CoDevelopment and Phase I and II Drug Studies

I deally, when a drug and a diagnostic are to be used in combination, the development of the drug and diagnostic should be coordinated as much as possible. For the drug candidate, CDER requires phase I studies to demonstrate drug safety and phase II studies to confirm proof of concept, determine dosing and expand on drug safety. In cases where biomarkers are being studied for possible use with a drug, the diagnostic work is generally exploratory but, ideally, should include initial biomarker validation.

Phase I and II drug studies do offer opportunities to gather preliminary data about associations between biomarkers and drug use. This information may include descriptive data on prevalence of the biomarker, association with adverse events or the safety profile being identified with early drug use, and/ or information on possible ability of the test to predict drug response. In addition, the information gathered helps improve benefit-risk analysis at an earlier stage of development. A number of interesting proposals have been made to streamline the path to market by expanding phase II studies to allow better selection and characterization of biomarkers for drug use. Jiang et al, [12] proposed design combines a test for overall treatment effect in all randomly assigned patients with the establishment and validation of a cut point for a prespecified biomarker for identifying the sensitive subpopulation. The procedure provides prospective tests of the hypotheses that the new treatment is beneficial for the entire patient population or that it is beneficial for a subset of patients defined by the biomarker. The good news is that this allows an opportunity to introduce a drug without or with a biomarker as circumstances may dictate. However, the bad news is that each separate hypothesis cannot be performed without a p-value penalty, so a recommendation is made that testing for the drug affect in the all-comers population be with p = 0.04 and, if needed, follow-up testing in the biomarker positive population occurs with a p = 0.01. Proposals have also been made to find mechanisms of adaptive design applying Bayesian statistics to allow phase II and III studies to be performed in a more seamless manner.

Prototype Assay Used Final Locked Device -► -►

Prototype Assay Used Final Locked Device -► -►

'Adapted from Drug-Diagnostic Co-Development Concept Paper (draft).

Figure 3 Co-development strategy timing.

'Adapted from Drug-Diagnostic Co-Development Concept Paper (draft).

Figure 3 Co-development strategy timing.

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Project Management Made Easy

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