POSTER PRESENTATION Open Access

The importance of planning for a seamlesstransition in an adaptive phase II randomised trialAndrea Marshall*, Janet A Dunn, Julie Fletcher, Helen B Higgins, Christopher J Poole

From Clinical Trials Methodology Conference 2011Bristol, UK. 4-5 October 2011

ObjectivesTo investigate the importance of incorporating adaptivedesigns of randomised phase II trials into the protocoland patient information sheets using NEO-ESCAPE asan illustrative example.

MethodsNEO-ESCAPE was a randomised two arm phase II studyin inoperable ovarian cancer designed as an externalpilot to inform a future phase III randomised controlledtrial. The primary objective was to assess the feasibilityof two new extended chemotherapy regimens with 44patients required on each arm. If one or both treatmentarms proved feasible, the trial would continue to recruitto the feasible treatment arm(s) to improve the esti-mates of outcomes to be used in the phase III trial.Stopping rules were essential to enable pre-planneddecisions on the futility of continuing to the required 44patients on each arm. Simulations to assess futility wereused in the decision making process.

ResultsAt the first pre-planned interim analysis when 56patients had been recruited (28 on each arm) and 21patients (11 on Arm A; 10 on Arm B) had finishedtreatment, it was clear that one arm of the trial wouldnot meet the feasibility criteria on completion ofrecruitment. On the advice of the Independent DataMonitoring Committee, this arm of the study closedto recruitment but follow-up for these patientscontinued.Closure of one arm of the study resulted in a tempor-

ary halt of the trial while the protocol was amended to asingle arm study, the patient information sheet was

updated and all the relevant ethics, MHRA and Researchand Development approvals were obtained. This tem-porary two month halt in recruitment to the study car-ried not only a loss of potential patients during theclosed period but also a loss of momentum of centreson re-opening of the study and hence resulted in adelay in completing recruitment.

ConclusionsOur experiences with this phase II study emphasise theneed for full details of any adaptive designs, includingall anticipated scenarios and subsequent actions, to befully incorporated into the protocol and patient informa-tion sheet to avoid the need for a temporary halt ofrecruitment. A detailed statistical analysis plan is alsoessential in ensuring optimal decision making withinthese types of studies. The dilemma remains on howbest to achieve a seamless transition in the adaptive ele-ment whilst not confusing patients with too much infor-mation about each possible future adaptation.

Published: 13 December 2011

doi:10.1186/1745-6215-12-S1-A7Cite this article as: Marshall et al.: The importance of planning for aseamless transition in an adaptive phase II randomised trial. Trials 201112(Suppl 1):A7.

Warwick Clinical Trials Unit, University of Warwick, Coventry, West Midlands,CV4 7AL, UK

Marshall et al. Trials 2011, 12(Suppl 1):A7http://www.trialsjournal.com/content/12/S1/A7 TRIALS

© 2011 Marshall et al; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative CommonsAttribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction inany medium, provided the original work is properly cited.