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This presentation will aim to give an overview about benefit assessment for reimbursement decision making from an international perspective. Examples will be used to highlight differences between countries in their legal frameworks, addressing methodological issues, uncertainty, quantification of extent[for full text, please go to the a.m. URL], GMDS 2013; 58. Jahrestagung der Deutschen Gesellschaft für Medizinische Informatik, Biometrie und Epidemiologie e.V. (GMDS)

Background: Instruments supporting the development and assessment of guidelines, such as GRADE and AGREE, are well established. Yet sound methods in the development of a guideline are no guarantee that a recommendation is (still) valid. Usually the assessment of the internal validity of a recommendation[for full text, please go to the a.m. URL], G-I-N Conference 2012

BACKGROUND: Black people have a greater prevalence of elevated blood pressure leading to excess morbidity and mortality. OBJECTIVES: To systematically review the effects of different antihypertensive drugs on mortality, morbidity and blood pressure black adults with elevated blood pressure. SEARCH STRATEGY: Medline, Embase, LILACS, African Index Medicus, the Cochrane Library November 2003; Pubmed September 2003 to March 2004. Searches were conducted without language restriction. SELECTION CRITERIA: Randomised controlled trials of drugs versus placebo (blood pressure outcomes) or versus placebo or other drugs (morbidity and mortality outcomes). DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data unblinded. Disagreements were resolved by discussion. Authors were contacted twice to obtain missing information. MAIN RESULTS: Full reports or abstracts from more than 2900 references of papers yielded 30 trials considering 53 interventions with 8 classes of antihypertensive drugs in 20,006 black patients from Africa, the Caribbean, and the United States of America, aged 18 to >80 years.In one large trial the main morbidity and mortality outcomes did not differ significantly between initial treatment drug classes when drugs were added to reach goal blood pressures. However, the comparison ACE Inhibitors vs diuretic favoured the diuretic for stroke 1.40 [1.17 to 1.68]; combined CHD 1.15 [1.02 to 1.30] and combined CVD 1.19 [1.09 to 1.30] and the comparison alpha blocker vs diuretic favoured the diuretic for combined CVD 1.40 [1.25 to 1.57]. In addition, all comparisons for heart failure favoured diuretic (1.47 [1.24 to 1.74] vs calcium blocker; 1.32 [1.11 to 1.58] vs ACE Inhibitor; and 2.18 [1.73 to 2.74] vs alpha blocker. The results also showed a greater occurrence of diabetes with diuretics.No significant differences were detected between placebo and beta adrenergic blockers in the reduction of systolic blood pressure (weighted mean difference [95% CI], -3.52 [-7.50 to 0.46] mm Hg). In addition, ACE inhibitors did not significantly differ from placebo in achievement of goal diastolic blood pressure (risk difference [95% CI], 5% [-10% to 21%]). Calcium blockers, diuretics, centrally acting agents, alpha adrenergic blockers and angiotensin II antagonists were all more effective than placebo in reducing blood pressure in the pooled analyses. Only calcium blockers remained effective in all prespecified subgroups, including baseline diastolic blood pressure >109 mm Hg. AUTHORS' CONCLUSIONS: When first-line drugs from different classes are compared in the treatment of black people, there is no evidence of differential effects on most mortality and morbidity outcomes. Those morbidity differences that were found favoured diuretics. Drugs differ in their ability to reduce blood pressure in black people. Calcium blockers were the only drug class that reduced blood pressure in all subgroups of black people including those with severe hypertension. Beta-blockers, angiotensin receptor blocker, alpha blockers and ACE Inhibitors were least good at reducing blood pressure in black adults

