Published in:
Open Access 01-12-2016 | Research Article
Testing for carryover effects after cessation of treatments: a design approach
Published in: BMC Medical Research Methodology | Issue 1/2016
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Background
Recently, trials addressing noisy measurements with diagnosis occurring by exceeding thresholds (such as diabetes and hypertension) have been published which attempt to measure carryover - the impact that treatment has on an outcome after cessation. The design of these trials has been criticised and simulations have been conducted which suggest that the parallel-designs used are not adequate to test this hypothesis; two solutions are that either a differing parallel-design or a cross-over design could allow for diagnosis of carryover.
Methods
We undertook a systematic simulation study to determine the ability of a cross-over or a parallel-group trial design to detect carryover effects on incident hypertension in a population with prehypertension. We simulated blood pressure and focused on varying criteria to diagnose systolic hypertension.
Results
Using the difference in cumulative incidence hypertension to analyse parallel-group or cross-over trials resulted in none of the designs having acceptable Type I error rate. Under the null hypothesis of no carryover the difference is well above the nominal 5 % error rate.
Conclusions
When a treatment is effective during the intervention period, reliable testing for a carryover effect is difficult. Neither parallel-group nor cross-over designs using the difference in cumulative incidence appear to be a feasible approach. Future trials should ensure their design and analysis is validated by simulation.