BackgroundMeta-analyses of antidepressant medications have reported only modest benefits over placebo treatment, and when unpublished trial data are included, the benefit falls below accepted criteria for clinical significance. Yet, the efficacy of the antidepressants may also depend on the severity of initial depression scores. The purpose of this analysis is to establish the relation of baseline severity and antidepressant efficacy using a relevant dataset of published and unpublished clinical trials.Methods and FindingsWe obtained data on all clinical trials submitted to the US Food and Drug Administration (FDA) for the licensing of the four new-generation antidepressants for which full datasets were available. We then used meta-analytic techniques to assess linear and quadratic effects of initial severity on improvement scores for drug and placebo groups and on drug–placebo difference scores. Drug–placebo differences increased as a function of initial severity, rising from virtually no difference at moderate levels of initial depression to a relatively small difference for patients with very severe depression, reaching conventional criteria for clinical significance only for patients at the upper end of the very severely depressed category. Meta-regression analyses indicated that the relation of baseline severity and improvement was curvilinear in drug groups and showed a strong, negative linear component in placebo groups.ConclusionsDrug–placebo differences in antidepressant efficacy increase as a function of baseline severity, but are relatively small even for severely depressed patients. The relationship between initial severity and antidepressant efficacy is attributable to decreased responsiveness to placebo among very severely depressed patients, rather than to increased responsiveness to medication.

This article reports an analysis of the efficacy data submitted to the U.S. Food and Drug Administration for approval of the 6 most widely prescribed antidepressants approved between 1987 and 1999. Approximately 80% of the response to medication was duplicated in placebo control groups, and the mean difference between drug and placebo was approximately 2 points on the 17-item (50-point) and 21-item (62-point) Hamilton Depression Scale. Improvement at the highest doses of medication was not different from improvement at the lowest doses. The proportion of the drug response duplicated by placebo was significantly greater with observed cases (OC) data than with last observation carried forward (LOCF) data. If drug and placebo effects are additive, the pharmacological effects of antidepressants are clinically negligible. If they are not additive, alternative experimental designs are needed for the evaluation of antidepressants.

The DASH diet plus reduced sodium intake is recommended to control blood pressure in diverse subgroups.

There have been no studies evaluating incisional NPWT as a prophylactic treatment to prevent infection and wound dehiscence of high-risk surgical incisions. Our data demonstrate that there is a decreased incidence of wound dehiscence and total infections after high-risk fractures when patients have NPWT applied to their surgical incisions after closure. There is also a strong trend for decreases in acute infections after NPWT. Based on our data in this multicenter prospective randomized clinical trial, NPWT should be considered for high-risk wounds after severe skeletal trauma.

Background: The US Food and Drug Administration has operated the Adverse Event Reporting System since 1998. It collects all voluntary reports of adverse drug events submitted directly to the agency or through drug manufacturers. Methods: Using extracts published for research use, we analyzed all serious adverse drug events and medication errors in the United States reported to the Food and Drug Administration from 1998 through 2005. Results: From 1998 through 2005, reported serious adverse drug events increased 2.6-fold from 34 966 to 89 842, and fatal adverse drug events increased 2.7-fold from 5519 to 15 107. Reported serious events increased 4 times faster than the total number of outpatient prescriptions during the period. In a subset of drugs with 500 or more cases reported in any year, drugs related to safety withdrawals accounted for 26% of reported events in that group in 1999, declining to less than 1% in 2005. For 13 new biotechnology products, reported serious events grew 15.8-fold, from 580 reported in 1998 to 9181 in 2005. The increase was influenced by relatively few drugs: 298 of the 1489 drugs identified (20%) accounted for 407 394 of the 467 809 events (87%). Conclusions: These data show a marked increase in reported deaths and serious injuries associated with drug therapy over the study period. The results highlight the importance of this public health problem and illustrate the need for improved systems to manage the risks of prescription drugs.

The DASH diet is likely to reduce coronary heart disease risk. The possible opposing effect on coronary heart disease risk of HDL reduction needs further study.

IMPORTANCE A critical question in health care is the extent of scientific evidence that should be required to establish that a new therapeutic agent has benefits that outweigh its risks. Estimating the costs of this evidence of efficacy provides an important perspective. OBJECTIVE To estimate costs and assess scientific characteristics of pivotal efficacy trials that supported the approval of new therapeutic agents by the US Food and Drug Administration (FDA) from 2015 to 2016. DESIGN AND SETTING This study identified 59 novel therapeutic drugs using the annual summary reports from the FDA Center for Drug Evaluation and Research. ClinicalTrials.gov, FDA reviews, and peer-reviewed publications that were publicly available in 2017 were used to identify 52 characteristics of each efficacy trial. Costs were calculated with a global clinical trial cost assessment tool available to contract research organizations and pharmaceutical sponsors. MAIN OUTCOMES AND MEASURES Estimated mean cost and 95% CIs based on industry benchmark data from 60 countries. Measures of trials' scientific characteristics included trial design (no control group, placebo, and active drug), end point (surrogate outcome, clinical scale, and clinical outcome), patient enrollment, and treatment duration. RESULTS A total of 138 pivotal clinical trials provided the basis for approval of 59 new therapeutic agents by the FDA from 2015 to 2016, with a median estimated cost of $19.

IMPORTANCE Severe impulse control disorders involving pathological gambling, hypersexuality, and compulsive shopping have been reported in association with the use of dopamine receptor agonist drugs in case series and retrospective patient surveys. These agents are used to treat Parkinson disease, restless leg syndrome, and hyperprolactinemia. OBJECTIVES To analyze serious adverse drug event reports about these impulse control disorders received by the US Food and Drug Administration (FDA) and to assess the relationship of these case reports with the 6 FDA-approved dopamine receptor agonist drugs. DESIGN, SETTING, AND PARTICIPANTS We conducted a retrospective disproportionality analysis based on the 2.7 million serious domestic and foreign adverse drug event reports from 2003 to 2012 extracted from the FDA Adverse Event Reporting System. MAIN OUTCOMES AND MEASURES Cases were selected if they contained any of 10 preferred terms in the Medical Dictionary for Regulatory Activities (MedDRA) that described the abnormal behaviors. We used the proportional reporting ratio (PRR) to compare the proportion of target events to all serious events for the study drugs with a similar proportion for all other drugs. RESULTS We identified 1580 events indicating impulse control disorders from the United States and 21 other countries: 710 for dopamine receptor agonist drugs and 870 for other drugs. The dopamine receptor agonist drugs had a strong signal associated with these impulse control disorders (n = 710; PRR = 277.6, P < .001). The association was strongest for the dopamine agonists pramipexole (n = 410; PRR = 455.9, P < .001) and ropinirole (n = 188; PRR = 152.5, P < .001), with preferential affinity for the dopamine D 3 receptor. A signal was also seen for aripiprazole, an antipsychotic classified as a partial agonist of the D 3 receptor (n = 37; PRR = 8.6, P < .001). CONCLUSIONS AND RELEVANCE Our findings confirm and extend the evidence that dopamine receptor agonist drugs are associated with these specific impulse control disorders. At present, none of the dopamine receptor agonist drugs approved by the FDA have boxed warnings as part of their prescribing information. Our data, and data from prior studies, show the need for more prominent warnings.