Maximizing the effectiveness of 1.5 mg levonorgestrel for emergency contraception: The case for precoital use.

Objectives: U.S. and World Health Organization Selected Practice Recommendations for Contraceptive Use state people may have an advanced supply of emergency contraception (EC) to minimize treatment delays.

Return to ovulation after Sayana Press is injected every 4 months for one year: Empirical and pharmacokinetic/pharmacodynamic modeling results.

Objective: To characterize return to ovulation after injecting Sayana Press (104 mg/0.65 mL medroxyprogesterone acetate [MPA] in the Uniject device) every 4 months for 1 year of treatment.

Study Design: We followed a subset of women for return to ovulation in a trial that demonstrated Sayana Press remains highly effective when the subcutaneous reinjection interval is extended from 3 to 4 months.

Ovulation suppression following subcutaneous administration of depot medroxyprogesterone acetate.

Objectives: To characterize the relationship between serum medroxyprogesterone acetate (MPA) concentrations and ovulation suppression, and to estimate the risk of ovulation for investigational subcutaneous regimens of Depo-Provera CI (Depo-Provera) and Depo-subQ Provera 104 (Depo-subQ).

Study Design: We performed a secondary analysis of 2 studies that assessed the pharmacokinetics and pharmacodynamics of MPA when Depo-Provera is administered subcutaneously rather than by the labeled intramuscular route. Each woman received a single 45 mg to 300 mg subcutaneous injection of Depo-Provera, a single 104 mg subcutaneous injection of Depo-subQ, or 2 injections of Depo-subQ at 3-month intervals.

A single-arm study to evaluate the efficacy, safety and acceptability of pericoital oral contraception with levonorgestrel.

Background: An oral dose of 0.75 mg levonorgestrel (LNG) taken shortly after sex was marketed as a routine, nonemergency contraceptive method until the 1990s. Because a hormonal method used only at the time of intercourse may be desirable for women who have infrequent sex, we conducted a study to reevaluate the potential of pericoital LNG as a primary means of contraception.

An adaptive design to bridge the gap between Phase 2b/3 microbicide effectiveness trials and evidence required for licensure.

Background: Vaginally and rectally applied microbicides are being developed to help prevent sexual acquisition of HIV. Due to the lack of surrogate outcomes, the path toward licensure typically moves directly from expanded safety studies to expensive Phase 2b/3 trials with rare incident infection outcomes. The need to confirm an initial trial's significant finding can lead to serious delays in implementing essential programs to reduce the spread of HIV.

Notes on the frequency of routinely collected and self-reported behavioral data in HIV prevention trials.

HIV prevention trials typically randomize thousands of participants to active or control intervention arms, with regular (e.g. monthly) clinic visits over one or more years of follow-up.

Statistical tests with accurate size and power for balanced linear mixed models.

The convenience of linear mixed models for Gaussian data has led to their widespread use. Unfortunately, standard mixed model tests often have greatly inflated test size in small samples. Many applications with correlated outcomes in medical imaging and other fields have simple properties which do not require the generality of a mixed model.

Analytic, Computational, and Approximate Forms for Ratios of Noncentral and Central Gaussian Quadratic Forms.

Many useful statistics equal the ratio of a possibly noncentral chi-square to a quadratic form in Gaussian variables with all positive weights. Expressing the density and distribution function as positively weighted sums of corresponding functions has many advantages. The mixture forms have analytic value when embedded within a more complex problem.

Estimating and comparing correct-use failure probabilities in clinical studies of condom functionality.

In a clinical study comparing the failure probabilities of two condom types, the sample of all reported acts of intercourse in which a study condom was used by a randomized participant is typically defined to be the primary analysis sample. However, it may also be desirable to make comparisons among only those acts in which the participants correctly followed all condom use instructions before, during, and after the act of intercourse (i.e.

Evaluating factors associated with STD infection in a study with interval-censored event times and an unknown proportion of participants not at risk for disease.

Sexually transmitted diseases (STD) are a major cause of morbidity and mortality world-wide. Because of their association with an increased risk of infection with human immunodeficiency virus, the prevention and control of STD are particularly important. Studies designed to evaluate factors associated with the transmission of STD can pose a number of statistical challenges, however.

Improved approximate confidence intervals for the mean of a log-normal random variable.

Data analysts often compute approximate 100 (1-alpha) per cent confidence intervals for the mean of a log-normal random variable due to the computational effort required for exact intervals. We evaluate two simple approximations and demonstrate that the probabilities with which the intervals fail to capture the population mean (that is, the coverage error) can range from well above the desired level, alpha, to very near zero in small to moderate sample sizes (n < or = 100). The performance of a more sophisticated approximation, implemented via numerical integration or bootstrap sampling, is noticeably improved, but also suffers from coverage errors that are too large when n < or = 25.

BIAS IN LINEAR MODEL POWER AND SAMPLE SIZE CALCULATION DUE TO ESTIMATING NONCENTRALITY.

Data analysts frequently calculate power and sample size for a planned study using mean and variance estimates from an initial trial. Hence power, or the sample size needed to achieve a fixed power, varies randomly. Such calculations can be very inaccurate in the General Linear Univariate Model (GLUM).

Computing Confidence Bounds for Power and Sample Size of the General Linear Univariate Model.

The power of a test, the probability of rejecting the null hypothesis in favor of an alternative, may be computed using estimates of one or more distributional parameters. Statisticians frequently fix mean values and calculate power or sample size using a variance estimate from an existing study. Hence computed power becomes a random variable for a fixed sample size.