[PD Test]COPD trials excluding the majority of would-be patient types

Health care practitioners should carefully gauge the suitability of data from clinical trials involving patients with chronic obstructive pulmonary disease (COPD), says one expert.

Translating clinical trial results into practice can be challenging, said Dr. Christine Jenkins, clinical professor at the Concord Clinical School at the University of Sydney in Australia.

Many patients with COPD are treated based on the results of randomized controlled trials (RCTs) that may not be applicable to them.

In a survey involving 749 adults from New Zealand, 117 were found to have COPD, of whom only 5 percent would have met inclusion criteria for a major COPD treatment RCT as recommended by Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines. [Respir Med 2007;101:1313-1320]

In other words, over 90 percent of COPD subjects who were taking medication were doing so based on trials for which they would not have been eligible, leading the researchers to suggest that GOLD treatment guideline-based COPD trials have limited external validity.

The same is true of non-pharmacokinetic therapy, Jenkins said, based on the number of patients who dropped out of randomized controlled pulmonary rehabilitation trials – up to 36 percent in intervention groups and up to 54 percent in control groups. [Clin Epidemiol 2010;2:73-83]

“We need to think about how we can include patients who truly represent the patients we look after so we can end up with a population … whom we’re going to give treatment to,” she said.

Because COPD is a heterogeneous disease, correlating changes in lung function as the disease progresses to patient outcomes can be challenging to measure comparatively. Forced expiratory volume (FEV1) can be useful as a static measure of lung function, but Jenkins pointed out that activity functions such as exercise capacity could be more useful for some patients.

Likewise, COPD exacerbations, although of divergent definition without objective criteria, have long been used to measure outcomes because they are potentially reducible. However, these can also cause patients to drop out of RCTs, reducing the effective trial population.

“Once we only recruit frequent exacerbators, are we excluding a whole population of COPD patients who we actually need to be intervening in and judging whether or not treatment is effective?” Jenkins said.

Some approaches to determining whether patients would benefit from treatments suggested by clinical trials would be to ask if diagnosis was confirmed among the patients in the study as well as the patient in question and whether the patient in question is aligned with the eligibility criteria and demographics of the study population.

Even if the patient would have been excluded from a particular trial, Jenkins pointed out that physicians can still consider the treatment and trial results for the patient, particularly when safety is not an issue.

Examining the characteristics of responders and non-responders to treatment can help to determine if the response would be clinically meaningful in a patient.