Adapting a trial design based on feasibility of recruitment where several treatment groups are possible and the outcome is long-term: pre-empt flexible-entry internal pilot study

Abstract

Background: Endometriosis occurs when the endometrium grows in abnormal locations outside of the womb, resulting in pain and reduced quality of life. See-and-treat surgery removes endometriotic lesions but the risk of recurrence is high. A HTA commissioning call asked to evaluate the long-term (three years) effectiveness of post-operative long-acting reversible contraceptives (LARCs) in preventing recurrence. A survey of gynaecologists indicated there was no consensus about which LARC (LNG-IUS or DMPA) or comparator (COCP or no treatment) should be evaluated. We designed a 'flexible-entry' internal pilot to assess whether a four-arm trial was feasible in light of possible strong patient preferences. Methods: During the pilot, patients could be randomised to two, three or four treatment options provided one was a LARC and one was a non-LARC. An assessment of feasibility based on recruitment to these options and a substantive trial design was considered by an independent oversight committee. This design was fixed to ensure adequate power at the end of the study. Results: The study ran for one year from April 2014 and 74 women were randomised. Only 5 (7%) women were happy to be randomised to all groups, with 60 (81%) having a LARC preference and 53 (72%) a non-LARC preference. Four-way and three-way designs were ruled out with a two-way (preferred LARC v COCP), stratified by LARC preference, considered feasible. Conclusions: Where multiple treatment options are available a flexible approach to randomisation in a pilot phase can be used to assess feasibility and adapt a trial design.