Technology Assessment Reports Research Articles

New Cervical Cancer Screening Guidelines on Both Sides of the Atlantic

Large population-based trials showed that the human papillomavirus (HPV) DNA test can be even more effective than Pap tests in preventing cervical cancer. Nevertheless, there are still many questions on how to implement HPV testing in screening, and particularly how to manage its lower specificity. In this paper, we compare the recommendations concerning the cervical cancer screening tools proposed by the most influential agencies and scientific societies in the last 3 years. We included six documents that evaluated the use of HPV DNA tests and formulated recommendations: the U.S. Preventive Services Task Force (USPSTF) systematic review and recommendations, the multi-societal USA, Canadian Task Force on Preventive Health Care (CTFPHC), the Dutch Health Council recommendations, and the Italian Health Technology Assessment report. The USPSTF review and the Canadian document concluded that there is no sufficient evidence to recommend HPV as a primary screening test, while the others conclude that HPV tests can be used as the primary screening test in patients starting from 30 years of age. The interval after a negative HPV test is 5 years for all the documents except the Dutch (5-10 year interval). The only relevant difference between recommendations is the role of cytology: co-testing in the USA, triage in Europe. The new European and USA guidelines on cervical cancer screening represent a further step towards protocol harmonisation, even if there are still some differences. This harmonisation was achieved through an evidence-based approach to the introduction of HPV as a primary test and through a general reduction of the intensity of screening protocols.

HT2 - Health Technology Assessment Report for Positron Emission Tomography in Patients with Cancer

HT2 - Health Technology Assessment Report for Positron Emission Tomography in Patients with Cancer

Health Technology Assessment report on the presurgical evaluation and surgical treatment of drug‐resistant epilepsy

Epilepsy is a neurologic disorder with major social impact. Surgery is a valuable option in patients who are not responding to antiepileptic drugs. The literature reports demonstrate that a proportion ranging from 40 to 100% of patients with epilepsy achieve seizure remission after surgery. A presurgical evaluation (clinical and instrumental) must be performed in all patients with drug-resistant epilepsy to assess their suitability for surgical intervention. Health Technology Assessment (HTA) represents a modern approach to the analysis of technologies used for health care. HTA could be considered a bridge between science that produces evidence and the decisions that can be taken on the basis of that evidence at different levels of the health care system. The aim of this study is the HTA of epilepsy surgery including clinical, ethical, social, and economic features. The present study includes an analysis of the diagnostic and surgical workup performed at the Italian centers for the diagnosis and treatment of drug-resistant epilepsy (DRE). The study includes the following issues: (1) social, ethical impact, and costs of the disease; (2) clinical results, efficacy, and safety of surgery; (3) ethics and quality of life after surgery; and (4) economic impact and productivity regained after surgery. The cost of managing a patient with DRE included in the presurgical study was estimated by the bottom-up microcosting technique that starts from a detailed collection of data on consumption of resources and full costing. The phases analyzed were (1) noninvasive diagnostic workup; (2) neurosurgical intervention; and (3) follow-up. The literature reports indicate epilepsy surgery as an effective treatment both on clinical results and on ethical, social, and quality of life aspects. The workup including the noninvasive presurgical study followed by surgery has a total cost of €20,827. Management of short-term follow-up increases the overhead to €22,291 at the first year, and then to €23,571 after 5years. According to the estimates made in this survey, funding based on diagnosis-related group (DRG) tariff for the noninvasive diagnostic stage involving hospital admission is not remunerative in Italy either at regional or national levels. Effectively the difference between full cost and DRG has a delta of €3,402 and €2,537 respectively. The total cost of the presurgical, surgical, and follow-up evaluation is not remunerative for €10,554 (national data). Economic surveys in Italy have shown that surgery for DRE is an advantageous treatment from the standpoint of third-party payers and is cost-effective for society. DRE presurgical evaluation and surgery are not remunerative either at regional or national levels.

