PubMed · 7728089
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S Voss, S George. 1995-04-22. Multiple significance tests.. https://doi.org/10.1136/bmj.310.6986.1073
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Despite the profusion of promising new vaccines against illnesses prevalent in developing countries, uncertainties about the balance between costs and benefits of new vaccines have retarded their use in public health practice. Conventional prelicensure trials of vaccine protection exacerbate these uncertainties by focusing on measurement of vaccine efficacy--the performance of a vaccine under idealized conditions. Vaccine effectiveness trials provide a more pragmatic perspective by addressing the performance of a vaccine under the ordinary conditions of a public health program, by capturing direct as well as indirect effects of vaccination, and by comprehensively addressing outcomes of public health concern. The use of effectiveness trials should enable more rational triaging of new vaccines for developing countries and may accelerate the introduction of new vaccines into public health practice by resolving speculative debates about practical costs and benefits.
BACKGROUND: The glutathione S-transferases (GST) mediate exposure to various cytotoxic and genotoxic agents, including those associated with increased risk of the myelodysplastic syndromes (MDS). Both GST M1 (GSTM1) and GST theta 1 (GSTT1) genes have a "null" variant allele, in which the entire gene is absent. We tested whether the homozygous null genotype of GSTM1 and GSTT1 altered the risk for MDS. METHODS: In a hospital-based case-control study we analysed lymphocyte or bone-marrow DNA samples from 96 patients with MDS and 201 cancer-free controls of similar age, race, and sex. We have restricted our report to the 92 white MDS patients. We analysed GSTM1 and GSTT1 genotypes by PCR. FINDINGS: The frequency of the GSTT1 null genotype was higher among MDS cases (46%) than among controls (16%). Inheritance of the GSTT1 null genotype conferred a 4.3-fold of MDS (odds ratio 4.3, 95% CI 2.5-7.4, p < 0.00001). The GSTM1 null genotype was not associated with increased risk of MDS (odds ratio 0.8, 0.5-1.3). INTERPRETATION: Individuals with the GSTT1 null genotype may have enhanced susceptibility to MDS. The mechanism might involve decreased detoxification of environmental or endogenous carcinogens.
The authors propose a method to perform a combined analysis of matched and unmatched case-control studies that is based on an adaptation of logistic regression and can be performed using standard software. This methodology can be used to do pooled analyses of studies with different designs. Likelihood ratio tests can be performed to assess association, heterogeneity, or trend. The standard errors of the coefficients allow the derivation of a Wald test and the calculation of confidence intervals. Another application is to compare relative risk estimators for the same risk factors studied in different phases of a disease in an effort to explore factors that may be more important in one phase than in another. Interaction terms of risk factors with variables that code the different pooled studies can be used for this purpose. The advantage of using this method is that a formal statistical comparison can be performed in which the regression coefficients of the interaction terms estimate the relative differences in risk (odds ratio ratios) between the studies. This estimation can be adjusted for other confounder factors. Two examples of application using data from case-control studies on cervical cancer and colorectal cancer are presented to illustrate the use of this epidemiologic method.