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Gloucester, United Kingdom

Whyte S.,Assessment Technology Group
Health technology assessment (Winchester, England) | Year: 2010

This paper presents a summary of the evidence review group (ERG) report into the clinical effectiveness and cost-effectiveness of bevacizumab in combination with fluoropyrimidine-based chemotherapy for the first-line treatment of metastatic colorectal cancer based on the manufacturer's submission to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal (STA) process. Evidence was available in the form of one phase III, multicentre, multinational, randomised, open-label study (NO16966 trial). This two-arm study was originally designed to demonstrate the non-inferiority of oral capecitabine plus oxaliplatin (XELOX) compared with 5-fluorouracil plus folinic acid plus oxaliplatin (FOLFOX)-4 in adult patients with histologically confirmed metastatic colorectal cancer who had not previously been treated. Following randomisation of 634 patients, the open-label study was amended to include a 2 × 2 factorial randomised (partially blinded for bevacizumab) phase III trial with the coprimary objective of demonstrating superiority of bevacizumab in combination with chemotherapy compared with chemotherapy alone. Measured outcomes included overall survival, progression-free survival, response rate, adverse effects of treatment and health-related quality of life. The manufacturer's primary pooled analysis of superiority (using the intention-to-treat population) showed that after a median follow-up of 28 months, the addition of bevacizumab to chemotherapy significantly improved progression-free survival and overall survival compared with chemotherapy alone in adult patients with histologically confirmed metastatic colorectal cancer who were not previously treated [median progression-free survival 9.4 vs 7.7 months (absolute difference 1.7 months); hazard ratio (HR) 0.79, 97.5% confidence interval (CI) 0.72 to 0.87; p = 0.0001; median overall survival 21.2 vs 18.9 months (absolute difference 2.3 months); HR 0.83, 97.5% CI 0.74 to 0.93; p = 0.0019]. The NO16966 trial was of reasonable methodological quality and demonstrated a significant improvement in both progression-free survival and overall survival when bevacizumab was added to XELOX or FOLFOX. However, the size of the actual treatment effect of bevacizumab is uncertain. The ERG believed that the modelling structure employed was appropriate, but highlighted several key issues and areas of uncertainty. At the time of writing, NICE was yet to issue the guidance for this appraisal.

Samson D.,Washington Technology | Schoelles K.M.,Assessment Technology Group
Journal of General Internal Medicine | Year: 2012

Topic development and structuring a systematic review of diagnostic tests are complementary processes. The goals of a medical test review are to identify and synthesize evidence to evaluate the impacts alternative testing strategies on health outcomes and to promote informed decisionmaking. A common challenge is that the request for a review may state the claim for the test ambiguously. Due to the indirect impact of medical tests on clinical outcomes, reviewers need to identify which intermediate outcomes link a medical test to improved clinical outcomes. In this paper, we propose the use of five principles to deal with challenges: the PICOTS typology (patient population, intervention, comparator, outcomes, timing, setting), analytic frameworks, simple decision trees, other organizing frameworks and rules for when diagnostic accuracy is sufficient. © 2012 Agency for Healthcare Research and Quality (AHRQ).

Main C.,Assessment Technology Group
The Cochrane database of systematic reviews | Year: 2013

