FDA Draft Guidance on Adaptive Design Clinical Trials: Pfizer's Perspective

Chuang‐Stein, Christy; Beltangady, Mohan

doi:10.1080/10543406.2010.514456

Cited by 10 publications

(8 citation statements)

References 6 publications

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“…Initiatives, predominately from a pharmaceutical drug development perspective, have been undertaken to understand and address some of the perceived barriers to the uptake of ADs in routine practice when they are considered appropriate [5–9]. Most importantly in this sector, regulatory bodies have drafted guidance documents or reflection papers on ADs to facilitate their use [6, 10–12]. …”

Section: Reviewmentioning

confidence: 99%

Adaptive designs undertaken in clinical research: a review of registered clinical trials

Hatfield

Allison

Flight

et al. 2016

Trials

103

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Adaptive designs have the potential to improve efficiency in the evaluation of new medical treatments in comparison to traditional fixed sample size designs. However, they are still not widely used in practice in clinical research. Little research has been conducted to investigate what adaptive designs are being undertaken. This review highlights the current state of registered adaptive designs and their characteristics. The review looked at phase II, II/III and III trials registered on ClinicalTrials.gov from 29 February 2000 to 1 June 2014, supplemented with trials from the National Institute for Health Research register and known adaptive trials. A range of adaptive design search terms were applied to the trials extracted from each database. Characteristics of the adaptive designs were then recorded including funder, therapeutic area and type of adaptation. The results in the paper suggest that the use of adaptive designs has increased. They seem to be most often used in phase II trials and in oncology. In phase III trials, the most popular form of adaptation is the group sequential design. The review failed to capture all trials with adaptive designs, which suggests that the reporting of adaptive designs, such as in clinical trials registers, needs much improving. We recommend that clinical trial registers should contain sections dedicated to the type and scope of the adaptation and that the term ‘adaptive design’ should be included in the trial title or at least in the brief summary or design sections.Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-016-1273-9) contains supplementary material, which is available to authorized users.

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Section: Reviewmentioning

confidence: 99%

Adaptive designs undertaken in clinical research: a review of registered clinical trials

Hatfield

Allison

Flight

et al. 2016

Trials

103

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“…The papers [36, 37, 38, 39, 40] in this special issue are viewpoints from biostatisticians from the pharmaceutical industry on the Draft Guidance, while [41, 42, 43] represent those from academia. In addition, [44, 45] summarize the highlights and a panel discussion in the Basel Conference on Perspectives on the Use of Adaptive Designs in Clinical Trials (March 12, 2010).…”

Section: Statistical and Regulatory Issuesmentioning

confidence: 99%

“…. The following points are made clear to sponsors: Interim results must remain inaccessible to personnel involved in trial conduct; standard operating procedures and charters will need to be more detailed and specific than in familiar monitoring settings; detailed descriptions will be required as to how the analysis will be performed, who will have access to the results, and under what conditions; it will be prospectively described and retrospectively documented how compliance with the specified procedures will be monitored. The papers [37], [38] and [39] provide further discussions on blinding and operational bias, together with other aspects of the Draft Guidance. Liu and Chi [40] give an insightful discussion of the history of regulatory research, legal basis, bias and blinding in connection with the Draft Guidance.…”

Section: Statistical and Regulatory Issuesmentioning

confidence: 99%

Adaptive design of confirmatory trials: Advances and challenges

Lai

Lavori

Tsang

2015

Contemporary Clinical Trials

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The past decade witnessed major developments in innovative designs of confirmatory clinical trials, and adaptive designs represent the most active area of these developments. We give an overview of the developments and associated statistical methods in several classes of adaptive designs of confirmatory trials. We also discuss their statistical difficulties and implementation challenges, and show how these problems are connected to other branches of mainstream Statistics, which we then apply to resolve the difficulties and bypass the bottlenecks in the development of adaptive designs for the next decade.

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“…In the simulations, ı was set equal to Q ı, L 1se , L 2se or M f as appropriate. When calculating assurance, we used results from the phase 2 study to construct the prior distribution instead of soliciting clinical opinion on the treatment effect from experts [11,13]. Despite the sources of bias described earlier, using evidence from completed trials often offers more objective information on the treatment effect.…”

Section: A Simulation Studymentioning

confidence: 99%

Discounting phase 2 results when planning phase 3 clinical trials

Kirby

Burke²,

Chuang‐Stein

et al. 2012

Pharmaceutical Statistics

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Sample size planning is an important design consideration for a phase 3 trial. In this paper, we consider how to improve this planning when using data from phase 2 trials. We use an approach based on the concept of assurance. We consider adjusting phase 2 results because of two possible sources of bias. The first source arises from selecting compounds with pre-specified favourable phase 2 results and using these favourable results as the basis of treatment effect for phase 3 sample size planning. The next source arises from projecting phase 2 treatment effect to the phase 3 population when this projection is optimistic because of a generally more heterogeneous patient population at the confirmatory stage. In an attempt to reduce the impact of these two sources of bias, we adjust (discount) the phase 2 estimate of treatment effect. We consider multiplicative and additive adjustment. Following a previously proposed concept, we consider the properties of several criteria, termed launch criteria, for deciding whether or not to progress development to phase 3. We use simulations to investigate launch criteria with or without bias adjustment for the sample size calculation under various scenarios. The simulation results are supplemented with empirical evidence to support the need to discount phase 2 results when the latter are used in phase 3 planning. Finally, we offer some recommendations based on both the simulations and the empirical investigations.

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FDA Draft Guidance on Adaptive Design Clinical Trials: Pfizer's Perspective

Cited by 10 publications

References 6 publications

Adaptive designs undertaken in clinical research: a review of registered clinical trials

Adaptive designs undertaken in clinical research: a review of registered clinical trials

Adaptive design of confirmatory trials: Advances and challenges

Discounting phase 2 results when planning phase 3 clinical trials

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