Real-world studies: bridging the gap between trial-assessed efficacy and routine care

Abstract

Even though randomized controlled clinical trials (RCTs) have been accepted as the gold standard for official assessment of novel interventions, there is a substantial gap between the efficacy observed in RCTs and the impact on clinical practice and in terms of patient benefit. While real-world studies (RWS) are emerging to confer valuable complementing evidence in this regard and beyond, the evolving role of RWS is yet to be agreed. This article delineates an updated profile of RWS covering effectiveness verification, rare adverse effects discovery, indication repurposing, to name a few. RWS tends not only to improve the efficiency of clinical investigations for regulatory approval, but also optimizes the whole-life cycle evaluation of biomedical/pharmaceutical products.

Untoward immune effects of modern medication

“…While autoimmunity signs of relevant organ pathology resulting from ICIs need to be mindfully monitored, medical management of these irAEs varies according to individual clinical grades [ 24 , 26 ] . Of note, the antibodies against the programmed cell death 1 (PD-1) receptor and its ligand (programmed death ligand 1, PD-L1) cause a lower incidence of any grade irAEs than the antibodies against cytotoxic T-lymphocyte antigen-4 (CTLA-4) do [ 9 , 24 ] . Intriguingly, whereas the mechanisms behind various mucocutaneous lesions upon treatment with differential anti-epithelial growth factor receptor (EGFR) are yet to be elucidated, a cellular immunity-based pathogenesis has been proposed [ 27 ] .…”

“…Over the past two decades, the biomedical landscape has been highlighted by the dramatic emergence of cellular therapy products, such as adaptive immune cells and stem cells, addressing unmet clinical needs of life-threatening illnesses [ 4 – 5 ] . In parallel, it is worth noting that the clinical application of these emerging biological products also comes with a high morbidity of irAEs because of bearing numerous cellular antigens and their potentially comprehensive immune mechanisms of action [ 5 , 9 ] . For example, chimeric antigen receptor T (CAR-T) cell therapy has achieved curative success in treating certain types of refractory hematological malignancies [ 4 ] .…”

“…While novel categories of medications, such as RNA formulations and viral vector-bearing agents, increasingly enter the landscape of the medical market, unwanted immunogenicity is continuously evolving to face clinical practice, pharmaceuticals, and regulatory assessment [ 4 , 8 ] . Moreover, along with real-world data accumulated through post-marketing surveillance, the emerging aberrant immunity-linked adverse events need to be timely monitored for certain existing drugs [ 9 ] . Therefore, the current study presents an updated profile of untoward immune effects for major representative types of biomedical products, with the pathogenesis mechanisms to inspire pharmaceutical mitigation ( Fig.…”

Machine Learning Methods in Real-World Studies of Cardiovascular Disease

“…The importance of RCTs with large sample sizes is well-recognized. Although RCTs generate the most credible and highest-level evidence for assessing the prevention and treatment effects of CVD, their applications are limited by cost, duration, lack of generalizability, ethical concerns, and technical feasibility [10,11].…”

Digital Health and Big Data Analytics: Implications of Real-World Evidence for Clinicians and Policymakers

“…Indeed, the successful implementation of EHRs in institutions across the globe has opened a novel research era with new challenges for the scientific medical research community. Even in comparison to randomized controlled clinical trials (RCTs), RWE studies are emerging as a post-market surveillance approach to confer valuable complementing evidence specially aiming to identify rare adverse events or long-term effects of existing drugs due to their potential to analyze larger patient populations across longer timelines [ 6 , 7 , 8 ]. Recently our group has been exploring the usefulness of RWD and RWE in several fields of medicine, namely in studying the prevalence of heart failure, type 2 diabetes mellitus, chronic kidney disease, to name a few [ 9 , 10 ].…”