Assessment of side effects in patients with chronic hepatitis C receiving combination therapy.

The purpose of this descriptive study is to review the adverse effects of combination therapy, interferon alfa-2b and ribavirin, in a sample of patients with chronic hepatitis C who were part of a larger multi-center trial (Bonkovsky, 1999). The sample (n = 13) was drawn from one hepatology practice in the northeastern United States. This secondary analysis reported sums, frequencies, means, and standard deviations for the sample. Patients who received 600 mg ribavirin per day in addition to interferon alfa-2B (Arm A) showed a mean of 9.5 different types of side effects. Patients who received 1000-1200 mg of ribavirin in addition to interferon alfa-2B (Arm B) had a mean of 8.6 different types of side effects. The highest-ranking side effects were fatigue (92%), insomnia (85%), alopecia (69%), and arthralgia (62%). A secondary analysis of the entire data set is required before confidence can be placed in the findings. Implications for nursing practice include the need for creative strategies to reduce the effects of fatigue, insomnia, alopecia, and arthralgia in patients with chronic hepatitis C.

Internal pilot studies II: comparison of various procedures.

The two-stage design involves sample size recalculation using an interim variance estimate. Stein proposed the design in 1945; biostatisticians recently have shown renewed interest in it. Wittes and Brittain proposed a modification aimed at greater efficiency; Gould and Shih proposed a similar procedure, but with a different interim variance estimate based on blinded data. We compare the power of Stein's original test, an idealized version of the Wittes-Brittain test, and a theoretical optimal test which can be approximated in practice. We also compare two procedures that control the conditional type I error rate given the actual final sample size: Gould and Shih's procedure and a newly proposed 'second segment' procedure. The comparison among the first three procedures indicates that the Stein test is, unexpectedly, the test of choice under the original design alternative, whereas the approximate-optimal and Wittes-Brittain procedures appear to have superior power for detecting smaller treatment differences. As between the latter two procedures, the second segment procedure is more powerful when many observations are likely to be taken after the interim resizing, whereas otherwise the Gould-Shih procedure is superior.

Inference for the association between coefficients in a multivariate growth curve model.

This paper generalizes the work of Blomqvist (1977, Journal of the American Statistical Association 72, 746-749) on inference for the relationship between the individual-specific slope and the individual-specific intercept in a linear growth curve model. The paper deals with longitudinal data involving one or more response variables and irregular follow-up times, with each response variable postulated to follow a linear growth curve model. The problem considered is inference concerning the association between one growth curve coefficient and another--for example, the slope and intercept for a selected response variable, or the two slopes for two different response variables--after adjusting for all remaining coefficients among all of the response variables. An inferential approach based on the method of moments and an inferential approach based on maximum likelihood are described, and the asymptotic properties of these procedures are presented. Extensions of the methodology to allow polynomial growth curves and baseline covariates are outlined. The methodology is illustrated with a practical example arising from a clinical trial in lung disease.

Statistical design of the Child and Adolescent Trial for Cardiovascular Health (CATCH): implications of cluster randomization.

This paper describes some statistical considerations for the Child and Adolescent Trial for Cardiovascular Health (CATCH), a large-scale community health trial sponsored by the National Heart, Lung, and Blood Institute. The trial involves randomization of entire schools rather than individual students to the experimental arms. The paper discussed the implications of this form of randomization for the design and analysis of the trial. The power calculations and analysis plan for the trial are presented in detail. The handling of outmigrating and immigrating students is also discussed.

Studying the relationship between change and initial value in longitudinal studies.

Blomqvist's problem of studying the relationship between change and initial value in a linear growth curve setting is reformulated from a random effects model perspective. First, a maximum likelihood estimate of the between-individual covariance matrix for a simple linear regression model with stochastic parameters is obtained via an EM algorithm as discussed by Laird and Ware. Second, the regression coefficient of the individual-specific slopes on the individual-specific intercepts is estimated as a ratio of elements of the between-individual covariance matrix as discussed by Zucker et al. Then a Fieller's type confidence interval for this ratio is proposed. Discussion is facilitated by recognizing the Laird-Ware model as a special case of a more general model discussed by Hocking.

