New clinical trial designs for establishing drug efficacy and safety in a precision medicine era

Abstract

Despite advances in pharmacotherapy, diabetic kidney disease (DKD) remains associated with a high burden of micro‐ and macrovascular complications often leading to premature mortality. New therapies are highly desirable to mitigate the burden of this disease. However, there are a number of barriers that hamper drug development in DKD. These include, amongst others, the lengthy and complex clinical trials required to prove drug efficacy and safety, inefficiencies in clinical trial conduct, and the high costs associated with these development programs. In this review a number of aspects are discussed, aiming to identify opportunities to transform and innovate drug development for DKD. Many clinical trials in DKD, as well as in other areas, face difficulties in timely and efficient enrolment of participants. To address this issue a network of sites should be created that are continuously recruiting individuals with DKD and collecting crucial information that can be used to understand prognosis and prognostic factors, and more importantly to serve as a pool of participants for recruitment to randomized trials. Second, the current clinical endpoints are late events in the progression of DKD. Endpoints based on lesser declines in estimated glomerular filtration rate (eGFR) or changes in albuminuria can shorten follow‐up and/or lead to smaller and cheaper trials. Enrichment by enrolling clinical trial populations based on biomarker profiles is another approach that may facilitate clinical trial efficiency and conduct. Biomarkers can be used to individualize treatment by targeting populations more likely to respond leading to smaller and more efficient trials. Finally, using new trial design such as basket, umbrella or more broadly platform trials to assess a number of therapies simultaneously offers the potential to transform the drug development process in DKD. There are a number of opportunities to transform development approaches for new therapies for DKD. Platform trials along with appropriate biomarker‐based enrichment strategies offer the possibility to foster drug development in a precision medicine era.

Pleiotropic effects of liraglutide in patients with type 2 diabetes and moderate renal impairment: Individual effects of treatment

“…Individual characteristics may influence the magnitude of the treatment response to liraglutide . We showed that a high baseline level of HbA1c, SBP and LDL‐cholesterol was associated with a greater response in the corresponding variable.…”

Recent Advances in Enabling Technologies in 3D Printing for Precision Medicine

“…In addition to these efforts, advanced clinical trial designs may help with translation for precision medicine. Different trial types, such as umbrella, basket or platform trials, can offer the framework needed for segmentation of patients during clinical trials, as well as methods to test multiple therapies in parallel to decrease costs …”

“…Different trial types, such as umbrella, basket or platform trials, can offer the framework needed for segmentation of patients during clinical trials, as well as methods to test multiple therapies in parallel to decrease costs. [134] www.advmat.de www.advancedsciencenews.com…”

Precision medicine in diabetes and diabetic kidney disease: Regulatory considerations

“…There is a caveat though, that is that these enrichment designs may be non‐informative on the biomarker‐negative population . As described elsewhere in this issue of the Journal, platform, basket and umbrella trials may offer additional innovative study designs for evidence generation in the setting of precision‐medicine . In addition, observational “real‐world” data may be increasingly considered to provide further evidence postapproval .…”