Presentational approaches used in the UK for reporting evidence synthesis using indirect and mixed treatment comparisons

To establish current guidance and practice in UK on presentation of indirect comparison and mixed treatment comparison analyses; to provide recommendations to improve indirect comparison/mixed treatment comparison reporting and to identify research priorities for improved presentation. Existing institutional guidance for conducting indirect comparison/mixed treatment comparison alongside current practice in health technology assessment was reviewed. Reports published in UK by the Health Technology Assessment programme since 1997, which utilized indirect comparison/mixed treatment comparison methods, were reviewed with respect to the presentation of study data, statistical models and results. Recommendations for presentation were developed. Guidance exists that provide the details necessary to conduct a successful indirect comparison/mixed treatment comparison analysis but recommendations on presentation are limited. Of 205 health technology assessment reports that contained evidence synthesis for effectiveness, 19 used indirect comparison/mixed treatment comparison methods. These reports utilized numerous presentational formats from which the following key components were identified: network table/diagram for presenting data; model description to allow reproducibility; and tables, forest plots, matrix tables and summary forest plots for presenting a range of results. Recommendations were developed to ensure that reporting is explicit, transparent and reproducible. Approaches most understandable by non-technical decision makers, and areas where future research is required, are outlined. There is no standard presentational style used in UK for reporting indirect comparison/mixed treatment comparison, and the use of graphical tools is limited. Standardization of reporting and innovation in graphical representation of indirect comparison/mixed treatment comparison results is required.

USE OF IMPLICIT AND EXPLICIT BAYESIAN METHODS IN HEALTH TECHNOLOGY ASSESSMENT

The aim of this study was to examine the use of implicit and explicit Bayesian methods in health technology assessments and to identify whether this has changed over time. A review of all health technology assessment (HTA) reports of secondary research published by the UK National Institute of Health Research (NIHR) between 1997 and 2011. Data were extracted on the use and implementation of Bayesian methods, whether defined as such by the original authors (i.e., explicit) or not (i.e., implicit). A total of 155 of 375 (41 percent) NIHR HTA reports, identified as relevant to this review, contained a Bayesian analysis. Of these, 128 (83 percent) contained an implicit Bayesian analysis, 3 (2 percent) an explicit Bayesian analysis and 24 (15 percent) both implicit and explicit Bayesian analyses. Of the twenty-seven reports that explicitly used Bayes theorem, only six included prior information in the form of (informative) prior distributions. Over time, the percentage of HTA reports that used Bayesian (implicit and/or explicit) methods increased from 0 percent in 1997 to nearly 80 percent in 2011. This review has shown that there has been an increase in the use of Bayesian methods in HTA, which is likely to be a result of the increase in freely available resources to implement the approach. Areas where Bayesian methods have the potential to advance healthcare evaluations in the future are considered in the discussion.

THE “LINKED EVIDENCE APPROACH” TO ASSESS MEDICAL TESTS: A CRITICAL ANALYSIS

A linked evidence approach (LEA) is the synthesis of systematically acquired evidence on the accuracy of a medical test, its impact on clinical decision making and the effectiveness of consequent treatment options. We aimed to assess the practical utility of this methodology and to develop a decision framework to guide its use. As Australia has lengthy experience with LEA, we reviewed health technology assessment (HTA) reports informing reimbursement decisions by the Medical Services Advisory Committee (August 2005 to March 2012). Eligibility was determined according to predetermined criteria and data were extracted on test characteristics, evaluation methodologies, and reported difficulties. Fifty percent of the evidence-base was independently analyzed by a second reviewer. Evaluations of medical tests for diagnostic (62 percent), staging (27 percent), and screening (6 percent) purposes were available for eighty-nine different clinical indications. Ninety-six percent of the evaluations used either the full LEA methodology or an abridged version (where evidence is linked through to management changes but not patient outcomes). Sixty-one percent had the full evidence linkage. Twenty-five percent of test evaluations were considered problematic; all involving LEA (n = 22). Problems included: determining test accuracy with an imperfect reference standard (41 percent); assessing likely treatment effectiveness in test positive patients when the new test is more accurate than the comparator (18 percent); and determining probable health benefits in those symptomatic patients ruled out using the test (13 percent). A decision framework was formulated to address these problems. LEA is useful for evaluating medical tests but a stepped approach should be followed to determine what evidence is required for the synthesis.

