To evaluate the short- (first year) and long-term (second year) cost of cardiovascular events (CVEs) in Belgium. The analysis included myocardial infarction (MI, excluding revascularization), unstable angina (UA, excluding revascularization), heart failure (HF), ischemic/hemorrhagic stroke (IS/HS) and transient ischemic attack (TIA). Coronary revascularization procedures (weighted average of coronary artery bypass grafting [CABG] and percutaneous coronary intervention [PCI]) were also evaluated. Index hospitalization costs (year 2012) as well as re-hospitalization costs up to 2 year after the index hospitalization were derived from the Belgian IMS real-world Hospital Disease Database (HDD). Other follow-up costs (rehabilitation, outpatient visits and ambulatory resource use [tests, imaging and drugs]) over 2 years were assessed by an independent 2-round expert-panel in 2014 (5 cardiologists, 6 neurologists). Costs of fatal CVEs were evaluated through the HDD. The combined perspective of public health care payer and patient was applied. Costs (€ in 2014) were calculated as unit costs (official listings) multiplied by the number of resources used. Total costs in the first year after CVEs ranged between €7,683 (UA) and €33,790 (HS). Costs for TIA, MI, HF and IS were €8,198, €11,119, €17,210 and €24,640, respectively. Follow-up costs over the second year ranged from €2,781 (UA) to €7,617(HS). Other CVEs costed €3,315 (TIA), €3,746 (MI), €7,233 (HF) and €7,399 (IS) in year 2. Hospitalization costs were the most important cost driver, independent of CVE type. Follow-up costs tended to be higher in patients with increased CVE risk. Revascularization costs were €13,373 and €2,763 during the first and second year of follow-up, respectively. Fatal events costed €4,698 (HS), €5,424 (UA), €6,122 (MI), €7,643 (IS) and €10,344 (HF). Patient co-payment varied between 3-11%. CVEs account for a significant economic burden in Belgium. Hospitalizations are the most important cost driver. Prevention of hospitalizations could lead to important savings.

Medication errors are unintentional errors in how medicines are prescribed, dispensed, administered, or monitored while controlled by a healthcare professional, patient, or consumer. Leendertse et al (2008) reported that 5.6% of acute hospital admissions are medication-related, of which 46.5% were potentially preventable. This study estimated the costs related to medication errors that lead to avoidable hospitalizations in Belgium. Based on the incidences from Leendertse et al (2008), the number of hospital admissions due to avoidable medication errors in Belgium was determined. The total avoidable costs attributable to medication errors was estimated, by multiplying the number of avoidable hospitalizations with the average cost of a hospital stay, calculated using the online official database of the Technical Cell (data from 2011). Costs were inflated to 2014. The estimated average cost of a hospital stay in Belgium was €4,886. Based on 2.6%, the incidence rate of total hospital admissions attributable to medication errors, 42,797 hospital admissions that could have been avoided due to medication errors were estimated. Avoiding these hospitalizations would produce potential savings of €209Mn per year. This study shows that the economic and health burden of preventable medication errors is high. As such, a synergic approach is warranted nationally and across national borders. This should entail communication and involvement from all different stakeholders (medical doctors, pharmacists, hospitals, national and international pharmacovigilance organizations) in the provision and delivery of care.

