Systematic reviews as a 'lens of evidence': Determinants of benefits and harms of breast cancer screening.

This systematic review, stimulated by inconsistency in secondary evidence, reports the benefits and harms of breast cancer (BC) screening and their determinants according to systematic reviews. A systematic search, which identified 9,976 abstracts, led to the inclusion of 58 reviews. BC mortality reduction with screening mammography was 15-25% in trials and 28-56% in observational studies in all age groups, and the risk of stage III+ cancers was reduced for women older than 49 years. Overdiagnosis due to mammography was 1-60% in trials and 1-12% in studies with a low risk of bias, and cumulative false-positive rates were lower with biennial than annual screening (3-17% vs 0.01-41%). There is no consistency in the reviews' conclusions about the magnitude of BC mortality reduction among women younger than 50 years or older than 69 years, or determinants of benefits and harms of mammography, including the type of mammography (digital vs screen-film), the number of views and the screening interval. Similarly, there was no solid evidence on determinants of benefits and harms or BC mortality reduction with screening by ultrasonography or clinical breast examination (sensitivity ranges, 54-84% and 47-69%, respectively), and strong evidence of unfavourable benefit-to-harm ratio with breast self-examination. The reviews' conclusions were not dependent on the quality of the reviews or publication date. Systematic reviews on mammography screening, mainly from high-income countries, systematically disagree on the interpretation of the benefit-to-harm ratio. Future reviews are unlikely to clarify the discrepancies unless new original studies are published.

Economic considerations and patients' preferences affect treatment selection for patients with rheumatoid arthritis: a discrete choice experiment among European rheumatologists.

OBJECTIVE: To compare the value that rheumatologists across Europe attach to patients' preferences and economic aspects when choosing treatments for patients with rheumatoid arthritis. METHODS: In a discrete choice experiment, European rheumatologists chose between two hypothetical drug treatments for a patient with moderate disease activity. Treatments differed in five attributes: efficacy (improvement and achieved state on disease activity), safety (probability of serious adverse events), patient's preference (level of agreement), medication costs and cost-effectiveness (incremental cost-effectiveness ratio (ICER)). A Bayesian efficient design defined 14 choice sets, and a random parameter logit model was used to estimate relative preferences for rheumatologists across countries. Cluster analyses and latent class models were applied to understand preference patterns across countries and among individual rheumatologists. RESULTS: Responses of 559 rheumatologists from 12 European countries were included in the analysis (49% females, mean age 48 years). In all countries, efficacy dominated treatment decisions followed by economic considerations and patients' preferences. Across countries, rheumatologists avoided selecting a treatment that patients disliked. Latent class models revealed four respondent profiles: one traded off all attributes except safety, and the remaining three classes disregarded ICER. Among individual rheumatologists, 57% disregarded ICER and these were more likely from Italy, Romania, Portugal or France, whereas 43% disregarded uncommon/rare side effects and were more likely from Belgium, Germany, Hungary, the Netherlands, Norway, Spain, Sweden or UK. CONCLUSIONS: Overall, European rheumatologists are willing to trade between treatment efficacy, patients' treatment preferences and economic considerations. However, the degree of trade-off differs between countries and among individuals.

Cost-effectiveness of Elective Endovascular Aneurysm Repair Versus Open Surgical Repair of Abdominal Aortic Aneurysms.

OBJECTIVE/BACKGROUND: The aim of this study was to estimate the lifetime cost-effectiveness of endovascular aneurysm repair (EVAR) versus open surgical repair (OSR) in the Netherlands, based on recently published literature. METHODS: A model was developed to simulate a cohort of individuals (age 72 years, 87% men) with an abdominal aortic aneurysm (AAA) diameter of at least 5.5 cm and considered fit for both repairs. The model consisted of two sub-models that estimated the lifetime cost-effectiveness of EVAR versus OSR: (1) a decision tree for the first 30 post-operative days; and (2) a Markov model for the period thereafter (31 days-30 years). RESULTS: In the base case analysis, EVAR was slightly more effective (4.704 vs. 4.669 quality adjusted life years) and less expensive (€24,483 vs. €25,595) than OSR. Improved effectiveness occurs because EVAR can reduce 30 day mortality risk, as well as the risk of events following the procedure, while lower costs are primarily due to a reduction in length of hospital stay. The cost-effectiveness of EVAR is highly dependent on the price of the EVAR device and the reduction in hospital stay, complications, and 30 day mortality. CONCLUSION: EVAR and OSR can be considered equally effective, while EVAR can be cost saving compared with OSR. EVAR can therefore be considered as a cost-effective solution for patients with AAAs.

