Different black box warning labeling for same-class drugs.

INTRODUCTION: Black box warnings (BBWs) are the strongest medication-related safety warnings in a drug's labeling information and highlight major risks. Absence of a BBW or asynchronous addition of a BBW among same-class drugs could have major implications. METHODS: We identified the 20 top-selling drugs in 2008 (10 with BBWs and 10 without BBWs on their label) that belonged to different drug classes. We collected labeling information on all drugs belonging in these 20 classes, and recorded differences in the presence and timing of acquisition of BBWs for same-class drugs. RESULTS: Across the 20 evaluated drug classes, we identified 176 different agents, of which 7 had been withdrawn for safety reasons. The reasons for the withdrawals became BBWs in other same-class agents only in two of the seven cases. Differences were identified in 9 of the 20 classes corresponding to 15 BBWs that were not present in all drugs of the same class. The information for 10 of the 15 different BBWs were included in the labels of same-class drugs as simple warnings or text, while it was absent entirely in 5 BBWs. The median interval from the time the BBW had appeared in another drug of the same class was 66 months. DISCUSSION: Differences in BBW labeling in same-class drugs are common and shape impressions about the safety of similar agents. BBW labeling needs to become more systematic.

Patient outcomes with teaching versus nonteaching healthcare: a systematic review.

BACKGROUND: Extensive debate exists in the healthcare community over whether outcomes of medical care at teaching hospitals and other healthcare units are better or worse than those at the respective nonteaching ones. Thus, our goal was to systematically evaluate the evidence pertaining to this question. METHODS AND FINDINGS: We reviewed all studies that compared teaching versus nonteaching healthcare structures for mortality or any other patient outcome, regardless of health condition. Studies were retrieved from PubMed, contact with experts, and literature cross-referencing. Data were extracted on setting, patients, data sources, author affiliations, definition of compared groups, types of diagnoses considered, adjusting covariates, and estimates of effect for mortality and for each other outcome. Overall, 132 eligible studies were identified, including 93 on mortality and 61 on other eligible outcomes (22 addressed both). Synthesis of the available adjusted estimates on mortality yielded a summary relative risk of 0.96 (95% confidence interval [CI], 0.93-1.00) for teaching versus nonteaching healthcare structures and 1.04 (95% CI, 0.99-1.10) for minor teaching versus nonteaching ones. There was considerable heterogeneity between studies (I(2) = 72% for the main analysis). Results were similar in studies using clinical and those using administrative databases. No differences were seen in the 14 studies fully adjusting for volume/experience, severity, and comorbidity (relative risk 1.01). Smaller studies did not differ in their results from larger studies. Differences were seen for some diagnoses (e.g., significantly better survival for breast cancer and cerebrovascular accidents in teaching hospitals and significantly better survival from cholecystectomy in nonteaching hospitals), but these were small in magnitude. Other outcomes were diverse, but typically teaching healthcare structures did not do better than nonteaching ones. CONCLUSIONS: The available data are limited by their nonrandomized design, but overall they do not suggest that a healthcare facility's teaching status on its own markedly improves or worsens patient outcomes. Differences for specific diseases cannot be excluded, but are likely to be small.

Comparison of evidence on harms of medical interventions in randomized and nonrandomized studies.

BACKGROUND: Information on major harms of medical interventions comes primarily from epidemiologic studies performed after licensing and marketing. Comparison with data from large-scale randomized trials is occasionally feasible. We compared evidence from randomized trials with that from epidemiologic studies to determine whether they give different estimates of risk for important harms of medical interventions. METHODS: We targeted well-defined, specific harms of various medical interventions for which data were already available from large-scale randomized trials (> 4000 subjects). Nonrandomized studies involving at least 4000 subjects addressing these same harms were retrieved through a search of MEDLINE. We compared the relative risks and absolute risk differences for specific harms in the randomized and nonrandomized studies. RESULTS: Eligible nonrandomized studies were found for 15 harms for which data were available from randomized trials addressing the same harms. Comparisons of relative risks between the study types were feasible for 13 of the 15 topics, and of absolute risk differences for 8 topics. The estimated increase in relative risk differed more than 2-fold between the randomized and nonrandomized studies for 7 (54%) of the 13 topics; the estimated increase in absolute risk differed more than 2-fold for 5 (62%) of the 8 topics. There was no clear predilection for randomized or nonrandomized studies to estimate greater relative risks, but usually (75% [6/8]) the randomized trials estimated larger absolute excess risks of harm than the nonrandomized studies did. INTERPRETATION: Nonrandomized studies are often conservative in estimating absolute risks of harms. It would be useful to compare and scrutinize the evidence on harms obtained from both randomized and nonrandomized studies.