Poor adherence to cardiovascular therapy is increasingly demonstrated to contribute to poor health outcomes, leading to increased hospitalization rates. This study aims to quantify the potential economic implications of non-adherence to statins in Belgium, from the payer perspective. Adherence levels were estimated based on IMS Health Lifelink Treatment Dynamics database (IMS Health LTD). The number of prescription re-fills and total days covered by prescriptions were counted. Patients were assumed to take one pill per day. Dividing the total number of pills by the days of follow-up per patient resulted in the %-adherence level. The number of avoidable hospitalizations corresponding to each adherence level was determined by: the hospitalization risk difference between patients at 80-100% adherence and less than 80% adherence (grouped per 20%, Sokol et al 2005), and multiplying the number of patients in each of the five adherence levels in Belgium (extrapolated from IMS Health LTD according to Pharmanet 2013 report). The total avoidable cost attributable to non-adherence was estimated, by multiplying the number of avoided hospitalizations due to non-adherence with the average cost of a cardiovascular hospitalization in Belgium in 2014 (€5,865), adding the extra drug cost needed to obtain a 80-100% adherence. Sixty-five percent of anonymized patients in the IMS Health LTD were below the acceptable 80% adherence level. A total of 25,716 cardiovascular hospitalizations in Belgium were possibly attributable to lack of adherence to statins therapy. The estimated total avoidable costs related to hospitalization would be €150.8Mn. If all patients raised their levels of adherence to 80-100%, treatment costs with statins would increase with €68.5Mn. Thus, the estimated total amount of savings would be around €82.4Mn. Correcting poor adherence, not only in the cardiovascular area, can lead to important savings and give air to the healthcare payer to invest in innovative drugs.

We aimed at estimating and comparing the total management costs of patients admitted to the emergency department (ED) with recent (<48 hours) atrial fibrillation (AF) between three types of cardioversion: direct current cardioversion (DCC), intravenous amiodarone or intravenous vernakalant. A decision analytic model was developed to mimic the pathways of patients admitted via the ED with recent AF and to calculate an average AF management cost per strategy. The cardioversion success rates were based on published observational studies (DCC 90%, amiodarone 68%, vernakalant 70%). In case of successful conversion the patient was released directly from the ED to home (DCC 50%, amiodarone 25%, vernakalant 100%) or admitted to the hospital for a median of 1 day (DCC) or 2 days (amiodarone) reflecting cardioversion-specific times to sinus rhythm. After a failed pharmacological cardioversion, patients were assumed to receive a DCC; failed DCC was followed by intravenous amiodarone. The associated inpatient costs were retrieved from the IMS Hospital Disease Database (HDD2011). ED treatments were costed using the national health care payer tariffs. Univariate and probabilistic sensitivity analyses were performed. The total AF management costs from ED to discharge were estimated at €952 (DCC), €1,894 (amiodarone) and €1.354 (vernakalant). Given the relative frequencies of amiodarone (55%) and DCC (45%) to treat recent FA in Belgian ED, the weighted average management cost was €1.470 (+ €116/treatment vs. vernakalant). The break-even situation is reached when 75% of successfully treated vernakalant patients avoid the hospitalization (base case 100%). Based on a probabilistic sensitivity analysis, vernakalant was cost saving in 55% of the 1,000 simulations vs. current management. In patients with recent AF, the rapid mode of action of vernakalant increases the chance of obtaining sinus rhythm within 48 hours, and its use was cost saving compared to the current average Belgian practice.

Linaclotide is the first drug that received EMA approval in the management of irritable bowel syndrome in its constipation form (IBS-C). We aimed at estimating the cost-utility of linaclotide, compared to standard of care (SoC) in Belgium. The analysis was conducted using data from a 6-month randomized trial of linaclotide 290µg once daily (N=401) versus placebo (N=403), which provided monthly EQ-5D measures, treatment duration, adverse events (diarrhoea) and responder status (abdominal pain/discomfort improvement ≥ 30% from baseline). Belgian EQ-5D tariffs were used to estimate utilities and trapezoidal rule to estimate QALYs. A Delphi panel including 6 general practitioners and 5 gastro-enterologists provided the resource use for IBS-C patients in different treatment phases: controlled with 2nd line or new drug else non-responders. Patient-level costs were applied using first-order Monte-Carlo simulation (gamma distribution function; per treatment arm and responder status; health care payer perspective). A stopping rule was implemented at 4 weeks for linaclotide non-responders. A non-parametric bootstrap with 1000 replications was performed. The 2012 Belgian GDP per capita (€34,000) was used as willingness-to-pay threshold. The responder rate at 4 weeks was 54.6% with linaclotide vs. 35.5% with SoC. There was on average 0.0129 QALYs gained per linaclotide patient vs SoC at 6 months (0.385 vs. 0.372), with an incremental cost of €95 (€1,376 vs. €1,280). The incremental cost-effectiveness ratio of was €7,364/QALY. The diarrhoea costs were higher with linaclotide (+€19.4) while savings were observed in clinical management (-€132.2) compared to SoC. Using a willingness-to-pay threshold of €34,000/QALY, 66% of the simulations were cost-effective. Due to improvements in abdominal pain/discomfort complaints in patients receiving linaclotide, savings were generated in the clinical management of IBS-C compared to SoC. Using the GDP per capita as willingness-to-pay threshold, linaclotide seems a cost-effective alternative to today SoC of IBS-C in Belgium.

