Unraveling the Mystery of Polyvalent Immunoglobulins in Belgium: Do We Have an Indication?

INTRODUCTION: Worldwide, polyvalent immunoglobulin (Ig) use is rising. Together with the limited supply, this puts pressure on Ig availability. A clear overview on a country's usage pattern helps in forecasting future needs. This research aims to provide an overview of Ig use in Belgium on the different indications, including an estimation of off-label use. METHODS: Multiple data sources were used. Existing claims data were explored for reimbursed Ig use between 2010 and 2018. General 2018 sales data from the firms were compared to the reimbursed use to serve as a proxy for off-label use. Indication-specific information was retrieved via a proxy: diagnostic codes available during day-care and inpatient hospitalization. RESULTS: In 2018, 7,556 patients had reimbursed Ig. The most prevalent indication, both in terms of patient numbers and volume, was primary immunodeficiency (PID). In Belgian hospitals, the currently reimbursed indications represented 84.4% of patients (PID [≈35%], secondary immunodeficiency [SID] [≈21%], primary immune thrombocytopenia [≈10%], chronic inflammatory demyelinating neuropathy [CIDP] [≈8%], Guillain-Barre syndrome [≈6%], Kawasaki [≈2%], streptococcal toxic shock [≈2%] and multiple motor neuropathy [≈1%]), and 82.4% of Ig use (predominantly PID [≈33%] and CIDP [≈21%]). Although no direct data on off-label use were available, crude estimates derived from indirect sources showed a proportion of around 15.4%. CONCLUSION: Our research offers the first comprehensive overview on Ig use in Belgium, including a detailed description of reimbursed use, as well as approximations to off-label use. In view of increasing pressure on Ig availability, better understanding Ig needs and trends, would benefit from an effective indication-specific national registry system (ideally covering both reimbursed and nonreimbursed use).

Economic evaluation of the use of point-of-care devices in patients with long term oral anticoagulation.

To examine the cost and cost-effectiveness of the use of point-of-care (POC) devices by the general practitioner (GP), in anticoagulation clinic or by the patient in self-testing (PST) and self-management (PSM), compared with standard laboratory testing to realize international normalized ratio tests for patients on long term anticoagulation therapy. An economic evaluation was performed from the Belgian health care payer's perspective using a Markov model. Outcomes data were derived from a meta-analysis and cost data were derived from claims databases. Several scenarios were tested based on number of tests and GP's contacts and probabilistic sensitivity analysis was used to handle uncertainty. Evidence on the impact of POC on mortality was only found for PSM. Therefore, a cost-effectiveness analysis was performed for PSM and for other strategies, only a cost comparison was done. With an unchanged number of tests, POC is cost-saving compared to laboratory testing (probability > 70%). In scenarios where POC induces more tests, results were different: with 52 tests/year, only PSM kept a probability of remaining cost-saving superior to 50%. Except in the case of 100% of GP consultations maintained and 52 tests/year performed, PSM resulted in significantly more "life years gained" (LYG) than usual care and was on average cost-saving. The organisation of long term oral anticoagulation monitoring should be directed towards PSM and, to a lesser extent, PST for selected and trained patients.

An EQ-5D-5L Value Set for Belgium.

OBJECTIVE: This study aimed to establish a Belgian EQ-5D-5L value set based on the preferences of the adult Belgian general population. METHODS: The most recent EuroQol Valuation Technology (EQ-VT 2.1) protocol for EQ-5D-5L valuation studies was followed. Computer-assisted personal interviews were carried out in a representative sample of the adult Belgian population. Potential respondents were randomly selected from the National Register using a multistage, stratified, cluster sampling with unequal probability design. Each respondent valued 10 or 11 health states using composite time trade-off (cTTO) and 14 health states in seven paired choice tasks using a discrete choice experiment (DCE). Different model specifications were explored and assessed based on logical consistency, goodness of fit, predictive accuracy and theoretical considerations. RESULTS: A total of 892 respondents were included in the analyses. The sample was representative of the Belgian adult population in terms of age, sex, region of residence, educational attainment, labour market status, self-assessed health status and health-related quality of life (HRQoL). The preferred model specification was a hybrid (DCE and cTTO data combined) multiplicative eight-coefficient model with intercept random effects and correction for heteroskedasticity. Values range from - 0.532 to 1. Loss of HRQoL is highest in the dimension pain/discomfort, closely followed by anxiety/depression. CONCLUSIONS: This study developed a Belgian EQ-5D-5L value set, based on the preferences of the Belgian adult general population. It provides opportunities for future clinical and economic evaluations in healthcare, for the measurement of patient-reported outcomes and for population health assessments.

