We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Rethinking non-inferiority: a practical trial design for optimising treatment duration.
- Authors
Quartagno, Matteo; Walker, A. Sarah; Carpenter, James R.; Phillips, Patrick P. J.; Parmar, Mahesh KB
- Abstract
Background: Trials to identify the minimal effective treatment duration are needed in different therapeutic areas, including bacterial infections, tuberculosis and hepatitis C. However, standard non-inferiority designs have several limitations, including arbitrariness of non-inferiority margins, choice of research arms and very large sample sizes. Methods: We recast the problem of finding an appropriate non-inferior treatment duration in terms of modelling the entire duration--response curve within a pre-specified range. We propose a multi-arm randomised trial design, allocating patients to different treatment durations. We use fractional polynomials and spline-based methods to flexibly model the duration--response curve. We call this a 'Durations design'. We compare different methods in terms of a scaled version of the area between true and estimated prediction curves. We evaluate sensitivity to key design parameters, including sample size, number and position of arms. Results: A total sample size of - 500 patients divided into a moderate number of equidistant arms (5-7) is sufficient to estimate the duration-response curve within a 5% error margin in 95% of the simulations. Fractional polynomials provide similar or better results than spline-based methods in most scenarios. Conclusion: Our proposed practical randomised trial 'Durations design' shows promising performance in the estimation of the duration-response curve; subject to a pending careful investigation of its inferential properties, it provides a potential alternative to standard non-inferiority designs, avoiding many of their limitations, and yet being fairly robust to different possible duration-response curves. The trial outcome is the whole duration-response curve, which may be used by clinicians and policymakers to make informed decisions, facilitating a move away from a forced binary hypothesis testing paradigm.
- Subjects
DOSE-response relationship in biochemistry; DRUG resistance in microorganisms; DECISION making in clinical medicine; SAMPLE size (Statistics); TREATMENT duration; STATISTICAL models
- Publication
Clinical Trials, 2018, Vol 15, Issue 5, p477
- ISSN
1740-7745
- Publication type
Article
- DOI
10.1177/1740774518778027