Treatment variation in stent choice in patients with stable or unstable coronary artery disease.

AIM: Variations in treatment are the result of differences in demographic and clinical factors (e.g. anatomy), but physician and hospital factors may also contribute to treatment variation. The choice of treatment is considered important since it could lead to differences in long-term outcomes. This study explores the associations with stent choice: i.e. drug-eluting stent (DES) versus bare-metal stents (BMS) for Dutch patients diagnosed with stable or unstable coronary artery disease (CAD). METHODS & RESULTS: Associations with treatment decisions were based on a prospective cohort of 692 patients with stable or unstable CAD. Of those patients, 442 patients were treated with BMS or DES. Multiple logistic regression analyses were performed to identify variables associated with stent choice. Bivariate analyses showed that NYHA class, number of diseased vessels, previous percutaneous coronary intervention, smoking, diabetes, and the treating hospital were associated with stent type. After correcting for other associations the treating hospital remained significantly associated with stent type in the stable CAD population. CONCLUSIONS: This study showed that several factors were associated with stent choice. While patients generally appear to receive the most optimal stent given their clinical characteristics, stent choice seems partially determined by the treating hospital, which may lead to differences in long-term outcomes.

Real world cost of human epidermal receptor 2-positive metastatic breast cancer patients: a longitudinal incidence-based observational costing study in the Netherlands and Belgium.

Currently, no country-specific metastatic breast cancer (MBC) observational costing data are available for the Netherlands and Belgium. Our aim is to describe country-specific resource use and costs of human epidermal receptor 2 (HER-2)-positive MBC in the Netherlands and Belgium, making use of real-world data. The eligibility period for patient selection was from April 2004 to April 2010. Inclusion and retrospective data collection begins at the time of first diagnosis of HER-2-positive MBC during the eligibility period and ends 24 months post-index diagnosis of MBC or at patient death. We identified 88 eligible patients in the Netherlands and 44 patients in Belgium. The total costs of medical treatment and other resource use utilisation per patient was €48,301 in the Netherlands and €37,431 in Belgium. Majority of costs was related to the use of trastuzumab in both countries, which was 50% of the total costs in the Netherlands and 56% in Belgium respectively. Our study provides estimates of resource use and costs for HER-2-positive MBC in the Netherlands and Belgium. We noticed various differences in resource use patterns between both countries demonstrating caution is needed when transferring cost estimates between countries.

Time-dependent resource use and costs associated with different states of disease in patients diagnosed with HER-2-positive metastatic breast cancer.

Adequate reflection of disease progression and costs over time is essential in cost-effectiveness analyses based on health state-transition models. However, costing studies normally investigate the burden of metastatic breast cancer (MBC) without explicitly examining the impact of specific-disease states on health care costs over time. The objective of this study was to assess time-dependent costs of different health states of human epidermal receptor-2 (HER-2) positive MBC and the factors contributing to these costs. In the Netherlands, HER-2-positive MBC patients were identified in three different hospitals. Resource use was collected during 24 months, which was linked to unit costs and related to time with respect to date of MBC diagnosis, disease progression and death for each individual patient. Subsequently, monthly costs for different health states were calculated. Finally, a nonlinear mixed-effect modelling approach was used to provide a quantitative description of the time course of cumulative progression costs. Costs during stable disease were constant over time with a mean of $4,158. In contrast, monthly costs for progressive disease demonstrated a change over time with the largest costs in the first 2 months after diagnosis (p < 0.005). The developed mixed-effect model adequately described cumulative cost-time course and associated variability. During the last months of life, costs varied over time, with the last month of life as the most expensive one with a mean of $5,811 per patient per month. To reflect costs of HER-2-positive MBC accurately in Markov models, costs for stable disease can be defined time independent, however, costs of progressive disease should be defined time dependent, and costs related to the final months of life should be modelled as such. The mixed-effect model we have developed could now be considered for adequate description of the time-dependent cost of progressive disease.

