Gaining Efficiency in Clinical Trials With Cardiac Biomarkers

Biomarkers in heart failure clinical trials. A review from the Biomarkers Working Group of the Heart Failure Association of the European Society of Cardiology

“…Many biomarkers have been proposed to guide the diagnosis and management of HF 14 (Figure 1). Ibrahim and Januzzi summarized in five points the characteristics of an ideal HF biomarker: (1) the method by which a biomarker is judged should be thorough;…”

“…Cardiovascular disorders remain the leading cause of morbidity and mortality worldwide, but the pace of drug and device development is considerably slower than for other conditions such as neoplastic disorders. 1 A possible reason is the high cost of clinical trials adequately powered for hard clinical endpoints. Problems with trial design might be another issue, as 20% of drugs completing the phase 3 stage are not approved by the United States (U.S.) Food and Drug Administration (FDA), and only 6% of all novel cardiovascular drugs entering phase 1 are ultimately approved.…”

“…3 Indeed, biomarkers might facilitate the enrolment of patients who are most likely to respond to therapeutic intervention, despite still having the sufficient number of events to meet the trial endpoints. 1 A biomarker (from 'biological marker') has been defined as 'a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention'. 4 The analysis of circulating substances is the most common form of biomarker measurement, and has become widespread in clinical research.…”

“…7 Despite the almost exclusive focus on B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP), many biomarkers reflecting different elements of HF pathophysiology exist, [8][9][10][11] and the identification of specific biomarkers for each drug has been proposed. 1 Building on the FDA document and some authoritative papers, 1,6,12,13 this review article provides specific suggestions for biomarker use in HF clinical trials.…”

Dissecting miRNA–Gene Networks to Map Clinical Utility Roads of Pharmacogenomics-Guided Therapeutic Decisions in Cardiovascular Precision Medicine

“…It has also been shown that the biomarker application in clinical trials of cardiovascular new drug development is much smaller than in other medical specialties such as oncology. Moreover, the inconsistences identified upon the use of biomarkers in clinical trials of CVDs have recently sparked discussions about the creation of international guidance on quality assurance in the selection and reliability of biomarkers, sample type, collection times, analytical methods, and storage for future research [ 193 ]. Complementary to this, lack of supportive cost-effectiveness of pharmacogenomics implementation in the everyday care of CVDs has been identified, thus calling for further improvement of clinical trial environment [ 194 ].…”