Technology Assessment Reports Research Articles

Effectiveness and Cost-Efficacy of Phosphate Binders in Hemodialysis

Objectives: Worldwide, incidence rates of chronic renal insufficiency have clearly increased over the past decade, especially in people of older age. Hyperphosphatemia is the strongest independent risk factor for mortality in renal patients. In order to reduce serum phosphate concentrations to recommended values, phosphate binders (P binders) are used to bind ingested phosphate in the digestive tract. Besides the traditional therapies with calcium and aluminium salts, sevelamer and lanthanum represent recent developments on the market. The purpose of the present health technology assessment (HTA) report was to compare the effectiveness and safety of different P binders in patients with chronic renal insufficiency. Methods: Based on a systematic literature search followed by a two-part selection process with predefined criteria 18 publications were included in the assessment. Results: All P binders effectively controlled serum phosphate, calcium and parathyroid hormone concentrations. The numbers of hypercalcemic episodes were higher when using calcium-containing P binders compared to sevelamer and lanthanum. Regarding mortality rate, cardiovascular calcification and bone metabolism no definite conclusions could be drawn; however, sevelamer seemed to be more effective than calcium in certain patient subgroups, such as older patients and patients with preexisting arterial calcification. Conclusions: From a medical point of view, sevelamer showed superiority over calcium-containing P binders at least for special indications.

The Use of Quality-Adjusted Life-Years in the Economic Evaluation of Health Technologies in Spain: A Review of the 1990–2009 Literature

Objective To appraise economic evaluations of health technologies that included quality-adjusted life-years (QALYs) as an outcome measure conducted over the past 20 years in Spain. Methods A systematic review of the literature was conducted. Economic evaluations that included QALYs as an outcome measure, conducted in Spain and published between January 1990 and December 2009 were identified. Primary and gray literature sources were reviewed. Results A total of 60 articles and 4 health technology assessment reports were included. Key findings were 1) the vast majority of articles (77.1%) referred to therapeutic interventions; 2) 63.2% dealt with pharmaceutical products and much fewer with preventive strategies, medical devices, or diagnostic interventions; 3) most evaluations referred to cardiovascular- (19.8%), respiratory- (16.3%), and cancer- (13.0%) related processes; 4) 80.3% were based on a theoretical model, most commonly Markov models (71.4%); 5) 67.3% adopted the National Health System perspective; 6) information on the methods used to describe the health states was given in 45.1% of studies; 7) 40.3% used the EuroQoL-5D to elicit preferences, whereas 66.1% gave no details on the methods applied to determine patients' choices; 8) it was possible to state who completed the questionnaires in only 17.7% of studies; 9) 77.1% of the interventions assessed were below the €30,000/QALY suggested affordable threshold in Spain. Conclusions An increasing number of economic evaluations using QALYs had been conducted. Most of them relied on theoretical models. Several methodological issues remain unsolved. Great disparity exists regarding the reporting of the methods used to determine health states and utility values.

Drug-eluting stents in patients at high risk of restenosis: Assessment for France

In unselected patients, the incidence of restenosis is lower after placement of drug-eluting stents (DES) than bare-metal stents (BMS) without difference in safety at a time horizon of 4 years. However, DES appears less effective in "off label" patients. The aim of the study was to assess available evidence of DES efficacy and safety by patient category to establish when DES placement may be recommended for reimbursement by the French national health insurance. Based on a systematic review by patient category (January 2002 to August 2009), two health technology assessment (HTA) reports and thirty-eight clinical studies not covered by the HTA reports (eleven meta-analysis including ours, eleven randomized trials and sixteen cohort studies) were selected. After assessment of the methodological quality, the studies mostly comparing DES with BMS were reviewed by a panel of health professionals who defined a priori the most relevant end points of safety and efficacy. Seven to fourteen patients treated with DES were needed to avoid one target lesion revascularization (TLR) in patients with lesions >15 mm long, vessel diameter <3 mm, or diabetes, and with some complex lesions (total coronary occlusion, BMS in-stent restenosis multivessel disease, unprotected left main stenosis). DES appeared as safe as other alternatives over a follow-up of up to 4 years when dual antiplatelet therapy was continued for at least 1 year, but statistical power remains limited to conclude for some clinical features. For reimbursement, DES use should be limited to certain categories of patients. Treatment of particular cases requires a multidisciplinary approach.

