Acting on Comparative Effectiveness Research in COPD

Abstract

COMPARATIVE EFFECTIVENESS RESEARCH (CER) HAS been defined by a report by the Federal Coordinating Council for Comparative Effectiveness as “the conduct and synthesis of research comparing the benefits and harms of different interventions and strategies to prevent, diagnose, treat, and monitor health conditions in ‘real world’ settings. The purpose of this research is to improve health outcomes by developing and disseminating evidence-based information to patients, clinicians, and other decision makers, responding to their expressed needs about which interventions are most effective for which patients under specific circumstances.” Comparative effectiveness research uses observational and clinical trial methods to compare different care strategies providedbytypicalhealthcareclinicians,addressingpossibleharms and benefits for heterogeneous patient populations in heterogenous health care settings. In contrast, traditional efficacy research compares treatment alternatives (including no treatmentorplacebo)incarefullyselectedpatientpopulationstreated inidealsettings.Thus,efficacyresearchanswersquestionssuch as“can this interventionwork?”whereasCERposesquestions morebroadly: “which interventionswhentranslated intopracticeimprovecareandincreasethelikelihoodofhealthbenefits?” The study reported by Lindenauer and colleagues in this issue of JAMA comparing the benefits and harms of lowdose oral corticosteroids and high-dose intravenous corticosteroids for patients hospitalized for exacerbations of chronic obstructive pulmonary disease (COPD), as well as an earlier publication from the same group examining the use of antibiotics, provide 2 examples of well-designed observational CER studies. Hospitalizations for COPD exacerbations are common complications associated with high morbidity and cost. Chronic obstructive pulmonary disease affects about 12 million to 24 million persons in the United States alone, leads to more than 500 000 hospitalizations each year, and results in $32 billion in health care expenditures. Further mortality from COPD is increasing, with COPD predicted to become the third leading cause of death in this decade. The efficacy of systemic corticosteroids (vs placebo) for the treatment of COPD exacerbations is well established. A metaanalysisofrandomizedcontrolledtrialsincludingapproximately 1000patientswithCOPDexacerbations (includingabout700 hospitalizedforCOPDexacerbations) foundthatsystemiccorticosteroids are associated with substantial benefit, including a reduction of approximately 50% in the combined end point of treatment failures, suchas treatment intensification, rehospitalization, and death. However, use of systemic corticosteroids was associated with a 2-fold increase in the risk of drug-relatedadverseeffectscomparedwithplacebo, including hyperglycemia, increasedappetite,weightgain, and insomnia. Multiple treatment guidelines recommend systemic corticosteroids for the treatment of COPD exacerbations. Although these guidelines acknowledge that data are insufficient to define the optimal dose or route of systemic corticosteroids, treatment recommendations suggest the use of oral corticosteroids at prednisone equivalent doses of 30 to 40 mg/d rather than higher intravenous doses. Oral corticosteroids are simpler to administer, are highly bioavailable, and therefore are likely to be as effective, and higher doses are more likely to result in adverse events. In this context, the study by Lindenauer et al provides new evidence. The investigators conducted an observational comparative effectiveness study using a registry linking administrative and billing data sets from about 80 000 hospitalizations for COPD exacerbations in more than 400 US hospitals. Hospitalized patients initially admitted to intensive care units were excluded. Illustrating the utility of linked registries, investigators found that clinicians in these real-world settings were much more likely to administer high-dose intravenous systemic corticosteroids (average 600 mg/d of prednisone equivalent) than administer low-dose oral corticosteroids (average60mg/dprednisoneequivalent) as initial therapy(92% and 8%, respectively). Thus, the real-world practice was largely inconsistent with current guideline recommendations to use lower doses of corticosteroids administered orally. Basedonanalysesusingsophisticatedmodeling techniques to control for possible confounding and selection bias, the in-