Bedside–to-Bench Translational Research for Chronic Heart Failure: Creating an Agenda for Clients who do Not Meet Trial Enrollment Criteria

Abstract

Congestive heart failure (CHF) is a chronic condition usually without cure. Significant developments, particularly those addressing pathophysiology, mainly started at the bench. This approach has seen many clinical observations initially explored at the bench, subsequently being trialed at the bedside, and eventually translated into clinical practice. This evidence, however, has several limitations, importantly the generalizability or external validity. We now acknowledge that clinical management of CHF is more complicated than merely translating bench-to-bedside evidence in a linear fashion. This review aims to help explore this evolving area from an Australian perspective. We describe the continuation of research once core evidence is established and describe how clinician–scientist collaboration with a bedside-to-bench view can help enhance evidence translation and generalizability. We describe why an extension of the available evidence or generating new evidence is occasionally needed to address the increasingly diverse cohort of patients. Finally, we explore some of the tools used by basic scientists and clinicians to develop evidence and describe the ones we feel may be most beneficial.

Heart Failure in Minority Populations - Impediments to Optimal Treatment in Australian Aborigines

“…Basic (Bench) Research: We have previously highlighted biomarkers, pharmaceuticals with extra class effects and genetics in the cardio-renal-metabolic axis as priorities [ 93 ]. It could be an avenue to fine-tune existing evidence to ensure greater external appeal or find new evidence to take to the bedside.…”

Phase 4 Studies in Heart Failure - What is Done and What is Needed?

“…‘Translation’, as defined by The National Center for Advancing Translational Sciences (NCATS), is the process that brings the bench observation into the clinical domain to help improve the health of individuals and their communities, and encompasses all facets from, diagnostics, therapeutics, to medical procedures and even behavioral changes. At the heart of all this is the search for efficacy, effectiveness and quality [ 1 , 2 , 15 - 18 ]. Box 1 explores these steps in greater detail.…”

“…It is our view that preclinical studies should be viewed twofold: firstly, studies that bring a novel therapy into the clinical domain (mainly industry); and secondly, studies that evolve from new hypothesis following post-marketing surveillance (mainly academia). This type of indication can form the basis for equivalence studies or expansion of an indication of drug within a class [ 15 , 16 , 26 - 33 ].…”

A Review of the External Validity of Clinical Trials with Beta-Blockers in Heart Failure

“…Phase IV trials, which involve postmarketing surveillance of the uncontrolled treatment of a patient population, are needed to advance understanding of external validity. [3][4][5] In this review, we have focused on patient demographics, diabetes mellitus (DM), chronic renal failure (CRF), and atrial fibrillation in CHF. Pathophysiological variations in responses to treatments are seen for the following factors: doses (eg, statin doses and Asian patients), class of agents used (eg, benefits of nitrates and hydralazine for CHF in African A Review of the External Validity of Clinical Trials with Beta-Blockers in Heart Failure American patients), 6 or a particular agent within a class (eg, the lack of effect of bucindolol in African American patients).…”

“…Phase IV trials, which involve postmarketing surveillance of the uncontrolled treatment of a patient population, are needed to advance understanding of external validity. 3–5…”