Objectives: The purpose of the European network for Health Technology Assessment (EUnetHTA) is to make HTA agencies collaborate sharing methods and tools thus avoiding duplication of evaluative efforts and allowing resource savings. From 2010 to 2012, the activities of the network were carried out through EUnetHTA Joint Action 1 and Work Package 4 Strand B aimed at producing two Core HTAs with two main objectives: to test the Web based Core model and the collaborative working models. Our objective in this article is to give an historical record of the Work Package activities highlighting what worked and what did not in the collaboration of researchers' groups coming from different agencies. Methods: A retrospective description of all the steps for the joint production of the two Core HTAs is provided starting from the first step of selecting technologies of common interest. Primary researchers' views on the whole process have been collected through a semi-structured telephonic interview supported by a questionnaire. Coordinators views were gathered during internal meetings and validated. Results: Majority of respondents thought topic selection procedure was not clear and well managed. About collaborative models, small groups were seen to enable more exchange, whatever the model. According to coordinators, loss of expertise and experience during the production process, different languages, and novelty of the Online Tool were main barriers. Conclusions: Lessons learned from this first experience in Joint Action 1 paved the path for the collaboration in Joint Action 2, as it allowed enhancements and changes in models of collaborations and coordination.
\n \n\n \n \nBackground: A framework for collaborative production and sharing of HTA information, the HTA Core Model, was originally developed within EUnetHTA in 2006-08. In this paper, we describe the further development of the Model to allow implementation and utilization of the Model online. The aim was to capture a generic HTA process that would allow effective use of the HTA Core Model and resulting HTA information while at the same time not interfering with HTA agencies' internal processes. Methods: The work was coordinated by a development team in Finland, supported by an international expert group. Two pilot testing rounds were organized among EUnetHTA agencies and two extensive core HTA projects tested the tool in a real setting. The final work was also formally validated by a group of HTA agencies. Results: The HTA Core Model Online - available at http://www.corehta.info - is a web site hosting a) a tool to allow electronic utilization of the HTA Core Model and b) a database of produced HTA information. While access to the HTA information is free to all, the production features are currently available to EUnetHTA member agencies only. A policy was crafted to steer the use of the Model and produced information. Conclusions: We have successfully enabled electronic use of the HTA Core Model and agreed on a policy for its utilization. The system is already being used in subsequent HTA projects within EUnetHTA Joint Action 2. Identified shortcomings and further needs will be addressed in subsequent development.
\n \n\n \n \nIntroduction: We present three systematic reviews carried out within the Cochrane Collaboration, focusing on a different influenza intervention in healthy adults: Vaccines; Ion Channel Inhibitor antivirals and Neuraminidase Inhibitor (NIs) antivirals. The objectives were to identify, retrieve and assess all studies evaluating the effects of these interventions in prophylaxis and early treatments of influenza and the frequency of adverse events. Additionally we present the results of the economic evaluation of effective alternatives in order to define the most cost-effective intervention. The economic evaluation is set in the context of the British Army. Methods: Studies were identified using a standard Cochrane search strategy. Any randomised or quasi-randomised studies in healthy individuals aged 14-60 years were considered for inclusion in the systematic review. Those which met inclusion criteria were assessed for quality and their data meta-analysed. The economic model was constructed using Cost-effectiveness and Cost-utility study designs. Results: Live aerosol vaccines reduced cases of clinical influenza A with virological confirmation (by serology and/or viral isolation) by 48% (95%CI: 24-64%), whilst recommended inactivated parenteral vaccines have an efficacy of 68% (95%CI: 49-79%). Vaccine effectiveness in reducing clinical influenza cases (i.e. without virological confirmation) was lower, with efficacies of 13 and 24% respectively. Use of the vaccine significantly reduced time off work, but only by 0.4 days (95%CI: 0.1-0.8 days). Analysis of vaccines