Economic Burden of Renal Cell Carcinoma

The economic burden of renal cell carcinoma (RCC) came into sharp focus when the UK National Institute for Health and Clinical Excellence (NICE) denied coverage (later reversed) of sunitinib for metastatic RCC. In the first of two articles that provide updated reviews and analyses of the economic burden of RCC, we conducted an updated literature review of RCC-related economic studies. We performed a literature search of PubMed, EMBASE and the Cochrane Library for English-language studies published from 1 January 2000 to 15 June 2010. We also performed a separate search for related studies in the Health Technology Assessment (HTA) reports published by the National Institute for Health Research HTA Programme in the UK. Identified articles were classified into three categories: cost studies, cost-effectiveness/cost-utility studies and cost-of-illness studies. All cost estimates were normalized to $US, year 2009 values. We identified 20 articles, including six cost, six cost-utility and eight cost-of-illness studies. In general, the studies found new surgical techniques, such as laparoscopic partial nephrectomy, to be potentially cost saving (in the range of $US181-5842). Targeted agents, such as bevacizumab, sunitinib, sorafenib and temsirolimus, were associated with higher lifetime costs ($US8537-72 254) and were not always considered to be cost effective by authors of the cost-effectiveness studies included in this review (incremental cost-effectiveness ratio [ICER]: $US49 959-272 418 per QALY). The literature reported annual estimates of the US economic burden of RCC between $US0.60 billion and $US5.19 billion, with per-patient costs of $US16 488-43 805. RCC is associated with substantial economic burden, although the estimates are wide ranging. Comparisons of the estimates across studies were hindered by variations in study methodology, choice of database and the associated timeframe, and limitations inherent to each database. More research is needed to assess the quality of the economic studies of RCC and to understand why the estimated costs differ across studies.

When the decision is what to decide: Using evidence inventory reports to focus health technology assessments

Health systems frequently make decisions regarding acquisition and use of new technologies. It is desirable to base these decisions on clinical evidence, but often these technologies are used for multiple indications and evidence of effectiveness for one indication does not prove effectiveness for all. Here, we describe two examples of evidence inventory reports that were performed for the purposes of identifying how much and what type of published clinical evidence was available for a given technology, and the contexts in which those technologies were studied. The evidence inventory reports included literature searches for systematic reviews and health technology assessment (HTA) reports, and systematic searches of the primary literature intended to count and categorize published clinical studies. The reports did not include analysis of the primary literature. The inventory reports were completed in 3 to 4 days each and were approximately ten pages in length, including references. Reports included tables listing the number of reported studies by specific indication for use, and whether or not there were randomized trials. Reports also summarized findings of existing systematic reviews and HTA reports, when available. Committees used the inventory reports to decide for which indications they wanted a full HTA report. Evidence inventory reports are a form of rapid HTA that can give decision makers a timely understanding of the available evidence upon which they can base a decision. They can help HTA providers focus subsequent reports on topics that will have the most influence on healthcare decision making.

Health-related quality of life and utility in patients receiving biological and non-biological treatments in rheumatoid arthritis

Biological treatments earn increasing significance in the treatment of rheumatoid arthritis (RA) but are associated with high incremental cost-effectiveness ratio compared to conventional antirheumatic treatments such as disease-modifying antirheumatic drugs. As the most important objective of medical technologies should be to increase life years and/or patients' health-related quality of life (HRQoL), measuring QoL and utility in RA patients treated with biological therapies is crucial. The objective of this study is to compare the utility and QoL of patients treated with biological (n = 85) and non-biological (n = 168) antirheumatic drugs in Hungary in a cross-sectional non-interventional study. A measure of impairment (Disease Activity Score (DAS)-28), QoL measure (EuroQol five Dimension (EQ-5D) Visual Analogue Scale (VAS), Rheumatoid Arthritis Quality of Life (RAQoL)) and utility measures (indirect: EQ-5D index, direct: time trade-off (TTO)) were applied using an interview method. The Pearson correlation was used to assess the strength of the relationship of different measures in the total study group (n = 253). The EQ-5D index (biological treatment: 0.608, non-biological treatment: 0.483; P = 0.012) and DAS-28 (biological treatment: 3.8, non-biological treatment: 4.5; P = 0.003) showed statistically significant difference between the two subcohorts after adjusting data by age, gender and disease duration. Our results indicate that patients on biological treatment have lower disease activity and higher utility; however, it was not statistically significant in all cases. According to our knowledge, TTO was not used previously in Hungarian RA patients. Utility data concerning biological treatments are essential for cost-utility models in health technology assessment reports for public reimbursement.

