External validity of randomized controlled trials in COPD.
BACKGROUND
COPD is a heterogeneous disease comprising a wide range of clinical phenotypes, depending on the degree to which emphysema, chronic bronchitis, reversible bronchospasm and small airways inflammation are present. Not all of these phenotypes may be represented among the subjects included in randomized controlled drug trials (RCTs) in COPD, making it difficult for doctors to know to what extent RCT evidence applies to individual patients. From a respiratory health survey of adults randomly selected from the community, we have estimated the proportion of subjects with COPD who would have been eligible for inclusion in major COPD RCTs.


METHODS
A postal survey was sent to 3500 randomly selected individuals aged 25-75 years. Respondents were invited to complete a detailed respiratory questionnaire and pulmonary function tests. Subjects with COPD defined by post-bronchodilator spirometry were assessed against the eligibility criteria of 18 major RCTs cited in the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines.


RESULTS
Of 749 subjects completing the full survey, 117 had COPD. Of these, a median of 5% (range 0-20%) of subjects met inclusion criteria for the major RCTs. Of 55 subjects with COPD receiving treatment, 0-9% (median 5%) met inclusion criteria for the major RCTs.


CONCLUSIONS
The major COPD RCTs on which the GOLD treatment guidelines are based may have limited external validity. Over 90% of the COPD subjects in the community who were taking medication, did so on the basis of RCTs for which they would not have been eligible.
Travers
Justin
J
Medical Research Institute of New Zealand, Wellington, New Zealand.
Marsh
Suzanne
S
Caldwell
Brent
B
Williams
Mathew
M
Aldington
Sarah
S
Weatherall
Mark
M
Shirtcliffe
Philippa
P
Beasley
Richard
R
D000328:Adult; D000368:Aged; D001993:Bronchodilator Agents / Q000627:therapeutic use; D004059:Diffusion of Innovation; D019317:Evidence-Based Medicine; D005541:Forced Expiratory Volume; D006801:Humans; D008875:Middle Aged; D018579:Patient Selection; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000503:physiopathology; D016032:Randomized Controlled Trials as Topic; D015203:Reproducibility of Results; D012129:Respiratory Function Tests; D012720:Severity of Illness Index
D001993:Bronchodilator Agents