title: A case-control evaluation of treatment efficacy: the example of magnesium sulfate prophylaxis against eclampsia in patients with preeclampsia.
abstract: Randomized trials are the optimal approach for evaluations of treatment efficacy but may not always be feasible. We study the adequacy of the case-control design in evaluating efficacy in a situation where the investigated therapy, namely the administration of magnesium sulfate for the prevention of eclampsia in patients with preeclampsia, has a suspected strong protective effect. A total of 66 cases of eclampsia were ascertained from among deliveries occurring between 1977 and 1992 at two hospitals in Houston, Texas. Randomly selected preeclamptic controls were matched to cases based on hospital and month of delivery. Magnesium sulfate administration prior to seizure occurrence had a strong protective effect against eclampsia in patients with preeclampsia (OR, 0.02; 95% CI, 0.01-0.05). This protective effect remained when controls were stratified by the degree of severity of preeclampsia (mild-to-moderate OR, 0.03, 95% CI, 0.01-0.09 and severe OR, 0.005; 95% CI, 0.0005-0.04) and when cases were stratified by the timing of the first seizure (antepartum and intrapartum seizures OR, 0.01; 95% CI, 0.003-0.05 and postpartum seizures OR, 0.03; 95% CI, 0.005-0.15). The effect also remained after adjustment for other important predictors in a multivariate logistic regression model (OR, 0.11; 95% CI, 0.03-0.38). The results of this study are in support of a recent randomized trial on the efficacy of magnesium sulfate as a prophylactic agent against eclampsia. Although there are serious potential sources of bias in this study, the magnitude of the protective effect of magnesium sulfate minimizes the likelihood that this effect can be explained by bias. Observational studies could be appropriate complements or alternatives to randomized trials in situations where a strong treatment effect is expected.
authors.affiliation: University of Texas Houston Health Science Center School of Public Health 77030, USA.
authors.forename: D
authors.initials: D
authors.lastname: Abi-Said
authors.forename: J F
authors.initials: JF
authors.lastname: Annegers
authors.forename: D
authors.initials: D
authors.lastname: Combs-Cantrell
authors.forename: R
authors.initials: R
authors.lastname: Suki
authors.forename: R F
authors.initials: RF
authors.lastname: Frankowski
authors.forename: L J
authors.initials: LJ
authors.lastname: Willmore
mesh_terms: D000328:Adult; D015982:Bias; D016022:Case-Control Studies; D018450:Disease Progression; D004461:Eclampsia / Q000517:prevention & control*; D005069:Evaluation Studies as Topic; D005260:Female; D006801:Humans; D016015:Logistic Models; D008278:Magnesium Sulfate / Q000627:therapeutic use*; D016017:Odds Ratio; D011225:Pre-Eclampsia / Q000188:drug therapy*; D011247:Pregnancy; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D015149:Tocolytic Agents / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D015149:Tocolytic Agents; D008278:Magnesium Sulfate