Answer to the letter to the editor of Carl Hans Fürstenberg et al. (2010) concerning manuscript “transforaminal endoscopic surgery for lumbar stenosis: a systematic review” by Jorm Nellensteijn, Raymond Ostelo, Ronald Bartels, Wilco Peul, Barend Van Royen, Maurits Van Tulder. Eur Spine J 19:879–886

In the letter to the editor it is suggested that we might have missed relevant evidence. Not including ‘discectomy’ in the search strategy is pointed out as the main reason. But apparently there is confusion regarding the fact that we published two systematic reviews, both on transforaminal endoscopic surgery. One focuses on symptomatic lumbar disc herniations [1] and the second one on lumbar stenosis [2]. We combined the search strategy for these two reviews for efficiency reasons. The keywords were used as MESH headings and free text words; discectomy was included in the search strategy [1]. The full search strategy is available upon request. In the present review we focus on stenosis. The SCIATICA-Med trial [3, 4] included patients with lumbar disc herniation and was therefore not eligible for this review. Moreover, it clearly uses a different technique than the transforaminal endoscopic surgery. Therefore, this study was also excluded from our systematic review on symptomatic lumbar disc herniations [1]. The German health technology assessment report [5] focuses on the treatment of disc prolapse and not stenosis. The study by Hermantin et al. [6] met the inclusion criteria for review on symptomatic lumbar disc herniations [1] and was included (see Ref. 11 of that review). The report by the Dutch Health Care Insurance also focuses on lumbar disc herniation and was based on our review [1]. The three key publications [7–9] that we reportedly ‘omitted’ were included in our review on symptomatic lumbar disc herniations [1] as they included patients with lumbar disc herniation. The study by Molyneux was not found as our search strategy was up to November 2009. Conference proceedings did not meet our definition of ‘published papers’ and therefore Lewandrowski [10] and Iprenburg [11] were not included. The reference by Morgenstern [12] could not be retrieved, as the European Musculoskeletal Review seems not to be indexed in the databases we searched. The study by Hoogland [13] includes patients with recurrent lumbar disc herniation, not stenosis. In assessing the risk of bias, we followed the guidelines of the Cochrane Back Review Group and, therefore, we think that the doubt the authors convey regarding ‘the publication quality assessment criteria’ is without any foundation. In conclusion, no randomized controlled trial, but only seven observational studies were identified and no relevant papers are missed. All these studies had a high risk of bias. Consequently, the conclusion that there is no valid evidence on the effectiveness of transforaminal endoscopic surgery for lumbar stenosis is supported by the data.

Letter to the editor concerning “Transforaminal endoscopic surgery for lumbar stenosis: a systematic review” (Nellensteijn et al.)

The recently published systematic review by Nellensteijn et al. [1] has identified seven observational studies on the effectiveness of transforaminal endoscopic surgery for lumbar stenosis. The authors conclude that there is a lack of valid evidence supporting the intervention. We believe that there is more evidence in the literature than that found. Probably, this is due to the authors not including discectomy as a major key word in their search strategy (Table 1). First and foremost, there are at least three systematic reviews that provide additional data. Gibson and Waddell [2] refer to the SCIATICA-Med Trial [3, 4] and a German health technology assessment report [5] identified three RCTs and 12 case series between 1998 and 2004 focusing on endoscopically assisted minimally invasive disc surgery. None of these is duplicated in the Nellensteijn review and, most interestingly, a former review with the same title and group of authors funded by the Dutch Health Care Insurance Board, yielded 8 controlled studies and 31 cohort studies [6]. The 2010 Nellensteijn review has also omitted three key publications on the grounds of lacking focus on lumbar stenosis [7–9] and data from several observational studies focusing on foraminal treatment access [10–15]. These data should at least have been referred to when considering the potential effectiveness of transforaminal endoscopic surgery in a full text evaluation. In addition to criticisms regarding missing data, there is some doubt about whether or not the publication quality assessment criteria used by the authors are appropriate and state of the art, as there are established instruments [16, 17] for this purpose. It should also be noted that the Prisma Flow diagram is not used in the review [18], which further impairs the quality of the paper. We respectfully suggest that there should be better documentation of the study selection process with detailed reporting of reasons for inclusions and exclusions.

Molecular Testing for Response to Treatment for Chronic Myeloid Leukemia (CML) Patients: Information Available to Decision Makers on the Costs and Analytical and Clinical Validity of Alternative Approaches.