Sequential monitoring of clinical trials: the role of information and Brownian motion.

Sequential monitoring has been a topic of major interest in clinical trials methodology over the past two decades. This paper presents a unified conceptual framework for sequential monitoring that covers a wide variety of monitoring procedures in a wide variety of clinical trial settings. The central elements of this framework consist of a suitable concept of statistical information and a scheme for using this concept as a basis for summarizing the accumulating results of a trial in a standardized form, through a stochastic process that can be shown to approximate classical Brownian motion. The ideas are developed in a simple step-by-step fashion and illustrated by several practical examples.

Lipid and lipoprotein distributions in children by ethnic group, gender, and geographic location--preliminary findings of the Child and Adolescent Trial for Cardiovascular Health (CATCH).

BACKGROUND: The Child and Adolescent Trial for Cardiovascular Health is a school-based study designed to test the effectiveness of dietary, physical activity, and educational interventions for reducing cardiovascular disease risk and teaching healthful behaviors to children. METHODS: As part of a pilot phase in 1989, lipid, lipoprotein, and anthropometric measures were taken in black (n = 90), Hispanic (n = 68), and white (n = 265) 8- to 10-year-old schoolchildren in California, Louisiana, Minnesota, and Texas. RESULTS: There were no significant differences in mean lipoprotein cholesterol values between fasting and nonfasting children. Therefore data from fasting and nonfasting children were pooled. Males and females within the same ethnic groups had similar mean levels of total cholesterol, low-density lipoprotein cholesterol, and very low-density lipoprotein cholesterol. However, levels of high-density lipoprotein cholesterol were higher among white and black males than among females from the same ethnic groups. Black males had higher total cholesterol than white males and higher high-density lipoprotein cholesterol than white males and Hispanic males. Similarly, black females had higher high-density lipoprotein cholesterol than white and Hispanic females. In all children combined high-density lipoprotein cholesterol was inversely correlated and low-density lipoprotein cholesterol was positively correlated with subscapular and tricep skinfold thickness, weight, and body mass index. There were significant differences in mean lipoprotein cholesterol levels between geographic sites. Total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol were highest in children from California followed by children from Texas, Minnesota, and Louisiana. CONCLUSION: Our results suggest that body fatness total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol differ in children by gender, ethnicity, and geographic location.

The efficiency of a weighed log-rank test under a percent error misspecification model for the log hazard ratio.

For comparison of two survival distributions, it is natural to use a weighted log-rank test with weight function given by the log hazard ratio function that is anticipated a priori. This paper investigates the efficiency of this test when the a priori estimate of the log hazard ratio is subject to a specified percentage error. The test is shown to be the maximum efficiency robust test over the class of alternatives in question and a simple expression for the maximum efficiency is established.

Research design and analysis issues.

The overall perspective of this article is the need for researchers of school-based health promotion to make more progressive use of existing statistical methods to improve both the rigor and the efficiency of school-based experiments. Investigative teams working in the school setting have an advantage over health education researchers working in communities or worksites in that they have greater choice of the experimental unit and usually easier access to large clusters of units. They are, therefore, in a position to make optimal use of a wide variety of experimental designs and observation strategies. In order to make full use of this advantage, however, researchers in this field need to assemble multidisciplinary teams, including researchers from other fields who are not restricted by the traditional approaches evident in many of the current school studies. Such teams should include statisticians and epidemiologists who have broadly-based experimental design and survey experience to work with the health educators and other behavioral and biomedical scientists.

Analysis issues in school-based health promotion studies.

In school-based research, usually the nature of the intervention or other practical factors indicate that assignment of treatment be done by school or classroom rather than by individual student. In this situation, randomization of schools (or classrooms) and analysis by school means (or classroom means) provide a firm statistical basis for internal validity of the study. When the number of schools available is small, this approach is not practicable, and therefore the investigator must be both more creative in developing solutions and more cautious in interpreting the results. This article provides a number of suggestions which the authors hope will assist the field in dealing with such circumstances. The authors stress that the best approach to assessing treatment effect is a well-designed, properly analyzed randomized experiment. The suggestions in this article attempt to indicate how one might make the most that one can from more limited data.