Provider volume and short term complications after elective total hip replacement: an analysis of Belgian administrative data.

The relationship between provider volume and short term complications after an elective total hip replacement was studied on Belgian hospital discharge administrative database from 2004. The analysis included 11 856 patients. Hospitals were classified in low-volume (< or = 60/interventions per year), medium volume (61-110) or high volume (>110). Surgeons were labelled low-volume (< or = 6), medium volume (7-20) or high volume (>20). After adjustment for age, sex, principal diagnosis and comorbidity, surgeon volume was much more predictive of short term complications than centre volume. Patients treated by small volume surgeons (respectively medium volume surgeons) had a 43% higher odds of complications than patients operated by high volume surgeons (respectively 37%). Despite some limitations, Belgian administrative hospital discharge databases can be used to assess the volume outcome relationship for orthopaedic surgery. The study has emphasized the need to closely monitor individual performance, for hospitals and surgeons. Providers requiring further auditing can be effectively identified with funnel plots used routinely in quality control programs.

Tiotropium's cost-effectiveness for the treatment of COPD: a cost-utility analysis under real-world conditions.

BACKGROUND: Tiotropium is reimbursed since March 2004 in Belgium for the treatment of Chronic Obstructive Pulmonary Disease (COPD). Questions however remain on this product's value for money. The purpose of this study is to calculate tiotropium's cost-effectiveness under real-world conditions. METHODS: Strengths of both observational and RCT data were combined in a model. A large longitudinal (2002-2006) observational dataset of regular tiotropium users (56,321 patients) was analysed to retrieve the baseline risk for exacerbations and exacerbation-related hospitalisations the year before the first delivery of tiotropium. The relative treatment effect from the UPLIFT (Understanding Potential Long-term Impacts on Function with Tiotropium) trial was then applied to this baseline risk to reflect the effect of tiotropium treatment and calculate the intervention's incremental cost-effectiveness ratio (ICER). RESULTS: After 1000 Latin Hypercube simulations, the incremental benefit expressed as quality-adjusted life years (QALY) gained is on average 0.00048 (95% confidence interval (CI) 0.00009-0.00092). In combination with a substantial mean incremental cost of €373 per patient (95% CI 279-475), this results in an unfavourable average ICER of €1,244,023 (95% CI 328,571-4,712,704) per QALY gained. Results were most sensitive to the treatment effect on hospitalisations. Based on our large observational database, up to 89% of the patients were not hospitalised for COPD in the year before the first tiotropium delivery. CONCLUSIONS: The main cause for tiotropium's unfavourable cost-effectiveness ratio is a combination of a relative high price for tiotropium, a low number of hospitalisations without tiotropium treatment (on average 0.14/year) and a non-significant treatment effect (on average 0.94) with respect to avoiding exacerbation-related hospitalisations. From an economic point of view, a revision of reimbursement modalities (e.g. with a lower price) would be justified and would entail a more efficient use of resources.

Cost-effectiveness analyses of drug eluting stents versus bare metal stents: a systematic review of the literature.