ASSESSING THE INTERNATIONAL USE OF HEALTH TECHNOLOGY ASSESSMENTS: EXPLORING THE MERITS OF DIFFERENT METHODS WHEN APPLIED TO THE NATIONAL INSTITUTE OF HEALTH RESEARCH HEALTH TECHNOLOGY ASSESSMENT (NIHR HTA) PROGRAMME

This study presents findings from a study that explores the merits of different methods for assessing the international use of UK funded research by the National Institute of Health Research Health Technology Assessment (NIHR HTA) Programme. The study adopted an exploratory approach and used three core methods: (i) Academic use was explored through bibliometric and citation analysis of the top ten most cited health technology assessment (HTA) reports. (ii) Internet use was assessed using Webtrends software to identify the proportion of international visits of the top ten most downloaded HTA reports from January 1, 2004 to June 30, 2010. (iii) International HTA use was assessed by searching the Center for Reviews and Dissemination (CRD) HTA database to explore the citation of NIHR HTA reports in reports by non-UK HTA agencies. Bibliometric analysis identified published output and international citations with 41 percent of the 549 journals citing NIHR HTA reports being based in the United States. Nine of ten most downloaded reports from the NIHR HTA Web site (www.hta.ac.uk) had in excess of 50 percent of visits outside the United Kingdom. Four of five selected NIHR HTA reports were cited in twenty-eight other HTA reports, eighteen of these outside the United Kingdom. Assessing international use is important when exploring the uptake of research evidence. Methods used in identifying research impact, such as bibliometrics and Webtrends, are helpful in generating evidence of international use. HTA agencies should consider these techniques and international use when assessing the uptake of findings from research they undertake and/or commission.

The right recommendations for the wrong reasons?

This editorial is endorsed by the Belgium Heart Rhythm Association (BeHRA) and the Belgian Society of Cardiology (BSC), and refers to ‘Effectiveness of catheter ablation of atrial fibrillation in Belgian practice: a cohort analysis on administrative data’ by Van Brabandt et al ., on page 663. The mission of a health technology assessment (HTA) consists of advising public authorities when they have to take decisions on health care and health insurance, in particular concerning new technologies. Health technology assessment reports are based on a comprehensive review of literature and the analysis of national data. These data are interesting because of the large sample size and the absence of reporting bias introduced by selective publication of results from specialized centres. Health technology assessment reports put forward recommendations to the authorities and this can lead to crucial decisions about the reimbursement and potential availability of a technique. Recently, the KCE, the Belgian Health Care Knowledge Centre, published a HTA report on catheter ablation of atrial fibrillation (CA-AF).1,2 Upon the publication of their report (https://kce.fgov.be), the authors issued a press release in which they stated unambiguously: ‘catheter ablation for a benign arrhythmia: less effective than hoped’. In this editorial, we discuss about the legitimacy and the potential implications of this conclusion. Atrial fibrillation is not a benign condition, as it is associated with increased stroke, hospitalization, and death. In younger patients, it can lead to a marked impairment of quality of life (QoL) due to symptoms of palpitations, dyspnoea, and fatigue. From its start, CA-AF has offered the promise to free patients of symptomatic AF.3 Numerous randomized controlled trials (RCTs), performed in young patients with paroxysmal AF, compared a ‘strategy of CA-AF’ (i.e. a policy of initial pulmonary vein isolation with a repeat isolation if appropriate) to antiarrhythmic drugs.4 …

PRM155 A Pragmatic Randomized Clinical Trials – Design and Quality Assessment of the Source of Effectiveness Data

Acquisition of scientific data required for the rational decisions on health policy has became an important tool in determining the validity of the financing methods of treatment from public funds based on the health technology assessment (HTA). The primary source of scientific evidence for health technology assessment are randomized controlled trials (RCTs), because of their features (e.g. randomization or blindness) reducing methodological bias. These features may become a disadvantage, which markedly reduces the possibility of the transfer of the results and conclusions to the everyday practice. In this situation an important role begin to play pragmatic randomized controlled trials (PRCTs), providing highly reliable information about the effectiveness in contrast to observational studies or registries. However, an important problem is correct design and quality assessment of such trials. A systematic review in Medline through Pubmed using the following queries: “(pragmatic OR practical OR naturalistic OR real world) AND (design OR quality)” was performed till June 2012 to gather and systematize the current information about pragmatic randomized trials to improve the quality of the practical effectiveness evaluation in health technology assessment reports. Using this search strategy nearly 28 000 hits were obtained. Preliminary evaluation of the found publications demonstrated that the best reflection of the conditions of routine practice (generalizability) in PRCTs can be obtained mostly through the development of broader inclusion criteria, minimizing the exclusion criteria or broadening the scope of patients evaluation. We found also suitable tools, which can be used both during the design and evaluation of reliability of PRCTs: PRECIS, PR-tool, Pragmascope tool or CONSORT. Properly assessed PRCTs data in conjunction with information about the efficacy from RCTs will serve as a whole to facilitate business decisions in medical practice, as well as health organizations and rationalization of cost-reimbursement of used or new medical technologies.