Evidence from systematic reviews of observational studies suggest that hormone replacement therapy (HT) may have beneficial effects in reducing the incidence of cardiovascular disease (CVD) events in post-menopausal women. This is an updated version of a Cochrane review first published in 2005 (Gabriel-Sanchez 2005). To assess the effects of HT for the prevention of CVD in post-menopausal women, and whether there are differential effects between use of single therapy alone compared to combination HT and use in primary or secondary prevention. We searched the following databases to April 2010: Cochrane Central Register of Controlled Trials (CENTRAL) on The Cochrane Library, MEDLINE, EMBASE and LILACS. Randomised controlled trials (RCTs) of women comparing orally administered HT with placebo with a minimum of six-months follow-up. Two authors independently assessed study quality and extracted data. Risk Ratios (RR) with 95% confidence intervals were calculated for each outcome. Results were combined using fixed-effect meta-analyses, and where possible, further stratified analyses conducted to assess the effect of time on treatment. Additionally, univariate meta-regression analyses were undertaken to assess whether length of trial follow-up, single or combination treatment, or whether treatment for primary or secondary prevention were potential predictors for a number of CVD outcomes in the trials. Four new trials were identified through the update; one trial included in the previous review was excluded. Therefore the review included 13 trials with a total of 38,171 post-menopausal women. Overall, single and combination HT in both primary and secondary prevention conferred no protective effects for all cause mortality, CVD death, non-fatal MI, or angina. There were no significant differences in the number of coronary artery by-pass procedures or angioplasties performed between the trial arms. However there was an increased risk of stroke for both primary and secondary prevention when combination and single HT was combined, RR 1.26 (95% CI 1.11 to 1.43), in venous thromboembolic events, RR 1.89 (95% CI 1.58 to 2.26) and in pulmonary embolism RR 1.84 (95% CI 1.42 to 2.37) relative to placebo. The associated numbers needed-to-harm (NNH) were 164, 109 and 243 for stroke, venous thromboembolism and pulmonary embolism respectively. Treatment with HT in post-menopausal women for either primary or secondary prevention of CVD events is not effective, and causes an increase in the risk of stroke, and venous thromboembolic events. HT should therefore only be considered for women seeking relief from menopausal symptoms. Short-term HT treatment should be at the lowest effective dose, and used with caution in women with predisposing risk factors for CVD events.

Objectives: The expected lifetime of a health technology is a critical parameter in value of information analysis and in two methodologies for cost-effectiveness analysis which have recently been suggested. The first method allows for the possibility that a superior technology will become available in the future. The second advocates modeling both the prevalent and all future incident patient cohorts. Unfortunately, for value of information analysis, the period of time over which information about the decision problem would be useful is very uncertain, and existing estimates are seemingly arbitrary. Furthermore, there is very little literature on the historical lifetimes of technologies. Here, I quantify and analyze the historical lifetimes of drugs in England. I then apply this information to inform the value of further research and the cost-effectiveness of health technologies. Methods: A Weibull regression model was fitted to the historical drug lifetimes of 455 drugs. These represented all British National Formulary drugs in England which were launched from 1981 to 2007, and which did not have very low sales volumes. Results: The mean drug lifetime was 57 years (95% confidence interval 39-79 years), and the median was 46 years (35-60 years). Drugs with low sales volumes tended to have shorter lifetimes. Under certain assumptions, the ratio of population level to per-year expected value of information is 21. Drug lifetimes are used to parameterize the two models of cost-effectiveness. Conclusions: The distribution function of the historical lifetimes of drugs can inform suitable time horizons for: 1) value of information; and 2) cost-effectiveness analyses related to drugs. © 2010, International Society for Pharmacoeconomics and Outcomes Research (ISPOR).

Cochrane reviews are one of the best known and most trusted sources of evidence-based information in health care. While steps have been taken to make Cochrane intervention reviews accessible to a diverse readership, little is known about the accessibility of the newcomer to the Cochrane library: diagnostic test accuracy reviews (DTARs). The current qualitative study explored how healthcare decision makers, who varied in their knowledge and experience with test accuracy research and systematic reviews, read and made sense of DTARs. A purposive sample of clinicians, researchers and policy makers (n = 21) took part in a series of think-aloud interviews, using as interview material the first three DTARs published in the Cochrane library. Thematic qualitative analysis of the transcripts was carried out to identify patterns in participants' 'reading' and interpretation of the reviews and the difficulties they encountered. Participants unfamiliar with the design and methodology of DTARs found the reviews largely inaccessible and experienced a range of difficulties stemming mainly from the mismatch between background knowledge and level of explanation provided in the text. Experience with systematic reviews of interventions did not guarantee better understanding and, in some cases, led to confusion and misinterpretation. These difficulties were further exacerbated by poor layout and presentation, which affected even those with relatively good knowledge of DTARs and had a negative impact not only on their understanding of the reviews but also on their motivation to engage with the text. Comparison between the readings of the three reviews showed that more accessible presentation, such as presenting the results as natural frequencies, significantly increased participants' understanding. The study demonstrates that authors and editors should pay more attention to the presentation as well as the content of Cochrane DTARs, especially if the reports are aimed at readers with various levels of background knowledge and experience. It also raises the question as to the anticipated target audience of the reports and suggests that different groups of healthcare decision-makers may require different modes of presentation.

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