AbstractAbstract 4489 Objectives:Several “home-brew” and commercially available BCR-ABL gene transcript molecular monitoring detection methodologies are in use for the detection of residual leukemia disease in patients with CML. However there are a large number of variables between sample collection and final result including different volumes and cell counts samples, different RNA extraction methods, different detection instrument platforms, different reference genes to compare BCR-ABL ratios to an internal control gene and different comparators for quantification. Overcoming this lack of comparability can be attempted by either a standardization of procedures or external calibration of results obtained with the different approaches. However even with standardization or external calibration it is difficult to compare results obtained from different laboratories because of the wide range of techniques used. Equally importantly, information is required for decision makers not only on the analytical and clinical validity of the tests but also on their overall cost and cost effectiveness. The objective of this study was to assess the quantity and quality of information available to decision makers to choose the most appropriate testing procedure. Methods:English language systematic literature review on the i) costs ii) cost effectiveness and iii) analytical and clinical validity (including intra- and inter-laboratory variability) of BCR-ABL molecular monitoring testing in CML. Results:From approximately 100 papers retrieved for detailed analysis we found no published studies which examined the costs or cost effectiveness of molecular testing in CML. We found one (now dated) health service technology assessment report which examined the cost effectiveness of polymerase chain reaction in the diagnosis and monitoring of patients with BCR-ABL gene rearrangement in CML. There are a number of studies which have compared alternative approaches using the same patient sample in molecular monitoring in the same laboratory. However, unambiguous conclusions from these studies are difficult to make due to i) the use of different comparators and or testing platforms, ii) studies being conducted in different time periods with consequent changes in technology and iii) wildly varying sample sizes which make comparisons of statistical significance difficult. There are several well conducted studies which have examined the variability of results from different laboratories in controlled environments. Conclusion:Decision makers require information on both the costs and benefits of competing approaches to molecular monitoring detection methodologies to make informed choices on the most appropriate form of patient management. Although there is a degree of evidence on the analytical validity for different approaches to CML molecular testing, information on the costs and cost effectiveness of molecular diagnostics in CML appear is essentially non-existent. Although it is known that testing variability has potentially serious implications for patient outcomes it is also the case that decision makers require information on the costs and cost-effectiveness of different approaches to CML testing to maximize the return on health budgets that are experiencing on-going financial pressures. Disclosures:Braendle:Novartis Pharmaceuticals: Employment. Hudson:phmrconsulting: Consultancy. Diego:Novartis Pharmaceuticals: Employment. Mark:phmrconsulting: Consultancy.

A systematic review of PET and PET/CT in oncology: a way to personalize cancer treatment in a cost-effective manner?

BackgroundA number of diagnostic tests are required for the detection and management of cancer. Most imaging modalities such as computerized tomography (CT) are anatomical. However, positron emission tomography (PET) is a functional diagnostic imaging technique using compounds labelled with positron-emitting radioisotopes to measure cell metabolism. It has been a useful tool in studying soft tissues such as the brain, cardiovascular system, and cancer. The aim of this systematic review is to critically summarize the health economic evidence of oncologic PET in the literature.MethodsEight electronic databases were searched from 2005 until February 2010 to identify economic evaluation studies not included in previous Health Technology Assessment (HTA) reports. Only full health economic evaluations in English, French, or German were considered for inclusion. Economic evaluations were appraised using published quality criteria for assessing the quality of decision-analytic models. Given the variety of methods used in the health economic evaluations, the economic evidence has been summarized in qualitative form.ResultsFrom this new search, 14 publications were identified that met the inclusion criteria. All publications were decision-analytic models and evaluated PET using Fluorodeoxyglucose F18 (FDG-PET). Eight publications were cost-effectiveness analyses; six were cost-utility analyses. The studies were from Australia, Belgium, Canada, France, Italy, Taiwan, Japan, the Netherlands, the United Kingdom, and the United States. In the base case analyses of these studies, cost-effectiveness results ranged from dominated to dominant. The methodology of the economic evaluations was of varying quality. Cost-effectiveness was primarily influenced by the cost of PET, the specificity of PET, and the risk of malignancy.ConclusionsOwing to improved care and less exposure to ineffective treatments, personalized medicine using PET may be cost-effective. However, the strongest evidence for the cost-effectiveness of PET is still in the staging of non-small cell lung cancer. Management decisions relating to the assessment of treatment response or radiotherapy treatment planning require further research to show the impact of PET on patient management and its cost-effectiveness. Because of the potential for increased patient throughput and the possible greater accuracy, the cost-effectiveness of PET/CT may be superior to that of PET. Only four studies of the cost-effectiveness of PET/CT were found in this review, and this is clearly an area for future research.