Background: The use of systematic literature review to inform evidence based practice in diagnostics is rapidly expanding. Although the primary diagnostic literature is extensive, studies are often of low methodological quality or poorly reported. There has been no rigorously evaluated, evidence based tool to assess the methodological quality of diagnostic studies. The primary objective of this study was to determine the extent to which variations in the quality of primary studies impact the results of a diagnostic meta-analysis and whether this differs with diagnostic test type. A secondary objective was to contribute to the evaluation of QUADAS, an evidence-based tool for the assessment of quality in diagnostic accuracy studies. Methods: This study was conducted as part of large systematic review of tests used in the diagnosis and further investigation of urinary tract infection (UTI) in children. All studies included in this review were assessed using QUADAS, an evidence-based tool for the assessment of quality in systematic reviews of diagnostic accuracy studies. The impact of individual components of QUADAS on a summary measure of diagnostic accuracy was investigated using regression analysis. The review divided the diagnosis and further investigation of UTI into the following three clinical stages: diagnosis of UTI, localisation of infection, and further investigation of the UTI. Each stage used different types of diagnostic test, which were considered to involve different quality concerns. Results: Many of the studies included in our review were poorly reported. The proportion of QUADAS items fulfilled was similar for studies in different sections of the review. However, as might be expected, the individual items fulfilled differed between the three clinical stages. Regression analysis found that different items showed a strong association with test performance for the different tests evaluated. These differences were observed both within and between the three clinical stages assessed by the review. The results of regression analyses were also affected by whether or not a weighting (by sample size) was applied. Our analysis was severely limited by the completeness of reporting and the differences between the index tests evaluated and the reference standards used to confirm diagnoses in the primary studies. Few tests were evaluated by sufficient studies to allow meaningful use of meta-analytic pooling and investigation of heterogeneity. This meant that further analysis to investigate heterogeneity could only be undertaken using a subset of studies, and that the findings are open to various interpretations. Conclusion: Further work is needed to investigate the influence of methodological quality on the results of diagnostic meta-analyses. Large data sets of well-reported primary studies are needed to address this question. Without significant improvements in the completeness of reporting of primary studies, progress in this area will be limited.

Background: Further investigation of confirmed UTI in children aims to prevent renal scarring and future complications. Methods: We conducted a systematic review to determine the most effective approach to the further investigation of confirmed urinary tract infection (UTI) in children under five years of age. Results: 73 studies were included. Many studies had methodological limitations or were poorly reported. Effectiveness of further investigations: One study found that routine imaging did not lead to a reduction in recurrent UTIs or renal scarring. Diagnostic accuracy: The studies do not support the use of less invasive tests such as ultrasound as an alternative to renal scintigraphy, either to rule out infection of the upper urinary tract (LR- = 0.57, 95%CI: 0.47, 0.68) and thus to exclude patients from further investigation or to detect renal scarring (LR+ = 3.5, 95% CI: 2.5, 4.8). None of the tests investigated can accurately predict the development of renal scarring. The available evidence supports the consideration of contrast-enhanced ultrasound techniques for detecting vesico-ureteric reflux (VUR), as an alternative to micturating cystourethrography (MCUG) (LR+ = 14.1, 95% CI: 9.5, 20.8; LR- = 0.20, 95%CI: 0.13, 0.29); these techniques have the advantage of not requiring exposure to ionising radiation. Conclusion: There is no evidence to support the clinical effectiveness of routine investigation of children with confirmed UTI. Primary research on the effectiveness, in terms of improved patient outcome, of testing at all stages in the investigation of confirmed urinary tract infection is urgently required.

Background 50 % of pregnancies are unwanted. For several reasons including difficulty in obtaining contraceptives no or ineffective contraception is used to prevent these unwanted pregnancies. The Lactational Amenorrhoea Method(LAM) however is a contraceptive method available and accessible for many women. Objectives To assess in fully breastfeeding women staying amenorrheic the efficacy of the Lactational Amenorrhoea Method as a contraceptive method. The efficacy of LAM as defined in 1988 in Bellagio was compared with alternative definitions of LAM; the outcomes were measured using pregnancy and menstruation life tables. Search strategy Data sources: Medline searches from 1966 until 2002 and Embase from 1988 until 2002; reference lists of studies and review articles; books related to LAM; published abstracts from breastfeeding reproductive health contraceptive conferences; and e-mail communication with coordinators of such studies. Selection criteria From 454 potentially relevant studies 154 investigated the risk of pregnancy during LAM or lactational amenorrhea. Two reviewers applied the following inclusion criteria: prospective study cases and -if available-controls had to be sexually active pregnancy had to be confirmed by physical examination or a pregnancy test. Life table menstruation rates and life table pregnancy rates were taken as endpoints. Thirteen publications reporting on 9 intervention groups and 2 control groups met the inclusion criteria and were included in this systematic review. Their quality was assessed. Data collection and analysis Two reviewers independently extracted data disagreements were resolved through discussion. Because of the heterogeneity of the included studies the studies were analyzed using narrative methods. Main results For the outcome two controlled studies of LAM users reported life table pregnancy rates at 6 months of 0.45 and 2.45 percent and 5 uncontrolled studies of LAM users reported 0-7.5 percent. Life table pregnancy rates of women fully breastfeeding and amenorrheic but not using any contraceptive method were 0.88 in one study and 0.9-1.2 percent (95% CI 0.0- 2.4) in a second study depending on the definition of menstruation used. The life table menstruation rate at 6 months in all studies varied between 11.1-39.4 percent. Reviewers conclusions No clear difference in life table pregnancy rates was found between women using LAM and supported in doing so and fully breastfeeding amenorroic women not using any method. Because the length of lactation amenorrhoea of women using LAM is too different between populations studied and population specific it is uncertain whether LAM extends lactational amenorrhoea. (authors)

The bootstrap is a simple but versatile technique for the statistical analysis of random simulations.This tutorial explains the basics of that technique, and applies it to the well-known M/M/1 queuing simulation.In that numerical example, different responses are studied.For some responses, bootstrapping indeed gives better statistical results than parametric statistical techniques do.

