Rebecca DerSimonian

Meta-analysis in clinical trials.

This paper examines eight published reviews each reporting results from several related trials. Each review pools the results from the relevant trials in order to evaluate the efficacy of a certain treatment for a specified medical condition. These reviews lack consistent assessment of homogeneity of treatment effect before pooling. We discuss a random effects approach to combining evidence from a series of experiments comparing two treatments. This approach incorporates the heterogeneity of effects in the analysis of the overall treatment efficacy. The model can be extended to include relevant covariates which would reduce the heterogeneity and allow for more specific therapeutic recommendations. We suggest a simple noniterative procedure for characterizing the distribution of treatment effects in a series of studies.

Epidural analgesia in association with duration of labor and mode of delivery: a quantitative review.

OBJECTIVE This study was undertaken to quantitatively summarize previous literature on the effects of epidural analgesia in labor on the duration of labor and mode of delivery. STUDY DESIGN Original studies published in English from 1965 through December 1997 were reviewed and assigned a quality score independently by 2 of the authors. Studies that met the minimal requirements were evaluated further. Data syntheses were performed separately according to study design and outcome measurements, including cesarean delivery, instrumental delivery, oxytocin augmentation, and durations of the first and second stages of labor. RESULTS Seven randomized clinical trials and 5 observational studies met the minimal requirements. Among them 4 studies of each sort were included in the data synthesis. Both types of studies showed that epidural analgesia increased risk of oxytocin augmentation 2-fold. Clinical trials suggested that epidural analgesia did not increase the risk of cesarean delivery either overall or for dystocia, nor did it significantly increase the risk of instrumental vaginal delivery; however, observational studies reported a more than 4-fold increased risk of cesarean and instrumental deliveries. Although most studies showed a longer labor among women with epidural analgesia than without it, especially during the second stage, most of the studies used inappropriate statistical analysis. CONCLUSION Epidural analgesia with low-dose bupivacaine may increase the risk of oxytocin augmentation but not that of cesarean delivery.

Trial of calcium for preeclampsia prevention (CPEP): Rationale, design, and methods

The results of ten clinical trials suggest that supplemental calcium may prevent preeclampsia. However, methodologic problems and differences in study design limit the acceptance of the results and their relevance to other patient populations. Many of the trials were conducted in countries where, unlike the United States, the usual daily diet contained little calcium. Moreover, none of the trials has reported the outcome of systematic surveillance for urolithiasis, a potential complication of calcium supplementation. In response to the need for a thorough evaluation of the effects of calcium supplementation for the prevention of preeclampsia in the United States, the trial of Calcium for Preeclampsia Prevention (CPEP) was undertaken at five university medical centers. Healthy nulliparous patients were randomly assigned to receive either 2 g supplemental calcium daily (n = 2295) or placebo (n = 2294) in a double-blind study. Study tablets were administered beginning from 13 to 21 completed weeks of gestation and continued until the termination of pregnancy. CPEP employed detailed diagnostic criteria, standardized techniques of measurement, and systematic surveillance for the major study endpoints and for urolithiasis. The nutrient intake of each patient was assessed at randomization and at 32-33 weeks gestation. This report describes the study rationale, design, and methods.

Serum Caffeine and Paraxanthine as Markers for Reported Caffeine Intake in Pregnancy

PURPOSE Previous studies of maternal caffeine use and pregnancy outcome have relied on self-reported use. Even if these were perfectly accurate, inter-individual differences in caffeine metabolism result in a relatively weak correlation between caffeine intake and serum concentration. The purpose of this study was to determine whether the serum concentration of caffeine or its primary metabolite, paraxanthine, obtained at an unknown time during working hours, is useful to distinguish between pregnant women who report consuming small and large amounts of caffeine. METHODS We selected from the Birmingham fetal growth study 60 women with normal pregnancy outcomes who reported consuming < or = 0.8 mg/kg/day of caffeine in a 24-hour dietary recall, 60 who consumed 0.81-2.5 mg/kg/day, 60 who consumed 2.51-5.0 mg/kg/day and 59 who consumed > or = 5.01 mg/kg/day. These women had serum drawn for storage during regular clinic hours on the same day as the recall interview. Caffeine and paraxanthine were measured in the stored serum using high performance liquid chromatography. RESULTS The weighted kappa coefficient between strata of caffeine intake and quartiles of serum paraxanthine was 0.58 among smokers and 0.53 among nonsmokers, versus 0.44 and 0.51, respectively, for quartiles of serum caffeine. The Pearson correlation coefficient between intake and paraxanthine was 0.50 for smokers and 0.53 for nonsmokers, and 0.37 and 0.51, respectively, for serum caffeine. These values are comparable to the correlation between reported smoking and serum cotinine in pregnancy. CONCLUSIONS The serum concentrations of paraxanthine, and to a lesser degree, caffeine are useful to distinguish between women with varying levels of caffeine intake.