Using measures of disease progression to determine therapeutic effect: a sirens' song.


Journal Article (Review)

With an increasing burden of cardiovascular disease and many promising novel treatments in development, the need for efficient systems to evaluate treatments has never been greater. To understand whether a treatment should be used in practice, we need to know whether it makes patients live longer, feel better, prevents adverse events, or does these things with better tolerability or lower cost. But therapeutic development is expensive, inefficient, and is generally focused on short-term treatment effects, rather than on prevention and on long-term impact. Could measures of disease progression, combined with trends on clinical outcomes and post-marketing surveillance to assess safety, serve as the foundation for therapeutic development? Experience and principles of clinical research tell us no. Especially in the field of heart failure, numerous treatments have appeared promising based on disease markers, yet caused harm when tested in studies that assessed clinical outcomes. The intersection of complex human disease, intended and unintended targets of therapy, and overall risk and benefit make it impossible to accurately predict the effect on clinical outcomes based on impact on a disease marker. While reliable measures of disease progression are important to guide which treatments to study in trials, clinical outcome trials must remain the basis for informing clinicians on which treatments improve clinical outcomes. Improved reliability and capacity require the development of more efficient clinical trial methods, streamlined regulatory processes, rational use of privacy protection, leveraging of electronic medical records, and recruitment of a larger proportion of the clinical community to participate in clinical trials.

Full Text

Duke Authors

Cited Authors

  • Granger, CB; McMurray, JJV

Published Date

  • August 1, 2006

Published In

Volume / Issue

  • 48 / 3

Start / End Page

  • 434 - 437

PubMed ID

  • 16875965

Pubmed Central ID

  • 16875965

Electronic International Standard Serial Number (EISSN)

  • 1558-3597

Digital Object Identifier (DOI)

  • 10.1016/j.jacc.2006.03.050


  • eng

Conference Location

  • United States