The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.
The problem of “protopathic bias” in case-control studies
Abstract
Among the many sources of bias that can affect the results of case-control research, protopathic bias occurs when a pharmaceutical agent is inadvertently prescribed for an early manifestation of a disease that has not yet been diagnostically detected. In a case-control study of estrogens and endometrial cancer, approximately 10 per cent of the patients exposed to estrogens specifically stated that oral estrogens had been prescribed by their physician to treat an episode of uterine bleeding. This result was consistent with another study in which seven of 23 estrogen users were given the medication for the treatment of uterine bleeding before the diagnosis of cancer was made. Protopathic bias, which may account for much of the allegedly protective effect of oral contraceptives on the development of benign breast disease, can also occur in studies of aspirin and myocardial infarction, sex steroids and birth defects, and bronchodilators and death from asthma. This empiric demonstration of protopathic bias helps to indicate the need for careful precautions against its effects.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
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?
Exposures in the four years before the index date were excluded to avoid protopathic bias.
“We excluded exposures in the four years before the index date to avoid protopathic bias, whereby the drug is given for a sign or symptom of dementia before a diagnosis of dementia.27”
From Anticholinergic drugs and risk of dementia: case-control study (2018) · cites this paper as [27]
Citations
Cites
CASE-CONTROL STUDIES IN THE EVALUATION OF DRUG-INDUCED ILLNESS
JICK, H., & VESSEY, M. P. (1978) · American Journal of Epidemiology · doi:10.1093/oxfordjournals.aje.a112502 · Cited by 123
Flagged first, then by citations
Research works printed but not linked: 12
- Sartwell, 1974, Retrospective studies, Ann Intern Med, 81, 381, 10.7326/0003-4819-81-3-381 · DOI
- Feinstein, 1973, The epidemiologic trohoc, the ablative risk ratio, and ‘retrospective’ research, Clin Pharmacol Ther, 14, 291, 10.1002/cpt1973142291 · DOI
- Horwitz, 1979, Methodologic standards and contradictory results in case-control studies, Am J Med, 66, 556, 10.1016/0002-9343(79)91164-1 · DOI
- Horwitz, 1089, Alternative analytic methods for case-control studies of estrogens and endometrial cancer, N Engl J Med, 1978, 299
- Ziel, 1975, Increased risk of endometrial carcinoma among users of conjugated estrogens, N Engl J Med, 293, 1167, 10.1056/NEJM197512042932303 · DOI
- Mack, 1976, Estrogens and endometrial cancer in a retirement community, N Engl J Med, 294, 1262, 10.1056/NEJM197606032942304 · DOI
- Miettinen, 1976, Estimability and estimation in case-referent studies, Am J Epidemiol, 3, 226, 10.1093/oxfordjournals.aje.a112220 · DOI
- Vessey, 1971, Investigation of the possible relationship between oral contraceptives and benign and malignant breast disease, Cancer, 28, 1395, 10.1002/1097-0142(197112)28:6<1395::AID-CNCR2820280610>3.0.CO;2-5 · DOI
- Sartwell, 1973, Epidemiology of benign breast lesions. Lack of association with oral contraceptive use, N Engl J Med, 288, 551, 10.1056/NEJM197303152881104 · DOI
- Kelsey, 1974, A case-control study of the epidemiology of benign breast diseases with reference to oral contraceptive use, Int J Epidemiol, 3, 333, 10.1093/ije/3.4.333 · DOI
- Fasal, 1976, Oral contraceptives and reduced risk of benign breast diseases, N Engl J Med, 294, 419, 10.1056/NEJM197602192940804 · DOI
- Janerich, 1977, Benign breast disease and oral contraceptive use, JAMA, 237, 2199, 10.1001/jama.1977.03270470035019 · DOI
Cited by
Sorted by citations
Anticholinergic drugs and risk of dementia: case-control study
Richardson, K., Fox, C., Maidment, I., Steel, N., Loke, Y. K., Arthur, A., Myint, P. K., Grossi, C. M., Mattishent, K., Bennett, K., et al. (2018) · BMJ · doi:10.1136/bmj.k1315 · Cited by 520
Tzeng, N.-S., Chung, C.-H., Chang, C.-C., Chang, H.-A., Kao, Y.-C., Chang, S.-Y., & Chien, W.-C. (2020) · Translational Psychiatry · doi:10.1038/s41398-020-01021-y · Cited by 63
Metadata
- Authors
- Horwitz, R. I., & Feinstein, A. R.
- Corresponding author
- Horwitz, Ralph I.
- ORCID
- Horwitz, Ralph I.
- Venue
- The American Journal of Medicine
- Publisher
- Elsevier BV
- Published
- 1980-02
- Volume
- 68
- Issue
- 2
- Pages
- 255-258
- ISSN
- 0002-9343 (ISSN-L)
- OpenAlex
- W2124876714
- Cited by
- 235
- References
- 1
- Citations by year
- 2026: 11 · 2025: 11 · 2024: 17 · 2023: 8 · 2022: 10 · 2021: 12 · 2020: 10 · 2019: 19 · 2018: 11 · 2017: 10 · 2016: 12 · 2015: 13 · 2014: 6 · 2013: 11 · 2012: 15
- FWCI
- 4.66
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The American Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Epidemiology
- Physical Sciences › Mathematics › Statistics and Probability › Advanced Causal Inference Techniques
- Health Sciences › Nursing › Research and Theory › Methodologies in Health Research and Practice
- Keywords
- protopathic bias, case-control study, estrogen exposure, endometrial cancer, uterine bleeding, oral contraceptives, benign breast disease, aspirin, myocardial infarction, sex steroids, congenital malformations, bronchodilators, asthma mortality
- MeSH terms
- Breast Diseases, Contraceptives, Oral, Estrogens, Female, Humans, Research Design, Retrospective Studies, Risk, Time Factors, Uterine Hemorrhage, Uterine Neoplasms
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.
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.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