How Mainstream Medicine Sees Photodynamic Therapy in the United Kingdom

Although photodynamic therapy (PDT) has been used successfully to treat an assortment of different types of cancer, it has yet to reach the level of mainstream medicine on either side of the Atlantic. Unsubstantiated claims of PDT's efficacy in the past may be part of the reason for this. However, perhaps the main obstacle to PDT's endorsement by conventional medicine is the limited number of high-quality randomized controlled trials (RCTs) comparing it with relevant comparators for all meaningful outcomes, including effectiveness, safety, adverse events, quality of life, survival, and cost. Based on a Health Technology Assessment report on the current status of PDT and consultation with professional groups, specialist societies, and clinical study groups in the United Kingdom, this article explores the current clinical guidelines for use of PDT in cancer treatment and the dearth of supportive data from RCTs.

The Importance Of Technology Usage In The Classroom, Does Gender Gaps Exist

The Importance Of Technology Usage In The Classroom, Does Gender Gaps Exist

What is the gold standard for intrapartum fetal monitoring?

The health authorities of Stockholm county recently published a Health Technology Assessment report: "Fetal monitoring with computerized STAN analysis during labor - a systematic review" with the aim to ensure that high quality research information on costs, effectiveness and broader impact of health technologies is analysed and presented in the most efficient way for those who use, manage and work in this field. The report claims to analyse available research in relation to ST interval analysis of fetal electrocardiogram (STAN) and concludes that scientific evidence for advantages of the STAN technology for maternal and fetal outcome was insufficient and that clinical use cannot be recommended and should be restricted to research protocols. The Norwegian reference group for fetal surveillance points out that the report suffers from two insufficiencies: selection bias by not providing a complete collection of the evidence for the clinical performance of the STAN technology and, secondly, that it does not provide evidence-based alternative methods.

Cetuximab in first line treatment of metastatic colorectal cancer

The present health technology assessment report evaluates the clinical and economic profile of cetuximab in first-line metastatic colorectal cancer (mCRC) in Italy. The first part of the report addresses the epidemiological, clinical, social and economic impact of mCRC. In the second part, evidence of efficacy, safety and cost-effectiveness of cetuximab and its available alternatives is shown. Finally, a model-based economic evaluation aimed at comparing cetuximab-based re­gimens vs. alternative therapeutic strategies indicated in mCRC in Italy is presented. The model estimates the incremental cost-effectiveness of adding cetuximab to FOLFOX-4 or FOLFIRI based on KRAS status, vs. adding bevacizumab to FOLFOX-4 or vs. FOLFOX-4 or FOLFIRI alone. A theoretical analysis vs. panitumumab has also been performed, despite panitumumab is not yet reimbursed in Italy in first-line mCRC. Survival outcomes, quality of life and costs of patient ma­nagement are estimated through a Markov model, using the Italian National Healthcare Service (NHS) perspective, over a 10 year period, taking into account KRAS status of patients. The results of the pharmaco-economic analysis show that cetuximab + FOLFOX-4 and cetuximab + FOLFIRI are associated with increased survival, increased cost and increased quality adjusted survival, compared to all other treatments currently indicated and reimbursed in Italy. Adding cetuximab to FOLFOX-4 or FOLFIRI, based on KRAS status shows favorable incremental cost-effectiveness ratio (ICER) vs. adding bevacizumab to FOLFIRI or vs. FOLFOX-4 or FOLFIRI alone. ICER of cetuximab (in combination with FOLFOX-4 or FOLFIRI), compared to currently reimbursed alternatives, is estimated between 6 and 13 thousand Euros per QALY gai­ned, depending on alternative treatment. These estimates are robust in extensive sensitivity analyses. As a final result, both clinical and economic evidence analyzed in this health technology assessment leads to recommend cetuximab as preferred option for the first-line treatment of mCRC KRAS wild-type patients in Italy.

