A call for action: Comparative effectiveness research in asthma

Abstract

Comparative effectiveness research (CER) has received considerable research attention in recent months, and efforts to promote CER are part of the newly enacted Patient Protection and Affordable Care Act. In this paper, we define CER, how it complements traditional efficacy research in asthma, and discuss how CER can help provide the basis for rational decision-making about the care of individual patients with asthma and how best to deliver this care in real-world settings. We present information about the challenges and opportunities to conduct CER, including enhanced patient registries for observational CER and effectiveness trials (also called pragmatic trials). We discuss the urgent need to define the appropriate methodologies for CER and to develop and prioritize a research agenda for CER studies in asthma with the help of a diverse group of stakeholders. KeywordsComparative effectiveness research; comparative clinical effectiveness research; observational studies; effectiveness trials; efficacy trials; pragmatic trials; explanatory trials; asthma Randomized controlled trials are the gold standard by which the benefits and harms of treatments have been established, because this approach greatly minimizes the risk of confounding and avoids selection bias. Such studies have traditionally employed an efficacy paradigm in which various approaches are used to amplify the signal-to-noise ratio in order to address the question "Can this intervention work?" Such studies are critical to the development of innovative approaches to patient care. A hallmark of the efficacy trials is the application of narrowly defined inclusion and exclusion criteria to select study subjects. A recent study found, for example, that a median of 6% (range 0 to 43%) of patients treated for asthma met eligibility criteria for major trials cited in evidence-based treatment guidelines. 1 A high level of selectiveness is employed in efficacy trials to ensure that study subjects are enriched with patients most likely to benefit and least likely to be harmed by the study interventions. MC 6076, Room M644, Chicago, IL 60637, jkrishna@medicine.bsd.uchicago.edu,. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Another feature of efficacy trials is the conduct of such studies in a research environment that promotes uniform application of the intervention to study subjects, often by expert clinicians and in resource intensive settings. The National Heart, Lung, and Blood Institutesponsored AsthmaNet, for example, is a multi-center network led by Principal Investigators with established research prog...

Randomized controlled trials and real life studies. Approaches and methodologies: a clinical point of view.

“…In particular, tobacco smoking, concomitant diseases, adherence to treatment should be considered because it affects responsiveness to corticosteroids [29,38,39], the first choice treatment for asthma.…”

“…Elderly asthmatic patients are another group traditionally excluded from RCTs, even though this clinically relevant population experiences high rates of hospitalization and asthma related death [29,44,45]. Excluding such patients and, for example those with comorbidities, results in a lack of treatment solutions in exactly the groups where they could have high clinical impact [29,46].…”

“…Excluding such patients and, for example those with comorbidities, results in a lack of treatment solutions in exactly the groups where they could have high clinical impact [29,46].…”

“…The lack of patient selection, one of the most distinctive characteristics of real life studies, makes it impossible to avoid unmeasured confounding factors [11,29], while the absence of blinding and randomization does not always allow factors potentially influencing the outcomes to be properly balanced [14,53,101]. This is particularly true in studies with subjective outcomes, which can be influenced even by the patient's awareness of the treatment they are assigned to [24,30].…”

Translational Behavioral Research in Respiratory Medicine

“…The potential benefi ts of such research are a better understanding of the heterogeneity of treatment effects and how best to deliver care in real-world settings. 36 Recognizing the importance of this potential, the American Recovery Reinvestment Act of 2009 provided $1.1 billion in funding to support CER, and in 2010, the Patient Protection and Affordable Care Act included funding guidance for increased CER research.…”