Performance-based risk-sharing arrangements-good practices for design, implementation, and evaluation: report of the ISPOR good practices for performance-based risk-sharing arrangements task force.

There is a significant and growing interest among both payers and producers of medical products for agreements that involve a "pay-for-performance" or "risk-sharing" element. These payment schemes-called "performance-based risk-sharing arrangements" (PBRSAs)-involve a plan by which the performance of the product is tracked in a defined patient population over a specified period of time and the amount or level of reimbursement is based on the health and cost outcomes achieved. There has always been considerable uncertainty at product launch about the ultimate real-world clinical and economic performance of new products, but this appears to have increased in recent years. PBRSAs represent one mechanism for reducing this uncertainty through greater investment in evidence collection while a technology is used within a health care system. The objective of this Task Force report was to set out the standards that should be applied to "good practices"-both research and operational-in the use of a PBRSA, encompassing questions around the desirability, design, implementation, and evaluation of such an arrangement. This report provides practical recommendations for the development and application of state-of-the-art methods to be used when considering, using, or reviewing PBRSAs. Key findings and recommendations include the following. Additional evidence collection is costly, and there are numerous barriers to establishing viable and cost-effective PBRSAs: negotiation, monitoring, and evaluation costs can be substantial. For good research practice in PBRSAs, it is critical to match the appropriate study and research design to the uncertainties being addressed. Good governance processes are also essential. The information generated as part of PBRSAs has public good aspects, bringing ethical and professional obligations, which need to be considered from a policy perspective. The societal desirability of a particular PBRSA is fundamentally an issue as to whether the cost of additional data collection is justified by the benefits of improved resource allocation decisions afforded by the additional evidence generated and the accompanying reduction in uncertainty. The ex post evaluation of a PBRSA should, however, be a multidimensional exercise that assesses many aspects, including not only the impact on long-term cost-effectiveness and whether appropriate evidence was generated but also process indicators, such as whether and how the evidence was used in coverage or reimbursement decisions, whether budget and time were appropriate, and whether the governance arrangements worked well. There is an important gap in the literature of structured ex post evaluation of PBRSAs. As an innovation in and of themselves, PBRSAs should also be evaluated from a long-run societal perspective in terms of their impact on dynamic efficiency (eliciting the optimal amount of innovation).

Compensation mechanisms for lost productivity: a comparison between four European countries.

OBJECTIVE: Productivity costs are usually estimated by multiplying the wage with the period absent. This can lead to an overestimation if compensation mechanisms occur. Until now only Dutch data are available on the influence of compensation mechanisms on lost productivity, but between-country differences in frequency and type of compensation mechanisms can be expected. The objective of this study was to understand whether compensation mechanisms for days absent from paid work differ in type and frequency across countries and to explore whether this would result in between-country differences in relevant lost productivity. METHODS: Data from a cross-sectional survey among respondents with rheumatic disorders from four countries were the basis for this study. Analyses focused on respondents with paid employment who reported absence in the last 3 months. The different compensation mechanisms are described and the resulting lost productivity in terms of days absent was calculated with and without taking compensation mechanisms into account. Logistic regression analyses were performed to examine which variables influence compensation mechanisms leading to relevant lost productivity. RESULTS: The results indicate that compensation mechanisms occur and are relevant in all four countries. Between-country differences in the type and frequency of compensation mechanisms and relevant lost productivity were observed. The logistic regression analyses indicate that, correcting for other variables, this is also the case for the use of compensation mechanisms leading to relevant lost productivity. CONCLUSIONS: Between-country differences in compensation mechanisms in case of absenteeism exist and could vary to such an extent that foreign relevant lost productivity data should be used with caution.

