ObjeCtiveTo study serious harms associated with selective serotonin and serotonin-norepinephrine reuptake inhibitors.Design Systematic review and meta-analysis. Main OutCOMe MeasuresMortality and suicidality. Secondary outcomes were aggressive behaviour and akathisia. Data sOurCesClinical study reports for duloxetine, fluoxetine, paroxetine, sertraline, and venlafaxine obtained from the European and UK drug regulators, and summary trial reports for duloxetine and fluoxetine from Eli Lilly's website.eligibility Criteria fOr stuDy seleCtiOn Double blind placebo controlled trials that contained any patient narratives or individual patient listings of harms. Data extraCtiOn anD analysisTwo researchers extracted data independently; the outcomes were meta-analysed by Peto's exact method (fixed effect model). resultsWe included 70 trials (64 381 pages of clinical study reports) with 18 526 patients. These trials had limitations in the study design and discrepancies in reporting, which may have led to serious underreporting of harms. For example, some outcomes appeared only in individual patient listings in appendices, which we had for only 32 trials, and we did not have case report forms for any of the trials. Differences in mortality (all deaths were in adults, odds ratio 1.28, 95% confidence interval 0.40 to 4.06), suicidality (1.21, 0.84 to 1.74), and akathisia (2.04, 0.93 to 4.48) were not significant, whereas patients taking antidepressants displayed more aggressive behaviour (1.93, 1.26 to 2.95). For adults, the odds ratios were 0.81 (0.51 to 1.28) for suicidality, 1.09 (0.55 to 2.14) for aggression, and 2.00 (0.79 to 5.04) for akathisia. The corresponding values for children and adolescents were 2.39 (1.31 to 4.33), 2.79 (1.62 to 4.81), and 2.15 (0.48 to 9.65). In the summary trial reports on Eli Lilly's website, almost all deaths were noted, but all suicidal ideation events were missing, and the information on the remaining outcomes was incomplete.

Identifying low-value health care practices for local disinvestment (total or partial) is both practically and politically challenging, yet it is necessary to manage health budgets. This project identified that Cochrane Reviews can potentially identify low value health care practices. However, each review has to be reinterpreted for the UK context and additional analysis has to be undertaken to facilitate local implementation. Recommendations to improve the usability of systematic reviews are made.

The evidence from trials for the use of benzodiazepines alone is not good. There were relatively little good data and most trials are too small to highlight differences in either positive or negative effects. Adding a benzodiazepine to other drugs does not seem to confer clear advantage and has potential for adding unnecessary adverse effects. Sole use of older antipsychotics unaccompanied by anticholinergic drugs seems difficult to justify. Much more high quality research is needed in this area.

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Background Delays in diagnosis and treatment of pulmonary tuberculosis are a major set-back to global tuberculosis control. There is currently no global evidence on the average delays thus, the most important contributor to total delay is unknown. We aimed to estimate average delay measures and to investigate sources for heterogeneity among studies assessing delay measures. Methods Systematic review of studies reporting mean (± standard deviation) or median (interquartile range, IQR) of patient, doctor, diagnostic, treatment, health system and/or total delays in journal articles indexed in PubMed. We pooled mean delays using random-effects inverse variance meta-analysis, investigated for variations in pooled estimates in subgroup analyses and explored for sources of heterogeneity using pre-specified explanatory variables. Results The systematic review included 198 studies (831,724 patients) from 78 countries. The median number of patients per study was 243 (IQR; 160–458) patients. Overall, the pooled mean total delay was 87.6 (95% CI: 81.4–93.9) days. The most important and largest contributor to total delay was patient delay with a pooled mean delay of 81 (95% CI: 70–92) days followed by doctor’s delay and treatment delay with pooled mean delays of 29.5 (95% CI: 25.9–33.0) and 7.9 (95% CI: 6.9–8.9) days respectively. There was considerable heterogeneity in all pooled analyses (I 2 > 95%). In the meta-regression models of mean delays, studies excluding extra-pulmonary tuberculosis patients reported increased mean doctor’s delay by 45 days on average, non-use of chest x-ray and conducting studies in high income countries decreased mean treatment delay by 20 and 22 days on average, respectively. Conclusion Strategies to address patients’ delay could have important implications for the success of the global tuberculosis control programmes.

Since its inception in 2003, Cost Effectiveness and Resource Allocation journal has come a long way over the past 18 years. Possibly much longer than many of its contemporaries in the blossoming science of health economics might have anticipated. Today, entering 2020 it celebrates the Age of Maturity. We believe that in the third decade of XXI century the interdisciplinary science of health economics, will rejuvenate and come back to us younger than ever from its early historical roots almost a century ago. The spreading of economic globalization in several distinctive ways, either led by multinational business corporations or newly emerged Asian leadership, or both, is likely to make challenges for contemporary health systems far more serious. The fourth industrial revolution (cyber physical systems and artificial intelligence technology) and accelerated innovation in the field of E-Health and digital health, will probably change the workflow in medical and health care, and inevitably transform the labour market in the upcoming decades. So, let us be up to the task. Let us provide academic centres, industry-sponsored pharmaceutical and medical device innovation hubs, and governing authorities alike, with a powerful forum for debate on cost-effective resource allocation in the years to come.

As decisions often need to be made in areas where there is a lack of published scientific evidence, CE is employed. Therefore to ensure its appropriateness the development of a validated CE data quality check-list to assist decision makers is essential and further research in this area is a priority.

Many countries are now considering the use of formal health economic methodologies to assess the value and prioritise health care interventions. However there is increasing recognition of the importance of values other than efficiency (cost effectiveness) in making acceptable decisions. This is manifest in the range of potential new approaches being developed including multiple criteria decision analysis.