Bridging case-control studies and randomized trials

Randomized trials and observational studies, such as case-control studies, are often seen as opposing approaches. However, in many instances results obtained by different designs may complement each other. For instance, case-control studies on aetiology of disease may help to give the direction of future trials. In this commentary, the author discusses the purpose of randomization and observation, and under which conditions one design may be preferred to another. Randomization is useful to combat 'confounding by indication', and is therefore the design of choice for most therapeutic trials. When this confounding is not an issue, as in studies of genetic risk factors or side-effects, then case-control studies are preferred

Minor injuries as a risk factor for venous thrombosis

BACKGROUND: Injuries increase the risk of venous thrombosis. So far, most research has focused on major injuries that are accompanied by other risk factors for venous thrombosis, such as plaster casts and surgery. We studied the association of venous thrombosis with common minor injuries, such as minor sural muscle ruptures and ankle sprains.\ud \ud METHODS: We performed a large, population-based, case-control study (the Multiple Environmental and Genetic Assessment of risk factors for venous thrombosis [MEGA] study), including consecutive patients with a first deep venous thrombosis of the leg or pulmonary embolism and control subjects. Participants with malignant neoplasms, those who underwent surgery, and those who had a plaster cast or extended bed rest were excluded.\ud \ud RESULTS: Of 2471 patients, 289 (11.7%), and of 3534 controls, 154 (4.4%) had a minor injury in the 3 months preceding the venous thrombosis (patients) or completion of the questionnaire (controls). Venous thrombosis was associated with previous minor injury (odds ratio adjusted for sex and age, 3.1; 95% confidence interval, 2.5-3.8). The association was strongest for injuries that occurred in the 4 weeks before thrombosis and was not apparent before 10 weeks. Thrombosis was more strongly associated with minor injuries located in the leg (odds ratio adjusted for sex and age, 5.1; 95% confidence interval, 3.9-6.7), while those located in other body parts were not associated. A 50-fold increased risk was found in factor V Leiden carriers with a leg injury compared with noncarriers without injury (odds ratio, 49.7; 95% confidence interval, 6.8-362.7).\ud \ud CONCLUSIONS: Minor injuries in the leg are associated with greater risk of venous thrombosis. Because minor injuries are common, they could be major contributors to the occurrence of venous thrombosis\u

A Systematic Review

Background and Purpose Hypercoagulability increases the risk of arterial thrombosis; however, this effect may differ between various manifestations of arterial disease. Methods In this study, we compared the effect of coagulation factors as measures of hypercoagulability on the risk of ischaemic stroke (IS) and myocardial infarction (MI) by performing a systematic review of the literature. The effect of a risk factor on IS (relative risk for IS, RRIS) was compared with the effect on MI (RRMI) by calculating their ratio (RRR = RRIS/RRMI). A relevant differential effect was considered when RRR was >1+ its own standard error (SE) or <1−SE. Results We identified 70 publications, describing results from 31 study populations, accounting for 351 markers of hypercoagulability. The majority (203/351, 58%) had an RRR greater than 1. A larger effect on IS risk than MI risk (RRE>1+1SE) was found in 49/343 (14%) markers. Of these, 18/49 (37%) had an RRR greater than 1+2SE. On the opposite side, a larger effect on MI risk (RRR<1-1SE) was found in only 17/343 (5%) markers. Conclusions These results suggest that hypercoagulability has a more pronounced effect on the risk of IS than that of MI

Suspected survivor bias in case–control studies: stratify on survival time and use a negative control

AbstractObjectivesSelection bias in case–control studies occurs when control selection is inappropriate. However, selection bias due to improper case sampling is less well recognized. We describe how to recognize survivor bias (i.e., selection on exposed cases) and illustrate this with an example study.Study Design and SettingA case–control study was used to analyze the effect of statins on major bleedings during treatment with vitamin K antagonists. A total of 110 patients who experienced such bleedings were included 18–1,018 days after the bleeding complication and matched to 220 controls.ResultsA protective association of major bleeding for exposure to statins (odds ratio [OR]: 0.56; 95% confidence interval: 0.29–1.08) was found, which did not become stronger after adjustment for confounding factors. These observations lead us to suspect survivor bias. To identify this bias, results were stratified on time between bleeding event and inclusion, and repeated for a negative control (an exposure not related to survival): blood group non-O. The ORs for exposure to statins increased gradually to 1.37 with shorter time between outcome and inclusion, whereas ORs for the negative control remained constant, confirming our hypothesis.ConclusionWe recommend the presented method to check for overoptimistic results, that is, survivor bias in case–control studies