OBJECTIVES

Use value of information methods to compare the economic value to the UK National Health Service (NHS) of an adaptive trial design with a conventional design on interventions for the prevention of surgical site infections (SSI).

METHODS

We developed a decision tree to compare the cost-effectiveness of simple dressing, tissue adhesive as a dressing, and no dressing for the prevention of SSIs following surgery from the perspective of the UK NHS. Relative effectiveness of preventing SSI was based on a network meta-analysis of 22 trials.

We used the decision tree to estimate the expected value of sample information (EVSI) of a conventional 3-arm trial comparing simple dressing, no dressing, and tissue adhesive in 2500 patients with 2:2:1 allocation ratio. This trial had a 5% type-1 error rate and 10% type-2 rate. We compared this with a 3-arm 2-stage trial with an interim futility calculation on the first 1250 patients deciding whether to drop the no dressing and/or tissue adhesive arms. We used a genetic algorithm to choose the optimal futility bounds for this design while preserving type-1 and type-2 error rates. Optimality was defined as the design minimising the average of the expected sample size (ESS) under the global null hypothesis and the maximum possible sample size. A lower ESS indicates fewer patients unnecessarily randomized and a reduced trial cost. We calculated the EVSI of this optimal design.

RESULTS

The conventional design with 2500 patients had a per-person EVSI for of £112 for the NHS. The optimal design had a per-person EVSI of £108 and an ESS of 1753 under the global null hypothesis, representing a roughly 30% reduction in required patients.

CONCLUSIONS

Adaptive trial designs, and specifically multi-stage designs, can achieve similar EVSI to conventional designs while exposing fewer patients to unnecessary randomization and with lower cost.