Patients suffering from irritable bowel syndrome (IBS) with constipation (IBS-C) receive laxatives as first line therapy. In spite of these laxatives most of them experience failure. We aimed at describing the current management and its costs of Belgian IBS-C patients who failed first line treatment. A 2-round Delphi panel was conducted including general practitioners (GP) and gastroenterologists. The type and frequency of medical resources used per year as second-line IBS-C therapy (consultations, exams/tests, drugs, hospitalizations) were collected, reflecting the expert’s own practice in the first round and finding a Belgian consensus in the second round. Two patients’ profiles were defined: second line current management and third line management in case of second line failure. Unit costs (2012 INAMI/RIZIV tariffs) were assigned to the resources used to calculate a cost per patient-year and a range based on the distribution of experts’ answers. Eleven experts participated (6 GPs/5 gastroenterologists). The drugs prescribed in second line were laxatives (71.4%, mainly osmotics), spasmolytics (72.2%), pain killers (11.5%) and antidepressants (6.0%). There were 7.7 consultations per patient-year on average (GP: 5.3; specialists: 2.4). Emergency room visits occurred in 10.4% and diagnostic tests included thyroid function (79.1%), rectosigmoidoscopy (39.8%) and abdominal echography (36.8%). There were 0.97 IBS-related admissions to hospital per patient-year. After a second line failure, resource use increased with more laxatives (75.5%), antidepressants (24.6%) and pain killers (17.3%), 11.6 consultations (GP: 7.5; specialist: 4.1), 14.5% emergency room visits and 1.25 hospitalizations. Diagnostic tests were also more frequent (rectosigmoidoscopy: 49.3%; abdominal echography: 43.6%) except thyroid function (70.0%). The annual cost of second line was €2,114 [1,509;2,819] versus €2,920 [2,072;3,917] after second line failure. Hospitalizations accounted for about 75% of the costs. IBS with constipation leads to significant resource use and high costs certainly in case of second line treatment failure.

The number of patients on dialysis has increased by about 50% in the past decade in Belgium. This growth is expected to continue, albeit at a slower pace, due to the ageing of the population and the increased prevalence of hypertension and diabetes, two of the main causes of end-stage kidney disease. The aim of this study was to assess the economic burden (i.e., dialysis procedure; hospitalizations; ambulatory care; medications; transport) to the public healthcare payer of patients undergoing dialysis in Belgium. Records of 130 Belgian patients on dialysis in 2006 were retrospectively reviewed to identify direct medical and non-medical resources used over a year. Official tariffs were used to cost the resources. Considering the prevalence of each dialysis modality in Belgium, the average cost of a dialysis patient was found to be 70,649 per year (haemodialysis: 72,350; peritoneal dialysis: 55,343). The dialysis procedure itself was the main cost driver (66% of all costs) followed by hospitalizations and ambulatory care (16% of all costs each). The dialysis procedure per se was 27% more expensive, while hospital and ambulatory services were respectively 28% and 45% more expensive for haemodialysis than peritoneal dialysis patients. Considering that there were 6,607 patients on dialysis in Belgium (0.06% of the Belgian population) at the end of 2006, it is estimated that the economic burden to the Belgian healthcare system was 467 million Euro or 2.45% of the healthcare budget. This study provides further evidence that home modalities, such as peritoneal dialysis, could help reduce the economic burden of dialysis on the healthcare budget.