OBJECTIVES: Drug eluting stents (DES) used to treat coronary lesions reduce rates of in-stent restenosis and therefore the need for repeat revascularization compared to bare metal stents (BMS). DES, however, are considerably more expensive than BMS. We evaluated whether DES are a cost-effective alternative for BMS. METHODS: Reports of Health Technology Assessment agencies were assessed and a systematic review of economic evaluations comparing DES with BMS was performed. RESULTS: Nineteen full economic evaluations were identified. Some studies indicate that DES may be cost-effective or even cost-saving in specific patients, when used for coronary lesions with a high propensity of restenosis such as long lesions, lesions in narrow vessels, or in patients with diabetes. Other studies mention DES is not cost effective at all with ICERs of more than 200,000 Canadian dollar per QALY gained. One of the main determining factors is the influence of protocol mandated angiographic follow-up in RCTs. The risk for a re-intervention using BMS ranges from 5% to 14% in registries and is much smaller than reported in RCTs (up to 30%). As a result, the absolute reduction in repeat revascularization by DES compared to BMS is smaller in real life. Moreover, using DES instead of BMS does not increase survival or decrease myocardial infarctions. The combination of (a) a higher cost (>euro700) for DES versus BMS; (b) no life-years gained; (c) a relatively small absolute reduction in repeat procedures; and (d) a small improvement in QoL for a short period (less than 0.15 during the first month after the re-intervention), results in unfavourable cost-effectiveness ratios. CONCLUSIONS: Although several studies conclude that DES may be cost effective in large subgroups of patients, under real-world conditions, the cost-effectiveness of DES is unfavourable in comparison with BMS.

A multi-criteria decision approach for ranking unmet needs in healthcare.

Early temporary reimbursement (ETR) schemes for new interventions targeting high unmet needs are increasingly applied in pharmaceutical policy. Crucial for these schemes is the assessment of unmet healthcare needs of patients and society. This study develops and tests a multi-criteria decision approach (MCDA) for assessing therapeutic and societal needs. The Belgian unmet needs commission, responsible for creating a list of unmet needs for the ETR programme, has tested this methodology to assess the needs in eight health conditions. For therapeutic need, three criteria were included (impact of the condition on quality of life and on life expectancy and inconvenience of current treatment); for societal need two criteria (condition-related healthcare expenditures per patient, prevalence). The results show that the proposed MCDA is feasible and acceptable for the unmet needs commission. Clear definitions of the criteria and regular repetition of these is needed to avoid variable interpretation of the criteria by the commission members. Quality assessment of the evidence is desired. Rankings resulting from the application have face validity. Considering therapeutic need separately from societal need is considered appropriate. Policy makers should consider the use of MCDA in assessing healthcare needs. MCDA improves the transparency and accountability of the decision making processes and is practical and feasible.

First- and second-line bevacizumab in ovarian cancer: A Belgian cost-utility analysis.

BACKGROUND: Currently, in Belgium, bevacizumab is reimbursed for ovarian cancer patients, based on a contract between the Minister and the manufacturer including confidential agreements. This reimbursement will be re-evaluated in 2018. OBJECTIVE: To support the reimbursement reassessment by calculating the cost-effectiveness of bevacizumab: (1) in addition to first-line chemotherapy; (2) in the treatment of recurrent ovarian cancer (platinum-sensitive or platinum-resistant). METHODS: A health economic model has been developed for the Belgian situation according to the Belgian guidelines for economic evaluations. The lifetime Markov model was set up from the perspective of the health care payer (government and patient), including direct healthcare related costs. Results are expressed as the extra costs per quality-adjusted life year (QALY). Calculations were based on results of four international trials. Both probabilistic and one-way sensitivity analyses were performed. RESULTS: Incremental cost-effectiveness ratios (ICERs) of first-line bevacizumab are on average 158 000/QALY (GOG-0218 trial) and 443 000/QALY (ICON7 trial). The most favourable scenario is based on the stage IV subgroup of the GOG-0218 trial (€52 000/QALY). Since subgroup findings are often exploratory and require confirmatory studies, results of the economic evaluation based on this subgroup analysis should be considered with caution. For second-line bevacizumab, ICERs are on average €587 000/QALY (OCEANS trial) and €172 000/QALY (AURELIA trial). Sensitivity analysis shows that results are most sensitive to the price of bevacizumab. CONCLUSION: From a health economic perspective, ICERs of bevacizumab are relatively high. The most favourable results are found for first-line treatment of stage IV ovarian cancer patients. Price reductions have a major impact on the estimated ICERs. It is recommended to take these findings into account when re-evaluating the reimbursement of bevacizumab in ovarian cancer.

What Does the Public Want? Structural Consideration of Citizen Preferences in Health Care Coverage Decisions.

