC03980730), an inhibitor of RAGE that can be administered orally [163].”
From Role of Oxidative Damage in Alzheimer’s Disease and Neurodegeneration: From Pathogenic Mechanisms to Biomarker Discovery (2021) · cites this paper as [163]
In the citing paper
“Ginkgo Biloba (NCT03090516) extracts are supposed to improve mitochondrial function and brain blood flow, acting as a cognitive enhancer [163].”
From Role of Oxidative Damage in Alzheimer’s Disease and Neurodegeneration: From Pathogenic Mechanisms to Biomarker Discovery (2021) · cites this paper as [163]
In the citing paper
“Of the 18 agents in phase 3 classified as disease-modifying treatments, three have OS as mechanism of action, two have metabolism/bioenergetic, two have antioxidant properties, and among the three agents acting on synaptic plasticity/neuroprotection, Azeliragon is also meant to ameliorate OS (Table 2).”
From Role of Oxidative Damage in Alzheimer’s Disease and Neurodegeneration: From Pathogenic Mechanisms to Biomarker Discovery (2021) · cites this paper as [163]
In the citing paper
“Looking at the clinical trials that have reached phase 3, beside the very recently approved Aducanumab, there is a progressive interest in the non-amyloid targets [163].”
From Role of Oxidative Damage in Alzheimer’s Disease and Neurodegeneration: From Pathogenic Mechanisms to Biomarker Discovery (2021) · cites this paper as [163]
In the citing paper
“Glucose metabolism amelioration in CNS is supposed to improve the cognitive decline of aMCI patients or prevent the cognitive decline in obese people [163,167].”
From Role of Oxidative Damage in Alzheimer’s Disease and Neurodegeneration: From Pathogenic Mechanisms to Biomarker Discovery (2021) · cites this paper as [163]
In the citing paper
“Indeed, some of the treatments are designed to modify the biology of the disease acting on synaptic dysfunction, mitochondrial dysfunction, microglial modulation, and reducing OS [163].”
From Role of Oxidative Damage in Alzheimer’s Disease and Neurodegeneration: From Pathogenic Mechanisms to Biomarker Discovery (2021) · cites this paper as [163]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated major: it would touch a result — a value a result rests on, reported and recomputed p-values on opposite sides of the significance level, two passages that conflict with no sign which is right, or a cited work retracted before this paper was published.
In the paper
“Five of the approved agents are DMTs involving neurodegeneration—2 for neuromyelitis optica, 1 for multiple sclerosis, 1 for Duchenne muscular dystrophy, and 1 for spinal muscular atrophy. Treatments for neuroblastoma, neurofibromatosis, migraine, on/off in Parkinson's disease, and an agent for sedation comprised the other CNS approvals. There were no new therapies for AD. Thirty‐six percent of the CNS approvals were for DMTs”
§ Alzheimer's disease drug development pipeline: 2021 > DISCUSSION
Reported 36 · recomputed 45.454545
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Biomarkers
“| Tau PET | 4 (7%) | 3 (14%) |”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Biomarkers
“Three (13%) of the Phase 3 DMT trials include tau PET imaging as an outcome and nine (12%) of Phase 2 DMT trials include tau PET imaging as an outcome.”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Global distribution of trials
“Thirty‐seven percent of Phase 3 trials involve North American only and 71% included North America and non–North American countries.”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Global distribution of trials
“| Both | 14 (34%) | 17 (20%) | 1 (4%) |”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
“| Academic medical centers/NIH | 8 (20%) | 27 (31%) | 9 (38%) | 49 (29%) | 33 (59%) |”
§ Alzheimer's disease drug development pipeline: 2021 > RESULTS > Trial sponsors
Reported 49 · recomputed 44
Citations
Cites
NIA‐AA Research Framework: Toward a biological definition of Alzheimer's disease
Jack, C. R., Bennett, D. A., Blennow, K., Carrillo, M. C., Dunn, B., Haeberlein, S. B., Holtzman, D. M., Jagust, W., Jessen, F., Karlawish, J., et al. (2018) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2018.02.018 · Cited by 10,537
Scheltens, P., De Strooper, B., Kivipelto, M., Holstege, H., Chételat, G., Teunissen, C. E., Cummings, J., & van der Flier, W. M. (2021) · The Lancet · doi:10.1016/s0140-6736(20)32205-4 · Cited by 5,465
Self-citationAdvancing research diagnostic criteria for Alzheimer's disease: the IWG-2 criteria
Dubois, B., Feldman, H. H., Jacova, C., Hampel, H., Molinuevo, J. L., Blennow, K., DeKosky, S. T., Gauthier, S., Selkoe, D., Bateman, R., et al. (2014) · The Lancet Neurology · doi:10.1016/s1474-4422(14)70090-0 · Cited by 3,321
Self-citationThe Achilles' heel of senescent cells: from transcriptome to senolytic drugs