Hypertension affects 41% of male and 31% of female adults in Belgium; 13% of these are believed to be refractory to standard hypertension treatment (uncontrolled with ≥ 3 different classes of antihypertensive therapy). Catheter-based renal denervation (RDN) is a novel, minimally invasive therapy for treatment-resistant hypertension. The aim of this study was to assess the cost-utility of RDN as compared to current standard of care (SoC) for refractory hypertension in Belgium. A lifetime state-transition, Markov model was used, with health-states encompassing possible long-term consequences of hypertension: stroke, myocardial infarction, angina, heart failure, end-stage renal disease. Risk equations were used to calculate the risk of events with changing systolic blood pressure (SBP). Reductions in SBP following RDN vs. SoC pertain to the results of the Symplicity HTN-2 randomized controlled trial. The underlying modeled cohort was defined similar to the same trial: mean baseline SBP 178 mmHg, mean age 58 years, 34% with diabetes mellitus. Costs pertained to published economic evaluations or public tariffs and reflected the Belgian payer perspective. Costs and health outcomes were discounted at a rate of 3%, and 1.5% respectively. Projected lifetime costs were 21,743€ and 24,558€ in the SoC and RDN arms respectively, while total projected life years were 16.43 and 17.23. RDN increased patients’ quality of life with 0.93 quality-adjusted life years (QALYs) vs. SoC. This resulted in an incremental cost-utility ratio (ICUR) of 3,020€/QALY. Results were most sensitive to changes in SBP reductions, and the cost of RDN procedure, but remained under a willingness to pay (WTP) threshold of 20,000€/QALY. Probabilistic sensitivity analyses showed acceptable cost-effectiveness in 100% of cases, under a WTP threshold of 20,000€/QALY. Results of these analyses suggest that, under the current model settings, catheter-based RDN procedure could be a cost-effective strategy for resistant hypertension in Belgium.

Background Chronic hepatitis because of the hepatitis C virus (CHC) is a major health problem that can lead to decompensated cirrhosis, hepatocellular carcinoma, and eventually death, all of which are associated with significant healthcare costs. Aim To update the cost of care of CHC according to the different severity stages of the disease in a west European country (Belgium). Methods Medical records of 157 patients, who were referred to the medical specialist at different stages of disease, were reviewed to identify the medical costs over a follow-up period of 3 years or 2 years in the case of liver transplantation (LT). Six disease stages were defined on the basis of histology (Metavir classification) and/or clinical data. Results In comparison with mild disease, the cost increased 1.6 times in the case of decompensated cirrhosis, 1.9 times in the case of hepatocellular carcinoma, and 3.4 in the case of LT. The costs for medication, hospitalization, and ambulatory care were, respectively, on the one hand, 81, 8, and 11% for mild disease and, on the other, 18, 79, and 3% for LT. In the case of a sustained viral response, the cost of follow-up within 3 years decreased by 45% for patients with mild and moderate disease. Conclusion Antiviral treatment is the most important factor governing cost in mild and moderate disease, but once complications of CHC occur, hospitalization costs far exceed the cost of antiviral therapy. Already during the first 3 years of follow-up, sustained viral response decreased the cost significantly. Treatment of patients with CHC in an early stage has the potential to be cost-effective.

