JAMA internal medicine
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JAMA internal medicine · Jul 2019
Review Comparative StudyAssessment of the Clinical Benefit of Cancer Drugs Receiving Accelerated Approval.
The US Food and Drug Administration's (FDA's) accelerated approval pathway allows investigational cancer drugs to be approved by demonstrating a beneficial effect on a surrogate measure (eg, progression-free survival) that is expected to predict a real clinical benefit (eg, overall survival). However, these drugs must undergo postapproval confirmatory studies to evaluate their actual clinical benefits. In an assessment of the accelerated approval pathway published in 2018, the FDA concluded that this pathway was successful because only 5 (5%) of 93 accelerated drug approvals had been withdrawn or revoked over the last 25 years. ⋯ Confirmatory trials for one-fifth (n = 19 of 93) of cancer drug indications approved via the FDA's accelerated approval pathway demonstrated improvements in overall patient survival. Reassessment of the requirements for confirmatory trials may be necessary to obtain more clinically meaningful information.
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JAMA internal medicine · Jul 2019
ReviewAn Overview of Cancer Drugs Approved by the US Food and Drug Administration Based on the Surrogate End Point of Response Rate.
Approximately one-third of cancer drugs are approved based on response rate (RR)-the percentage of patients whose tumors shrink beyond an arbitrary threshold-typically assessed in a single-arm study. ⋯ Many cancer drugs approved on the basis of response rate offer numerically low or modest response rates. Most premarket studies accrue more than 100 patients. Some of these drugs could potentially be tested in premarket randomized clinical trials measuring directly end points that demonstrate clinical benefit.
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JAMA internal medicine · Feb 2019
Meta AnalysisAssociation of Corticosteroid Treatment With Outcomes in Adult Patients With Sepsis: A Systematic Review and Meta-analysis.
Although corticosteroids are widely used for adults with sepsis, both the overall benefit and potential risks remain unclear. ⋯ The findings suggest that administration of corticosteroids is associated with reduced 28-day mortality compared with placebo use or standard supportive care. More research is needed to associate personalized medicine with the corticosteroid treatment to select suitable patients who are more likely to show a benefit.
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JAMA internal medicine · Jan 2019
Assessment of Pregabalin Postapproval Trials and the Suggestion of Efficacy for New Indications: A Systematic Review.
After a drug receives regulatory approval, researchers often pursue small, underpowered trials, called exploratory trials, aimed at testing additional indications. If favorable early findings from exploratory trials are not promptly followed by confirmatory trials, then physicians, patients, and payers can be left uncertain about a drug's clinical value (clinical agnosticism). Such findings may encourage the off-label use of ineffective drugs. ⋯ After initial approval, exploratory evidence suggesting the value of pregabalin for new indications often went unconfirmed for extended periods of time. Poor coordination between exploratory and confirmatory testing may represent an important vehicle through which off-label prescription is recommended in clinical practice guidelines and encouraged in the absence of confirmatory trial evidence.
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JAMA internal medicine · Dec 2018
Meta AnalysisEvaluation of Interventions Intended to Increase Colorectal Cancer Screening Rates in the United States: A Systematic Review and Meta-analysis.
Colorectal cancer screening (CRC) is recommended by all major US medical organizations but remains underused. ⋯ Fecal blood test outreach and patient navigation, particularly in the context of multicomponent interventions, were associated with increased CRC screening rates in US trials. Fecal blood test outreach should be incorporated into population-based screening programs. More research is needed on interventions to increase adherence to continued FBTs, follow-up of abnormal initial screening test results, and cost-effectiveness and other implementation barriers for more intensive interventions, such as navigation.