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Confounder adjustment in observational studies investigating multiple risk factors: a methodological study
Yinyan Gao, Linghui Xiang, Hang Yi, Jinlu Song, Dingkui Sun, Boya Xu, Guochao Zhang, Xinyin Wu. BMC Medicine, 2025-03-04
Topic: Risk, prevention and care in population studies
A total of 162 studies were included, with 88 (54.3%) exploring potential risk factors and 74 (45.7%) examining specific risk factors. The current status of confounder adjustment was unsatisfactory: only ten studies (6.2%) used the recommended method, all of which aimed at examining several specific risk factors; in contrast, mutual adjustment was adopted in over 70% of the studies. The remaining studies either adjusted for the same confounders across all risk factors, or unable to judge. There is substantial variation in the methods for confounder adjustment among studies investigating multiple risk factors. Mutual adjustment was the most commonly adopted method, which might lead to overadjustment bias and misleading effect estimates. Future research should avoid indiscriminately including all risk factors in a multivariable model to prevent inappropriate adjustment.
Key findings
- A total of 162 studies were included, with 88 (54.3%) exploring potential risk factors and 74 (45.7%) examining specific risk factors.
- The current status of confounder adjustment was unsatisfactory: only ten studies (6.2%) used the recommended method, all of which aimed at examining several specific risk factors; in contrast, mutual adjustment was adopted in over 70% of the studies.
- The remaining studies either adjusted for the same confounders across all risk factors, or unable to judge.
- There is substantial variation in the methods for confounder adjustment among studies investigating multiple risk factors.
- Mutual adjustment was the most commonly adopted method, which might lead to overadjustment bias and misleading effect estimates.
Why it matters
This methodological study examined how observational studies adjust for confounding when investigating multiple risk factors, and found that most used a method that might cause overadjustment bias and misleading estimates. It is about improving how risk factor research is conducted, not about treating, curing, or preventing Alzheimer's disease.
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Study details
- Study designcase-control study
- Participants162
- Effect size54.3%; 45.7%; 6.2%
- Evidence strengthModerate
How this study scored 64/100
Published in a peer-reviewed journal, and it is a case-control study. Scored zero for randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (BMC Medicine) |
| Journal's citation record | 3 / 4 | BMC Medicine: journal h-index 259 (OpenAlex, 2026-10-29) |
| Study design | 6 / 12 | A case-control study |
| 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 | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 2 / 4 | 162 participants |
| Effect reported | 2 / 3 | Effect reported as a number, without an interval or test |
| 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 | 4 / 7 | Cited 51 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 17.0 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 6 / 6 | Cited 44.3× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 3 / 4 | Cited 51 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Xinyin Wu: h-index 36 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Chinese Academy of Medical Sciences & Peking Union Medical College: institution h-index 950 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40038753) |
| Free to read | 2 / 2 | Free to read |
| Total | 64 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record names 8 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
APA 7th
Gao, Y., Xiang, L., Yi, H., Song, J., Sun, D., Xu, B., et al. (2025). Confounder adjustment in observational studies investigating multiple risk factors: a methodological study. BMC Medicine. https://doi.org/10.1186/s12916-025-03957-8
Vancouver
Gao Y, Xiang L, Yi H, Song J, Sun D, Xu B, et al. Confounder adjustment in observational studies investigating multiple risk factors: a methodological study. BMC Medicine. 2025. doi:10.1186/s12916-025-03957-8. PMID: 40038753.
BibTeX
@article{gao2025-40038753,
author = {Gao, Yinyan and Xiang, Linghui and Yi, Hang and Song, Jinlu and Sun, Dingkui and Xu, Boya and Zhang, Guochao and Wu, Xinyin},
title = {{Confounder adjustment in observational studies investigating multiple risk factors: a methodological study}},
journal = {BMC Medicine},
year = {2025},
doi = {10.1186/s12916-025-03957-8},
pmid = {40038753},
url = {https://doi.org/10.1186/s12916-025-03957-8}
}