Economic evaluation of bevacizumab in the treatment of non-small cell lung cancer (NSCLC)

BackgroundDelivering affordable cancer care is becoming increasingly important. Bevacizumab (BEV) is a costly molecular targeted agent effective for a variety of cancer including lung cancer. The objective of this review is to assess published economic evaluation of BEV in the treatment of non-small cell lung cancer (NSCLC).MethodsA literature search in PubMed, Cochrane, and the Health Technology Assessment reports for English-language publications before February 2012 was performed. Studies were independently screened by two reviewers, and eight publications were included in the review. The results of these eight articles were tabulated and all cost estimates were reported in 2011 US dollars.ResultsAmong the eight articles, three were cost studies and five were cost-effectiveness/utility analysis. For first-line treatment, BEV-containing regimen was reported to be the most costly regimen in one study but cost saving when compared with pemetrexed/cisplatin in another study. When compared with other regimens, BEV-containing regimen was reported to be cost effective in two cost-effectiveness studies (incremental cost-effectiveness ratio [ICER] in the range of US$30,318–US$54,317 per life year) but not cost effective in the other three studies (ICER over US$300,000 per life year).ConclusionIn this review of economic evaluation of BEV in the treatment of NSCLC, it was found that the literature was not conclusive on the economic benefit of BEV. The role of BEV in other treatment settings for NSCLC was unknown. Further studies, such as clinical trials with adequate power to compare the efficacy between low dose and high dose BEV, potential impact of predictive biomarkers for BEV, and comprehensive economic evaluation will strengthen the current state of knowledge on the economic value of BEV in NSCLC.

Dasatinib, high-dose imatinib and nilotinib for the treatment of imatinib-resistant chronic myeloid leukaemia: a systematic review and economic evaluation.

The present report was commissioned as a supplement to an existing technology assessment report produced by the Peninsula Technology Assessment Group (PenTAG), which evaluated the clinical effectiveness and cost-effectiveness of dasatinib and nilotinib in patients who are either resistant or intolerant to standard-dose imatinib. This report evaluates the clinical effectiveness and cost-effectiveness of dasatinib, nilotinib and high-dose imatinib within their licensed indications for the treatment of people with chronic myeloid leukaemia (CML) who are resistant to standard-dose imatinib. Bibliographic databases were searched from inception to January 2011, including The Cochrane Library, MEDLINE (Ovid), EMBASE (Ovid), and MEDLINE In-Process & Other Non-Indexed Citations. Bibliographies of related papers were screened, key conferences were searched, and experts were contacted to identify additional published and unpublished references. This report includes systematic reviews of clinical effectiveness and cost-effectiveness studies, an independent appraisal of information submitted by drug manufacturers to the National Institute for Health and Clinical Excellence (NICE), an independent appraisal of the PenTAG economic evaluation, and new economic analyses adapting the PenTAG economic model. Standard systematic procedures involving two reviewers to maintain impartiality and transparency, and to minimise bias, were conducted. Eleven studies met the inclusion criteria. Four of these studies included new data published since the PenTAG report; all of these were in chronic-phase CML. No relevant studies on the clinical effectiveness of nilotinib were found. The clinical effectiveness studies on dasatinib [one arm of a randomised controlled trial (RCT)] and high-dose imatinib (one arm of a RCT and three single-arm cohort studies) had major methodological limitations. These limitations precluded a comparison of the different arms within the RCT. Data from the studies are summarised in this report, but caution in interpretation is required. One economic evaluation was identified that compared dasatinib with high-dose imatinib in patients with chronic-phase CML who were CML resistant to standard-dose imatinib. Two industry submissions and the PenTAG economic evaluation were critiqued and differences in the assumptions and results were identified. The PenTAG economic model was adapted and new analyses conducted for the interventions dasatinib, nilotinib and high-dose imatinib and the comparators interferon alfa, standard-dose imatinib, stem cell transplantation and hydroxycarbamide. The results suggest that the three interventions, dasatinib, nilotinib and high-dose imatinib, have similar costs and cost-effectiveness compared with hydroxycarbamide, with a cost-effectiveness of around £30,000 per quality-adjusted life-year gained. However, it is not possible to derive firm conclusions about the relative cost-effectiveness of the three interventions owing to great uncertainty around data inputs. Uncertainty was explored using deterministic sensitivity analyses, threshold analyses and probabilistic sensitivity analyses. The paucity of good-quality evidence should be considered when interpreting this report. This review has identified very limited new information on clinical effectiveness of the interventions over that already shown in the PenTAG report. Limitations in the data exist; however, the results of single-arm studies suggest that the interventions can lead to improvements in haematological and cytogenetic responses in people with imatinib-resistant CML. The economic analyses do not highlight any one of the interventions as being the most cost-effective; however, the analysis results are highly uncertain owing to lack of agreement on appropriate assumptions. Recommendations for future research made by PenTAG, for a good-quality RCT comparing the three treatments remain.