Background. Multi-criteria decision analysis can improve the legitimacy of health care reimbursement decisions by taking societal preferences into account when weighting decision criteria. This study measures the relative importance of health care coverage criteria according to the Belgian general public and policy makers. Criteria are structured into three domains: therapeutic need, societal need, and new treatments' added value. Methods. A sample of 4,288 citizens and 161 policy makers performed a discrete choice experiment. Data were analyzed using multinomial logistic regression analysis. Level-independent criteria weights were determined using the log-likelihood method. Results. Both the general public and policy makers gave the highest weight to quality of life in the appraisal of therapeutic need (0.43 and 0.53, respectively). The general public judged life expectancy (0.14) as less important than inconvenience of current treatment (0.43), unlike decision makers (0.32 and 0.15). The general public gave more weight to "impact of a disease on public expenditures" (0.65) than to "prevalence of the disease" (0.56) when appraising societal need, whereas decision makers' weights were 0.44 and 0.56, respectively. When appraising added value, the general public gave similar weights to "impact on quality of life" and "impact on prevalence" (0.37 and 0.36), whereas decision makers judged "impact on quality of life" (0.39) more important than "impact on prevalence" (0.29). Both gave the lowest weight to impact on life expectancy (0.14 and 0.21). Limitations. Comparisons between the general public and policy makers should be treated with caution because the policy makers' sample size was small. Conclusion. Societal preferences can be measured and used as decision criteria weights in multi-criteria decision analysis. This cannot replace deliberation but can improve the transparency of health care coverage decision processes.

The 2016 proposal for the reorganisation of urgent care provision in Belgium: A political struggle to co-locate primary care providers and emergency departments.

Internationally the number of emergency department (ED) visits is on the rise while evidence suggests that a substantial proportion of these patients do not require emergency care but primary care. This paper presents the Belgian 2016 proposal for the reorganisation of urgent care provision and places it into its political context. The proposal focused on re-designing patient flow aiming to reduce inappropriate ED visits by improving guidance of patients through the system. Initially policymakers envisaged, as cornerstone of the reform, to roll-out as standard model the co-location of primary care centres and EDs. Yet, this was substantially toned down in the final policy decisions mainly because GPs strongly opposed this model (because of increased workload and loss of autonomy, hospital-centrism, etc.). In fact, the final compromise assures a great degree of autonomy for GPs in organising out-of-hours care. Therefore, improvements will depend on future developments in the field and continuous monitoring of (un-)intended effects is certainly indicated. This policy process makes clear how important it is to involve all relevant stakeholders as early as possible in the development of a reform proposal to take into account their concerns, to illustrate the benefits of the reform and ultimately to gain buy-in for the reform.

Acquired lightheadedness in response to odors after hyperventilation.

OBJECTIVE: This study aimed to investigate whether lightheadedness in response to odors could be acquired through previous associations with hyperventilation-induced hypocapnia. METHODS: Diluted ammonia and acetic acid served as conditional odor cues (CSs) in a differential associative learning paradigm. Hyperventilation-induced hypocapnia (unconditional stimulus [US]) was used to induce lightheadedness. In a training phase, participants (n = 28) performed three hypocapnic and three normocapnic overbreathing trials of 60 seconds each. One odor was consistently paired with the hypocapnic overbreathing (CS+); the other (control) odor was paired with normocapnic overbreathing (CS-). In the test phase, each odor was presented once during spontaneous breathing and once during normocapnic overventilation. Lightheadedness was assessed online during each breathing trial, which was followed by an extensive hyperventilation symptom checklist. Fractional end-tidal CO2, breathing frequency, and inspiratory volume were measured throughout the experiment. RESULTS: In the test phase, participants experienced lightheadedness more quickly in response to the odor that had been paired with hypocapnic overbreathing compared with the control odor. They also scored higher on the symptom "feeling unreal." CONCLUSION: Lightheadedness in response to odors can be acquired easily. The present results may help to elucidate the paradox that both avoidance and exposure to chemicals seem to be effective in reducing symptoms in idiopathic environmental illness.

US-inflation in a differential odor-conditioning paradigm is not robust: relevance for medically unexplained symptoms.

