COPD Treatment in Real Life and Randomized Controlled Trials: Is There Any Difference between Both Settings?

Abstract

EditorialIn the last decade, for treatment of patients with chronic obstructive pulmonary disease (COPD) a myriad of new medications, mostly administered in new inhalation devices were introduced on the market. In addition, All, but one (Roflumilast) of these "new" drugs rely on old and well proven principles of long acting bronchodilation. Nonetheless, for gaining regulatory approval many randomized controlled trials (RCT's) were accomplished for long-acting beta2 agonists (LABA's) and long-acting anticholinergics (LAMA's) and their fixed combinations, respectively, Inhaled corticosteroids (ICS) as anti-inflammatory therapy are available on the market for a long time, but their indication for COPD is controversial [1,2] and new fixed combinations emerged. Hence even more RCT's for pharmacological treatment of COPD were recently completed. Therefore, enough high grade evidence from RCT's should exist for pharmacological treatment of COPD patients.For efficacy of a treatment for a given indication, RCT's are generally considered as the gold standard study design. In other words, they have the highest internal validity. On the other hand, the external validity of the above mentioned RCT's is highly biased by low external validity, i.e. effectiveness of the treatment in a large "real life" population. This is due to several well-known factors. Strict inclusion and exclusion criteria in RCT's apply to a small minority of real life patients with COPD. This proportion can be as low as 5% [3,4]. For example the most delicate patients with co-morbidities are mostly excluded. Severity distribution of in RCT included patients can also differ from real life cohorts. Probably a much less recognized fact is, that outcome targets of pivotal trials, in COPD usually exacerbations and FEV1 are determined by regulatory authorities, i.e. Food and Drug Administration (FDA) and European Medicine Agency (EMA). Symptoms like dyspnoea, cough, exercise capacity, and other important patient related outcomes are frequently not proven. Moreover, persistence on treatment and real life treatment adherence cannot be tested in RCT's. What are, if any, the alternatives?Register studies are retrospective in nature and use data from electronic healthcare registries. They are large and observational, but register data are seldom complete and often miss disease severity and symptoms. Moreover, robustness of register diagnoses is questionable and in COPD important information on smoking habits is usually missing.The "A two-year evaluation of the 'real life' impact of COPD on patients in Germany: The DACCORD observational study" published in Respiratory Medicine 2017 [5] will add to fill the gaps of RCT's and register studies. DACCORD (Die ambulante Versorgung mit langwirksamen Bronchodilatatoren: COPD Register in Deutschland, English translation: Outpatient Care with Long-Acting Bronchodilators: COPD Registry in Germany) is an ongoing observational, non-interventional study being conducted in almost 500 German primary and secondary care centres. Thi...