Sugammadex is registered for decurarization of moderate/deep neuromuscular blockade induced by rocuronium or vecuronium. The advantages compared to the well-known decurarization drugs like neostigmine is that undesirable side-effects (bradycardia-bronchoconstriction-hypersalivation-nausea-vomiting) are avoided and deeper levels of blockade can be reversed. In Belgium its reimbursement is restricted to certain conditions (impossible intubation or rapid decurarization of deep blockade when medically required or rapid decurarizaton moderate blockade in patients with obstructions (stomach/bowel, bile duct, urinary tract) or when administration of neostigmine is contra-indicated). The objective of this study was to evaluate Belgian real-life use of sugammadex one year after reimbursement was granted. The medical records of 330 adult patients being treated with sugammadex during the first half year of 2011 (6 hospitals selecting 55 consecutive patients) were retrospectively reviewed. Data collection included baseline patient-characteristics, hospital-, surgery- and sugammadex-related info. In addition, a 2-round expert-panel among 12 physicians was organized. Based on the expert-panel (in combination with published data), it was estimated that in Belgium rocuronium is used in about 58,100 surgical interventions per year. Reversal with sugammadex is performed in 21.5% of them. Mean age of the patients using sugammadex was 54 years (+/− 17 SD), 45% of the patients belonged to ASA (American Society of Anesthesiologists) category I-II (healthy-mild systemic disease), 33% to category>III, 84% had co-morbidities. Sugammadex is mainly used after gastroenterological surgery (53%; high contribution of bariatric-surgery), followed by gynaecological interventions (12%), estimates confirmed by the expert-panel. According to the experts, in 29% of the patients reversal with sugammadex was used outside the reimbursement conditions. The study confirms that, in Belgium, sugammadex is used when medically needed, a substantial part being used outside the reimbursement conditions.

To study real-life patient characteristics, treatment patterns and costs associated with DME and visual acuity (VA) level. The study aimed to recruit 100 patients distributed evenly over 4 categories defined by last measured VA. 1-year retrospective data were collected from medical records. Annual direct costs were calculated from resource use in medical records and official unit costs (€ 2011). Self-reported economic burden was collected via Short Form Health and Labour Questionnaire (SF-HLQ). Indirect costs (€ 2011) included personal expenses and caregiver burden (SF-HLQ). Thirteen Belgian ophthalmologists recruited 32, 12, 14 and 6 DME patients for VA categories ≥20/50, 20/63-20/160, 20/200-20/400 and <20/400 respectively. VA was stable during the study in 86% of patients. Recruitment for lower VA categories was difficult due to long-term vision conservation with current treatments, lack of differentiation between lowest categories in medical records and discontinuation of ophthalmologist care in lowest categories. 75% of patients had bilateral DME. 68% were treated for DME during the study, of which 60% in both eyes. 50% received photocoagulation, 33% intravitreal drugs. Less than 4% of patients had paid work; 17% received disability replacement income. Total direct medical costs in patients receiving active treatment ranged from €960 (lowest VA) to €3,058. 59% of direct costs were due to monitoring and vision support, 39% to DME treatment. Indirect cost trends were less intuitive due to small samples and large variations. Annual costs grouped by 2 highest and 2 lowest VA levels, were respectively €114 and €312 for visual aids, €407 and €3,854 for home care. The majority of DME patients had bilateral disease. Except for the lowest VA, direct medical costs increased with VA decrease. Indirect costs were substantially higher at lower VA levels. Low sample sizes in some categories did not allow statistical analysis of cost differences.

The aim of this study was to assess disease stage dependent resource use and costs in chronic genotype 1 hepatitis C (CHC) patients in Belgium. The medical records of 157 CHC patients were reviewed to identify medical costs over a follow up period of 3 years. Six disease stages were defined based on histology/clinical data: mild disease (F0-F2), moderate disease (F3) or compensated cirrhosis without varices (F4), compensated cirrhosis with varices (F4), decompensated cirrhosis, hepatocellular carcinoma (HCC) and liver transplantation (LT). Data collected were baseline demographic characteristics, HCV-related data and detailed resource use (hospitalizations, day-clinic visits, surgery/interventions, physician visits, diagnostic tests and drug use). Resource use items were multiplied with unit costs (2010) to calculate costs. The public health care payer's (HCP) perspective was taken including the health insurance and patient co-payment. Intravenous/intranasal drug use was reported in circa 20% of patients, 63% had co-morbidities at study start. Nineteen patients (12%) died during the study period, whereof 79% attributable to HCV. Average number of hospitalizations during the study period ranged between 0.4 (mild disease) and 5.3 (HCC). Cost of care during the study period ranged from €18,993 for mild disease (in 81% due to HCV drug treatment) to €35,987 for patients with HCC (in 83% due to hospitalization, 11% due to medication and in 6% due to ambulatory care) and €65,120 for patients who underwent a liver transplant (79% hospitalization, 18% medication, 3% ambulatory care). Cost of diagnosis of the disease stage ranged between €790 (F3-F4 without varices) and €4142 (decompensated cirrhosis). Antiviral treatment is the most important cost driver in mild & moderate disease, but once complications of CHC occur, the associated costs far exceed this cost of antiviral therapy.

