Multiplicity and flexibility in clinical trials.
نویسندگان
چکیده
Flexible designs offer a large amount of flexibility in clinical trials with control of the type I error rate. This allows the combination of trials from different clinical phases of a drug development process. Such combinations require designs where hypotheses are selected and/or added at interim analysis without knowing the selection rule in advance so that both flexibility and multiplicity issues arise. The paper reviews the basic principles and some of the common methods for reaching flexibility while controlling the family-wise error rate in the strong sense. Flexible designs have been criticized because they may lead to different weights for the patients from the different stages when reassessing sample sizes. Analyzing the data in a conventional way avoids such unequal weighting but may inflate the multiple type I error rate. In cases where the conditional type I error rates of the new design (and conventional analysis) are below the conditional type I error rates of the initial design the conventional analysis may, however, be done without inflating the type I error rate. Focusing on a parallel group design with two treatments and a common control, we use this principle to investigate when we can select one treatment, reassess sample sizes and test the corresponding null hypotheses by the conventional level alpha z-test without compromising on the multiple type I error rate.
منابع مشابه
Practical guidelines for multiplicity adjustment in clinical trials.
Multiplicity in clinical trials may appear under several different guises: multiple endpoints, multiple treatment arm comparisons, and multiple looks at the data during interim monitoring, to name a few. It is well recognized by statisticians and nonstatisticians alike that multiplicity inflates the type I error rate of the experiment, and this has prompted the development of many multiple comp...
متن کاملCharacteristics of Clinical Trials in Iran: A Sample of 5000 Trials Registered in IRCT
Background and Objectives: A considerable number of clinical trials are conducted in Iran each year. Not much is known about the characteristics of them, this study aimed to investigate key characteristics of Iranian clinical trials. Methods: All clinical trial protocols registered in IRCT until November 2013 were selected. Text mining techniques were used to extract information from data t...
متن کاملAre multiple primary outcomes analysed appropriately in randomised controlled trials? A review.
OBJECTIVES To review how multiple primary outcomes are currently considered in the analysis of randomised controlled trials. We briefly describe the methods available to safeguard the inferences and to raise awareness of the potential problems caused by multiple outcomes. METHODS/DESIGN We reviewed randomised controlled trials (RCTs) in neurology and psychiatry disease areas, as these frequen...
متن کاملMultiplicity Problems in Clinical Trials: A Regulatory Perspective
Confirmatory controlled clinical trials, also known as Phase III clinical trials, when successful, are significant achievements in medical research as they provide evidence that new treatments (e.g., test drugs or other types of interventions) studied in these trials are clinically effective in treating targeted diseases, and are also safe as far as judgment is possible on taking into account t...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Pharmaceutical statistics
دوره 6 3 شماره
صفحات -
تاریخ انتشار 2007