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SUMMARY:Virtual Seminar: ‘The DURATIONS design: a practical trial design
  to optimise treatment duration’ - Dr Matteo Quartagno\, MRC Clinical Tr
 ials Unit\, UCL
DTSTART:20201215T140000Z
DTEND:20201215T150000Z
UID:TALK153958@talks.cam.ac.uk
CONTACT:Alison Quenault
DESCRIPTION:Introduction: Trials to identify the minimal effective treatme
 nt duration are needed in different therapeutic areas\, including antibiot
 ics\, TB and Hepatitis C. However\, standard non-inferiority designs have 
 several limitations\, including arbitrariness of choice of shorter duratio
 n arms and large sample sizes.\n\nMethods: We propose a multi-arm trial de
 sign\, allocating patients to different treatment durations. We recast the
  problem of testing for non-inferiority of a single shorter treatment dura
 tion in terms of modelling the entire duration-response curve within a pre
 -specified range. We use fractional polynomials to flexibly model the dura
 tion-response curve. We compare different methods to draw inference from t
 he estimated curve\, i.e. to choose the “optimal” duration. We explore
  both different estimands and estimation methods\, in terms of newly devel
 oped operating characteristics.\n\nResults: Through simulations we show th
 at\, in a variety of scenarios\, when using fractional polynomials 5-7 equ
 idistant duration arms are generally enough to get a good estimate of the 
 duration response curve. In order to draw inference from this curve\, the 
 simplest estimand to target is the shortest duration non-inferior to the c
 ontrol one within a certain non-inferiority margin. The margin can itself 
 be dependent on duration.  In terms of estimation method\, using bootstrap
  is preferable\, as it accounts for model selection variability\, and lead
 s to type-1 error rates within the nominal level in all scenarios consider
 ed.\n\nDiscussion: Our proposed practical trial design is an alternative t
 o standard non-inferiority designs\, avoiding many of their limitations\, 
 and yet being fairly robust to different possible duration-response curves
 .
LOCATION:Virtual Seminar 
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