Application and investigation of a bound for outcome reporting bias

Williamson, Paula R ORCID: 0000-0001-9802-6636 and Gamble, Carrol ORCID: 0000-0002-3021-1955
(2007) Application and investigation of a bound for outcome reporting bias. TRIALS, 8 (1). 12-.

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<h4>Background</h4>Retention time (time to treatment failure) is a commonly used outcome in antiepileptic drug (AED) studies.<h4>Methods</h4>Two datasets are used to demonstrate the issues in a competing risks analysis of AEDs. First, data collection and follow-up considerations are discussed with reference to information from 15 monotherapy trials. Recommendations for improved data collection and cumulative incidence analysis are then illustrated using the SANAD trial dataset. The results are compared to the more common approach using standard survival analysis methods.<h4>Results</h4>A non-significant difference in overall treatment failure time between gabapentin and topiramate (logrank test statistic = 0.01, 1 degree of freedom, p-value = 0.91) masked highly significant differences in opposite directions with gabapentin resulting in fewer withdrawals due to side effects (Gray's test statistic = 11.60, 1 degree of freedom, p = 0.0007) but more due to poor seizure control (Gray's test statistic = 14.47, 1 degree of freedom, p-value = 0.0001). The significant difference in overall treatment failure time between lamotrigine and carbamazepine (logrank test statistic = 5.6, 1 degree of freedom, p-value = 0.018) was due entirely to a significant benefit of lamotrigine in terms of side effects (Gray's test statistic = 10.27, 1 degree of freedom, p = 0.001).<h4>Conclusion</h4>Treatment failure time can be measured reliably but care is needed to collect sufficient information on reasons for drug withdrawal to allow a competing risks analysis. Important differences between the profiles of AEDs may be missed unless appropriate statistical methods are used to fully investigate treatment failure time. Cumulative incidence analysis allows comparison of the probability of failure between two AEDs and is likely to be a more powerful approach than logrank analysis for most comparisons of standard and new anti-epileptic drugs.

Item Type: Article
Additional Information: 161BG Times Cited:2 Cited References Count:32## TULIP Type: Articles/Papers (Journal) ## official_url: <Go to ISI>://000245988700001
Uncontrolled Keywords: tonic clonic seizures, comparative monotherapy trial, multicenter comparative trial, controlled clinical-trial, newly-diagnosed epilepsy, long-term retention, sodium valproate, double-blind, onset epilepsy, carbamazepine
Subjects: ?? RC0321 ??
Divisions: Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Faculty of Health and Life Sciences
Depositing User: Symplectic Admin
Date Deposited: 27 Jun 2008 12:59
Last Modified: 16 Dec 2022 16:59
DOI: 10.1186/1745-6215-8-9
Publisher's Statement : © 2007 Williamson et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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