Study design (if review, criteria of inclusion for studies)
Randomized, placebo-controlled trial
Participants
260 participants with CF and pulmonary exacerbations (PEs, defined using a priori criteria).
Interventions
Antibiotic therapy. Physician initiated antibiotic therapy (PIT) not meeting the PE endpoint was characterized and its impact on treatment effect assessed.
Outcome measures
Courses of PIT in the absence of a PE (not fulfilling the PE definition).
Main results
40% (104/260) of participants were prescribed 188 courses of PIT in the absence of a PE; 19% (25/129) of placebo and 10% (13/131) of AZ participants received >/=2 courses of PIT and never fulfilled the PE definition (9% difference,95% confidence interval:1%,18%,p=0.04). Accounting for PIT through use of a composite endpoint including time to PE or need for repeated PIT altered treatment effect estimates (a 56% reduction in the event rate comparing AZ to placebo [p<0.0001] as compared to a 50% reduction not accounting for PIT [p=0.003]).
Authors' conclusions
PIT is common in CF and may impact treatment effect estimates. Optimization of the PE endpoint to include meaningful events necessitating treatment may improve our ability to conduct efficient trials by reducing sample size 30-50%, ultimately enabling rapid evaluation of new therapies.