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

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. Aim: To calculate 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 25-75 years. Respondents were invited to complete a detailed respiratory questionnaire and pulmonary function testing. Participants 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 participants completed the full survey, of whom 179 had current asthma. A median 4% of participants with current asthma (range 0-36%) met the eligibility criteria for the included RCTs. A median 6% (range 0-43%) of participants with current asthma on treatment met the eligibility criteria. Interpretation: This study shows 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. Most of the participants with current asthma on treatment in the community would not have been eligible for these RCTs.

Patterns of airway disease and the clinical diagnosis of asthma in the Busselton population

“…Additional phenotypic analysis, such as assays of interleukin-6 or transforming growth factor-b which appear to segregate with acquired and innate immune responses, may further advance the understanding of the airway phenotype-genotype relationships and may help to guide treatment with the advent of novel specific therapies in the future [32]. Similarly, more precise differentiation of the underlying physiological abnormalities or the morphological information provided by (highresolution) computed tomography could better guide therapy and genetic investigation (especially of COPD).…”

Azithromycin for Bronchial Asthma in Adults: An Effectiveness Trial

“…39 Standard exclusion criteria in adult asthma efficacy trials include restricted age ranges, pulmonary function parameters, current and previous smoking, and lung comorbidities such as coexisting COPD. 4,5 As a result, 95% of asthma subjects have been systematically excluded from the trials used to support guideline recommendations. 4,5 Thus, asthma efficacy trials and the guidelines derived from them may not generalize well to the broader population of asthma sufferers.…”

“…On average, 19 of 20 people with physician-diagnosed asthma were excluded from the clinical research 4,5 and more than half of adults with asthma may remain poorly controlled, even when they are treated. 6 Thus, it is important to test therapies for asthma in generalizable effectiveness trials.…”

De bindende kracht van een universeel specialisme

“…Vaak moeten honderden patiënten gescreend worden om met de grootste moeite enkelen te vinden die aan alle selectiecriteria van de trial voldoen. 26 Bovendien wordt er scherp op gelet dat de patiënten het middel innemen, terwijl in het 'normale' leven meer dan de helft wel eens vergeet zijn medicijnen in te nemen. 27 Zo komt het dat registratietrials die door de industrie gesponsord zijn vaak een gunstiger uitkomst hebben dan vergelijkbaar geneesmiddelenonderzoek dat uit andere bronnen is gefinancierd.…”