Wielding the Double-Edge Sword of Cardiac Biomarkers in Clinical Trials: A Discussion with Dr. James Januzzi, MD

Validated cardiac biomarkers have been instrumental in drug and device development for the last several decades and have accelerated market approval by the regulatory authorities. Yet despite the salutary effects of biomarker utilization in cardiovascular clinical trials, inconsistencies in biomarker application and interpretation in clinical trials have hindered the realization of its full impact and arguably contributed to a stagnation of new drug development in cardiovascular disease, at a time when the need for new therapies is at an unprecedented peak.

In cardiovascular trials, surrogate biomarkers often appear in different regalia, as clinical endpoints, for eligibility criteria, and/or for safety monitoring. On the one hand, cardiac biomarkers may be used to help precisely carve out the right study population with surgical precision. On the other hand, biomarkers, if used inappropriately, may bluntly and inefficiently whittle the trial population and objectives.

Determination of appropriate study endpoints is the backbone of any drug development program. Cardiovascular clinical research requires a precise approach to ensuring that study targets are met. Thus, carefully planned applications of each biomarker must be clearly outlined at the start of development and should be used in conjunction with functional and quality of life endpoints to measure safety and efficacy of new therapeutic options.

Selecting appropriate biomarkers and thresholds for patient eligibility and patient safety monitoring throughout the course of a clinical trial can improve the efficiency of the study, duration of study enrolment, and enhance selection of the most appropriate trial population. Cardiac biomarkers, when used in conjunction with standard safety assessments can help to pinpoint safety concerns or identify markers of trial success.

Speakers

James Januzzi, MD, Hutter Family Professor of Medicine, Harvard Medical School

James L. Januzzi, MD, is the Hutter Family Professor of Medicine at Harvard Medical School, a staff cardiologist at Massachusetts General Hospital, and Senior Cardiometabolic Faculty at Baim Institute for Clinical Research. He is an experienced, world-renowned clinician, teacher and clinical trialist.  His research has focused on the understanding of cardiac biomarker testing as it pertains to diagnosis, prognosis, and therapy intervention in various forms of heart disease, including heart failure and acute myocardial infarction.  Dr Januzzi has deep experience in clinical trial design and execution; he has been previously involved in numerous pivotal multicenter trials for drugs and devices, and is presently involved in trials of therapies for heart failure and diabetes.  He has published more than 650 manuscripts, book chapters and review articles, and has edited six text books on cardiac biomarker testing. He is an Associate Editor at JACC as well as JACC Heart Failure, and serves on the editorial board of numerous scientific journals.  He is currently a Trustee of the American College of Cardiology. He earned his MD from New York Medical College. 

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Richard Lee, MD, Senior Medical Director, Medical Department

Dr. Richard S. Lee is a board-certified cardiothoracic surgeon with an extensive background in a full range of adult cardiac surgery, including valve repair and replacement, coronary artery bypass grafting, aortic aneurysm surgery, surgery for atrial fibrillation, and transcatheter aortic valve replacement. Dr. Lee graduated summa cum laude from Yale University with a degree in Molecular Biophysics and Biochemistry. After graduating, he earned his medical degree, cum laude, from Harvard Medical School in Boston Massachusetts. He completed a residency in general surgery at Massachusetts General Hospital as well as a residency in cardiothoracic surgery from Stanford University Medical Center in California. He has solid research experience in transplantation immunology. Dr. Lee has been board certified in cardiothoracic surgery since 2007.

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Liz Moore, DNP, MSN, CPNP-AC, CPN, Advanced Clinical Practitioner Manager, Medpace

Dr. Moore is a board-certified acute care pediatric nurse practitioner with more than ten years of clinical experience in the acute care setting at Cincinnati Children’s Hospital. As a bedside nurse in a Level IV NICU, Ms. Moore managed the care of critically ill infants with infantile, surgical, and pediatric rare diseases. As a Nurse Practitioner, Ms. Moore was a provider in the CICU to patients within the full spectrum of cardiac indications, including both pediatric and adult congenial heart diseases, heart and lung transplant, and device. Since joining Medpace, her clinical trial experience has been focused on indications within cardiology, pediatrics, and rare disease including cardiomyopathy, arrhythmia, PAH, metabolic disease, and cardiac device. Ms. Moore leverages her clinical expertise to support both medical and operational aspects of clinical trial conduct, such as providing scientific background, disease education, CRA training, site/patient materials, and assistance with feasibility and recruitment activities.

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Kelly Millhaem, MHA, Senior Clinical Trial Manager, Medpace

Kelly Millhaem is an experienced Clinical Trial Manager with over twelve years of experience in clinical research. Ms. Millhaem has overseen multiple global trials and her experience includes management of trials in cardiovascular, neuromuscular, metabolic, hepatic and endocrine indications, with a special focus on rare/orphan diseases and pediatrics. Ms. Millhaem’s leadership and communication skills are reflected in her work with sponsors, vendors, site staff, and study team members to ensure successful navigation of complex protocols, achieve recruitment and retention goals, meet study timelines, and ensure quality data in the overall conduct of trials. Ms. Millhaem’s past experience as a Global lead CRA in complex indications allows her special insight in implementing optimized, high quality monitoring strategies. Ms. Millhaem has an educational background in biology with a Master’s degree in Health Administration.

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