Evidence-Based Medicine Breaking the Borders - The European Union as a Paradigm

Evidence-based medicine has instigated a shift in medical paradigms over the last decade. Systematic reviews and meta-analyses in particular have a strong impact on the way we practice medicine today. Although evidence-based medicine focuses on results at an individual patient level, the assumption that an increase in the practicing of evidence-based medicine will lead to health improvements of the general population seems to be a causal chain. The influence of evidence-based medicine is continually extending beyond clinical decision- making to act as a foundation for health policy decisions. The European Union has realized the potential benefits of evidence-based health care. Under the umbrella of thee-Health initiative, the European Union plans to implement a telematic (telecommunication and informatics) health network by the end of 2004. The objective of this network is to facilitate information exchange and to provide databases of the best evidence available in health care. Health care providers and the general public will be able to access these databases through the internet free of charge. Evaluations of the network will have to focus on the extent and depth health care decision makers accept, use and apply not only the databases but clinical guidelines as well. The only substantial official publication of the EU regarding this program is a report by the European Commission on evidence-based health care. The document mentions three components to improve evidence-based health care in the European Union: (1) Evidence-based medicine; (2) Clinical practice guidelines and; (3) Health technology assessment. However, no official information about the structure of a telematic health network has become available yet. The challenge though is unique - to link 15 different health systems with 11 different languages. This paper first gives some background information about the practice of evidence-based medicine - a description of the status quo; a review of its development; and a critical appraisal of its usage - including benefits and risks of evidence-based medicine and a detailed look at its influence on health policy in general. Next, the paper provides an overview of the health systems of the European Union and the political and theoretical framework of a telematic health network. Based on these premises, a hypothetical structure of evidence-based databases is proposed. This concept takes the heterogeneity of the European Union into consideration and examines factors that will be crucial for the acceptance of evidence-based databases and clinical practice guidelines by health care decision makers. It discusses lessons that could be learned from existing databases on national and internationill levels. It also describes the necessity of a parallel evaluation program and outlines methods of evaluation that could be successfully used to assess the impact and effectiveness of the program and provide a base for cybernetic decision - making.Master of Public Healt

The Impact of Inclusion Criteria in Health Economic Assessments

The article of record as published may be found at https://doi.org/10.2165/11590150-000000000-00000This study aims to present complex network models which analyze professional swimmers of 50-m freestyle Olympic competitions, comparing characteristics and variables that are considered performance determinants. This comparative research includes Olympic medalists’ versus non-medalists’ behavior. Using data from 40 athletes with a mean age, weight and height of 26 ± 2.9 years, 87 ± 5.59 kg, 193 ± 3.85 cm, respectively, at the Olympics of 2000, 2004, 2008, 2012, and 2016 (16-year interval), we built two types of complex networks (graphs) for each edition, using mathematical correlations, metrics and the spectral decomposition analysis. It is possible to show that complex metrics behave differently between medalists and non-medalists. The spectral radius (SR) proved to be an important form of evaluation since in all 5 editions it was higher among medalists (SR results: 3.75, 3.5, 3.39, 2.91, and 3.66) compared to non- medalists (2.18, 2.51, 2.23, 2.07, and 2.04), with significantly differences between. This study introduces a remarkable tool in the evaluation of the performance of groups of swimming athletes by complex networks, and is relevant to athletes, coaches, and even amateurs, regarding how individual variables relate to competition results and are reflected in the SR for the best performance. In addition, this is a general method and may, in the future, be developed in the analysis of other competitive sports

How effective are common medications: a perspective based on meta-analyses of major drugs

Study protocol. (PDF 161 kb

SAMURAI: Sensitivity analysis of a meta-analysis with unpublished but registered analytical investigations (software)

Abstract Background The non-availability of clinical trial results contributes to publication bias, diminishing the validity of systematic reviews and meta-analyses. Although clinical trial registries have been established to reduce non-publication, the results from over half of all trials registered in ClinicalTrials.gov remain unpublished even 30 months after completion. Our goals were i) to utilize information available in registries (specifically, the number and sample sizes of registered unpublished studies) to gauge the sensitivity of a meta-analysis estimate of the effect size and its confidence interval to the non-publication of studies and ii) to develop user-friendly open-source software to perform this quantitative sensitivity analysis. Methods The open-source software, the R package SAMURAI, was developed using R functions available in the R package metafor. The utility of SAMURAI is illustrated with two worked examples. Results Our open-source software SAMURAI, can handle meta-analytic datasets of clinical trials with two independent treatment arms. Both binary and continuous outcomes are supported. For each unpublished study, the dataset requires only the sample sizes of each treatment arm and the user predicted ‘outlook’ for the studies. The user can specify five outlooks ranging from ‘very positive’ (i.e., very favorable towards intervention) to ‘very negative’ (i.e., very favorable towards control). SAMURAI assumes that control arms of unpublished studies have effects similar to the effect across control arms of published studies. For each experimental arm of an unpublished study, utilizing the user-provided outlook, SAMURAI randomly generates an effect estimate using a probability distribution, which may be based on a summary effect across published trials. SAMURAI then calculates the estimated summary treatment effect with a random effects model (DerSimonian & Laird method), and outputs the result as a forest plot. Conclusions To our knowledge, SAMURAI is currently the only tool that allows systematic reviewers to incorporate information about sample sizes of treatment groups in registered but unpublished clinical trials in their assessment of the potential impact of publication bias on meta-analyses. SAMURAI produces forest plots for visualizing how inclusion of registered unpublished studies might change the results of a meta-analysis. We hope systematic reviewers will find SAMURAI to be a useful addition to their toolkit