Reported somatic symptoms without clear relation to physiological processes are studied. A learning paradigm was used with two odors (CSs) and the inhalation of CO(2)-enriched air (US), while measuring symptom levels and respiratory behavior. After paring one odor with the CO(2)-enriched air and the other odor with air, half of the participants received a US-inflation manipulation (information manipulation and enhanced US). Subsequently, all participants received both odors with air (test). A difference between the odor previously paired with CO(2)-enriched air and the odor previously paired with air was found for the symptom measure, US-expectancy ratings, and, to a lesser extent, for respiratory volume. No differences, however, were found between the group receiving the US-inflation manipulation and a group not receiving this manipulation. The results indicate that, despite a successful learning of reported symptoms, US-inflation does not seem to be robust.

Imagined risk of suffocation as a trigger for hyperventilation.

OBJECTIVE: Although hyperventilation has been hypothesized to play a role in many pathologies, its critical triggers remain poorly understood. The present experiment aimed to test whether stronger hyperventilation responses occur in response to suggested risk of suffocation compared with other fearful situations in high- and low-trait anxious women. METHODS: Fractional end-tidal CO2-concentration (FetCO2), respiratory frequency, and inspiratory volume were measured nonintrusively in high- (n = 24) and low- (n = 24) trait anxious women during imagery of 3 fear, 1 tension, 1 depressive, and 3 relaxation scripts. The fear scripts were equal in ratings of unpleasantness and arousal but differed regarding the inclusion of suggested risk of suffocation and entrapment. After each imagery trial, participants rated the emotional dimensions of pleasantness, arousal, and dominance and the vividness of their imagery. RESULTS: Decreases in FetCO2 occurred in all fear scripts. High-trait anxious women showed a stronger reduction in FetCO2 compared with low-trait anxious women during the fear script suggesting risk of suffocation but not during the other fear scripts. This effect was unrelated to any of the self-reported fear ratings. Self-reported fear of entrapment was associated with an overall lower FetCO2 but not with enhanced reactivity to imagined entrapment. CONCLUSION: High-trait anxiety is associated with stronger respiratory responsivity to imagined risk of suffocation and may constitute a specific vulnerability factor for the development of panic disorder and claustrophobia.

Accuracy of respiratory symptom perception in different affective contexts.

OBJECTIVE: The accuracy of respiratory symptom perception was investigated in different affective contexts in participants (N=48) scoring high or low for negative affectivity (NA). METHODS: Within-subject correlations were calculated between two subjective ratings and their respective physiological referent (the rating of "deeper breathing" and respiratory volume, and rating of "faster breathing" and breathing frequency) across nine consecutive breathing trials. Three different air mixtures were used: room air, air enriched with 7.5% CO(2), and with 10% CO(2). For half the participants, the trials were framed in a pleasant context, created by adding a pleasant odour to the air mixture in addition to information announcing pleasant feelings as a result of breathing the air mixtures. The other half received the trials in a distressing context: A foul smelling odour was added and the information announced unpleasant feelings. RESULTS: High-NA persons were overall less accurate than were low-NA persons in the perception of respiratory volume. For breathing frequency, high-NA persons were significantly less accurate in the distressing condition than in the pleasant one, whereas for low-NA persons, the information frame did not matter. CONCLUSION: The study shows that the accuracy of respiratory symptom reports is reduced in high-NA persons, especially in a distressing context.

Media warnings about environmental pollution facilitate the acquisition of symptoms in response to chemical substances.

OBJECTIVE: Previous studies showed that somatic symptoms can be acquired in response to chemical substances using an associative learning paradigm, but only when the substance was foul smelling and not when it smelled pleasant. In this study, we investigated whether warnings about environmental pollution would facilitate acquiring symptoms, regardless of the pleasantness of the smell. METHOD: One group received prior information framing the study in the context of the rapidly increasing chemical pollution of our environment. Another group received no prior information. Conditional odor stimuli (CS) were diluted ammonia (foul-smelling) and niaouli (neutral-positive smelling); the unconditional stimulus (UCS) was 10% CO2-enriched air. Each subject breathed one odor mixed with CO2 and a control odor mixed with air in 80-sec breathing trials. The type of odor mixed with CO2 was counterbalanced across participants. Next, the same breathing trials were administered without CO2. Breathing behavior was measured during each trial; subjective symptoms were assessed after each trial. RESULTS: Only participants who had been given warnings about environmental pollution reported more symptoms to the odor that had previously been associated with CO2, compared with the control odor. This was so for both the foul- and the pleasant-smelling odor. Symptom learning did not occur in the group that did not receive warnings. The elevated symptom level could not be accounted for by altered respiratory behavior, nor by experimental demand effects. CONCLUSIONS: Raising environmental awareness through warnings about chemical pollution facilitates learning of subjective health symptoms in response to chemical substances.

