The effect of COPD severity and study duration on exacerbation outcome in randomized controlled trialsEriksson, G., Calverley, P. M., Jenkins, C. R., Anzueto, A. R., Make, B. J., Lindberg, M., Fageras, M. & Postma, D. S., 15-May-2017, In : International Journal of Chronic Obstructive Pulmonary Disease. 12, p. 1457-1468 12 p.
Research output: Contribution to journal › Article › Academic › peer-review
Background: When discontinuation in COPD randomized controlled trials (RCTs) is unevenly distributed between treatments (differential dropout), the capacity to demonstrate treatment effects may be reduced. We investigated the impact of the time of differential dropout on exacerbation outcomes in RCTs, in relation to study duration and COPD severity.
Methods: A post hoc analysis of 2,345 patients from three RCTs of 6-and 12-month duration was performed to compare budesonide/formoterol and formoterol in moderate, severe, and very severe COPD. Outcomes were exacerbation rate, time-to-first exacerbation, or discontinuation; patients were stratified by disease severity. Outcomes were studied by censoring data monthly from 1 to 12 months.
Results: In patients treated with budesonide/formoterol, annualized exacerbation rates (AERs) were comparable for each study duration (rate ratio [RR] = 0.6). With formoterol, the AER decreased with study duration (RR = 1.20 at 1 month to RR = 0.86 at 12 months). There was a treatment-related difference in exacerbation rates of 45%-48% for shorter study durations (
Conclusions: COPD severity and study duration impact exacerbation as an outcome in double-blind RCTs. This effect is most obvious in patients with severe/very severe COPD and in studies that are longer than 4 months. Early differential dropout particularly impacts study outcome, producing a "healthy survivor effect," which reduces estimations of treatment impact on exacerbations.
|Number of pages||12|
|Journal||International Journal of Chronic Obstructive Pulmonary Disease|
|Publication status||Published - 15-May-2017|
- healthy survivor effect, exacerbation outcomes, early differential dropout, RCT, disease severity, OBSTRUCTIVE PULMONARY-DISEASE, METERED-DOSE INHALER, PREMATURE DISCONTINUATION, CLINICAL-TRIAL, DOUBLE-BLIND, FLUTICASONE, WITHDRAWAL, EFFICACY, BUDESONIDE/FORMOTEROL, PROPIONATE