P36– Is a literature search in the Cochrane Library enough when preparing health technology assessment reports or clinical guidelines with focus on treatment outcome?

P36– Is a literature search in the Cochrane Library enough when preparing health technology assessment reports or clinical guidelines with focus on treatment outcome?

The GRADE approach for assessing new technologies as applied to apheresis devices in ulcerative colitis

BackgroundIn the last few years, a new non-pharmacological treatment, termed apheresis, has been developed to lessen the burden of ulcerative colitis (UC). Several methods can be used to establish treatment recommendations, but over the last decade an informal collaboration group of guideline developers, methodologists, and clinicians has developed a more sensible and transparent approach known as the Grading of Recommendations, Assessment, Development and Evaluation (GRADE). GRADE has mainly been used in clinical practice guidelines and systematic reviews. The aim of the present study is to describe the use of this approach in the development of recommendations for a new health technology, and to analyse the strengths, weaknesses, opportunities, and threats found when doing so.MethodsA systematic review of the use of apheresis for UC treatment was performed in June 2004 and updated in May 2008. Two related clinical questions were selected, the outcomes of interest defined, and the quality of the evidence assessed. Finally, the overall quality of each question was taken into account to formulate recommendations following the GRADE approach. To evaluate this experience, a SWOT (strengths, weaknesses, opportunities and threats) analysis was performed to enable a comparison with our previous experience with the SIGN (Scottish Intercollegiate Guidelines Network) method.ResultsApplication of the GRADE approach allowed recommendations to be formulated and the method to be clarified and made more explicit and transparent. Two weak recommendations were proposed to answer to the formulated questions. Some challenges, such as the limited number of studies found for the new technology and the difficulties encountered when searching for the results for the selected outcomes, none of which are specific to GRADE, were identified. GRADE was considered to be a more time-consuming method, although it has the advantage of taking into account patient values when defining and grading the relevant outcomes, thereby avoiding any influence from literature precedents, which could be considered to be a strength of this method.ConclusionsThe GRADE approach could be appropriate for making the recommendation development process for Health Technology Assessment (HTA) reports more explicit, especially with regard to new technologies.

Comparison of tools for assessing the methodological quality of primary and secondary studies in health technology assessment reports in Germany.

Health care policy backgroundFindings from scientific studies form the basis for evidence-based health policy decisions.Scientific backgroundQuality assessments to evaluate the credibility of study results are an essential part of health technology assessment reports and systematic reviews. Quality assessment tools (QAT) for assessing the study quality examine to what extent study results are systematically distorted by confounding or bias (internal validity). The tools can be divided into checklists, scales and component ratings.Research questionsWhat QAT are available to assess the quality of interventional studies or studies in the field of health economics, how do they differ from each other and what conclusions can be drawn from these results for quality assessments?MethodsA systematic search of relevant databases from 1988 onwards is done, supplemented by screening of the references, of the HTA reports of the German Agency for Health Technology Assessment (DAHTA) and an internet search. The selection of relevant literature, the data extraction and the quality assessment are carried out by two independent reviewers. The substantive elements of the QAT are extracted using a modified criteria list consisting of items and domains specific to randomized trials, observational studies, diagnostic studies, systematic reviews and health economic studies. Based on the number of covered items and domains, more and less comprehensive QAT are distinguished. In order to exchange experiences regarding problems in the practical application of tools, a workshop is hosted.ResultsA total of eight systematic methodological reviews is identified as well as 147 QAT: 15 for systematic reviews, 80 for randomized trials, 30 for observational studies, 17 for diagnostic studies and 22 for health economic studies. The tools vary considerably with regard to the content, the performance and quality of operationalisation. Some tools do not only include the items of internal validity but also the items of quality of reporting and external validity. No tool covers all elements or domains. Design-specific generic tools are presented, which cover most of the content criteria.DiscussionThe evaluation of QAT by using content criteria is difficult, because there is no scientific consensus on the necessary elements of internal validity, and not all of the generally accepted elements are based on empirical evidence. Comparing QAT with regard to contents neglects the operationalisation of the respective parameters, for which the quality and precision are important for transparency, replicability, the correct assessment and interrater reliability. QAT, which mix items on the quality of reporting and internal validity, should be avoided.ConclusionsThere are different, design-specific tools available which can be preferred for quality assessment, because of its wider coverage of substantive elements of internal validity. To minimise the subjectivity of the assessment, tools with a detailed and precise operationalisation of the individual elements should be applied. For health economic studies, tools should be developed and complemented with instructions, which define the appropriateness of the criteria. Further research is needed to identify study characteristics that influence the internal validity of studies.

