The importance of real-world studies of chronic diseases and conditions

In one of the first real-world studies of newly diagnosed Chronic Obstructive Pulmonary Disease (COPD) patients, Carelon Research sought to estimate the magnitude and duration of risk of cardiovascular events and death following COPD exacerbations and determine whether risks varied by number and severity of exacerbation. Researchers found an increased risk of death and cardiovascular events that persisted for up to two years following moderate and severe exacerbations and increased with each exacerbation.  

While randomized controlled trials are viewed as the gold standard for studying causal effects, real-world observational studies like this one offer the ability to follow larger populations of patients for longer periods of time to study rare, serious health outcomes, and can examine exposures that are difficult to randomize, such as COPD exacerbations. Automated databases often used in real-world studies, such as the Healthcare Integrated Research Database (HIRD®), can be linked electronically to a variety of other databases, including the National Death Index, to give a comprehensive view of serious adverse events.

Because cardiovascular events and all-cause mortality are rare among newly diagnosed COPD patients, answering the research question required a large population with several years of follow-up. This study was able to follow many patients for over three years and generate estimates of increased risk after the acute exacerbation subsided.  

While randomization is the gold standard for creating balanced comparison groups, not all exposures can be randomly assigned. In this study, the exposure of interest was an acute exacerbation of COPD. Patients experiencing exacerbations are different from those who do not, and careful analytic techniques are needed to disentangle extraneous effects such as disease severity. Real-world data provides extensive medical and prescription history as well as demographic characteristics that can be integrated into statistical techniques that demonstrate good comparability.   

The richness of real-world data in the HIRD can be expanded through deterministic and probabilistic linkage of identifiable databases such as disease and mortality registries. This capability broadens the real-world evidence horizon beyond what is possible using only healthcare claims. Neither all-cause mortality nor cardiovascular mortality can be reliably ascertained from healthcare claims. In this study, experts linked the claims database to the National Death Index to identify all-cause mortality and deaths due to cardiovascular events to uncover serious persistent risks.  

Data from the American Community Survey was also linked to the HIRD to study subsets of the patient population by neighborhood income and urbanicity. This capability allowed researchers to drill down to specific populations that may be at higher risk and better understand which patients are most in need of long-term monitoring and continuity of care.  

This study exemplifies how real-world evidence can complement clinical trials and offer unique insights that can improve patient care. At Carelon Research, we are excited to contribute to the rapidly expanding and novel applications of real-world evidence in improving patient care.