Regulatory Framework To Accommodate Codeveloping Drug Diagnostics

The lifecycle to obtain marketing approval for the development of a new drug is outlined in FDA law and regulation and progresses through a well-defined multistep process: basic research, prototype design or discovery, preclinical development, clinical development (phases I, II, and III), FDA filing/approval/ launch, and postlaunch (phase IV).

Figure 1 (A) Drug and (B) device development pathways.

Figure 1 (A) Drug and (B) device development pathways.

The development of a new diagnostic also goes through a well-defined multistep process: basic research, feasibility studies, analytical validation, clinical validation, and FDA approval/clearance. The developmental pathways for a drug and device are illustrated in Figure 1. When use of a diagnostic test is identified as important in selecting which patients receive or avoid a new drug or are to be given a higher or lower dose of a drug, the efficacy/ safety of the drug becomes inextricably linked to the effectiveness of the diagnostic. Drug performance will only be as good as the ability of the diagnostic to properly select patients for that drug treatment.

Drug performance is judged based on an assessment of the drug to meet appropriate clinical endpoints or responses with a reasonable safety profile. Diagnostic studies are based on demonstrating that a test properly identifies an outcome or target of interest. When the diagnostic is used to detect drug response, the outcome of interest becomes the drug response or avoidance of drug toxicity. The test parameters of interest in the context of co-development with a new drug do not differ from those of ubiquitous interest in the study of a new diagnostic.

Standardized techniques to establishing test performance have been promoted in the literature and in FDA guidances. Clinical parameters of importance include sensitivity—in this case the ability of the test to identify patients who will exhibit the desired drug response of interest—and specificity—in this case the ability of the test to identify patients who will not demonstrate the drug response of interest. Alternative useful techniques include a definition of the predictive value of a positive result (the fraction of test positives who respond), the predictive value of a negative result (the fraction of test negatives who do not respond), or the likelihood ratio of drug response after testing. The hazard ratio (HR) in prospective studies/analysis and the odds ratio (OR) in retrospective analysis could be used when interpreting probabilities in a different context of use.

Project Management Made Easy

Project Management Made Easy

What you need to know about… Project Management Made Easy! Project management consists of more than just a large building project and can encompass small projects as well. No matter what the size of your project, you need to have some sort of project management. How you manage your project has everything to do with its outcome.

Get My Free Ebook


Post a comment