The need for increased pragmatism in cardiovascular clinical trials

Abstract

The majority of cardiovascular randomized controlled trials (RCTs) test interventions in selected patient populations under explicitly protocol-defined settings. Although these ‘explanatory’ trial designs optimize conditions to test the efficacy and safety of an intervention, they limit the generalizability of trial findings in broader clinical settings. The concept of ‘pragmatism’ in RCTs addresses this concern by providing counterbalance to the more idealized situation underpinning explanatory RCTs and optimizing effectiveness over efficacy. The central tenets of pragmatism in RCTs are to test interventions in routine clinical settings, with patients who are representative of broad clinical practice, and to reduce the burden on investigators and participants by minimizing the number of trial visits and the intensity of trial-based testing. Pragmatic evaluation of interventions is particularly important in cardiovascular diseases, where the risk of death among patients has remained fairly stable over the past few decades despite the development of new therapeutic interventions. Pragmatic RCTs can help to reveal the ‘real-world’ effectiveness of therapeutic interventions and elucidate barriers to their implementation. In this Review, we discuss the attributes of pragmatism in RCT design, conduct and interpretation as well as the general need for increased pragmatism in cardiovascular RCTs. We also summarize current challenges and potential solutions to the implementation of pragmatism in RCTs and highlight selected ongoing and completed cardiovascular RCTs with pragmatic trial designs.

Diversity, Equity, and Inclusion in Clinical Research: A Path Toward Precision Health for Everyone

“…Pragmatic trials, on the other hand, can provide methodological flexibility for research that may require intermediate balanced approaches, for instance minimizing analytical bias present in RWD studies, and still expand beyond the constraints of traditional clinical studies. 62 Evidence generated by digital technology wearables represents another avenue likely to push the traditional clinical research boundaries, and it is the ultimate approach to decentralization and "meeting study participants where they are." These technologies can enrich data sets that still rely on more traditional clinical measurements, or increasingly be the sole basis of full studies.…”

“…RWD can also trace longitudinal patient trajectories, shedding light on the full delivery of complex care across the continuum of diseases or conditions that a patient may experience. Pragmatic trials, on the other hand, can provide methodological flexibility for research that may require intermediate balanced approaches, for instance minimizing analytical bias present in RWD studies, and still expand beyond the constraints of traditional clinical studies 62 …”

The challenge of addressing heart failure in low and middle‐income countries

“…This is reassuring, in the sense that it confirms the validity of the KCCQ in reflecting the severity of heart failure, and that relieving congestion and alleviating symptoms should be the primary aim irrespective of the patients' country of origin. The correlation between HRQL and symptom severity may also enable the use of patient‐reported HRQL assessments as useful surrogate endpoints in pragmatic clinical trials 5 . In addition, the article directly and indirectly reflects the unique challenges in battling heart failure in LMICs.…”

“…The correlation between HRQL and symptom severity may also enable the use of patient-reported HRQL assessments as useful surrogate endpoints in pragmatic clinical trials. 5 In addition, the article directly and indirectly reflects the unique challenges in battling heart failure in LMICs. This is illustrated by the younger age, lower proportion of patients with health insurance and much worse clinical presentation of patients enrolled from LMICs compared to those enrolled from HICs.…”

Frequency of Anemia in Patients Admitted with Acute Decompensated Heart Failure in Tertiary Care Cardiac Hospital

“…In Pakistan the data is quite old but estimates a prevalence of 2.8 million people suffering from heart failure [3]. On the other due to better treatment facilities, mortality due to acute myocardial infarction and acute onset of cerebrovascular accident has reduced drastically because of available acute management strategies such as primary percutaneous coronary intervention (PPCI) [4][5][6]. The survival rate in patients with heart failure reduces each year from 75.9% at one year to 12.7% at 15 years [7].…”