Validating biomarkers for effective drug development
As the relationship between a drug or class of drugs and a biomarker becomes better understood, there is hope that clinical assays can be developed to identify patients most likely to benefit from the drug. Although prognostic biomarkers that provide information on the natural course of disease after standard treatments are useful, predictive biomarkers are of greater value in clinical decision making and will be essential tools for tailoring treatments.
Drug and assay developers, regulators, and clinical investigators face many dilemmas in the course of developing targeted drugs and associated predictive biomarkers.
In my meetings with FDA (both public and private) they repeatedly cite the CAST study as great example of a false positive. In many cases collaboration between industry and academia is crucial to provide the large amount of patient data to qualify a biomarker.
TB drug clinical development programs take a minimum of six years to complete -- far longer than most trials for other infectious diseases.
New drugs and drug combinations must prove safe for human use, and they must demonstrate their efficacy against , which requires months of treatment.
For example, HIV/AIDS drug development was revolutionized by the validation of biomarkers like viral load and CD4 counts, which reliably predict success of treatment and allowed for a dramatic reduction in the duration of clinical trials.
Biomarkers will help streamline clinical development of new TB cures.Frustration follows when a drug company provides data on biomarkers to support its claim and FDA responds with a “sorry, the biomarker is not proven.” In 2011, FDA issued a guidance and roadmap for validation and qualification of biomarkers (ref 1).