Pragmatic trials for asthma and COPD
How we design clinical trials for asthma and COPD - and how much of our research results from tightly-controlled studies that may not reflect everyday reality in the clinic and community - gets my vote for most underappreciated problem.
As I posted recently, in the case of asthma, a 2011 NEJM paper reported that eligibility criteria in most RCT treatment trials excluded an estimated 95% of patients with a current diagnosis of asthma.
Now we have a good analysis of the situation in COPD. A brand new paper in AJRCCM, titled Prognosis of Patients with Chronic Obstructive Pulmonary Disease Not Eligible for Major Clinical Trials, analyzed a large community database from Copenhagen and found that more than half of individuals with COPD would be excluded from major clinical trials when applying commonly-used eligibility criteria.
Randomized controlled trials primarily study whether an intervention works and therefore require the important outcomes (eg exacerbations) occur with some frequency. As a result, sponsors design trials to select individuals more likely to experience such outcomes in a reasonable time period. But this raises questions about whether results also apply to the less severe population commonly encountered in clinical practice.
These Danish data show the entry criteria for RCTs working as designed. But the flip side is that the majority of people with COPD would not be allowed to enter treatment trials. As one example, 35% of the ineligible COPD participants had a history of comborbid asthma. Others had a smoking history of less than 10 years.
The paper shows that such people go on to experience severe exacerbations and are more likely to die. In short, over time, this illness is not trivial even among those not considered clinically severe enough to be included in a trial.
All of this is summed up well in an accompanying editorial, Understanding the People Excluded from Chronic Obstructive Pulmonary Disease Clinical Trials, by Jamuna Krishnan and Peter Calverley.