Representativeness of the patient population in randomized controlled trials vs. real world data including disease registries and effectiveness and safety of medication in subgroups.
To enable use of real-world data (RWD) to assess effectiveness and safety in subgroups of patients who are poorly represented in randomized controlled trials (RCTs).
A concern of randomised controlled clinical trials is an underrepresentation of specific (sub)groups, such as women, people with a race/ethnicity other than Caucasian, elderly, people with comorbidity, and people with low social economic status. In the most recent trials of for instance patients with heart failure with reduced ejection fraction (PARADIGM-HF, DAPA-HF, EMPEROR-Reduced, GALACTIC-HF and VICTORIA) less than a quarter of the study population was female, there were almost no patients >80 years old, <3% had New York Heart Association class IV (severe symptoms), and severe kidney disease and cancer were exclusion criteria in most cases. This also leads to low representation of patients with multiple comorbidities, frailty, and receiving polypharmacy. These patients do not represent a minority in the real-world heart failure population but are those more often seen in the clinics. Currently, there is distrust in registry-based studies with regards to the reliability of study outcomes, i.e., ability to address confounding and concern of transparency by regulators and HTAs. To address confounding, adequate epidemiological measures such as propensity score matching will be applied in our studies. In this case study, we will further test – independently – if more state-of-the-art methods, such as the ‘target trial emulation designs’ lead to more reliable outcomes that align better with RCT results. This case study will focus on recently approved drugs in heart failure and will answer how effectiveness and safety estimates may be impacted in subgroups of patients who are poorly represented in RCTs. A network meta-analysis will provide further insight into relative effectiveness of drugs and provide information that is important for HTA/payer decision-making.
Swedish Heart Failure registry (SwedeHF) (www.swedeHF.se)