Vitamin D deficiency as a risk factor for dementia: a systematic review and meta-analysis

Abstract Background Sunlight exposure and high vitamin D status have been hypothesised to reduce the risk of developing dementia. The objective of our research was to determine whether lack of sunlight and hypovitaminosis D over time are associated with dementia. Methods We systematically searched MEDLINE (via PubMed), Cochrane Library, EMBASE, SCOPUS, Web of Science, ICONDA, and reference lists of pertinent review articles from 1990 to October 2015. We conducted random effects meta-analyses of published and unpublished data to evaluate the influence of sunlight exposure or vitamin D as a surrogate marker on dementia risk. Results We could not identify a single study investigating the association between sunlight exposure and dementia risk. Six cohort studies provided data on the effect of serum vitamin D concentration on dementia risk. A meta-analysis of five studies showed a higher risk for persons with serious vitamin D deficiency (<25\ua0nmol/L or 7\u201328\ua0nmol/L) compared to persons with sufficient vitamin D supply (\u226550\ua0nmol/L or 54\u2013159\ua0nmol/L) (point estimate 1.54; 95% CI 1.19\u20131.99, I 2 \u2009=\u200920%). The strength of evidence that serious vitamin D deficiency increases the risk of developing dementia, however, is very low due to the observational nature of included studies and their lack of adjustment for residual or important confounders (e.g. ApoE \u3b54 genotype), as well as the indirect relationship between Vitamin D concentrations as a surrogate for sunlight exposure and dementia risk. Conclusions The results of this systematic review show that low vitamin D levels might contribute to the development of dementia. Further research examining the direct and indirect relationship between sunlight exposure and dementia risk is needed. Such research should involve large-scale cohort studies with homogeneous and repeated assessment of vitamin D concentrations or sunlight exposure and dementia outcomes

Efficacy and safety of donepezil, galantamine, and rivastigmine for the treatment of Alzheimer’s disease: A systematic review and meta-analysis

Pharmacologic treatments for Alzheimer’s disease include the cholinesterase inhibitors donepezil, galantamine, and rivastigmine. We reviewed their evidence by searching MEDLINE®, Embase, The Cochrane Library, and the International Pharmaceutical Abstracts from 1980 through 2007 (July) for placebo-controlled and comparative trials assessing cognition, function, behavior, global change, and safety. Thirty-three articles on 26 studies were included in the review. Meta-analyses of placebo-controlled data support the drugs’ modest overall benefits for stabilizing or slowing decline in cognition, function, behavior, and clinical global change. Three open-label trials and one double-blind randomized trial directly compared donepezil with galantamine and rivastigmine. Results are conflicting; two studies suggest no differences in efficacy between compared drugs, while one study found donepezil to be more efficacious than galantamine, and one study found rivastigmine to be more efficacious than donepezil. Adjusted indirect comparison of placebo-controlled data did not find statistically significant differences among drugs with regard to cognition, but found the relative risk of global response to be better with donepezil and rivastigmine compared with galantamine (relative risk = 1.63 and 1.42, respectively). Indirect comparisons also favored donepezil over galantamine with regard to behavior. Across trials, the incidence of adverse events was generally lowest for donepezil and highest for rivastigmine

German language questionnaires for assessing implementation constructs and outcomes of psychosocial and health-related interventions: a systematic review