Consumer preferences for health and nonhealth outcomes of health promotion: results from a discrete choice experiment.

OBJECTIVE: Health promotion (HP) interventions have outcomes that go beyond health. Such broader nonhealth outcomes are usually neglected in economic evaluation studies. To allow for their consideration, insights are needed into the types of nonhealth outcomes that HP interventions produce and their relative importance compared with health outcomes. This study explored consumer preferences for health and nonhealth outcomes of HP in the context of lifestyle behavior change. METHODS: A discrete choice experiment was conducted among participants in a lifestyle intervention (n = 132) and controls (n = 141). Respondents made 16 binary choices between situations that can be experienced after lifestyle behavior change. The situations were described by 10 attributes: future health state value, start point of future health state, life expectancy, clothing size above ideal, days with sufficient relaxation, endurance, experienced control over lifestyle choices, lifestyle improvement of partner and/or children, monetary cost per month, and time cost per week. RESULTS: With the exception of "time cost per week" and "start point of future health state," all attributes significantly determined consumer choices. Thus, both health and nonhealth outcomes affected consumer choice. Marginal rates of substitution between the price attribute and the other attributes revealed that the attributes "endurance," "days with sufficient relaxation," and "future health state value" had the greatest impact on consumer choices. The "life expectancy" attribute had a relatively low impact and for increases of less than 3 years, respondents were not willing to trade. CONCLUSIONS: Health outcomes and nonhealth outcomes of lifestyle behavior change were both important to consumers in this study. Decision makers should respond to consumer preferences and consider nonhealth outcomes when deciding about HP interventions.

Cost-effectiveness of involving nurse specialists for adult patients with urinary incontinence in primary care compared to care-as-usual: an economic evaluation alongside a pragmatic randomized controlled trial.

AIMS: To determine the 12-month, societal cost-effectiveness of involving urinary incontinence (UI) nurse specialists in primary care compared to care-as-usual by general practitioners (GPs). METHODS: From 2005 until 2008 an economic evaluation was performed alongside a pragmatic multicenter randomized controlled trial comparing UI patients receiving care by nurse specialists with patients receiving care-as-usual by GPs in the Netherlands. One hundred eighty-six adult patients with stress, urgency, or mixed UI were randomly allocated to the intervention and 198 to care-as-usual; they were followed for 1 year. Main outcome measures were Quality Adjusted Life Year (QALY(societal) ) based on societal preferences for health outcomes (EuroQol-5D), QALY(patient) based on patient preferences for health outcomes (EuroQol VAS), and Incontinence Severity weighted Life Year (ISLY) based on patient-reported severity and impact of UI (ICIQ-UI SF). Health care resource use, patient and family costs, and productivity costs were assessed. Data were collected by three monthly questionnaires. Incremental cost-effectiveness ratios were calculated. Uncertainty was assessed using bootstrap simulation, and the expected value of perfect information was calculated (EVPI). RESULTS: Compared to care-as-usual, nurse specialist involvement costs € 16,742/QALY(societal) gained. Both QALY(patient) and ISLY yield slightly more favorable cost-effectiveness results. At a threshold of € 40,000/QALY(societal,) the probability that the intervention is cost-effective is 58%. The EVPI amounts to € 78 million. CONCLUSIONS: Based on these results, we recommend adopting the nurse specialist intervention in primary care, while conducting more research through careful monitoring of the effectiveness and costs of the intervention in routine practice.

[The costs and benefits of an integrated approach to dementia]. / De kosten en opbrengsten van een geïntegreerde aanpak bij dementie.

