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Predicting Amyloid Burden to Accelerate Recruitment of Secondary Prevention Clinical Trials
Langford O, Raman R, Sperling RA, Cummings J, Sun CK, Jimenez-Maggiora G, Aisen PS, Donohue MC.. The journal of prevention of Alzheimer's disease, 2020-01-01
Topic: Amyloid, tau and blood-test diagnosis
Background Screening to identify individuals with elevated brain amyloid (Aβ+) for clinical trials in Preclinical Alzheimer's Disease (PAD), such as the Anti-Amyloid Treatment in Asymptomatic Alzheimer's disease (A4) trial, is slow and costly. The Trial-Ready Cohort in Preclinical/Prodromal Alzheimer's Disease (TRC-PAD) aims to accelerate and reduce costs of AD trial recruitment by maintaining a web-based registry of potential trial participants, and using predictive algorithms to assess their likelihood of suitability for PAD trials. Objectives Here we describe how algorithms used to predict amyloid burden within TRC-PAD project were derived using screening data from the A4 trial. Design We apply machine learning techniques to predict amyloid positivity. Demographic variables, APOE genotype, and measures of cognition and function are considered as predictors. Model data were derived from the A4 trial. Setting TRC-PAD data are collected from web-based and in-person assessments and are used to predict the risk of elevated amyloid and assess eligibility for AD trials. Participants Pre-randomization, cross-sectional data from the ongoing A4 trial are used to develop statistical models. Measurements Models use a range of cognitive tests and subjective memory assessments, along with demographic variables. Amyloid positivity in A4 was confirmed using positron emission tomography (PET). Results The A4 trial screened N=4,486 participants, of which N=1323 (29%) were classified as Aβ+ (SUVR ≥ 1.15). The Area under the Receiver Operating Characteristic curves for these models ranged from 0.60 (95% CI 0.56 to 0.64) for a web-based battery without APOE to 0.74 (95% CI 0.70 to 0.78) for an in-person battery. The number needed to screen to identify an Aβ+ individual is reduced from 3.39 in A4 to 2.62 in the remote setting without APOE, and 1.61 in the remote setting with APOE. Conclusions Predictive algorithms in a web-based registry can improve the efficiency of screening in future secondary prevention trials. APOE status contributes most to predictive accuracy with cross-sectional data. Blood-based assays of amyloid will likely improve the prediction of amyloid PET positivity.
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APA 7th
Langford, O., Raman, R., Sperling, R. A., Cummings, J., Sun, C. K., Jimenez-Maggiora, G., et al. (2020). Predicting Amyloid Burden to Accelerate Recruitment of Secondary Prevention Clinical Trials. The journal of prevention of Alzheimer's disease. https://doi.org/10.14283/jpad.2020.44
Vancouver
Langford O, Raman R, Sperling RA, Cummings J, Sun CK, Jimenez-Maggiora G, et al. Predicting Amyloid Burden to Accelerate Recruitment of Secondary Prevention Clinical Trials. The journal of prevention of Alzheimer's disease. 2020. doi:10.14283/jpad.2020.44. PMID: 32920622.
BibTeX
@article{langford2020-32920622,
author = {Langford, O. and Raman, R. and Sperling, R. A. and Cummings, J. and Sun, C. K. and Jimenez-Maggiora, G. and Aisen, P. S. and Donohue, M. C.},
title = {{Predicting Amyloid Burden to Accelerate Recruitment of Secondary Prevention Clinical Trials}},
journal = {The journal of prevention of Alzheimer's disease},
year = {2020},
doi = {10.14283/jpad.2020.44},
pmid = {32920622},
url = {https://doi.org/10.14283/jpad.2020.44}
}
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Key findings
- Results The A4 trial screened N=4,486 participants, of which N=1323 (29%) were classified as Aβ+ (SUVR ≥ 1.15).
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Study details
- Study designcross-sectional
- Participants4,486
- Evidence strengthModerate
How this study scored 62/100
Published in a peer-reviewed journal, and it is a snapshot of people at one point in time. Scored zero for effect reported and randomised / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 36 of the 58 points we could judge it on, which is 62 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (The journal of prevention of Alzheimer's disease) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 4 / 12 | A snapshot of people at one point in time |
| Strength of evidence | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 2 / 5 | 2020 — within 10 year(s) of the newest study here |
| Sample size | 3 / 4 | 4,486 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 32920622) |
| Free to read | 2 / 2 | Free to read |
| Points | 36 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 36 of the 58 points we could judge it on is 62 out of 100. |
| Total | 62 / 100 | — |
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