The combined contraceptive vaginal ring, NuvaRing: an international study of user acceptability.

The acceptability of the combined contraceptive vaginal ring, NuvaRing, was assessed during two trials conducted in North America and Europe. Women completed a questionnaire about the ring's clarity of instructions, ease of use, sexual comfort, cycle-related characteristics and satisfaction after 3, 6 and 13 cycles of use. A total of 1,950 women (82% of those recruited) completed a questionnaire at cycle 3. At baseline, 66% of participants preferred oral contraceptives, but after three cycles of ring use 81% preferred the ring. On study completion, 97% agreed that the instructions for use were clear; 85% of women and 71% of their partners never/rarely felt the ring during intercourse and 94% of partners never/rarely minded that the woman was using the ring. Overall acceptance was high, 96% were satisfied with the ring and 97% would recommend the ring. Similar responses were seen for women who prematurely discontinued from the studies, except that slightly fewer women were satisfied (60%) and would recommend the ring (75%). Reasons for liking the ring included 'not having to remember anything' (45%) and 'ease of use' (27%). In conclusion, there is a high level of user and partner acceptability for the contraceptive ring.

Use of small-sample-based reference limits on a group basis.

The evaluation of a biochemical or hematological quantity measured in a study group of employees during occupational health assessments involves a comparison with a reference sample group. Part of this evaluation consists of checking whether the percentage of values larger than a predetermined upper reference limit is significantly larger than the percentage normally expected (2.5%, if the 97.5 percentile is used as the upper reference limit). The reference limit, however, is estimated from a random reference sample, the size of which, for many reasons, may be relatively small; as a consequence, the reference limit estimate will be imprecise. In situations in which the reference sample size is smaller than or not much larger than the study sample size, this imprecision results in the usual binomial test of significance being highly inappropriate. We provide an exact nonparametric test valid for all reference sample sizes.

General approach to correction for bias in analytical performance in longitudinal studies illustrated by estimating the effect of age on gamma-glutamyltransferase activity.

For studying trends in blood biochemistry analytes of an individual or a group of individuals, the outcome may be influenced by analytical changes that may have occurred during the study. An observed trend may well represent a drift in analytical performance instead of a truly biological finding. We developed a model that allows for retrospective correction of analytical changes with time. This model is based on the concept of adjustment of an individual's longitudinal blood biochemistry data by comparing the long-term results of the laboratory with those of other laboratories in an external quality-control survey program. Factors responsible for the analytical bias of our laboratory were identified by multiple regression analysis. The resulting procedure for assessing analytical bias and variability was applied to study in two mutually exclusive cohorts of employees of the Shell petrochemical complex in Rotterdam (a) the true nature of the changes (analytical or biological) in gamma-glutamyltransferase (GGT) and (b) the effect of age on GGT. The first cohort consisted of employees who attended a periodic health assessment in 1984 and in 1989; the second, employees who attended periodic health assessments in 1985 and in 1988. Thus we studied 3- and 5-year changes of GGT corrected for analytical bias. Whereas standard cross-sectional results apparently showed an increase of GGT up to age 50 years, the longitudinal findings corrected for analytical changes, as indicated above, do not support these cross-sectional results.

Recommendation for confidence interval and sample size calculation for the Pearl Index.

A new guideline on the clinical investigation of steroid contraceptives in women, which has been released by the European Agency for the Evaluation of Medicinal Products (EMEA), calls for the calculation of a confidence interval for the Pearl Index, a widely used measure to describe the effectiveness of a contraceptive method. However, the interpretation of the Pearl Index as a statistical parameter, for which a confidence interval can be calculated, needs further clarification. The guideline does not provide the necessary definitions. In this paper, two statistical models, the Bernoulli model and the Poisson model, are compared; both can be used for the calculation of the Pearl Index and its upper confidence limit. The Poisson model proved to be more suitable, because it can accommodate incomplete treatment cycles. Unambiguous definitions and statistical formulae for the calculation of overall Pearl Index and the Method Failure Pearl Index are given. Finally, the sample sizes required to fulfill the EMEA's guideline are given.

Morphometry, densitometry and pattern analysis of plastic-embedded histologic material from urothelial cell carcinoma of the bladder.

An image analysis method of grading histologic sections of bladder carcinoma was tested. The method was new in four respects. First, for fixation of the biopsies a coagulant fixative was used. Second, 2-microns plastic sections were used to ensure the reproducibility of nuclear imaging. Third, a new stereologic approach was used for calculation of the nuclear volume and DNA content. Fourth, for the classification rule the morphometric, densitometric and texture features were used in concert. The IBAS 2000 instrument was used for the measurements. Texture analysis of the chromatin patterns was performed using Markovian texture features. Using discriminant analysis, of 22 parameters, 2 morphometric, 2 densitometric and 3 texture features were selected for the classification rule. With them, 89% of the bladder carcinomas were correctly classified into the three grades. All grade III tumors were classified correctly. Among the features tested, the densitometry of the DNA had the highest F values. All of the grade III tumors and 45% of the grade II tumor group had DNA histograms indicating aneuploidy. This study showed that plastic-embedded material is well suited to morphometry and densitometry and can be used for quantitative grading of bladder carcinoma.