Availability of large-scale evidence on specific harms from systematic reviews of randomized trials.

PURPOSE: To assess how frequently systematic reviews of randomized controlled trials convey large-scale evidence on specific, well-defined adverse events. METHODS: We searched the Cochrane Database of Systematic Reviews for reviews containing quantitative data on specific, well-defined harms for at least 4000 randomized subjects, the minimum sample required for adequate power to detect an adverse event due to an intervention in 1% of subjects. Main outcome measures included the number of reviews with eligible large-scale data on adverse events, the number of ineligible reviews, and the magnitude of recorded harms (absolute risk, relative risk) based on large-scale evidence. RESULTS: Of 1727 reviews, 138 included evidence on > or =4000 subjects. Only 25 (18%) had eligible data on adverse events, while 77 had no harms data, and 36 had data on harms that were nonspecific or pertained to <4000 subjects. Of 66 specific adverse events for which there were adequate data in the 25 eligible reviews, 25 showed statistically significant differences between comparison arms; most pertained to serious or severe adverse events and absolute risk differences <4%. In 29% (9/31) of a sample of large trials in reviews with poor reporting of harms, specific harms were presented adequately in the trial reports but were not included in the systematic reviews. CONCLUSION: Systematic reviews can convey useful large-scale information on adverse events. Acknowledging the importance and difficulties of studying harms, reporting of adverse effects must be improved in both randomized trials and systematic reviews.

Safety reporting in randomized trials of mental health interventions.

OBJECTIVE: The authors aimed to evaluate the adequacy of the reporting of safety information in publications of randomized trials of mental-health-related interventions. METHOD: The authors randomly selected 200 entries from the PsiTri registry of mental-health-related controlled trials. This yielded 142 randomized trials that were analyzed for adequacy and relative emphasis of their content on safety issues. They examined drug trials as well as trials of other types of interventions. RESULTS: Across the 142 eligible trials, 103 involved drugs. Twenty-five of the 142 trials had at least 100 randomly chosen subjects and at least 50 subjects in a study arm. Among drug trials, only 21.4% had adequate reporting of clinical adverse events, and only 16.5% had adequate reporting of laboratory-determined toxicity, while 32.0% reported both the numbers and the reasons for withdrawals due to toxicity in each arm. On average, drug trials devoted 1/10 of a page in their results sections to safety, and 58.3% devoted more space to the names and affiliations of authors than to safety. None of the trials of nondrug interventions had adequate or even partially adequate reporting of either clinical adverse events or laboratory-determined toxicity. In multivariate modeling, long-term trials and trials conducted in the United States devoted even less space to safety, while schizophrenia trials devoted more space to safety than did trials in other areas. CONCLUSIONS: Safety reporting is largely neglected across trials of mental-health-related interventions, thus hindering the assessment of risk-benefit ratios for rational decision making in mental health care.

Awareness of the side effects of possessed medications in a community setting.

OBJECTIVE: To evaluate in a community setting the extent of and parameters related with awareness of side effects of medications by health consumers. METHODS: We performed in-house interviews in an entire community. The population of the community of Chalki, Greece, was surveyed. Detailed information was recorded on all medications possessed by each individual. The main outcome measure was awareness of medication side effects. RESULTS: A total of 1079 medications were recorded among 279 subjects. Among 180 subjects for whom direct information was available, and who possessed at least one medication only 47 (26%) were aware of the side effects of at least one of their medications. Side effects awareness was more frequent in subjects who had experienced some adverse event themselves (76%), in those with completed university education (67%), ex-smokers (46%), housewives (45%), and never married adults (41%) and was less frequent in more permanent island residents (odds ratio 0.76 per 10% of lifetime spent in the island) and economic immigrants (0%). Side effects awareness existed for only 8% of the possessed medications and was more frequent when an adverse event had been experienced (54%), for medications not provided locally initially (28%), and for medications for joint and musculoskeletal problems (15%). Awareness rates were unrelated to availability of prescription, specialist involvement, or follow-up by a physician concerning the specific medication. CONCLUSIONS: Awareness of side effects was infrequent in this community setting and was determined mostly by live experiences of adverse events and social parameters. There is a need to improve the dissemination of adequate safety information among consumers in the ambulatory use of pharmaceuticals.