External validity of randomised controlled trials in asthma: to whom do the results of the trials apply?

Justin Travers ¹, Suzanne Marsh ¹, Mathew Williams ¹, Mark Weatherall ², Brent Caldwell ¹, Philippa Shirtcliffe ¹, Sarah Aldington ¹ and Richard Beasley ^1*

¹ Medical Research Institute of New Zealand, New Zealand
² Wellington School of Medicine & Health Sciences, New Zealand

^* To whom correspondence should be addressed. E-mail: richard.beasley{at}mrinz.ac.nz.

Accepted 9 October 2006

Abstract

Background: Asthma is a heterogeneous disease with a wide range of clinical phenotypes, not all of which may be encompassed in the subjects included in randomised controlled trials (RCTs). This makes it difficult for clinicians to know to what extent the evidence derived from RCTs applies to a given patient. We have calculated the proportion of individuals with asthma who would have been eligible for the major asthma RCTs from the data of a random community survey of respiratory health.

Methods: A postal survey was sent to 3500 randomly selected individuals aged 25 to 75 years. Respondents were invited to complete a detailed respiratory questionnaire and pulmonary function testing. Subjects with current asthma were assessed against the eligibility criteria of the 17 major asthma RCTs cited in the Global Initiative for Asthma (GINA) guidelines.

Findings: A total of 749 subjects completed the full survey of whom 179 subjects had current asthma. A median 4% of subjects with current asthma (range 0 to 36%) met the eligibility criteria for the included RCTs. A median 6% (range 0 to 43%) of subjects with current asthma on treatment met the eligibility criteria.

Interpretation: This study demonstrates that the major asthma RCTs on which the GINA guidelines are based may have limited external validity as they have been performed on highly selected patient populations. The majority of subjects with current asthma on treatment in the community would not have been eligible for these RCTs.

Keywords: asthma, exclusion criteria, external validity, generalisability, randomised controlled trial

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