| Course | HEP 444 Epidemiology |
|---|---|
| Module | Module 3 |
| Paper type | Article review |
| Length | About 592 words, 5 pages |
| Format | APA 7 student paper |
| School | Arizona State University |
| Program | BS in Health Education and Health Promotion |
| Updated | October 2026 |
Free sample paper for HEP 444 Module 3
Eight Cases, Thirty-Two Controls: A Review of the Case-Control Study Linking Diethylstilbestrol to Vaginal Cancer
Student Name
BS in Health Education and Health Promotion, Arizona State University
HEP 444: Epidemiology
Instructor Name
Month Day, Year
Eight Cases, Thirty-Two Controls: A Review of the Case-Control Study Linking Diethylstilbestrol to Vaginal Cancer
Citation and Purpose
Herbst et al. (1971) set out to explain an unusual cluster of adenocarcinoma of the vagina, a tumor previously thought to occur almost only in older women, among patients aged 15 to 22 treated at a Boston hospital in the late 1960s.
Methods
Design. A matched case-control study, which compares the past exposures of people with and without a disease (Macera et al., 2013).
Cases. Eight young women with vaginal adenocarcinoma diagnosed between 1966 and 1969.
Controls. Four controls per case, matched on birth date, birth hospital and type of hospital service, for 32 in all.
Exposure measurement. The mothers of cases and controls were interviewed with a standard questionnaire about the pregnancy, including medications, bleeding, prior pregnancy losses, smoking and other exposures.
Analysis. The frequency of each factor was compared between case and control mothers.
Results
All but one of the case mothers had used diethylstilbestrol, a synthetic estrogen given at the time in hopes of preventing miscarriage, beginning early in pregnancy. None of the 32 control mothers had taken it, a difference that was highly statistically significant (Herbst et al., 1971). Bleeding in the pregnancy and earlier pregnancy losses were also more common among case mothers, which fits the reasons the drug was prescribed.
Strengths
A case-control design was the only practical approach for a cancer this rare; a cohort would have needed to follow huge numbers of exposed daughters for decades. Matching on birth date, hospital and service controlled for time period, place and social factors that might affect both prescribing and disease. Using a standard questionnaire for all mothers reduced differences in how information was gathered. The contrast between groups was so large that chance is very unlikely to explain it.
Weaknesses
The sample was tiny, so estimates are imprecise and the odds ratio cannot even be calculated in the usual way, since no control was exposed. Mothers of daughters with cancer may have searched their memories harder than control mothers, a form of recall bias, although a prescription drug taken for months is a memorable exposure. Cases came from one hospital, and the study examined many pregnancy factors, which raises the chance of a spurious finding for weaker associations.
Hill's Criteria Applied
Hill (1965) warned that no single criterion is required. Here, the strength of association, the time order and the specificity are so striking that the study changed prescribing within the year, before full replication.
| Criterion | Evidence in the study | Supported? |
|---|---|---|
| Strength | Seven of eight exposed cases against none of 32 controls | Yes, very strong |
| Consistency | One small study cannot show this; later case series and registries were needed | Not testable here |
| Specificity | A single rare cancer linked to a single drug | Yes, an unusual case where specificity helps |
| Temporality | Exposure in the womb preceded cancer by 15 to 22 years | Yes |
| Biological gradient | Dose and timing were not analyzed by level | Not assessed |
| Plausibility | A potent estrogen given during early fetal development could alter reproductive tissue | Yes |
| Coherence | The cluster appeared about 15 to 20 years after the drug came into wide use | Yes |
| Experiment | No experimental evidence in the study | Not assessed |
| Analogy | Other hormones are known to influence cancers of reproductive organs | Partly |
Conclusion
The Herbst study shows how a well-designed case-control study can identify a cause of a rare disease from very few cases. Its findings needed confirmation, but they gave strong early evidence that diethylstilbestrol taken in pregnancy could harm daughters years later.
References
Herbst, A. L., Ulfelder, H., & Poskanzer, D. C. (1971). Adenocarcinoma of the vagina: Association of maternal stilbestrol therapy with tumor appearance in young women. New England Journal of Medicine, 284(16), 878-881. https://doi.org/10.1056/NEJM197104222841604
Hill, A. B. (1965). The environment and disease: Association or causation? Proceedings of the Royal Society of Medicine, 58(5), 295-300. https://doi.org/10.1177/003591576505800503
Macera, C. A., Shaffer, R. A., & Shaffer, P. M. (2013). Introduction to epidemiology: Distribution and determinants of disease. Delmar Cengage Learning.
What the HEP 444 Module 3 instructions ask for
The case-control Article Review in HEP 444 is the second of two reviews, worth 30 points. Choose a published case-control study as your instructor directs, then give a summary of the methods, an assessment of strengths and weaknesses and a reading of the tables and figures for evidence on Hill's criteria. Case-control designs begin from the disease, comparing people who developed it with similar people who did not and working backward to exposures, so focus on how cases and controls were selected and how exposure was measured. Paraphrase every source; quotations cost a point each under the syllabus. Choose a study whose full text you can read, not only its abstract.
How this HEP 444 Module 3 example is built
The sample gives the citation and purpose, then summarizes methods under design, cases, controls, exposure measurement and analysis. The results report the key comparison in plain numbers. Strengths explain why the design fit a rare disease and what matching achieved, and weaknesses cover sample size, recall bias, a single site and multiple comparisons. A Hill's criteria table marks two criteria as not assessed, and a conclusion places the study in context. The review explains why no conventional odds ratio could be computed and why the finding still mattered. The weaknesses section balances the risk of recall bias against how memorable a months-long prescription would be, which shows judgment rather than a list.
HEP 444 Module 3 rubric: what earns full marks
The review is worth 30 points. Readers check that the student understands how case-control studies select participants and measure exposure, that strengths and weaknesses are specific to the article, that biases are named and explained and that Hill's criteria are applied with evidence rather than asserted. Marks drop for reviews that confuse case-control with cohort designs, that ignore control selection, that list biases without saying how they could change the result and that quote the article. Strong reviews describe how controls were matched and why, explain what matching can and cannot control and say what later research would be needed to confirm the finding. A clear statement of the study's main result in numbers also helps.
HEP 444 Module 3 help from the desk
Write down exactly how cases were found and how controls were chosen before anything else. Ask whether controls came from the same population as cases. Consider recall and interviewer bias for any interview-based exposure. Look for an odds ratio and its confidence interval, or explain why one is missing. Be willing to say a Hill criterion was not assessed. If you are unsure which bias applies, the desk can help. Classic case-control studies are short and readable, which makes them good choices. Note whether exposure information came from interviews or records. Check whether the authors considered other explanations, and say whether you agree with their conclusion. Paraphrase throughout.
Write yours, or have the desk draft it
This paper is an original model document written by our desk, not a submitted student paper and not an official Arizona State University document. Read it for the moves, then write your own to the instructions in your classroom. If you want one built to your exact prompt and rubric, the first custom sample is free and arrives in 24 to 48 hours.
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HEP 444 Module 3 questions, answered
Where can I find a free HEP 444 Module 3 sample paper?
The full review of the 1971 diethylstilbestrol and vaginal cancer study is on this page.
Why use a case-control design for a rare disease?
Beginning from the few existing cases avoids following huge exposed groups for decades.
What is recall bias?
Systematic differences in how accurately cases and controls remember past exposures.
What did the Herbst study find?
Seven of eight young women with vaginal adenocarcinoma had mothers who took diethylstilbestrol, compared with none of 32 controls.
Do all Hill's criteria need to be met?
No; Hill presented them as aids to judgment, and no single criterion is required.