During the discovery phase, the analysis of the biological targets as well as medical chemistry will allow selection of lead molecules with the best BRA potential over hundreds of candidate molecules.1,2 During the preclinical development of the drug, the evidence obtained from animal models of the disease is compared with the preclinical safety data obtained from toxicological studies, and the preclinical BRA will determine whether

a candidate drug will be administered lor the first time in humans.3 The BRA is not a static process, and it evolves during the clinical development, the registration process, and the marketing period, when the drug is administered to patients. However, at all Inhibitors,research,lifescience,medical Inhibitors,research,lifescience,medical times, BRA remains a major and complex concept. In general, the dynamic aspects of BRA are due to new findings that better characterize the safety profile of a drug and sometimes uncover side effects, making the safety profile of the drug less favorable. Drugs which have been on the market lor years can be withdrawn because the Inhibitors,research,lifescience,medical revised safety evaluation confronted with

the efficacy findings, no longer supports a favorable BRA, even for drugs with “blockbuster” status.4 A revision of the BRA can be justified by the introduction of risk management measures such as a restriction of the indication or monitoring measures. For example, the multiple Inhibitors,research,lifescience,medical sclerosis monoclonal antibody natalizumab was registered with significant restrictions in the target patient population following suspension of clinical trials due to some cases of severe infections. Exceptionally, there are examples where unfavorable BRAs have turned positive, for example when the discovery of a new indication for an old drug increases the positive aspects of its BRA: the relaunch of thalidomide in the indications Inhibitors,research,lifescience,medical of multiple myeloma and erythema nodosum leprosum is an example.5 The above comments indicate that the BRA of a drug is not an LY2603618 research buy isolated exercise,

since it occurs in a global medical and pharmaceutical context. The type of indication for which the drug is planned is critical in this assessment. A drug with a safety profile including risks of severe ADRs, potentially lethal, may be accepted in oncology, but it should not of be introduced for the treatment of less severe disorders. In absolute terms, the BRA of a drug is independent of the existence of alternative therapeutics, but it is clear that when other therapeutics are available in a given indication, regulatory authorities and prescribers will prefer the drug with the more favorable BRA. Economic considerations intervene here as well, and may influence this value scale. In this review, we discuss the relative value for the BRA based on evidence collected by randomized clinical trials versus naturalistic studies.