Good Practices for Adaptive Clinical Trials in Pharmaceutical Product Development

Abstract

This article is a summary of good adaptive practices for the planning and implementation of adaptive designs compiled from experiences gained in the pharmaceutical industry. The target audience is anyone involved in the planning and execution of clinical trials. The first step prior to planning an adaptive design is to assess the appropriateness of its use. Hence, strategic points to consider when assessing if an adaptive design is the right choice for a trial are discussed. In addition, strategic points for consideration at the design and implementation stage are included from operational, regulatory, clinical, and statistical perspectives. Good practices for trial simulation, trial documentation, and data monitoring committees are provided.

Perspectives on the Use of Adaptive Designs in Clinical Trials. Part I. Statistical Considerations and Issues

“…With this distinction, the notion of an operational seamless two-stage design, such as those described in Gaydos et al (2009), i.e., separating stage 1 from stage 2 without making use of the stage 1 learning data when making the statistical inference, would not apply.…”

FDA Draft Guidance on Adaptive Design Clinical Trials: Pfizer's Perspective

“…Incidentally, we encourage FDA to consider referencing PhRMA's position paper on Good Practice for Adaptive Clinical Trials (Gaydos et al, 2009) in the final guidance. The paper contains good discussions on documentation and simulation report.…”

Designing Studies to Find Early Signals of Efficacy

“…A number of actions have been taken to try and improve efficiency of the development process in light of this risky environment: for example, the FDA's Critical Path Initiative (FDA, 2004), EU's Innovative Medicines Initiative (2007) (http://www.imi.europa.eu/index_en.html), and the recent focus on developing adaptive design methodology (Bretz et al, 2006;Bornkamp et al, 2007;Gallo et al, 2006;Gaydos et al, 2009). While many of the efforts in study design have focused on efficiency at the trial level, there is room for improvement in efficiently detecting signals of efficacy when there are limited resources available.…”