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One of the most effective ways in which regulatory agencies communicate with sponsors and guide drug development is through the issuance of guidances or guidelines. These can be issued domestically in a given region such as the United States by the Food and Drug Administration (FDA) or internationally through the International Conference on Harmonization.(More)
In recent years, several authors have argued that placebo-controlled trials are invariably unethical when known effective therapy is available for the condition being studied, regardless of the condition or the consequences of deferring treatment. Some have also disputed the value of placebo-controlled trials in such a setting, asserting that the comparison(More)
OBJECTIVE To examine the risk of suicidal behaviour within clinical trials of antidepressants in adults. DESIGN Meta-analysis of 372 double blind randomised placebo controlled trials. SETTING Drug development programmes for any indication in adults. PARTICIPANTS 99 231 adults assigned to antidepressants or placebo. Median age was 42 and 63.1% were(More)
Predicting clinically significant drug interactions during drug development is a challenge for the pharmaceutical industry and regulatory agencies. Since the publication of the US Food and Drug Administration's (FDA's) first in vitro and in vivo drug interaction guidance documents in 1997 and 1999, researchers and clinicians have gained a better(More)
n engl j med 362;3 nejm.org january 21, 2010 189 and to decrease the need for transfusions.” Although epoetin alfa and darbepoetin alfa, a related erythropoiesis-stimulating agent (ESA) approved in 2001, have been widely accepted for this indication, optimal hemoglobin targets have never been established. A number of small studies conducted in the late(More)
O October 19, 2010, the Food and Drug Administration (FDA) approved dabigatran for the reduction of the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. Approval was based on a multicenter, active-control trial, the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY),1 in which patients were randomly(More)
N ew chemical entities developed by the pharmaceutical industry as potentially useful drugs undergo extensive preclinical evaluation followed by clinical trials to evaluate efficacy and safety in human subjects. In the United States, the Food and Drug Administration (FDA) is charged with evaluating requests from pharmaceutical sponsors for approval to(More)
n engl j med 359;1 www.nejm.org july 3, 2008 95 To the Editor: Carpenter et al. (March 27 is­ sue)1 report that new molecular entities (NMEs) approved in the 2 months before the first review deadlines established under the Prescription Drug User Fee Act (PDUFA) showed a higher rate of postmarketing safety problems — as measured by safety­based withdrawals,(More)
To optimize drug therapy for individuals, it is critical to understand how various intrinsic (e.g., age, gender, race, genetics, organ impairment) and extrinsic factors (e.g., diet, smoking, concomitantly administered drugs) affect drug exposure and response.(1) Up to now, it has been far easier to discover effects on exposure caused by these factors, and(More)