Zhu, Y., Tchkonia, T., Pirtskhalava, T., Gower, A. C., Ding, H., Giorgadze, N., Palmer, A. K., Ikeno, Y., Hubbard, G. B., Lenburg, M., et al. (2015) · Aging Cell · doi:10.1111/acel.12344 · Cited by 2,584
2020 Alzheimer's disease facts and figures
(2020) · Alzheimer's & Dementia · doi:10.1002/alz.12068 · Cited by 2,353
Palmqvist, S., Janelidze, S., Quiroz, Y. T., Zetterberg, H., Lopera, F., Stomrud, E., Su, Y., Chen, Y., Serrano, G. E., Leuzy, A., et al. (2020) · JAMA · doi:10.1001/jama.2020.12134 · Cited by 1,603
Senescent cells: an emerging target for diseases of ageing
Childs, B. G., Gluscevic, M., Baker, D. J., Laberge, R.-M., Marquess, D., Dananberg, J., & van Deursen, J. M. (2017) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2017.116 · Cited by 1,284
High-precision plasma β-amyloid 42/40 predicts current and future brain amyloidosis
Schindler, S. E., Bollinger, J. G., Ovod, V., Mawuenyega, K. G., Li, Y., Gordon, B. A., Holtzman, D. M., Morris, J. C., Benzinger, T. L. S., Xiong, C., et al. (2019) · Neurology · doi:10.1212/wnl.0000000000008081 · Cited by 885
Alzheimer's disease drug development pipeline: 2019
Cummings, J., Lee, G., Ritter, A., Sabbagh, M., & Zhong, K. (2019) · Alzheimer's & Dementia: Translational Research & Clinical Interventions · doi:10.1016/j.trci.2019.05.008 · Cited by 762
Self-citationMattsson, N., Cullen, N. C., Andreasson, U., Zetterberg, H., & Blennow, K. (2019) · JAMA Neurology · doi:10.1001/jamaneurol.2019.0765 · Cited by 726
Research works printed but not linked: 4
- Food and Drug Administration, 2018, U.S. Department of Health and Human Services, Food and Drug Administration
- International Alzheimer's and Related Dementia Research Portfolio
- Food and Drug Administration, 2020, Advancing Health Through Innovation: New Drug Therapy Approvals 2020
- IQVIA, 2019, The Changing Landscape of Research and Development
Cited by
Sorted by citations
Revised criteria for diagnosis and staging of Alzheimer's disease: Alzheimer's Association Workgroup
Jack, C. R., Andrews, J. S., Beach, T. G., Buracchio, T., Dunn, B., Graf, A., Hansson, O., Ho, C., Jagust, W., McDade, E., et al. (2024) · Alzheimer's & Dementia · doi:10.1002/alz.13859 · Cited by 2,803
“182 Despite the importance of these mechanisms, there is a dearth of available I biomarkers.”
2022 Alzheimer's disease facts and figures
Anonymous (2022) · Alzheimer s & Dementia · doi:10.1002/alz.12638 · Cited by 2,469
Global estimates on the number of persons across the Alzheimer's disease continuum
Gustavsson, A., Norton, N., Fast, T., Frölich, L., Georges, J., Holzapfel, D., Kirabali, T., Krolak‐Salmon, P., Rossini, P. M., Ferretti, M. T., et al. (2023) · Alzheimer's & Dementia · doi:10.1002/alz.12694 · Cited by 895
Alzheimer’s disease drug development pipeline: 2022
Cummings, J., Lee, G., Nahed, P., Kambar, M. E. Z. N., Zhong, K., Fonseca, J., & Taghva, K. (2022) · Alzheimer's & Dementia: Translational Research & Clinical Interventions · doi:10.1002/trc2.12295 · Cited by 665
Alzheimer’s disease drug development pipeline: 2023
Cummings, J., Zhou, Y., Lee, G., Zhong, K., Fonseca, J., & Cheng, F. (2023) · Alzheimer's & Dementia: Translational Research & Clinical Interventions · doi:10.1002/trc2.12385 · Cited by 477
Self-citation
Metadata
- Authors
- Cummings, J., Lee, G., Zhong, K., Fonseca, J., & Taghva, K.
- Affiliations
- University of Nevada, Las Vegas (US)
- Biogen (United States) (US)
- Howard R. Hughes College of Engineering Department of Computer Science University of Nevada, Las Vegas (UNLV) Las Vegas Nevada USA
- Corresponding author
- Cummings, Jeffrey
- Venue
- Alzheimer's & Dementia: Translational Research & Clinical Interventions
- Publisher
- Wiley
- Published
- 2021-01
- Volume
- 7
- Issue
- 1
- Pages
- e12179-e12179
- ISSN
- 2352-8737 (ISSN-L)
- PMC
- PMC8145448
- OpenAlex
- W3164214667
- Semantic Scholar
- bbab7a44a3b914a574816f1b4885797eb472650c
- Cited by
- 539
- References
- 40
- Citations by year
- 2026: 48 · 2025: 95 · 2024: 81 · 2023: 102 · 2022: 156 · 2021: 54
- FWCI
- 61.81
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Alzheimer s & Dementia Translational Research & Clinical Interventions (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Digital Scholarship - UNLV (University of Nevada Reno) (submittedVersion, cc-by-nc-nd)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institute on Aging (P20AG068053)
- National Institute of General Medical Sciences (P20GM109025)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Pharmacology (medical) › Cholinesterase and Neurodegenerative Diseases
- Keywords
- Alzheimer's disease, drug development pipeline, clinical trials, disease-modifying therapy, cognitive enhancement, neuropsychiatric symptoms, drug repurposing, biomarkers, ClinicalTrials.gov
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-10, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-10 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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