+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Flexible stopping boundaries when changing primary endpoints after unblinded interim analyses

Flexible stopping boundaries when changing primary endpoints after unblinded interim analyses

Journal of Biopharmaceutical Statistics 24(4): 817-833

It has been widely recognized that interim analyses of accumulating data in a clinical trial can inflate type I error. Different methods, from group sequential boundaries to flexible alpha spending functions, have been developed to control the overall type I error at prespecified level. These methods mainly apply to testing the same endpoint in multiple interim analyses. In this article, we consider a group sequential design with preplanned endpoint switching after unblinded interim analyses. We extend the alpha spending function method to group sequential stopping boundaries when the parameters can be different between interim, or between interim and final analyses.

Please choose payment method:

(PDF emailed within 0-6 h: $19.90)

Accession: 053260552

Download citation: RISBibTeXText

PMID: 24697500

DOI: 10.1080/10543406.2014.901341

Related references

Flexible implementations of group sequential stopping rules using constrained boundaries. Biometrics 59(4): 770-777, 2004

Flexible Implementations of Group Sequential Stopping Rules Using Constrained Boundaries. Biometrics 59(4): 0-7, 2003

Early stopping, interim analyses, and monitoring committees: what are the tradeoffs?. Journal of Clinical Oncology 5(9): 1314-1315, 1987

Stopping rules, interim analyses and data monitoring committees. British Journal of Cancer 68(6): 1047-1050, 1993

Interim analyses and stopping rules in cancer clinical trials. British Journal Of Cancer. 68(6): 1179-1185, 1993

Inference on Multiple Endpoints in Clinical Trials with Adaptive Interim Analyses. Biometrical Journal 41(3): 261-277, 1999

Interim analyses, stopping rules and data monitoring in clinical trials in Europe. Statistics in Medicine 12(5-6): 509-520, 1993

Design of clinical trials with failure-time endpoints and interim analyses: An update after fifteen years. Contemporary Clinical Trials 45(Pt A): 103-112, 2016

Stopping a clinical trial very early based on unplanned interim analyses: a group sequential approach. Biometrics 51(3): 1152-1162, 1995

Group sequential tests for bivariate response: Interim analyses of clinical trials with both efficacy and safety endpoints. Biometrics 49(3): 741-752, 1993

Determination of power and sample size in the design of clinical trials with failure-time endpoints and interim analyses. Controlled Clinical Trials 20(5): 423-438, 1999

An analysis of protocols and publications suggested that most discontinuations of clinical trials were not based on preplanned interim analyses or stopping rules. Journal of Clinical Epidemiology 69: 152-160, 2016

Quantifying the bias in the estimated treatment effect in randomized trials having interim analyses and a rule for early stopping for futility. Statistics in Medicine 36(9): 1506-1518, 2017

Interim evaluation of efficacy or futility in group-sequential trials with multiple co-primary endpoints. Biometrical Journal. Biometrische Zeitschrift 59(4): 703-731, 2016

When should an interim analysis be unblinded to the data monitoring committee?. Journal of Clinical Epidemiology 63(4): 350-352, 2010