Resting end-tidal CO2 and negative affectivity.

OBJECTIVE: Dhokalia, Parsons, and Anderson (Psychosom Med 1998;60:33-37) found a positive correlation between a trait measure of negative affectivity (NA; neuroticism) and resting end-tidal fractional concentration of CO2 (FetCO2) (fractional-concentration of end-tidal carbon dioxide) in a nonclinical sample. This contrasts sharply with studies reporting a negative association of FetCO2 with state measures of NA and with studies reporting no or a negative relationship between FetCO2 and trait NA. In two studies we aimed to clarify this paradox. MATERIALS AND METHODS: In the first study, 110 participants (83 women) completed the PANAS and a Checklist for Psychosomatic Symptoms in daily life. FetCO2 was measured noninvasively during 5 minutes via a nose cannula connected to a capnograph. In the second study, FetCO2 of high (N= 20, 10 men) and low (N= 20, 10 men) NA participants was sampled once with a nasal cannula and once while breathing through a mouthpiece for 6 minutes each during rest, completion of the NEO-PI-R questionnaire, and completion of a verbal knowledge test. RESULTS: The first study found no association between trait NA and resting FetCO2 after partialling out the effects of gender, menstrual phase, and use of oral contraceptives. The second study showed that FetCO2 increased significantly in the high NA group only when the particpants filled out the questionnaires, regardless of its type. CONCLUSIONS: Overall, no association between dispositional NA and cross-situational FetCO2 was observed. Apparently inconsistent findings may be caused by lack of control for hormonal status and mental load during testing.

Developing and measuring a set of process and outcome indicators for breast cancer.

PURPOSE: This study aimed at developing and measuring a set of indicators to monitor the quality of breast cancer care, to make comparisons over time and to support quality improvement for all practitioners and centres involved in the care of breast cancer women. METHODS: Quality indicators were identified from a systematic literature search and the 2010 Belgian evidence-based clinical practice guideline. The selection process involved an expert panel evaluating reliability, relevance, interpretability and actionability of each indicator. The quality indicators were tested using the Belgian Cancer Registry data linked with claims data for all women registered with breast cancer in Belgium between 2001 and 2006 (n=50,039). RESULTS: The selection process led to a final set of 32 indicators. Of these, 12 were measurable using the available data, while 1 indicator was measurable using proxy information. Five-year relative survival was 98%, 87%, 68% and 29% for pStage I, II, III and cStage IV respectively. Overall 5-year survival slightly improved for pStage II, III and cStage IV between 2001 and 2004. Of the surgically treated women, 60% underwent breast conserving surgery, 85% received adjuvant systemic treatment and 86% were irradiated postoperatively. In 80% of women treated for breast cancer, at least one mammography was performed within one year after the last treatment. CONCLUSION: The present study demonstrates the feasibility to develop a multidisciplinary set of quality indicators for breast cancer. Using national cancer registry data linked to claims data, 13 indicators were measurable, showing results that largely correspond to other studies in the field.

Quality indicators for testicular cancer: a population-based study.

PURPOSE: This study aimed at developing and measuring an indicator set to monitor the quality of testicular cancer care, to make comparisons over time and to support quality improvement for all practitioners and centres involved in the care of testicular cancer patients. METHODS: Quality indicators were identified from a systematic literature search and from the 2010 Belgian evidence-based clinical practice guidelines. The selection process involved an expert panel evaluating reliability, relevance, interpretability and actionability of each indicator. The quality indicators were pilot tested using the Belgian Cancer Registry (BCR) data linked with claims data for 1307 men with testicular cancer diagnosed between 2001 and 2006. The variability between centres was displayed using funnel plots. RESULTS: Of the 12 finally selected indicators, 5 were fully and 1 was partly measurable, while 2 indicators were measurable using proxy information. Five-year relative survival was 97%, 95% and 76% for pStage I-III, respectively. Overall 5-year survival slightly improved from 91% in 2001 to 94% in 2004. Between 2004 and 2006, 14 of 97 centres performed ≥10 orchidectomies. Large variability was found between centres. The nine centres with a 5-year observed survival below the lower limit treated less than 20 patients between 2001 and 2006. CONCLUSIONS: The present study demonstrates the feasibility to develop a multidisciplinary set of quality indicators for testicular cancer. Using national cancer registry data linked to claims data, eight indicators were measurable, showing a mixed picture of the quality of care for testicular cancer patients in Belgium.