Abstract Background Over the past years, implementation science has gained more and more importance in German-speaking countries. Reliable and valid questionnaires are needed for evaluating the implementation of evidence-based practices. On an international level, several initiatives focused on the identification of questionnaires used in English-speaking countries but limited their search processes to mental health and public health settings. Our aim was to identify questionnaires used in German-speaking countries measuring the implementation of interventions in public health and health care settings in general and to assess their psychometric properties. Methods We searched five different bibliographic databases (from 1985 to August 2017) and used several other search strategies (e.g., reference lists, forward citation) to obtain our data. We assessed the instruments, which were identified in an independent dual review process, using 12 psychometric rating criteria. Finally, we mapped the instruments’ scales and subscales in regard to the constructs of the Consolidated Framework for Implementation Research (CFIR) and the Implementation Outcome Framework (IOF). Results We identified 31 unique instruments available for the assessment of implementation science constructs. Hospitals and other health care settings were the ones most often investigated (23 instruments), while education and childcare settings, workplace settings, and community settings lacked published instruments. Internal consistency, face and content validity, usability, and structural validity were the aspects most often described. However, most studies did not report on test-retest reliability, known-groups validity, predictive criterion validity, or responsiveness. Overall, the majority of studies did not reveal high-quality instruments, especially regarding the psychometric criteria internal consistency, structural validity, and criterion validity. In addition, we seldom detected instruments operationalizing the CFIR domains intervention characteristics, outer setting, and process, and the IOF constructs adoption, fidelity, penetration, and sustainability. Conclusions Overall, a sustained and continuous effort is needed to improve the reliability and validity of existing instruments to new ones. Instruments applicable to the assessment of implementation constructs in public health and community settings are urgently needed. Trial registration The systematic review protocol was registered in PROSPERO on October 19, 2017, under the following number: CRD42017075208

Crowdsourcing and COVID-19: a case study of Cochrane Crowd

Cochrane has used crowdsourcing effectively to identify health evidence since 2014. To date, over 175,000 trialshave been identified for Cochrane’s Central Register of Controlled Trials via Cochrane Crowd (https://crowd.cochrane.org), Cochrane’s citizen science platform, engaging a Crowd of over 20,000 people from 166 countries. The COVID-19 pandemic presented the evidence synthesis community with the enormous challenge of keeping up with the exponential output of COVID-19 research. This case study will detail the new tasks we developed to aid the production of COVID-19 rapid reviews and supply the Cochrane COVID-19 study register. The pandemic initially looked set to disrupt the Crowd team’s plans for 2020 but has in fact served to further our understanding of the potential role crowdsourcing can play in the health evidence ecosystem

Hormone Therapy for the Primary Prevention of Chronic Conditions in Postmenopausal Women: Evidence Report and Systematic Review for the US Preventive Services Task Force

Importance: Postmenopausal status coincides with increased risks for chronic conditions such as heart disease, osteoporosis, cognitive impairment, or some types of cancers. Previously, hormone therapy was used for the primary prevention of these chronic conditions. Objective: To update evidence for the US Preventive Services Task Force on the benefits and harms of hormone therapy in reducing risks for chronic conditions. Data Sources: MEDLINE, Cochrane Library, EMBASE, and trial registries from June 1, 2011, through August 1, 2016. Surveillance for new evidence in targeted publications was conducted through July 1, 2017. Study Selection: English-language randomized clinical trials reporting health outcomes. Data Extraction and Synthesis: Dual review of abstracts, full-text articles, and study quality; meta-analyses when at least 3 similar studies were available. Main Outcomes and Measures: Beneficial or harmful changes in risks for various chronic conditions. Results: Eighteen trials (n = 40 058; range, 142-16 608; mean age, 53-79 years) were included. Women using estrogen-only therapy compared with placebo had significantly lower risks, per 10 000 person-years, for diabetes (-19 cases [95% CI, -34 to -3]) and fractures (-53 cases [95% CI, -69 to -39]). Risks were statistically significantly increased, per 10 000 person-years, for gallbladder disease (30 more cases [95% CI, 16 to 48]), stroke (11 more cases [95% CI, 2 to 23]), venous thromboembolism (11 more cases [95% CI, 3 to 22]), and urinary incontinence (1261 more cases [95% CI, 880 to 1689]). Women using estrogen plus progestin compared with placebo experienced significantly lower risks, per 10 000 person-years, for colorectal cancer (-6 cases [95% CI, -9 to -1]), diabetes (-14 cases [95% CI, -24 to -3), and fractures (-44 cases [95% CI, -71 to -13). Risks, per 10 000 person-years, were significantly increased for invasive breast cancer (9 more cases [95% CI, 1 to 19]), probable dementia (22 more cases [95% CI, 4 to 53]), gallbladder disease (21 more cases [95% CI, 10 to 34]), stroke (9 more cases [95% CI, 2 to 19]), urinary incontinence (876 more cases [95% CI, 606 to 1168]), and venous thromboembolism (21 more cases [95% CI, 12 to 33]). Conclusions and Relevance: Hormone therapy for the primary prevention of chronic conditions in menopausal women is associated with some beneficial effects but also with a substantial increase of risks for harms. The available evidence regarding benefits and harms of early initiation of hormone therapy is inconclusive