Rationalizing endpoints for prospective studies of pulmonary exacerbation treatment response in cystic fibrosis.
J Cyst Fibros
; 16(5): 607-615, 2017 09.
Article
in En
| MEDLINE
| ID: mdl-28438499
ABSTRACT
BACKGROUND:
Given the variability in pulmonary exacerbation (PEx) management within and between Cystic Fibrosis (CF) Care Centers, it is possible that some approaches may be superior to others. A challenge with comparing different PEx management approaches is lack of a community consensus with respect to treatment-response metrics. In this analysis, we assess the feasibility of using different response metrics in prospective randomized studies comparing PEx treatment protocols.METHODS:
Response parameters were compiled from the recent STOP (Standardized Treatment of PEx) feasibility study. Pulmonary function responses (recovery of best prior 6-month and 12-month FEV1% predicted and absolute and relative FEV1% predicted improvement from treatment initiation) and sign and symptom recovery from treatment initiation (measured by the Chronic Respiratory Infection Symptom Score [CRISS]) were studied as categorical and continuous variables. The proportion of patients retreated within 30days after the end of initial treatment was studied as a categorical variable. Sample sizes required to adequately power prospective 11 randomized superiority and non-inferiority studies employing candidate endpoints were explored.RESULTS:
The most sensitive endpoint was mean change in CRISS from treatment initiation, followed by mean absolute FEV1% predicted change from initiation, with the two responses only modestly correlated (R2=.157; P<0.0001). Recovery of previous best FEV1 was a problematic endpoint due to missing data and a substantial proportion of patients beginning PEx treatment with FEV1 exceeding their previous best measures (12.1% >12-month best, 19.6% >6-month best). Although mean outcome measures deteriorated approximately 2-weeks post-treatment follow-up, the effect was non-uniform 62.7% of patients experienced an FEV1 worsening versus 49.0% who experienced a CRISS worsening.CONCLUSIONS:
Results from randomized prospective superiority and non-inferiority studies employing mean CRISS and FEV1 change from treatment initiation should prove compelling to the community. They will need to be large, but appear feasible.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Respiratory Tract Infections
/
Randomized Controlled Trials as Topic
/
Outcome Assessment, Health Care
/
Endpoint Determination
/
Cystic Fibrosis
/
Anti-Bacterial Agents
Type of study:
Clinical_trials
/
Diagnostic_studies
/
Etiology_studies
/
Guideline
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Adult
/
Female
/
Humans
/
Male
Language:
En
Journal:
J Cyst Fibros
Year:
2017
Document type:
Article