BACKGROUND: An integrated approach to dementia is generally recommended because no one discipline is adequately equipped it deal with the complex psychic, physical and social problems that are inherent in dementia. A multidisciplinary approach, however, leads inevitably to higher costs. It is not known what the cost/benefit ratio will be. AIM: To describe our research into the costs and benefits of an integrated approach to dementia involving the use of a diagnostic research centre for psycho-geriatrics and thereafter to compare our findings with the results of other studies of the costs and benefits of an integrated approach. METHOD: We performed a prospective and randomised efficiency study and we compared our findings with the results of other studies of the costs and benefits of an integrated approach. We reviewed recent literature. RESULTS: The DRC-PG was more effective than normal care as far as the patients' quality of life was concerned, but was not more expensive. It can therefore be regarded as a cost-effective facility for ambulatory patients with dementia. Three other studies provided additional empirical evidence of the success of a similar integrated approach in various sectors involved in the care of patients with dementia. CONCLUSION: An integrated approach with regard to the diagnosis, treatment and management of dementia produces favourable results. More research is needed into the efficacy and cost-effectiveness of integrated care programmes. This should result in improvements in the care and treatment of patients with dementia.

Systematic reviews as a "lens of evidence": Determinants of participation in breast cancer screening.

OBJECTIVE: To assess the determinants of the participation rate in breast cancer screening programs by conducting a systematic review of reviews. METHODS: We conducted a systematic search in PubMed via Medline, Scopus, Embase, and Cochrane identifying the literature up to April 2019. Out of 2258 revealed unique abstracts, we included 31 reviews, from which 25 were considered as systematic. We applied the Walsh & McPhee Systems Model of Clinical Preventive Care to systematize the determinants of screening participation. RESULTS: The reviews, mainly in high-income settings, reported a wide range for breast cancer screening participation rate: 16-90%. The determinants of breast cancer screening participation were simple low-cost interventions such as invitation letters, basic information on screening, multiple reminders, fixed appointments, prompts from healthcare professionals, and healthcare organizational factors (e.g. close proximity to screening facility). More complex interventions (such as face-to-face counselling or home visits), mass media or improved access to transport should not be encouraged by policy makers unless other information appears. The repeated participation in mammography screening was consistently high, above 62%. Previous positive experience with screening influenced the repeated participation in screening programs. The reviews were inconsistent in the use of terminology related to breast cancer screening participation, which may have contributed to the heterogeneity in the reported outcomes. CONCLUSIONS: This study shows that consistent findings of systematic reviews bring more certainty into the conclusions on the effects of simple invitation techniques, fixed appointments and prompts, as well as healthcare organizational factors on promoting participation rate in screening mammography.

A prospective randomized multicenter comparison on health-related quality of life: the value of add-on arrhythmia surgery in patients with paroxysmal, permanent or persistent atrial fibrillation undergoing valvular and/or coronary bypass surgery.

INTRODUCTION: This is a multicenter, prospective, randomized controlled trial to determine the effect of add-on arrhythmia surgery on health-related quality of life during 1-year follow-up of cardiac surgery patients with atrial fibrillation. METHODS: 150 patients with documented atrial fibrillation were randomly assigned to undergo cardiac surgery with or without add-on surgery. Patients completed quality of life questionnaires, comprising the RAND 36-item Health Survey 1.0 (SF-36), Multidimensional Fatigue Inventory-20 (MFI-20) and EuroQoL (EQ-5D and VAS) at baseline and 3, 6, and 12 months following operation. RESULTS: 132 patients completed the questionnaires at a minimum of one time-point during follow-up. At baseline patient characteristics, operative data and health-related quality of life were comparable. At 12-month follow-up 62 patients were free of atrial fibrillation without significant differences between groups (P = 0.28). Conversion to SR occurred in 69.8% (37/53) of patients with paroxysmal AF, in 28.2% (11/39) of patients with permanent AF and in 44.4% (12/27) of patients in persistent AF. Cardiac surgery in general resulted in an overall improvement of the RAND SF-36 and the MFI-20. However, the EQ-5D showed a significant deterioration in the subscale Pain/Discomfort for both groups (P < 0.001), with a significant worse outcome for the control group (P = 0.006). CONCLUSIONS: Health-related quality of life in patients with paroxysmal, permanent and persistent atrial fibrillation improves after cardiac surgery regardless of giving add-on surgery or not, but this improvement is presumably more affected by treating the underlying heart disease than by restoring sinus rhythm.