Potential benefits of using a toolkit developed to aid in the adaptation of HTA reports: a case study considering positron emission tomography (PET) and Hodgkin's disease.

BackgroundThe preparation of HTA reports requires a great deal of time, effort and resource, and there is a desire to improve efficiency, avoid duplication of effort and facilitate the transfer of knowledge between countries. This is of particular importance for countries with more limited resources which have less capacity to produce their own reports. The aim of this study was to investigate the extent of duplication of published Health Technology Assessment (HTA) reports, on the same technology, for the same indication; using positron emission tomography (PET) for lung cancer and Hodgkin's disease as a case study. This was done in order to assess the potential usefulness of a toolkit developed to aid in the adaptation of HTA reports from one context or country to another.MethodsA systematic search of the National Institute for Health Research (NIHR) CRD HTA database was conducted in June 2008 in order to identify full HTA reports containing information on the use of PET for lung cancer and Hodgkin's disease, written in English, and readily available on the web. The contents of the reports identified were then examined to assess the extent of duplication of content between reports and potential for the use of the toolkit.ResultsFrom 132 records of HTA reports about PET, 8 reports were identified as fulfilling all the criteria set, and therefore demonstrating potential duplication of effort. All these reports covered four similar domains, technology use, safety, effectiveness and economic evaluation. Five of the reports also considered organisational aspects.ConclusionsThere was some duplication of effort in the preparation of HTA reports concerned with the use of PET for lung cancer and Hodgkin's disease. This is an example of where resource could have been conserved and time saved by the use of a toolkit developed to aid in the adaptation of HTA reports from one context to another.

Reporting bias in medical research - a narrative review.

Reporting bias represents a major problem in the assessment of health care interventions. Several prominent cases have been described in the literature, for example, in the reporting of trials of antidepressants, Class I anti-arrhythmic drugs, and selective COX-2 inhibitors. The aim of this narrative review is to gain an overview of reporting bias in the medical literature, focussing on publication bias and selective outcome reporting. We explore whether these types of bias have been shown in areas beyond the well-known cases noted above, in order to gain an impression of how widespread the problem is. For this purpose, we screened relevant articles on reporting bias that had previously been obtained by the German Institute for Quality and Efficiency in Health Care in the context of its health technology assessment reports and other research work, together with the reference lists of these articles.We identified reporting bias in 40 indications comprising around 50 different pharmacological, surgical (e.g. vacuum-assisted closure therapy), diagnostic (e.g. ultrasound), and preventive (e.g. cancer vaccines) interventions. Regarding pharmacological interventions, cases of reporting bias were, for example, identified in the treatment of the following conditions: depression, bipolar disorder, schizophrenia, anxiety disorder, attention-deficit hyperactivity disorder, Alzheimer's disease, pain, migraine, cardiovascular disease, gastric ulcers, irritable bowel syndrome, urinary incontinence, atopic dermatitis, diabetes mellitus type 2, hypercholesterolaemia, thyroid disorders, menopausal symptoms, various types of cancer (e.g. ovarian cancer and melanoma), various types of infections (e.g. HIV, influenza and Hepatitis B), and acute trauma. Many cases involved the withholding of study data by manufacturers and regulatory agencies or the active attempt by manufacturers to suppress publication. The ascertained effects of reporting bias included the overestimation of efficacy and the underestimation of safety risks of interventions.In conclusion, reporting bias is a widespread phenomenon in the medical literature. Mandatory prospective registration of trials and public access to study data via results databases need to be introduced on a worldwide scale. This will allow for an independent review of research data, help fulfil ethical obligations towards patients, and ensure a basis for fully-informed decision making in the health care system.

Medical and health economic evaluation of prevention- and control measures related to MRSA infections or -colonisations at hospitals.

