Choice of non-inferiority (NI) margins does not protect against degradation of treatment effects on an average – an observational study of registered and published NI trials
Abstract: Objective: NI margins have to be chosen appropriately to control the risk of degradation of treatment effects in noninferiority (NI) trials. We aimed to study whether the current choice of NI margins protects sufficiently against a degradation of treatment effect on an average.
Study Design and Setting: NI trials reflecting current practice were assembled and for each trial, the NI margin was translated into a likelihood of degradation. The likelihood of degradation was calculated as the conditional probability of a treatment being harmful given that it is declared non-inferior in the trial, using simulation. Its distribution among the NI trials was then studied to assess the potential risk of degradation.Results: The median (lower/upper quartile) NI margin among 112 binary outcome NI trials corresponded to an odds ratio of 0.57(0.45, 0.66), while among 38 NI trials with continuous outcome, to a Cohen’s d of 20.42(20.54, 20.31) and a hazard ratio of 0.82(0.73, 0.86) among 24 survival outcome NI trials. Overall, the median likelihood of degradation was 56% (45%, 62%).
Conclusion: Only two fifths of the current NI trials had a likelihood of degradation lower than 50%, suggesting hat, in majority of the NI trials, there is no sufficient protection against degradation on an average. We suggest a third hurdle for the choice of NI margins, thus contributing a sufficient degree of protection
- Standort
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Deutsche Nationalbibliothek Frankfurt am Main
- Umfang
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Online-Ressource
- Sprache
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Englisch
- Anmerkungen
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PLoS ONE. 9, 7 (2014), e103616, DOI 10.1371/journal.pone.0103616, issn: 1932-6203
IN COPYRIGHT http://rightsstatements.org/page/InC/1.0 rs
- Schlagwort
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Iatrogene Krankheit
Therapie
Compliance
- Ereignis
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Veröffentlichung
- (wo)
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Freiburg
- (wer)
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Universität
- (wann)
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2014
- Urheber
- Beteiligte Personen und Organisationen
- DOI
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10.1371/journal.pone.0103616
- URN
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urn:nbn:de:bsz:25-freidok-119822
- Rechteinformation
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- Letzte Aktualisierung
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14.08.2025, 10:58 MESZ
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- 2014
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