matching the circulating strain gave higher estimates of efficacy, whilst inclusion of all other vaccines reduced the efficacy. When compared to placebo for the prevention of influenza, oral amantadine was 61% (95%CI: 51-69%) efficacious (RR 0.39 - 95%CI: 0.31-0.49), and oral rimantadine was 64% (95%CI: 41-78%) efficacious (RR 0.36 - 95%CI: 0.22-0.59). When compared to placebo for the treatment of influenza, oral amantadine significantly shortened duration of fever (by 1.00 days - 95%CI: 0.73-1.29), and oral rimantadine significantly shortened duration of fever (by 1.27 days - 95%CI: 0.77-1.77). When compared to placebo, NIs were 74% (95%CIs: 50-87%) effective in preventing naturally occurring cases of clinically defined influenza. In a treatment role, NIs shortened the duration of symptoms by one day (Weighted Mean Difference - 1.0; 95%CIs: -1.3 to - 0.6) when a clinical case definition is used. The economic results show that in healthy adults, inactivated vaccines appear the best buy. Conclusions: If assessed from the point of view of effectiveness and efficiency, vaccines are undoubtedly the best preventive means for clinical influenza in healthy adults. However, when safety and quality of life considerations are included, parenteral vaccines have such low effectiveness and high incidence of trivial local adverse effects that the trade-off is unfavourable. This is so even when the incidence of influenza is high and adverse effect quality of life preferences are rated low. We reached similar conclusions for antivirals and NIs even at high influenza incidence levels. On current evidence we conclude in healthy adults aged 14-60 the most cost-effective option is not to take any action.
\n \n\n \n \nContext: The quality of a process can only be tested against its agreed objectives. Editorial peer-review is widely used, yet there appears to be little agreement about how to measure its effects or processes. Methods: To identify outcome measures used to assess editorial peer review as performed by biomedical journals, we analyzed studies identified from 2 systematic reviews that measured the effects of editorial peer review on the quality of the output (ie, published articles) or of the process itself (eg, reviewers' comments). Results: Ten studies used a variety of instruments to assess the quality of articles that had undergone peer review. Only 1, nonrandomized study compared the quality of articles published in peer-reviewed and non-peer-reviewed journals. The others measured the effects of variations in the peer-review process or used a before-and-after design to measure the effects of standard peer review on accepted articles. Eighteen studies measured the quality of reviewers' reports under different conditions such as blinding or after training. One study compared the time and cost of different review processes. Conclusions: Until we have properly defined the objectives of peer-review, it will remain almost impossible to assess or improve its effectiveness. The research needed to understand the broader effects of peer review poses many methodologic problems and would require the cooperation of many parts of the scientific community.
\n \n\n \n \nContext: Reviews performed almost a decade ago showed considerable gaps in the quality of reporting and methods applied to economic evaluations of health care interventions. Measures taken by the research community to address the issue included the promulgation of guidelines and the publicizing of good practice in economic evaluation. Methods: To assess the quality of methods of systematic reviews, economic evaluations in health care, and reporting methods, we conducted full-text searches of private and public databases for the period 1990 through March 2001 and corresponded with researchers active in the field. A total of 102 reports were identified, but only 39 were included. Quality of systematic reviews was assessed by a 6-item checklist. Results: Quality of review methods was reasonable, but more attention needs to be paid to search methods and standardization of evaluation instruments. The reviews found consistent evidence of serious methodological flaws in a significant number of economic evaluations. Lack of clear descriptions of methods, lack of explanation and justification for the framework and approach used, and low-quality estimates of effectiveness for the interventions evaluated were the most frequent flaws. Modest improvements in quality of conducting and reporting economic evaluations appear to have taken place in the last decade. Conclusions: Proper allocation of resources on the basis of economic evaluations remains uncertain. Editorial teams and regulatory bodies should perform quality assurance based on a single widely accepted and validated standard instrument.