IntroductionMethicillin-resistant Staphylococcus aureus (MRSA) are dangerous agents of nosocomial infections. In 2007 the prevalence of MRSA is 20.3% in Germany (Oxacilline-resistance according to EUCAST-criteria [EUCAST = European Committee on Antimicrobial Susceptibility Testing]).ObjectivesWhich measurements are effective in the prevention and control of MRSA-infections in the hospital?How effective are contact precautions, screening, decolonisation, education and surveillance?Which recommendations can be given to health care politics on the basis of cost-effectiveness studies?Have there been any adverse effects on patients and clinical staff?What kind of liability problems exist?MethodsBased on a systematic review of the literature studies are included which have been published in German or English language since 2004.Results1,508 articles have been found. After having surveyed the full text, 33 medical, eight economic and four ethical/juridical studies are included for the Health Technology Assessment (HTA) report.The key result of the HTA report is that different measurements are effective in the prevention and control of MRSA-infections in hospitals, though the majority of the studies has a low quality. Effective are the conduction of differentiated screening measurements if they take into account the specific endemic situation, the use of antibiotic-control programs and the introduction and control of hygienic measurements. The break even point of preventive and control measurements cannot be defined because the study results differ too much. In the future it has to be more considered that MRSA-infections and contact precautions lead to a psycho-social strain for patients.DiscussionIt is hardly possible to describe causal efficacies because in the majority of the studies confounders are not sufficiently considered. In many cases bundles of measurements have been established but not analyzed individually. The internal and external validity of the studies is too weak to evaluate single interventions. Hygienic measurements prove to be effective in combination with other measurements. But it cannot be said which of the single measurements (gloves, washing hands, wearing gowns or masks) has the strongest effect on the reduction of MRSA. It is irritating that there are high differences in the compliance concerning hand hygiene between different studies. A general decolonisation is questionable for different reasons: first because of the side-effects for patients, second because of the high rate of spontaneous remissions in the untreated control group, third because of the differentiated process from colonisation to infection. Severalfold Hawthorne effects have been reported. One of them is that the competition between hospitals to reduce MRSA-rates leads already to a reduction.ConclusionsIt is evident that selective screening programs of risk patients considering the particular MRSA-prevalence are of use. The application of rapid tests seems to be only recommendable for risk patients and a high MRSA-prevalence. The improvement of the compliance of hand hygiene should be the basis of any prevention strategy. Training of staff members (with feedback mechanisms) is effective to improve compliance and to optimise the use of antibiotics. Antibiotic management programs are effective as well. Obviously multimodal approaches can lead to overadditive effects. Therefore the catalogue of preventive and control measurements has to be further evaluated. Good cost-efficacy studies are missing in Germany. The psychosocial effects of MRSA-infections are not researched in Germany. There is only punctual information on the risk management of hospitals.

EVITA: a tool for the early EValuation of pharmaceutical Innovations with regard to Therapeutic Advantage

BackgroundNew drugs are generally claimed to represent a therapeutic innovation. However, scientific evidence of a substantial clinical advantage is often lacking. This may be the result of using inadequate control groups or surrogate outcomes only in the clinical trials. In view of this, EVITA was developed as a user-friendly transparent tool for the early evaluation of the additional therapeutic value of a new drug.MethodsEVITA does not evaluate a new compound per se but in an approved indication in comparison with existing therapeutic strategies. Placebo as a comparator is accepted only in the absence of an established therapy or if employed in an add-on strategy on top. The evaluation attributes rating points to the drug in question, taking into consideration both therapeutic benefit and risk profile. The compound scores positive points for superiority in efficiency and/or adverse effects as demonstrated in randomized controlled trials (RCTs), whilst negative points are awarded for inferiority and/or an unfavorable risk profile. The evaluation follows an algorithm considering the clinical relevance of the outcomes, the strength of the therapeutic effect and the number of RCTs performed. Categories for therapeutic aim and disease severity, although essential parts of the EVITA assessment, are attributed but do not influence the EVITA score which is presented as a color-coded bar graph. In case the available data were unsuitable for an EVITA calculation, a traffic-type yield sign is assigned instead to criticize such practice. The results are presented online http://www.evita-report.de together with all RCTs considered as well as the reasons for excluding a given RCT from the evaluation. This allows for immediate revision in response to justified criticism and simplifies the inclusion of new data.ResultsAs examples, four compounds which received approval within the last years were evaluated for one of their clinical indications: lenalidomide, pioglitazone, bupropion and zoledronic acid. Only the first achieved an EVITA score above zero indicating therapeutic advantage.ConclusionsThe strength of EVITA appears to lie in its speedy assessment of the potential therapeutic advantage of a new drug for a given indication. At the same time, this approach draws attention to the typical deficits of data used for drug approval. EVITA is not intended to replace classical health technology assessment reports but rather serves as a screening tool in the sense of horizon scanning.