Transferability of National Institute for Health and Clinical Excellence recommendations for pharmaceutical therapies in oncology to Central-Eastern European countries

The health burden of malignancies is greater in Central-Eastern Europe than in Western Europe. Furthermore, these countries have more limited healthcare resources, and therefore transparent decision criteria for innovative cancer therapies, including the assessment of cost-effectiveness, are an absolute necessity. Transferability of good-quality technology assessment reports, especially those prepared by National Institute for Health and Clinical Excellence (NICE) in the UK, could be highly beneficial to prevent duplication of efforts and save resources for local technology assessment. Our objective was to summarise key factors influencing the transferability of NICE recommendations in oncology for policy makers and oncologists in Central-Eastern Europe without personal experience in health technology assessment. In general, NICE recommendations are not transferable without adjustment of the analyses to local data. Even if the recommendation is positive, the conclusion can still be negative in lower-income countries, mainly due to relative price differences and the significance of the local budget impact. Technologies with negative NICE recommendations can still be cost-effective in Central-Eastern Europe due to the worse health status and therefore the greater potential health gain of the targeted population. The appropriateness of reimbursement decisions must be improved in Central-Eastern Europe, but copying NICE recommendations without local adjustment may do more harm than good.

Why Is It So Difficult to Evaluate Nursing Interventions in Dementia

Two recent health technology assessment (HTA) reports published in Germany focused on non-pharmacological interventions for patients with dementia. One of the major results was the poor methodological quality of the studies in this field. This paper concisely presents the main quantitative and qualitative findings of the HTA report published by the German Agency for HTA at the Institute of Medical Information and Documentation (dahta@DIMDI), followed by a detailed discussion of the major methodological problems observed for the inclusion criteria, interventions, the setting, number of patients included, duration of observation, comparators, clinical endpoints, health economics, and, most obvious, the impossibility of blinding and eliminating placebo effects for future clinical studies. We conclude with several suggestions addressing these challenges for future research in this field.

The effectiveness and cost-effectiveness of donepezil, galantamine, rivastigmine and memantine for the treatment of Alzheimer’s disease (review of Technology Appraisal No. 111): a systematic review and economic model.

