Adaptive Bayesian Designs for Dose-Ranging Drug Trials

Berry, Donald A.; Müller, Peter; Grieve, Andy; Smith, Michael K.; Parke, Tom; R, Blazek; Mitchard, Neil; Krams, Michael

doi:10.1007/978-1-4613-0035-9_2

Cited by 94 publications

(108 citation statements)

References 20 publications

Supporting

Mentioning

106

Contrasting

Unclassified

Order By: Relevance

“…Our study design owes much to the Acute Stroke Therapy by Inhibition of Neutrophils (ASTIN) trial design 3,17,18 but has incorporated several additional novel features. Adaptations in ASTIN were based on a single efficacy measure, whereas our adaptive algorithm and doseselection criteria are based on a CUI inclusive of safety, desirability, and efficacy measures.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, the ASTIN trial suffered from unrealistic assumptions and limited updating of the linear regression models used in its longitudinal modeling. Our trial used exponential growth models, which are not susceptible to the parameterization issues described by Berry and coauthors 3 and by Grieve and coauthors 18 and are much more robust to influential observations that may not be representative of the population. We update the longitudinal models from the start of the trial.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Application of Adaptive Design Methodology in Development of a Long-Acting Glucagon-like Peptide-1 Analog (Dulaglutide): Statistical Design and Simulations

Skrivanek

Berry

et al. 2012

J Diabetes Sci Technol

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Application of Adaptive Design Methodology in Development of a Long-Acting Glucagon-like Peptide-1 Analog (Dulaglutide): Statistical Design and Simulations

Skrivanek

Berry

et al. 2012

J Diabetes Sci Technol

View full text Add to dashboard Cite

“…Among the possible goals of phase II clinical studies are (1) to demonstrate the response different from placebo; (2) to estimate the minimum effective dose (MED), that is, the smallest dose with discernible useful effect compared with placebo; (3) to identify the range of doses with high response rates; and (4) to assess the shape of the dose-response curve. Correct identification of the dose is the key in the entire process of drug development.…”

Section: Introductionmentioning

confidence: 99%

“…This allows for the possibility of using an adaptive design: adaptive with respect to allocation to doses and sequential monitoring with the possibility to stop the trial early for futility or efficacy. Berry et al [2] suggested an adaptive design for a dose-finding study with the goal of estimating ED95, the smallest dose at which 95 per cent of the maximal response is achieved. Their method was proposed for trials where monotonicity could not be assumed.…”

Section: Introductionmentioning

confidence: 99%

Adaptive dose finding based on t‐statistic for dose–response trials

Ivanova

Bolognese

Perevozskaya

2008

Statistics in Medicine

View full text Add to dashboard Cite

SUMMARYThe goals of phase II dose-response studies are to prove that the treatment is effective and to choose the dose for further development. Randomized designs with equal allocation to either a high dose and placebo or to each of several doses and placebo are typically used. However, in trials where response is observed relatively quickly, adaptive designs might offer an advantage over equal allocation. We propose an adaptive design for dose-response trials that concentrates the allocation of subjects in one or more areas of interest, for example, near a minimum clinically important effect level, or near some maximal effect level, and also allows for the possibility to stop the trial early if needed. The proposed adaptive design yields higher power to detect a dose-response relationship, higher power in comparison with placebo, and selects the correct dose more frequently compared with a corresponding randomized design with equal allocation to doses.

show abstract

“…Nor was there reference to Tamura et al [5] who applied the methods successfully to a clinical trial in depression. In addition, given the fact that the Pfizer ASTIN trial has been well published (see [6]), we were very surprised to not see it mentioned in this section or in the section on Bayesian methods (although the references do include the paper by Berry et al [7] on which the statistical methods are based).…”

mentioning

confidence: 99%