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Factors associated with: problems of using exploratory multivariable regression to identify causal risk factors
Dan Lewer, Thomas D. Brothers, Elizabeth O’Nions, John Pickavance. BMJ Medicine, 2025-10-01
Topic: Risk, prevention and care in population studies
Many medical and epidemiological studies use multivariable regression to test whether several independent variables (exposures) are causal determinants of a health outcome. Where mutually adjusted regression coefficients are significant, the exposures are labelled as risk factors for the outcome. We call this study design “factors associated with.” In this article, we argue that this method is flawed due to a lack of reasoning about which variables are treated as confounders, multiple statistical testing, and post hoc interpretation of the results. In some cases, researchers use algorithmic or stepwise approaches to select exposure variables, which further exacerbates these problems. Although the results of factors associated with studies often seem reasonable, these problems mean that the method can also produce implausible results, such as dementia reducing the risk of death in patients admitted to hospital for trauma, 1 diabetes reducing the risk of venous thromboembolism in the general population,2 and lack of food reducing the risk of post-traumatic stress disorder in refugees.3 Many of these studies are published every year, including in well respected journals. We argue that these studies are misleading and contribute to research waste, and the “factors associated with” method should be abandoned.
Key findings
- Where mutually adjusted regression coefficients are significant, the exposures are labelled as risk factors for the outcome.
- We call this study design “factors associated with.” In this article, we argue that this method is flawed due to a lack of reasoning about which variables are treated as confounders, multiple statistical testing, and post hoc interpretation of the results.
- Although the results of factors associated with studies often seem reasonable, these problems mean that the method can also produce implausible results, such as dementia reducing the risk of death in patients admitted to hospital for trauma, 1 diabetes reducing the risk of venous thromboembolism in the general population,2 and lack of food reducing the risk of post-traumatic stress disorder in refugees.3 Many of these studies are published every year, including in well respected journals.
- We argue that these studies are misleading and contribute to research waste, and the “factors associated with” method should be abandoned.
Why it matters
This paper argues that the common 'factors associated with' study design, which labels variables as risk factors based on regression results, is flawed and can produce implausible findings. It recommends abandoning this method, which means many reported dementia risk factors from such studies should be treated with caution.
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Study details
- Evidence strengthLow
How this study scored 41/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (BMJ Medicine) |
| Journal's citation record | 0 / 4 | BMJ Medicine: journal h-index 39 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” 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 | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 3 / 7 | Cited 19 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 6.3 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 4 / 6 | Cited 16.6× 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 | 2 / 4 | Cited 19 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 1 / 4 | Last-listed author John Pickavance: h-index 6 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University College London: institution h-index 2,029 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41181819) |
| Free to read | 2 / 2 | Free to read |
| Total | 41 / 100 | — |
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Read the original
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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. Check the citation against the original before you use it.
APA 7th
Lewer, D., Brothers, T. D., O’Nions, E., & Pickavance, J. (2025). Factors associated with: problems of using exploratory multivariable regression to identify causal risk factors. BMJ Medicine. https://doi.org/10.1136/bmjmed-2025-001375
Vancouver
Lewer D, Brothers TD, O’Nions E, Pickavance J. Factors associated with: problems of using exploratory multivariable regression to identify causal risk factors. BMJ Medicine. 2025. doi:10.1136/bmjmed-2025-001375. PMID: 41181819.
BibTeX
@article{lewer2025-41181819,
author = {Lewer, Dan and Brothers, Thomas D. and O’Nions, Elizabeth and Pickavance, John},
title = {{Factors associated with: problems of using exploratory multivariable regression to identify causal risk factors}},
journal = {BMJ Medicine},
year = {2025},
doi = {10.1136/bmjmed-2025-001375},
pmid = {41181819},
url = {https://doi.org/10.1136/bmjmed-2025-001375}
}