Economic evaluation of online computerised cognitive-behavioural therapy without support for depression in primary care: randomised trial.

BACKGROUND: Evidence about the cost-effectiveness and cost utility of computerised cognitive-behavioural therapy (CCBT) is still limited. Recently, we compared the clinical effectiveness of unsupported, online CCBT with treatment as usual (TAU) and a combination of CCBT and TAU (CCBT plus TAU) for depression. The study is registered at the Netherlands Trial Register, part of the Dutch Cochrane Centre (ISRCTN47481236). AIMS: To assess the cost-effectiveness of CCBT compared with TAU and CCBT plus TAU. METHOD: Costs, depression severity and quality of life were measured for 12 months. Cost-effectiveness and cost-utility analyses were performed from a societal perspective. Uncertainty was dealt with by bootstrap replications and sensitivity analyses. RESULTS: Costs were lowest for the CCBT group. There are no significant group differences in effectiveness or quality of life. Cost-utility and cost-effectiveness analyses tend to be in favour of CCBT. CONCLUSIONS: On balance, CCBT constitutes the most efficient treatment strategy, although all treatments showed low adherence rates and modest improvements in depression and quality of life.

Glucosamine sulphate in the treatment of knee osteoarthritis: cost-effectiveness comparison with paracetamol.

INTRODUCTION: The aim of this study was to explore the cost-effectiveness of glucosamine sulphate (GS) compared with paracetamol and placebo (PBO) in the treatment of knee osteoarthritis. For this purpose, a 6-month time horizon and a health care perspective was used. MATERIAL AND METHODS: The cost and effectiveness data were derived from Western Ontario and McMaster Universities Osteoarthritis Index data of the Glucosamine Unum In Die (once-a-day) Efficacy trial study by Herrero-Beaumont et al. Clinical effectiveness was converted into utility scores to allow for the computation of cost per quality-adjusted life year (QALY) For the three treatment arms Incremental Cost-Effectiveness Ratio were calculated and statistical uncertainty was explored using a bootstrap simulation. RESULTS: In terms of mean utility score at baseline, 3 and 6 months, no statistically significant difference was observed between the three groups. When considering the mean utility score changes from baseline to 3 and 6 months, no difference was observed in the first case but there was a statistically significant difference from baseline to 6 months with a p-value of 0.047. When comparing GS with paracetamol, the mean baseline incremental cost-effectiveness ratio (ICER) was dominant and the mean ICER after bootstrapping was -1376 euro/QALY indicating dominance (with 79% probability). When comparing GS with PBO, the mean baseline and after bootstrapping ICER were 3617.47 and 4285 euro/QALY, respectively. CONCLUSION: The results of the present cost-effectiveness analysis suggested that GS is a highly cost-effective therapy alternative compared with paracetamol and PBO to treat patients diagnosed with primary knee OA.

Clinical effectiveness of online computerised cognitive-behavioural therapy without support for depression in primary care: randomised trial.

BACKGROUND: Computerised cognitive-behavioural therapy (CCBT) might offer a solution to the current undertreatment of depression. AIMS: To determine the clinical effectiveness of online, unsupported CCBT for depression in primary care. METHOD: Three hundred and three people with depression were randomly allocated to one of three groups: Colour Your Life; treatment as usual (TAU) by a general practitioner; or Colour Your Life and TAU combined. Colour Your Life is an online, multimedia, interactive CCBT programme. No assistance was offered. We had a 6-month follow-up period. RESULTS: No significant differences in outcome between the three interventions were found in the intention-to-treat and per protocol analyses. CONCLUSIONS: Online, unsupported CCBT did not outperform usual care, and the combination of both did not have additional effects. Decrease in depressive symptoms in people with moderate to severe depression was moderate in all three interventions. Online CCBT without support is not beneficial for all individuals with depression.