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      Estimating the sample size for a pilot randomised trial to minimise the overall trial sample size for the external pilot and main trial for a continuous outcome variable

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          Abstract

          Sample size justification is an important consideration when planning a clinical trial, not only for the main trial but also for any preliminary pilot trial. When the outcome is a continuous variable, the sample size calculation requires an accurate estimate of the standard deviation of the outcome measure. A pilot trial can be used to get an estimate of the standard deviation, which could then be used to anticipate what may be observed in the main trial. However, an important consideration is that pilot trials often estimate the standard deviation parameter imprecisely. This paper looks at how we can choose an external pilot trial sample size in order to minimise the sample size of the overall clinical trial programme, that is, the pilot and the main trial together. We produce a method of calculating the optimal solution to the required pilot trial sample size when the standardised effect size for the main trial is known. However, as it may not be possible to know the standardised effect size to be used prior to the pilot trial, approximate rules are also presented. For a main trial designed with 90% power and two-sided 5% significance, we recommend pilot trial sample sizes per treatment arm of 75, 25, 15 and 10 for standardised effect sizes that are extra small (≤0.1), small (0.2), medium (0.5) or large (0.8), respectively.

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          Design and analysis of pilot studies: recommendations for good practice.

          Pilot studies play an important role in health research, but they can be misused, mistreated and misrepresented. In this paper we focus on pilot studies that are used specifically to plan a randomized controlled trial (RCT). Citing examples from the literature, we provide a methodological framework in which to work, and discuss reasons why a pilot study might be undertaken. A well-conducted pilot study, giving a clear list of aims and objectives within a formal framework will encourage methodological rigour, ensure that the work is scientifically valid and publishable, and will lead to higher quality RCTs. It will also safeguard against pilot studies being conducted simply because of small numbers of available patients.
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            The statistical interpretation of pilot trials: should significance thresholds be reconsidered?

            Background In an evaluation of a new health technology, a pilot trial may be undertaken prior to a trial that makes a definitive assessment of benefit. The objective of pilot studies is to provide sufficient evidence that a larger definitive trial can be undertaken and, at times, to provide a preliminary assessment of benefit. Methods We describe significance thresholds, confidence intervals and surrogate markers in the context of pilot studies and how Bayesian methods can be used in pilot trials. We use a worked example to illustrate the issues raised. Results We show how significance levels other than the traditional 5% should be considered to provide preliminary evidence for efficacy and how estimation and confidence intervals should be the focus to provide an estimated range of possible treatment effects. We also illustrate how Bayesian methods could also assist in the early assessment of a health technology. Conclusions We recommend that in pilot trials the focus should be on descriptive statistics and estimation, using confidence intervals, rather than formal hypothesis testing and that confidence intervals other than 95% confidence intervals, such as 85% or 75%, be used for the estimation. The confidence interval should then be interpreted with regards to the minimum clinically important difference. We also recommend that Bayesian methods be used to assist in the interpretation of pilot trials. Surrogate endpoints can also be used in pilot trials but they must reliably predict the overall effect on the clinical outcome.
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              Pilot and feasibility studies: is there a difference from each other and from a randomised controlled trial?

              A crucial part in the development of any intervention is the preliminary work carried out prior to a large-scale definitive trial. However, the definitions of these terms are not clear cut and many authors redefine them. Because of this, the terms feasibility and pilot are often misused.
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                Author and article information

                Journal
                Stat Methods Med Res
                Stat Methods Med Res
                SMM
                spsmm
                Statistical Methods in Medical Research
                SAGE Publications (Sage UK: London, England )
                0962-2802
                1477-0334
                19 June 2015
                June 2016
                : 25
                : 3 , Special issue on Pilot Trials
                : 1057-1073
                Affiliations
                [1 ]Medical Statistics Group, Design, Trials and Statistics Group, School of Health and Related Research, University of Sheffield, Sheffield, UK
                [2 ]Clinical Trials Research Unit, Design, Trials and Statistics Group, School of Health and Related Research, University of Sheffield, Sheffield, UK
                Author notes
                [*]Amy L Whitehead, Medical Statistics Group, Design, Trials and Statistics Group, School of Health and Related Research, University of Sheffield, Sheffield, UK. Email: a.whitehead@ 123456sheffield.ac.uk
                Article
                10.1177_0962280215588241
                10.1177/0962280215588241
                4876429
                26092476
                c52e0f2d-97a6-4970-90fe-46b9085e7b44
                © The Author(s) 2015

                This article is distributed under the terms of the Creative Commons Attribution 3.0 License ( http://www.creativecommons.org/licenses/by/3.0/) which permits any use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

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                pilot trial,rct,sample size,power,continuous outcome
                pilot trial, rct, sample size, power, continuous outcome

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