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Understanding the neural implementation of value-based choice has been an important focus of neuroscience for several decades. Although a consensus has emerged regarding the brain regions involved, including ventromedial prefrontal cortex (vmPFC), posterior parietal cortex (PPC), and the ventral striatum (vSTR), the multifaceted nature of decision processes is one cause of persistent debate regarding organization of the value-based choice network. In the current study, we isolate neural activity related to valuation and choice selection using a gambling task where expected gains and losses are dissociated from choice outcomes. We apply multilevel mediation analysis to formally test whether brain regions identified as part of the value-based choice network mediate between perceptions of expected value and choice to accept or decline a gamble. Our approach additionally makes predictions regarding interregional relationships to elucidate the chain of processing events within the value-based decision network. Finally, we use dynamic causal modelling (DCM) to compare plausible models of interregional relationships in value-based choice. We observe that activity in vmPFC does not predict take/pass choices, but rather is highly associated with outcome evaluation. By contrast, both PPC and bilateral vSTR (bilaterally) mediate the relationship between expected value and choice. Interregional mediation analyses reveal that vSTR fully mediates between PPC and choice, and this is supported by DCM. Together these results suggest that vSTR, and not vmPFC nor PPC, functions as an important driver of choice.

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"For-cause" inspections are initiated during the review of bioequivalence (BE) data submitted to Abbreviated New Drug Applications when possible scientific misconduct and study irregularities are discovered. We investigated the common reasons for initiating "for-cause" inspections related to the clinical, analytical, and dissolution study sites associated with BE studies. This information may help the pharmaceutical industry to understand the root causes of compliance failures in BE studies and help them to improve compliance with FDA's regulations, thereby facilitating more rapid approval of safe and effective generic drugs.

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Highly variable (HV) drugs are defined as those for which within-subject variability (%CV) in bioequivalence (BE) measures is 30% or greater. Because of this high variability, studies designed to show whether generic HV drugs are bioequivalent to their corresponding HV reference drugs may need to enroll large numbers of subjects even when the products have no significant mean differences. To avoid unnecessary human testing, the US Food and Drug Administration's Office of Generic Drugs developed a reference-scaled average bioequivalence (RSABE) approach, whereby the BE acceptance limits are scaled to the variability of the reference product. For an acceptable RSABE study, an HV generic drug product must meet the scaled BE limit and a point estimate constraint. The approach has been implemented successfully. To date, the RSABE approach has supported four full approvals and one tentative approval of HV generic drug products.

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PURPOSE: A generic product must meet the standards established by the Food and Drug Administration (FDA) to be approved for marketing in the USA. FDA approves a generic product for marketing if it is proved to be therapeutically equivalent to the reference product. Bioequivalence (BE) between a proposed generic product and its corresponding reference product is one of the major components of therapeutic equivalence. These approvals may be delayed if the BE portion of the submission is determined to be deficient. Many of these BE deficiencies recur commonly and can be avoided. METHOD: We conducted a survey of the BE submissions to abbreviated new drug applications (ANDAs) over years 2001 to 2008 to identify the most commonly occurring BE deficiencies. RESULTS: Recurring deficiencies are found in a majority of the ANDAs reviewed by FDA's Division of Bioequivalence. The most common deficiencies were the two deficiencies related to dissolution (method and specifications) found in 23.3% of the applications and analytical method validation and/or report found in 16.5% of the applications. The approval of generic drugs would be greatly accelerated if these deficiencies could be avoided.

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BACKGROUND AND PURPOSE: HIV/AIDS prevalence among Asian-American Pacific Islanders (APIs) is low yet rapidly increasing. Prior research from other populations indicates that HIV risk behaviors are associated with specific adverse/risk factors including depression, drug use, history of child sexual abuse, and forced sex. However, no studies have explored the attitudes about sexual risk behaviors and condom use between API women with adverse experiences versus women without such experiences. This qualitative study compares descriptions of sexual history and condom use between the two groups of women. METHODS: A random sample of 24 sexually active API women (16 in the adverse group and 8 in the non-adverse group) was selected for in-depth interviews from a larger study, which included 501 Korean, Chinese, and Vietnamese survey participants. FINDINGS: 14 out of the 16 women in the adverse group described complex sexual histories, with greater number of partners, more casual partners, and the combined use of alcohol/drugs and sex. The 8 women in the non-adverse group had fewer partners who were more long term. However, for both groups of women, condom use was inconsistent. Also, the majority of the women in both groups reported that either they themselves or they together with their partners had decided whether or not to use condoms. Yet 4 women in the adverse group showed lower gender power, with their partners being the primary decision-maker for condom use. CONCLUSION: Given the inconsistent condom use for both groups, all women in this study were at risk for HIV/AIDS. Consistent with prior research, a sub-group of the women in the adverse group with lower gender power seemed particularly at higher risk. Future HIV prevention interventions need to target all API women while screening for lower gender power to identify those with the highest risk of HIV.