+ 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

Early stopping rules in clinical trials based on sequential monitoring of serious adverse events

Early stopping rules in clinical trials based on sequential monitoring of serious adverse events

Medical Decision Making 29(3): 343-350

Several multistage or group sequential statistical methods have been developed for defining stopping rules in terms of efficacy in phase II and III clinical trials, but they rely on interim analyses after the inclusion of a fixed number of patients. These methods, however, need to be adapted for the evaluation of serious adverse events (SAEs), which can occur relatively early in the trial. A high frequency of their occurrence may require the trial to close early. The methods developed here define stopping rules after the occurrence of each SAE by comparing the number of patients included to the number of patients satisfying maximum SAE criteria. The nominal type I error, power, and average sample number (ASN) under specific hypotheses are obtained through simulations. Data from a clinical trial are presented as an example.

Please choose payment method:

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

Accession: 052764016

Download citation: RISBibTeXText

PMID: 19073996

DOI: 10.1177/0272989x08327332

Related references

Issues in designing sequential stopping rules for monitoring side effects in clinical trials. Controlled Clinical Trials 8(4): 327-337, 1987

A Bayesian Stopping Rule for Sequential Monitoring of Serious Adverse Events. Therapeutic Innovation and Regulatory Science 48(4): 444-452, 2014

Sequential stopping rules in clinical trials. Statistics in Medicine 9(6): 595-600, 1990

On the frequentist and likelihood controversy over sequential stopping rules in clinical trials. Controlled Clinical Trials 4(3): 261-263, 1983

Software to compute and conduct sequential Bayesian phase I or II dose-ranging clinical trials with stopping rules. Computer Methods and Programs in Biomedicine 72(2): 117-125, 2003

SAE: an R package for early stopping rules in clinical trials. Computer Methods and Programs in Biomedicine 104(2): 243-248, 2012

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

Effects on overviews of early stopping rules for clinical trials. Statistics in Medicine 6(3): 361-369, 1987

Comparison of four sequential methods allowing for early stopping of comparative clinical trials. Clinical Science 98(5): 569-578, 2000

Rejoinder: statistical inference from trials with sequential stopping rules. Controlled Clinical Trials 4(1): 27-33, 1983

A comparison of a new multinomial stopping rule with stopping rules of fleming and gehan in single arm phase II cancer clinical trials. Bmc Medical Research Methodology 11: 95, 2011

Workshop on Early Stopping Rules in Cancer Clinical Trials. Cambridge, United Kingdom, 13-15 April 1993. Statistics in Medicine 13(13-14): 1289-1499, 1994

Early stopping clinical trials of binomial response with an exact group sequential method. Statistics in Medicine 26(8): 1724-1729, 2007

Early precut sphincterotomy does not increase the risk of adverse events for patients with difficult biliary access: A systematic review of randomized clinical trials with meta-analysis and trial sequential analysis. Medicine 97(36): E12213, 2018

Early stopping in clinical trials and epidemiologic studies for "futility": conditional power versus sequential analysis. Journal of Clinical Epidemiology 56(7): 610-617, 2003