Prognostic value, clinical effectiveness, and cost-effectiveness of high-sensitivity C-reactive protein as a marker for major cardiac events in asymptomatic individuals: A health technology assessment report

The aim of this study was to compare the predictive value, clinical effectiveness, and cost-effectiveness of high-sensitivity C-reactive protein (hs-CRP)-screening in addition to traditional risk factor screening in apparently healthy persons as a means of preventing coronary artery disease. The systematic review was performed according to internationally recognized methods. Seven studies on risk prediction, one clinical decision-analytic modeling study, and three decision-analytic cost-effectiveness studies were included. The adjusted relative risk of high hs-CRP-level ranged from 0.7 to 2.47 (p < .05 in four of seven studies). Adding hs-CRP to the prediction models increased the areas under the curve by 0.00 to 0.027. Based on the clinical decision analysis, both individuals with elevated hs-CRP-levels and those with hyperlipidemia have a similar gain in life expectancy following statin therapy. One high-quality economic modeling study suggests favorable incremental cost-effectiveness ratios for persons with elevated hs-CRP and higher risk. However, many model parameters were based on limited evidence. Adding hs-CRP to traditional risk factors improves risk prediction, but the clinical relevance and cost-effectiveness of this improvement remain unclear.

Combining multicriteria decision analysis, ethics and health technology assessment: applying the EVIDEM decisionmaking framework to growth hormone for Turner syndrome patients

ObjectivesTo test and further develop a healthcare policy and clinical decision support framework using growth hormone (GH) for Turner syndrome (TS) as a complex case study.MethodsThe EVIDEM framework was further developed to complement the multicriteria decision analysis (MCDA) Value Matrix, that includes 15 quantifiable components of decision clustered in four domains (quality of evidence, disease, intervention and economics), with a qualitative tool including six ethical and health system-related components of decision. An extensive review of the literature was performed to develop a health technology assessment report (HTA) tailored to each component of decision, and content was validated by experts. A panel of representative stakeholders then estimated the MCDA value of GH for TS in Canada by assigning weights and scores to each MCDA component of decision and then considered the impact of non-quantifiable components of decision.ResultsApplying the framework revealed significant data gaps and the importance of aligning research questions with data needs to truly inform decision. Panelists estimated the value of GH for TS at 41% of maximum value on the MCDA scale, with good agreement at the individual level (retest value 40%; ICC: 0.687) and large variation across panelists. Main contributors to this panel specific value were "Improvement of efficacy", "Disease severity" and "Quality of evidence". Ethical considerations on utility, efficiency and fairness as well as potential misuse of GH had mixed effects on the perceived value of the treatment.ConclusionsThis framework is proposed as a pragmatic step beyond the current cost-effectiveness model, combining HTA, MCDA, values and ethics. It supports systematic consideration of all components of decision and available evidence for greater transparency. Further testing and validation is needed to build up MCDA approaches combined with pragmatic HTA in healthcare decisionmaking.

The health technology assessment adaptation toolkit: Description and use

Adapting health technology assessment (HTA) reports for different contexts could reduce the need for multiple reports on the same health technology with resultant saving of time and resources. This article describes an instrument, the adaptation toolkit, which has been developed to aid in the process of adaptation of HTA reports. The toolkit was developed by a partnership of HTA agencies and networks from across Europe. The role of the toolkit is to guide the user through the process of selecting possible relevant material from these report(s), assessing the relevance, reliability, and transferability of the material, and adapting it for the desired context. The adaptation toolkit has been developed, it comprises a collection of resources that help the user assess whether data and information in existing HTA reports should and could be adapted for their own setting. The toolkit contains two sections: a preliminary speedy sifting section and the main toolkit. The main toolkit includes five domains: (i) technology use and development, (ii) safety, (iii) effectiveness (including efficacy), (iv) economic evaluation, and (v) organizational aspects. Legal, ethical, and social aspects are beyond the scope of the toolkit. The toolkit is designed for the adaptation of evidence synthesis rather than primary research. The completed current version of the toolkit contains checklists and resources to aid in the adaptation of HTA reports. This collection of resources is available for use by all HTA agencies and can be accessed at: http://www.eunethta.net/upload/WP5/EUnetHTA_HTA_Adaptation_Toolkit_October08.pdf..