Variations in treatment effects between drug trials are usually attributed to different patient characteristics, variations in outcome assessment, and random error. We have previously hypothesized that part of the variation in treatment effects between drug trials might be caused by differences in nonspecific factors. In a randomized clinical trial, we aimed to investigate whether experimentally induced expectancy can modify the analgesic effect of tramadol relative to placebo in chronic pain patients. In a 2 x 2 factorial, randomized, placebo-controlled, double-blind trial, chronic pain patients attending a chronic pain outpatient clinic were randomized to receive a single oral dose of 50 mg tramadol or placebo, and they were further randomized to receive positive or neutral information, verbally expressed by the physician, regarding the expected analgesic effect of the drug. Pain intensity was measured using a 10 centimeter visual analogue scale at baseline, and 0.5, 1, 2, 4, 6, and 8 hours after baseline. The one-hour pain intensity difference, calculated as the sum of pain intensity differences between baseline and 0.5 and 1 hour, was taken as main outcome measure. The one-hour sum of pain intensity differences of 28 patients treated after positive expectation and randomized to tramadol was 1.4 cm, while in 27 patients randomized to placebo, it was 0.8 cm. This corresponds with an analgesic effect of tramadol relative to placebo of 0.6 cm (95% confidence interval [CI], -0.5 cm to 1.8 cm). The 28 patients in the neutral expectancy group who were randomized to tramadol reported a 1.4 cm decrease on the sum of pain intensity differences, while 28 patients in the placebo group reported a 0.9 cm decrease. This corresponds with an analgesic effect of tramadol relative to placebo of 0.5 cm (95% CI, -0.9 cm to 1.8 cm). The 0.1 cm difference (0.6 cm - 0.5 cm) in analgesic effect between positive and neutral expectancy group was not statistically significant (95% CI, -0.7 cm to 1.0 cm). This trial did not discern a significant difference in the analgesic effect of tramadol between a positive and neutral expectancy group. This means that the phenomenon either does not exist, or we had an inappropriate model to demonstrate it. Regardless, this study demonstrates the type of quality trial that should be done to find out which non-specific factors, such as information regarding the expected effect, can modify treatment effects

Objective: The U.K. NHS Economic Evaluation Database (EED) project is commissioned to identify papers on economic evaluations of health technologies and to disseminate their findings to NHS decision makers by means of structured abstracts that are available through a public database and the Cochrane Library. This paper discusses current issues relating to the economic aspects of producing NHS EED abstracts. Methods: A review of NHS EED was undertaken between 1994 and 1999 to determine the methodologies adopted and issues that influence the usefulness of economic evaluations. Methods adopted to improve the quality of NHS EED abstracts are also reported. Results: Eighty-five percent of NHS EED abstracts are cost-effectiveness analyses (CEAs), 9.3% are cost-utility analyses (CUAs), and only 1.4% are cost-benefit analyses (CBAs). Of the total abstracts, 65.9% are based on single studies, 19.5% on reviews, 3.9% on estimates of effectiveness, and 10.7% on combinations of these sources. Models are utilized in 16.7% of CEAs, 60.2% of CUAs, and 20% of CBAs. Analyses of CBA studies reveal a degree of misuse of well-established definitions. NHS EED internal control mechanisms are reported that provide a means of ensuring that abstracts are based on sound academic principles. Conclusions: Most economic evaluations are conducted by means of CEA, followed by CUA, while CBA accounts for an extreme minority of cases. Single studies form the principal source of effectiveness data, although models are widely used, principally in CUA. The structure of NHS EED abstracts provides decision makers with the principal results and an interpretation of the relative strengths and weaknesses of economic evaluations.

Contains fulltext : 148826.pdf (author's version ) (Open Access) This paper deals with the validation ideas of three fields, namely hard OR, soft OR, and system dynamics. Validation is an important, yet a very controversial, issue on model based fields. Even though everyone seems to agree that the validation of models must be assessed, the viewpoints on what validation is and how it should be established differ widely. The purpose of this paper is to (a) describe the similarities and differences (both within and between) the three fields (b) to provide explanations for the differences, in order to (c) create mutual awareness and understanding, and (d) to increase our understanding of the issues surrounding validation. We will first start with the validation opinions of the three fields and then describe and explain the differences in these opinions and their reasons. 20 juli 1999 17 p.