Background: Two phase II trials (POWER 1 and 2) have demonstrated that darunavir co-administered with low-dose ritonavir (DRV/r) provides significant clinical benefit compared with control protease inhibitors (PIs) in highly treatment-experienced, HIV-1-infected adults, when co-administered with optimized background therapy (OBR).

BACKGROUND:Basal cell carcinoma (BCC) is the most common form of skin cancer worldwide. Different treatment options exist. The efficacy of photodynamic therapy with methyl aminolevulinate (MAL-PDT) has been established in several randomized controlled trials (RCTs). Real life data can differ greatly from data derived from randomized controlled trials (RCTs).OBJECTIVES:To describe the results of a Belgian observational study concerning superficial BCC (sBCC) vis-a-vis clinical and health economic outcomes in order to evaluate the real-life practice of MAL-PDT.METHODS:This study was a prospective, single-arm, open study conducted at eight dermatological institutions during six months after the first MAL-PDT treatment. Eligible patients had to present with lesions, suitable for MAL-PDT according to Belgian reimbursement criteria. Resource use was collected during the study period. Clinical Response (CR) and Cosmetic Outcome (CO), as well as cost of care were evaluated. A subset analysis of patients with sBCC only was conducted.RESULTS:Ninety patients were identified for the analysis (mean age 65 years; 61% female). The mean number of lesions per patient was 1.6, mostly located on the face, the back and the chest. For the entire period, the mean number of visits to a dermatologist was 4 per patient including two MAL-PDT sessions. The average, cumulative amount of MAL used per treatment was 1,256 mg. Two patients experienced adverse events at the application site, none of them serious; all resolved completely. The CR rate was 89% at the end of the study. The CO was "excellent" or "good" in 96% of the patients. Total cost of care was Euro 289 ($414 U.S.) per patient. Cost per lesion was Euro 195 ($280 U.S.).CONCLUSION:The results from the real-life practice study confirm the efficacy found in prior, prospective randomized trials. About four visits and less than one tube of MAL are needed for the full treatment of sBCC in one patient.

OBJECTIVES: To assess the cost per QALY (quality-adjusted life years) of pregabalin in the management of peripheral neuropathic pain. METHODS: We compared pregabalin on top of "usual care" with "usual care" alone. In this study, usual care was defined as a mix of drug therapies, excluding anti-epileptic drugs (AEDs), because the latter represented only 9% of current use, and clinical evidence of pregabalin was demonstrated versus usual care without anti-epileptic drugs. A Markov mode[ was developed to simulate the evolution of a patient cohort over 1 year, and applied cycles of 4 weeks. During each cycle, patients remained in 1 out of 4 possible states: severe, moderate or mild pain, and therapy withdrawal. The health care payers perspective was taken into account. Clinical data were obtained from a trial comparing usual care plus placebo to usual care plus pregabalin, at either 150,300, or 300/600 mg/day (the latter depending on clearance of creatinin). Resulting effects on pain were transformed into transition-probabilities between different pain levels. Cost and SF36 utility data of pain levels were obtained from a 1-month observational study in 88 patients. RESULTS: Usual care resulted in a yearly cost of :E 6,200 compared to epsilon 5,984 for an all dose pregabalin-mix, meaning a cost saving of epsilon 216 per patient. Utility increase was 0.01 for the pregabalin-mix (QALY 0.510 usual care; 0.520 pregabatin-mix). MonteCarlo analysis showed cost savings were not significant. However, the utility gain, albeit small,was statistically significant. CONCLUSIONS: Based on this analysis, it may be concluded, that in the considered patient population, at the specialist level, pregabalin is at [east cost neutral to current usual care (without AEDs) and offers a slight but significant increase in quality of life.