Effect of hospital volume on processes of care and 5-year survival after breast cancer: a population-based study on 25000 women.

PURPOSE: To compare processes of care and survival for breast cancer by hospital volume in Belgium, based on 11 validated process quality indicators. METHODS: Three databases were linked at the patient level: the Cancer Registry, the population and the claims databases. All women with a diagnosis of invasive breast cancer between 2004 and 2006 were selected. Hospitals were classified according to their annual volume of treated patients: <50 (very low), 50-99 (low), 100-149 (medium) and ≥ 150 patients (high). Cox and logistic regression models were used to test differences in 5-year survival and in achievement of process indicators across volume categories, adjusting for age, tumor grade and stage. RESULTS: A total of 25178 women with invasive breast cancer were treated in 111 hospitals. Half of the hospitals (N=57) treated <50 patients per year. Six of eleven process indicators showed higher rates in high-volume hospitals: multidisciplinary team meeting, cytological and/or histological assessment before surgery, use of neoadjuvant chemotherapy, breast-conserving surgery rate, adjuvant radiotherapy after breast-conserving surgery, and follow-up mammography. Higher volume was also associated with improved survival. The 5-year observed survival rates were 74.9%, 78.8%, 79.8% and 83.9% for patients treated in very-low-, low-, medium- and high-volume hospitals respectively. After case-mix adjustment, patients treated in very-low- or low-volume hospitals had a hazard ratio for death of 1.26 (95% CI 1.12, 1.42) and 1.15 (95% CI 1.01, 1.30) respectively compared with high-volume hospitals. CONCLUSION: Survival benefits reported in high-volume hospitals suggest a better application of recommended processes of care, justifying the centralization of breast cancer care in such hospitals.

A cost-utility analysis of transcatheter aortic valve implantation in Belgium: focusing on a well-defined and identifiable population.

BACKGROUND: Patients with severe aortic stenosis and coexisting non-cardiac conditions may be at high risk for surgical replacement of the aortic valve or even be no candidates for surgery. In these patients, transcatheter aortic valve implantation (TAVI) is suggested as an alternative. Results of the PARTNER (Placement of AoRTic TraNscathetER Valve) trial comparing the clinical effectiveness of TAVI with surgical valve replacement and standard therapy were published. The authors assessed the cost-effectiveness of TAVI in Belgium. METHODS: A Markov model of incremental costs, effects (survival and quality of life) and incremental cost-effectiveness of TAVI was developed. The impact on survival, number of events and quality of life was based on the PARTNER trial. Costs per event were context specific. RESULTS: In high-risk operable patients, even if the minor differences in 30-day and 1-year mortality are taken into account, the incremental cost-effectiveness ratio (ICER) remains on average above €750 000 per quality-adjusted life-year (QALY) gained (incremental cost: €20 400; incremental effect: 0.03 QALYs). In inoperable patients, an ICER of €44 900 per QALY (incremental cost: €33 200; incremental effect: 0.74 QALYs) is calculated, including a life-long extrapolation of the mortality benefit. This result was sensitive to the assumed time horizon. The subgroup of anatomically inoperable patients had better outcomes than medically inoperable patients, with ICERs decreasing more than €10 000/QALY. CONCLUSIONS: It is inappropriate to consider reimbursement of TAVI for high-risk operable patients. Reimbursing TAVI in inoperable patients in essence is a political decision. From an economic perspective, it would be prudent to first target patients that are inoperable because of anatomical prohibitive conditions. In the search for evidence, the authors identified non-published negative results from a randomised controlled TAVI trial. The study sponsor should be more willing to share this information to allow balanced evaluations and policy recommendations. Payers should require these data before taking reimbursement decisions.