Bevacizumab and ranibizumab for neovascular age-related macular degeneration: an updated meta-analysis of randomised clinical trials.

PURPOSE: Neovascular age-related macular degeneration (AMD) is the main cause of central vision loss among individuals aged 50 years or older in developed countries. The aim of this study was to review systematically the effect of bevacizumab compared to ranibizumab in patients with AMD at 1 year. METHODS: A systematic review was performed on Medline, Embase, and the Cochrane Library and Trial registers to October 2013. Eligibility criteria for selecting studies were randomised controlled trials (RCT) comparing bevacizumab with ranibizumab in patients with neovascular AMD. Odds ratio (OR) and mean difference (MD) estimates were synthesized under fixed- and random-effects models. Heterogeneity was assessed using the Q statistic and I(2). RESULTS: Five RCTs were included, representing 2,686 randomised patients. The meta-analysis confirmed the non-inferiority of bevacizumab compared to ranibizumab for change in visual acuity at 1 year (MD 0.57 letters, -1.80 to 0.66, p = 0.37, I(2) = 0 %). Better anatomical results were found for ranibizumab. Bevacizumab was associated with a 34 % increase in the number of patients with at least one serious systemic adverse event (OR 1.34, 1.08 to 1.66, p = 0.01, I(2) = 0 %). CONCLUSIONS: The pooled evidence confirmed that, compared with ranibizumab, bevacizumab was associated with equivalent effects on visual acuity at 1 year and with a higher risk of systemic serious adverse events. The current available data do not show which types of adverse events occur more frequently. In practice, bevacizumab should be used under a risk-management plan until further studies have been carried out to assess accurately the increased risk of systemic adverse events.

Fate of protocols submitted to a French national funding scheme: a cohort study.

BACKGROUND: The fate of clinical research projects funded by a grant has been investigated, but there is no information on the projects which did not receive funding. The fate of these projects is not known: do they apply for and/or receive funding from other sources or are they carried out without specific funding? PURPOSE: The aim of the study was to describe all clinical research projects submitted to a French national funding scheme (PHRC 2000) and to assess project initiation, completion and publication status taking into account whether or not they received funding. METHODS: This study is a retrospective cohort. The initial project characteristics were retrieved from the submission files and follow-up information was collected from the primary investigator. The percentages of projects started, completed and published were studied. RESULTS: A total of 481 projects were studied. Follow-up information was obtained for 366. Overall, 185 projects were initiated (51%); 139 of them were funded by the PHRC 2000 or other sources. The most commonly cited reason for not initiating a project was a lack of funding. Subsequently, 121 of the projects initiated were completed (65%). Accrual difficulties were the main reason cited to explain why studies were stopped prematurely or were still ongoing. Finally, 88 of the completed projects were published (73%). Amongst the completed projects, the only factor explaining publication was the statistical significance of the results. CONCLUSIONS: Obtainment of funding was a determining factor for project initiation. However, once initiated, the funding did not influence completion or publication.

Medical device assessment: scientific evidence examined by the French national agency for health - a descriptive study.

BACKGROUND: Scientific evidence supports decision-making on the use of implantable medical devices (IMDs) in clinical practice, but IMDs are thought to be far less investigated than drugs. In the USA, studies have shown that approval process of high-risk medical devices was often based on insufficiently robust studies, suggesting that evidence prior to marketing may not be adequate. This study aimed to ascertain level of evidence available for IMDs access to reimbursement in France. METHODS: The objective was to examine the scientific evidence used for IMDs assessment by the French National Authority for Health. We collected all public documents summarising supportive clinical data and opinions concerning IMDs issued in 2008. An opinion qualifies the expected benefit (EB) of the IMD assessed as sufficient or insufficient, and if sufficient, the level of improvement of the expected benefit (IEB) on a scale from major (level I) to no improvement (level V). For each opinion, the study with the highest level of evidence of efficacy data, and its design were collected, or, where no studies were available, any other data sources used to establish the opinion. RESULTS: One hundred and two opinions were analysed, with 72 reporting at least one study used for assessment (70.6%). When considering the study with the highest level of evidence: 34 were clinical non-comparative studies (47.2%); 29 were clinical comparative studies of which 25 randomised controlled trials (40.3%); 5 were meta-analyses of randomised controlled trials (6.9%); and 4 were systematic literature reviews (5.6%). The opinions were significantly different according to the study design (p < 0.001). The most frequent design for insufficient EB, IEB level V and IEB level IV was a non-comparative study (10/19, 52.6%; 15/24, 62.5%; and 8/15, 53.3%; respectively). For the 30 opinions with no supporting clinical study, 16 (53.3%) were based on an expert-based process, 9 (30.0%) were based on the conclusions of a previous opinion (all concluding IEB level V), and 5 (16.7%) reported no data (concluding insufficient EB for 4 and IEB level V for 1). CONCLUSIONS: This study confirmed that level of evidence of clinical evaluation of IMDs is low and needs to be improved.