Alzheimer’s disease (AD) is the most commonly occurring form of dementia. It is predominantly a disease of later life, affecting 5% of those over 65 in the UK.Review and update guidance to the NHS in England and Wales on the clinical effectiveness and cost-effectiveness of donepezil, galantamine, rivastigmine [acetylcholinesterase inhibitors (AChEIs)] and memantine within their licensed indications for the treatment of AD, which was issued in November 2006 (amended September 2007 and August 2009).Electronic databases were searched for systematic reviews and/or metaanalyses, randomised controlled trials (RCTs) and ongoing research in November 2009 and updated in March 2010; this updated search revealed no new includable studies. The databases searched included The Cochrane Library (2009 Issue 4, Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Trials), MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, PsycINFO, EconLit, ISI Web of Science Databases--Science Citation Index, Conference Proceedings Citation Index, and BIOSIS; the Centre for Reviews and Dissemination (CRD) databases--NHS Economic Evaluation Database, Health Technology Assessment, and Database of Abstracts of Reviews of Effects.The clinical effectiveness systematic review was undertaken following the principles published by the NHS CRD. We included RCTs whose population was people with AD. The intervention and comparators depended on disease severity, measured by the Mini Mental State Examination (MMSE).mild AD (MMSE 21-26)--donepezil, galantamine and rivastigmine; moderate AD (MMSE 10-20)--donepezil, galantamine, rivastigmine and memantine; severe AD (MMSE < 10)--memantine. Comparators: mild AD (MMSE 21-26)--placebo or best supportive care (BSC); moderate AD (MMSE 10-20)--donepezil, galantamine, rivastigmine, memantine, placebo or BSC; severe AD (MMSE < 10)--placebo or BSC. The outcomes were clinical, global, functional, behavioural, quality of life, adverse events, costs and cost-effectiveness. Where appropriate, data were pooled using pair-wise meta-analysis, multiple outcome measures, metaregression and mixedtreatment comparisons. The decision model was based broadly on the structure of the three-state Markov model described in the previous technology assessment report, based upon time to institutionalisation, parameterised with updated estimates of effectiveness, costs and utilities.Notwithstanding the uncertainty of our results, we found in the base case that the AChEIs are probably cost saving at a willingness-to-pay (WTP) of £’30,000 per qualityadjusted life-year (QALY) for people with mild-to-moderate AD. For this class of drugs, there is a > 99% probability that the AChEIs are more cost-effective than BSC. These analyses assume that the AChEIs have no effect on survival. For the AChEIs, in people with mild to moderate AD, the probabilistic sensitivity analyses suggested that donepezil is the most cost-effective, with a 28% probability of being the most cost-effective option at a WTP of £’30,000 per QALY (27% at a WTP of £’20,000 per QALY). In the deterministic results, donepezil dominates the other drugs and BSC, which, along with rivastigmine patches, are associated with greater costs and fewer QALYs. Thus, although galantamine has a slightly cheaper total cost than donepezil (£’69,592 vs £’69,624), the slightly greater QALY gains from donepezil (1.616 vs 1.617) are enough for donepezil to dominate galantamine.The probability that memantine is cost-effective in a moderate to severe cohort compared with BSC at a WTP of £’30,000 per QALY is 38% (and 28% at a WTP of £’20,000 per QALY). The deterministic ICER for memantine is £’32,100 per/QALY and the probabilistic ICER is £’36,700 per/QALY.Trials were of 6 months maximum follow-up, lacked reporting of key outcomes, provided no subgroup analyses and used insensitive measures. Searches were limited to English language, The model does not include behavioural symptoms and there is uncertainty about the model structure and parameters.The additional clinical effectiveness evidence identified continues to suggest clinical benefit from the AChEIs in alleviating AD symptoms, although there is debate about the magnitude of the effect. Although there is also new evidence on the effectiveness of memantine, it remains less supportive of this drug’s use than the evidence for AChEIs. The conclusions concerning cost-effectiveness are quite different from the previous assessment. This is because both the changes in effectiveness and costs between drug use and non-drug use underlying the ICERs are very small. This leads to highly uncertain results, which are very sensitive to change. RESEARCH PRIORITIES: RCTs to include mortality, time to institutionalisation and quality of life, powered for subgroup analysis.The National Institute for Health Research Health Technology Assessment programme.

Robot technology in the Italian Health-care system: Cost-efficacy economic analysis

Robotic technology is used in multiple fields of surgery, especially radical prostatectomy in patients with prostate cancer. The purpose of this study was to evaluate the introduction of robotic technology in the Italian Public Heath-care context, from the perspective of the Health Technology Assessment (HTA). An economic analysis that compares the costs and effectiveness of the method was developed. Data were compared with those of the most important international literature, analyzing structural and organizational problems related to the method. A systematic review of literature on tertiary literature (Health Technology Assessment reports) and secondary (systematic reviews) published since 2002 was conducted. The review was also conducted on more recent primary literature regarding the clinical effectiveness and the economic analysis in the fields of surgery where Da Vinci robot is most promising. 18 studies were selected out of a total of 65 evaluated. The "Break-Even Point" (BEP) is the minimum number of cases needed to be treated in order to achieve a balance between costs and revenues, below which the system is losing money. It was calculated that the total fixed costs are € 378,000 and variable costs are € 3,810 per surgery. Considering that the current value of DRG (Diagnosis-Related Group) refunded by the public Health-care system is actually € 4,553, the BEP would be achieved performing 508 surgeries, so that the robotic technology does not generate neither profit nor loss. It is not possible to demonstrate the superiority of robotic surgery in terms of efficacy. The robotic surgery is safe and effective only if performed by surgical teams with relevant experience. Considering the reported case of an Italian University Hospital with public Health-care system refund, the BEP target of 508 radical prostatectomies could be achieved after a few years. The use of the robot in multiple fields on one hand shortens recovery time costs, but on the other hand increases costs due to organizational issues. The value of the DRG refund does not appear adequate to new robotic technology.

NICE guidance on CardioQTM oesophageal Doppler monitoring

NICE guidance on CardioQTM oesophageal Doppler monitoring