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Postmarketing safety surveillance studies address two actionable questions: (1) Is the test product riskier than a standard? (2) Is the risk associated with the test product within some tolerable margin by comparison to the standard? Established techniques, not commonly applied to the setting of such complementary one-sided hypotheses, lead to useful conclusions in practice. For two-group studies, a search over possible one-sided binomial test results yields sample sizes that guarantee that the confidence bounds exclude one or the other of the hypotheses. With continuous monitoring, simple curtailment reduces the sample size. Point and interval estimates follow from the binomial distribution of events at the end of the study or from component negative binomials for crossing a bound of simple curtailment with continuous monitoring and earlier stopping. An asymptotic derivation corresponds to the problem of constructing a confidence interval that is smaller than the distance between the parameter values for tolerable excess and the absence of excess risk. Studies with guaranteed rejection of one of the pair of complementary hypotheses are somewhat larger than corresponding studies of a single hypothesis under usual power requirements, but the increase may be tolerable in return for certainty that there will be an actionable conclusion. [ABSTRACT FROM AUTHOR]

Estimating risks associated with the use of childhood vaccines is challenging. The authors propose a new approach for studying short-term vaccine-related risks. The method uses a cubic smoothing spline to flexibly estimate the daily risk of an event after vaccination. The predicted incidence rates from the spline regression are then compared with the expected rates under a log-linear trend that excludes the days surrounding vaccination. The 2 models are then used to estimate the excess cumulative incidence attributable to the vaccination during the 42-day period after vaccination. Confidence intervals are obtained using a model-based bootstrap procedure. The method is applied to a study of known effects (positive controls) and expected noneffects (negative controls) of the measles, mumps, and rubella and measles, mumps, rubella, and varicella vaccines among children who are 1 year of age. The splines revealed well-resolved spikes in fever, rash, and adenopathy diagnoses, with the maximum incidence occurring between 9 and 11 days after vaccination. For the negative control outcomes, the spline model yielded a predicted incidence more consistent with the modeled day-specific risks, although there was evidence of increased risk of diagnoses of congenital malformations after vaccination, possibly because of a “provider visit effect.” The proposed approach may be useful for vaccine safety surveillance. [ABSTRACT FROM PUBLISHER]

Rates of abdominopelvic surgery, with a particular focus on gallbladder procedures, were measured in patients with irritable bowel syndrome (IBS) (n = 108,936) and compared with those in a general population sample (n = 223,082). The patient sample was selected from persons who were members of a managed care organization during the years 1995-2000. Medical records from a randomly selected subset of IBS patients were reviewed to confirm the diagnosis. Crude and standardized rates and adjusted rate ratios for surgery were calculated. The incidence of abdominopelvic surgery, excluding gallbladder procedures, was 87% higher in patients with IBS than that for the general population. The incidence of gallbladder surgery was threefold higher in IBS patients than the general population. Patients with IBS have an increased risk for abdominopelvic and gallbladder surgery and, thus, an associated risk for experiencing morbidity and mortality associated with these surgical procedures. [ABSTRACT FROM AUTHOR]

Abstract: The areas of overlap of confidence intervals from several studies can be used to create summary confidence regions. These summary regions lend themselves to graphical display, have readily derivable statistical properties, and can carry information about the influence both of available studies and of hypothetical future investigations. The case of a region covered by at least N-1 out of N confidence intervals is presented in some detail. (Am J Public Health 1988; 78:961-966.) [ABSTRACT FROM AUTHOR]