\n \n\n \n \nContext: Editorial peer review is widely used to select submissions to journals for publication and is presumed to improve their usefulness. Sufficient research on peer review has been published to consider a synthesis of its effects. Methods To examine the evidence of the effects of editorial peer-review processes in biomedical journals, we conducted electronic and full-text searches of private and public databases to June 2000 and corresponded with the World Association of Medical Editors, European Association of Science Editors, Council of Science Editors, and researchers in the field to locate comparative studies assessing the effects of any stage of the peer-review process that made some attempt to control for confounding. Nineteen of 135 identified studies fulfilled our criteria. Because of the diversity of study questions, methods, and outcomes, we did not pool results. Results: Nine studies considered the effects of concealing reviewer/author identity. Four studies suggested that concealing reviewer or author identity affected review quality (mostly positively); however, methodological limitations make their findings ambiguous, and other studies' results were either negative or inconclusive. One study suggested that a statistical checklist can improve report quality, but another failed to find an effect of publishing another checklist. One study found no evidence that training referees improves performance and another showed increased interrater reliability; both used open designs, making interpretation difficult. Two studies of how journals communicate with reviewers did not demonstrate any effect on review quality. One study failed to show reviewer bias, but the findings may not be generalizable . One nonrandomized study compared the quality of articles published in peer-reviewed vs other journals. Two studies showed that editorial processes make articles more readable and improve the quality of reporting, but the findings may have limited generalizability to other journals. Conclusions: Editorial peer review, although widely used, is largely untested and its effects are uncertain.
\n \n\n \n \nObjective: To review systematically the evidence of effectiveness of physical interventions to interrupt or reduce the spread of respiratory viruses. Data sources: Cochrane Library, Medline, OldMedline, Embase, and CINAHL, without restrictions on language or publication. Data selection: Studies of any intervention to prevent the transmission of respiratory viruses (isolation, quarantine, social distancing, barriers, personal protection, and hygiene). A search of study designs included randomised trials, cohort, case-control, crossover, before and after, and time series studies. After scanning of the titles, abstracts and full text articles as a first filter, a standardised form was used to assess the eligibility of the remainder. Risk of bias of randomised studies was assessed for generation of the allocation sequence, allocation concealment, blinding, and follow-up. Non-randomised studies were assessed for the presence of potential confounders and classified as being at low, medium, or high risk of bias. Data synthesis: 58 papers of 59 studies were included. The quality of the studies was poor for all four randomised controlled trials and most cluster randomised controlled trials; the observational studies were of mixed quality. Meta-analysis of six case-control studies suggested that physical measures are highly effective in preventing the spread of severe acute respiratory syndrome: handwashing more than 10 times daily (odds ratio 0.45, 95% confidence interval 0.36 to 0.57; number needed to treat=4, 95% confidence interval 3.65 to 5.52), wearing masks (0.32, 0.25 to 0.40; NNT=6, 4.54 to 8.03), wearing N95 masks (0.09, 0.03 to 0.30; NNT=3, 2.37 to 4.06), wearing gloves (0.43, 0.29 to 0.65; NNT=5, 4.15 to 15.41), wearing gowns (0.23, 0.14 to 0.37; NNT=5, 3.37 to 7.12), and handwashing, masks, gloves, and gowns combined (0.09, 0.02 to 0.35; NNT=3, 2.66 to 4.97). The combination was also effective in interrupting the spread of influenza within households. The highest quality cluster randomised trials suggested that spread of respiratory viruses can be prevented by hygienic measures in younger children and within households. Evidence that the more uncomfortable and expensive N95 masks were superior to simple surgical masks was limited, but they caused skin irritation. The incremental effect of adding virucidals or antiseptics to normal handwashing to reduce respiratory disease remains uncertain. Global measures, such as screening at entry ports, were not properly evaluated. Evidence was limited for social distancing being effective, especially if related to risk of exposure - that is, the higher the risk the longer the distancing period. Conclusion: Routine long term implementation of some of the measures to interrupt or reduce the spread of respiratory viruses might be difficult. However, many simple and low cost interventions reduce the transmission of epidemic respiratory viruses. More resources should be invested into studying which physical interventions are the most effective, flexible, and cost effective means of minimising the impact of acute respiratory tract infections.
