How Will Preknowledge of Genetic Susceptibility to Pharmacologically Predictable Adverse Events or Nonresponse Obtained in Early Phase Development Affect the Risk Benefit Assessment and Product Labeling

If a pharmacogenetic and pharmacogenomic subgroup had improved efficacy or safety, how the information is included in the label would be dependent on the risk/benefit assessment, with life-threatening events being considered different from less severe adverse events. The pharmacogenetic and pharmacogenomic relationship may be described under "Clinical Pharmacology," "Indications and Usage," "Warnings or Precautions," or "Dosage and Administration." The label would inform clinicians that there is a genotype or phenotype test available, but it may not have to be done prior to dosing unless warranted. If the diagnostic test must be done prior to dosing, then it may be stated under "Indications and Usage" (e.g., approved labeling for Herceptin® [trastuzumab]).

The decision of whether a pharmacogenetic and pharmacogenomic test is necessary prior to dosing will be dependent on many factors, including the following: (1) if safety, the seriousness of the adverse event; (2) if efficacy, the consequences of nonresponse; (3) the incidence of the clinical outcome; (4) the variability in the clearance of the drug; (5) how well an adverse event can be managed (i.e., if it can be recognized easily without a genetic test and whether toxicity is reversible); (6) need for education of physicians and third-party payers; and (7) feasibility of accessing and using the test in clinical practice. For example, oncologists would be more likely to use a pharmacogenetic and pharma-cogenomic test prior to treatment if it would improve efficacy or safety. On the other hand, an allergist who has a patient with allergies may want immediate relief for the patient and is unlikely to wait several days to a week before writing a prescription so that a genetic test can be run to predict whether the patient is at risk for a drug-related headache.

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