Clinical pharmacology and therapeutics
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Clin. Pharmacol. Ther. · May 2015
The role of nonrandomized trials in the evaluation of oncology drugs.
Although randomized trials provide the most reliable evidence of a drug's safety and efficacy, there are situations where randomized trials are not possible or ethical. In this article we discuss when and how single-arm trials can be used to support full approval of oncology drugs. These include situations in which an unprecedented effect on tumor response is observed in a setting of high unmet medical need, clinical trial patients have been well characterized, enabling a target population to be clearly defined, experience exists in a sufficient number of patients to allow adequate assessment of the risk:benefit relationship, and a proper historical context can be provided for analysis. We also discuss how response rates might be considered predictive of long-term outcomes or clinically meaningful in and of themselves in certain contexts.
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Clin. Pharmacol. Ther. · Apr 2015
ReviewImproving drug delivery to primary and metastatic brain tumors: strategies to overcome the blood-brain barrier.
Brain tumor diagnosis has an extremely poor prognosis, due in part to the blood-brain barrier (BBB) that prevents both early diagnosis and effective drug delivery. The infiltrative nature of primary brain tumors and the presence of micro-metastases lead to tumor cells that reside behind an intact BBB. ⋯ However, the majority of these agents are unable to penetrate an intact BBB, leading to one mechanism by which the invasive brain tumor cells effectively escape treatment. The diagnosis and treatment of a brain tumor remains a serious challenge and new therapeutic agents that either penetrate the BBB or disrupt mechanisms that limit brain penetration, such as endothelial efflux transporters or tight junctions, are required in order to improve patient outcomes in this devastating disease.
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Clin. Pharmacol. Ther. · Mar 2015
ReviewRacial/ethnic differences in drug disposition and response: review of recently approved drugs.
Race and ethnicity can contribute to interindividual differences in drug exposure and/or response, which may alter risk-benefit in certain populations. Approximately one-fifth of new drugs approved in the past 6 years demonstrated differences in exposure and/or response across racial/ethnic groups, translating to population-specific prescribing recommendations in a few cases. When data from diverse populations were lacking, additional postmarketing studies were recommended. In this review we highlight several cases where race/ethnicity was central to regulatory decision-making.
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Clin. Pharmacol. Ther. · Feb 2015
EditorialPharmacological treatment of pain: future trends and novel insights.
The pharmacological treatment of chronic pain is generally hampered by a limited clinical outcome. Hence, there is a strong need for new therapeutic concepts considering the identification of novel targets and related drugs, but also optimization of established therapeutic regimes through individualization. In this issue, focused on "Pain," we discuss some of the recent new concepts in pain treatment, understanding of pain heterogeneity, and subsequent optimization of analgesic treatment, but also novel insights into interactions of nonopioids.