\n \n\n \n \nBackground: A systematic review found that 3% of working adults who had received influenza vaccine and 5% of those who were unvaccinated had laboratory-proven influenza per season; in healthcare workers (HCWs) these percentages were 5% and 8% respectively. Healthcare workers may transmit influenza to patients. Objectives: To identify all randomised controlled trials (RCTs) and non-RCTs assessing the effects of vaccinating healthcare workers on the incidence of laboratory-proven influenza, pneumonia, death from pneumonia and admission to hospital for respiratory illness in those aged 60 years or older resident in long-term care institutions (LTCIs). Search methods: We searched CENTRAL (2015, Issue 9), MEDLINE (1966 to October week 3, 2015), EMBASE (1974 to October 2015) and Web of Science (2006 to October 2015), but Biological Abstracts only from 1969 to March 2013 and Science Citation Index-Expanded from 1974 to March 2013 due to lack of institutional access in 2015. Selection criteria: Randomised controlled trials (RCTs) and non-RCTs of influenza vaccination of healthcare workers caring for individuals aged 60 years or older in LTCIs and the incidence of laboratory-proven influenza and its complications (lower respiratory tract infection, or hospitalisation or death due to lower respiratory tract infection) in individuals aged 60 years or older in LTCIs. Data collection and analysis: Two authors independently extracted data and assessed risk of bias. Effects on dichotomous outcomes were measured as risk differences (RDs) with 95% confidence intervals (CIs). We assessed the quality of evidence with GRADE. Main results: We identified four cluster-RCTs and one cohort study (n = 12,742) of influenza vaccination for HCWs caring for individuals \u2265 60 years in LTCIs. Four cluster RCTs (5896 residents) provided outcome data that addressed the objectives of our review. The studies were comparable in their study populations, intervention and outcome measures. The studies did not report adverse events. The principal sources of bias in the studies related to attrition, lack of blinding, contamination in the control groups and low rates of vaccination coverage in the intervention arms, leading us to downgrade the quality of evidence for all outcomes due to serious risk of bias. Offering influenza vaccination to HCWs based in long term care homes may have little or no effect on the number of residents who develop laboratory-proven influenza compared with those living in care homes where no vaccination is offered (RD 0 (95% CI -0.03 to 0.03), two studies with samples taken from 752 participants; low quality evidence). HCW vaccination probably leads to a reduction in lower respiratory tract infection in residents from 6% to 4% (RD -0.02 (95% CI -0.04 to 0.01), one study of 3400 people; moderate quality evidence). HCW vaccination programmes may have little or no effect on the number of residents admitted to hospital for respiratory illness (RD 0 (95% CI -0.02 to 0.02, one study of 1059 people; low quality evidence). We decided not to combine data on deaths from lower respiratory tract infection (two studies of 4459 people) or all cause deaths (four studies of 8468 people). The direction and size of difference in risk varied between the studies. We are uncertain as to the effect of vaccination on these outcomes due to the very low quality of evidence. Adjusted analyses, which took into account the cluster design, did not differ substantively from the pooled analysis with unadjusted data. Authors' conclusions: Our review findings have not identified conclusive evidence of benefit of HCW vaccination programmes on specific outcomes of laboratory-proven influenza, its complications (lower respiratory tract infection, hospitalisation or death due to lower respiratory tract illness), or all cause mortality in people over the age of 60 who live in care institutions. This review did not find information on co-interventions with healthcare worker vaccination: hand-washing, face masks, early detection of laboratory-proven influenza, quarantine, avoiding admissions, antivirals and asking healthcare workers with influenza or influenza-like illness (ILI) not to work. This review does not provide reasonable evidence to support the vaccination of healthcare workers to prevent influenza in those aged 60 years or older resident in LTCIs. High quality RCTs are required to avoid the risks of bias in methodology and conduct identified by this review and to test further these interventions in combination.
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