Controlled clinical trials最新文献

Success of blinding is a fundamental issue in many clinical trials. The validity of a trial may be questioned if this important assumption is violated. Although thousands of ostensibly double-blind trials are conducted annually and investigators acknowledge the importance of blinding, attempts to measure the effectiveness of blinding are rarely discussed. Several published papers proposed ways to evaluate the success of blinding, but none of the methods are commonly used or regarded as standard. This paper investigates a new approach to assess the success of blinding in clinical trials. The blinding index proposed is scaled to an interval of −1 to 1, 1 being complete lack of blinding, 0 being consistent with perfect blinding and −1 indicating opposite guessing which may be related to unblinding. It has the ability to detect a relatively low degree of blinding, response bias and different behaviors in two arms. The proposed method is applied to a clinical trial of cholesterol-lowering medication in a group of elderly people.

There has been persistent controversy regarding possible favorable or adverse effects of statins or of cholesterol reduction on cognition, mood and behavior (including aggressive or violent behavior), muscle function, and quality of life. The UCSD Statin Study seeks to ascertain the beneficial or adverse effects of statin cholesterol-lowering drugs on a set of noncardiac endpoints, including cognition, behavior, and serotonin biochemistry. The study will enroll 1000 subjects (minimum 20% female) of mixed ethnicity from San Diego. Subjects must be age 20 and older, postmenopausal if female, without known cardiovascular disease or diabetes, and with LDL-cholesterol between 115 and 190 mg/dl. Subjects will be randomized to a double-blind, placebo-controlled trial with assignment 1/3, 1/3, 1/3 to placebo, simvastatin 20 mg, or pravastatin 40 mg (equipotent LDL-cholesterol-lowering doses for drug arms with simvastatin and pravastatin chosen to represent the extremes of the lipophilicity spectrum) for 6 months of treatment followed by 2 months postcessation follow-up. Primary outcomes are cognition (cognitive battery), irritability/aggression (behavior measure), and serotonin (gauged by whole blood serotonin), assessed as the difference between baseline and 6 months, judging combined statin groups vs. placebo. Secondary outcomes include mood (CES-D and Wakefield depression inventory), quality of life (SF-12V), sleep (Leeds sleep scale, modified), and secondary aggression measures (Conflict Tactics Scale; Overt Aggression Scale, Modified). Cardiovascular reactivity will be examined in a 10% subset. As additional secondary endpoints, primary and selected secondary outcomes will be assessed by statin assignment (lipophilic simvastatin vs. hydrophilic pravastatin). “Reversibility” of changes, if any, at 2 months postcessation will be determined. If effects (favorable or unfavorable) are identified, we will seek to ascertain whether there are baseline variables that predict who will be most susceptible to these favorable or adverse noncardiac effects (i.e., effect modification).

A number of researchers have discussed phase II clinical trials from a Bayesian perspective. A recent article by Tan and Machin focuses on sample size calculations, which they determine by specifying a diffuse prior distribution and then calculating a posterior probability that the true response will exceed a prespecified target. In this article, we extend these sample size calculations to include informative prior distributions using various strategies that allow researchers with both optimistic and pessimistic priors direct involvement in the sample size decision making. We select the informative priors via multiple methods determined by the mean, median or mode of the conjugate prior. These cases can result in varying sample sizes.

The Prostate Cancer Prevention Trial is a randomized double blind chemoprevention trial of 18,882 men. It is designed to test the difference in the histologically proven prostate cancer prevalence between a group of participants given finasteride and another given placebo for 7 years. We present an overview of the study design, details of the administrative structure of the study and a description of the successful implementation of the accrual phase.

Repeated measures are exploited to study reliability in the context of psychiatric health sciences. It is shown how test–retest reliability can be derived using linear mixed models when the scale is continuous or quasi-continuous. The advantage of this approach is that the full modeling power of mixed models can be used. Repeated measures with a different mean structure can be used to usefully study reliability, correction for covariate effects is possible, and a complicated variance–covariance structure between measurements is allowed. In case the variance structure reduces to a random intercept (compound symmetry), classical methods are recovered. With more complex variance structures (e.g., including random slopes of time and/or serial correlation), time-dependent reliability functions are obtained. The methodology is motivated by and applied to data from five double-blind randomized clinical trials comparing the effects of risperidone to conventional antipsychotic agents for the treatment of chronic schizophrenia. Model assumptions are investigated through residual plots and by investigating the effect of influential observations.

In large clinical trials where outcome assessment is possible using questionnaires, it may be more cost-effective to mail them to patients than to conduct interviews in-person. However, nonresponse to mailed questionnaires reduces the effective sample size and can introduce bias. We conducted a systematic review and meta-analysis of randomized controlled trials evaluating the effect of questionnaire length on response rates. We searched 14 electronic bibliographic databases, the reference lists of relevant trials, and we contacted the authors of eligible trials to ask about unpublished data. For each trial identified, we used logistic regression to estimate the odds ratio for response per one page increase in the number of pages included in the questionnaire. We pooled the regression coefficients in a random effects meta-analysis. Heterogeneity among the coefficients was assessed using a chi-square test at a 5% significance level. We specified a priori that the reduction in the odds of response per one page increase would be greatest among trials comparing relatively short questionnaires. We used meta regression to examine the relationships between the regression coefficients, the length of the questionnaires used in each trial, and other study characteristics. A total of 38 randomized controlled trials were identified where participants were allocated to questionnaires of differing lengths and where the number of pages used was known. There was significant heterogeneity between the regression coefficients estimated from each trial. In meta regression, most of the heterogeneity was explained by variation in the length of the questionnaires used in each trial. Among trials in which the shortest questionnaire was a postcard, the odds of response were more than halved for each additional page used (0.39; 95% CI 0.34 to 0.45). In the remaining trials, pooled effect sizes were much smaller. In trials of one page compared with either two or three pages, the odds of response per one page increase was 1.01 (95% CI 0.82 to 1.24). For one page compared with four or more pages, and for two or more pages compared with longer alternatives, the odds ratios per one page increase were 0.90 (95% CI 0.83 to 0.98) and 0.98 (95% CI 0.96 to 0.99), respectively. There were no statistically significant associations between trial results and other study characteristics. It appears that response can be increased by using a shorter questionnaire. Moderate changes to the length of shorter questionnaires will be more effective than moderate changes to the length of longer questionnaires. If a choice of follow-up questionnaire exists for a clinical trial, the shorter one should be used. If a new follow-up questionnaire is to be designed, it should be made as short as possible without compromising the data collection requirements of the trial.