In the COU-AA-301 trial, abiraterone acetate with low-dose prednisone (AA) was found to extend survival in metastatic castrate resistant prostate cancer (mCRPC) patients progressing after docetaxel chemotherapy compared to placebo with low-dose prednisone. This study aimed to evaluate AA treatment duration in routine clinical practice in mCRPC patients in four European countries. Treatment sequencing and survival data were assessed to place the treatment duration into context. Results for France and the Netherlands are reported. The study was designed as a retrospective chart review. Patients were identified through treating oncologists and urologists. Eligible mCRPC patients were aged ≥18 years, previously treated with docetaxel and naïve to prior AA treatment. Baseline patient characteristics were described using summary statistics. Kaplan-Meier survival analyses were performed for AA treatment duration, overall survival (OS) and time to prostate-specific antigen (PSA) progression endpoints. A total of 68 physicians (France and the Netherlands) reported data on 269 mCRPC patients treated with AA. Median PSA (ng/mL) of patients from France and the Netherlands at baseline were 56.0 (interquartile range [IQR]: 28.0-120.0) and 174.5 (IQR: 69.5-371.5), respectively. The median time (months) between mCRPC diagnosis and AA initiation was 12.6 (IQR: 7.0-27.2) in France and 18.3 (IQR: 9.6-30.2) in the Netherlands. Median (months) AA treatment duration, median OS and median time to PSA progression in France was 11.3 (95% confidence interval [95%CI]: 8.3-13.7), 21.6 (95%CI: 14.5-.) and 13.8 (95%CI: 11.0-14.7), respectively. In the Netherlands, it was 4.9 (95%CI: 3.4-6.4), 11.0 (95%CI: 7.3-13.0) and 4.9 (95%CI: 3.0-7.3), respectively. Here we describe the real-world treatment of mCRPC patients receiving AA in the post-chemotherapy setting in two EU countries. This study suggests that initiating AA earlier in the post chemotherapy mCRPC setting may result in better health outcomes.

To describe chemotherapy exposure, healthcare utilization, overall survival (OS) and progression-free survival (PFS) among patients diagnosed with chronic lymphoid leukemia (CLL). Newly diagnosed CLL patients who received chemotherapy were selected from the Eindhoven Cancer Registry between 1998-2011, linked on a patient-level to the PHARMO Database Network including data on in- and out-patient drug dispensings, hospitalizations and clinical laboratory measurements. Chemotherapy was classified in regimens of use based on chemotherapy combinations. OS and PFS were determined after diagnosis and after chemotherapy. Healthcare utilization was assessed in the year before diagnosis and in the year after chemotherapy. 125 CLL patients received chemotherapy: 52 patients (42%) started chemotherapy within 6 months and 73 patients (58%) started chemotherapy more than 6 months after diagnosis. Mean (±SD) age was 67(±10) years and 68% was male. About 50% had one treatment line and about 25% two lines of treatment. Chlorambucil was the most common type of first line chemotherapy (37 (71%) of patients starting chemotherapy within 6 months and 55 (75%) of patients starting chemotherapy more than 6 months after diagnosis). Among patients receiving chlorambucil as first line, 39% were hospitalized for any cause and 93% had at least one drug dispensing before diagnosis. After chlorambucil chemotherapy, all patients had at least one dispensing and 49% were hospitalized. One-year survival rate was 96% after diagnosis and 74% after chlorambucil chemotherapy. Five-year survival rate after diagnosis was 75%. Median PFS after first line chlorambucil was 19 months for patients starting within 6 months and 21 months for patients starting more than 6 months after diagnosis. Most CLL patients receiving chemotherapy were treated with chlorambucil. Among those, 96% were still alive one year after diagnosis. Median PFS after first line chlorambucil chemotherapy ranged from 19 to 21 months, depending on the timing of chemotherapy.

Despite the availability of a wide number of treatments for relapsed/refractory (r/r) chronic lymphocytic leukemia (CLL) and r/r mantle cell lymphoma (MCL), no standard of care has emerged. There are no studies evaluating preferences for treatment outcomes for r/r CLL and r/r MCL. This study was designed to elicit preferences for r/r MCL and r/r CLL treatment outcomes among patients, the general public and physicians experienced in treating CLL/MCL in Germany. Interviews (90 minutes) in German of 6 CLL/6 MCL hematologists, 6 r/r CLL and 5 r/r MCL patients were conducted (total 23 interviews). Participants were asked to state their most important treatment outcomes. Transcripts were translated to English and analyzed by counting the number of times each outcome was mentioned. We present here results of patient and physician preferences. r/r CLL patients mention overall survival (OS; 5 counts), mode of treatment administration (4), quality of life (QOL) aspects (4) and progression free survival (PFS) disease control (4). A tolerable side effect (SE) profile/controlling disease symptoms was mentioned by 3 patients. Other treatment outcomes were infections, nausea (2 each), fatigue, weight loss, pain, fever, polyneuropathy and long treatment intervals (1 each). CLL physicians mentioned OS (4), QOL (4) and PFS (4). r/r MCL patients mentioned efficacy benefits such as cure (4) and OS (2), PFS (1); various QOL aspects (5) and a tolerable SE profile/controlling disease (3). Other treatment outcomes were long-term organ damage (2), hair loss, nausea and night sweat (1 each). MCL physicians mentioned OS (6), QOL (5) and a tolerable SE profile (4). Extending life, disease control, maintaining QOL and avoiding SE are important r/r MCL/CLL treatment outcomes to German patients and physicians.

BACKGROUND:Systemic Candida infections (SCI) occur predominantly in intensive care unit patients and are a common cause of morbidity and mortality. Recently, changes in Candida epidemiology with an increasing prevalence of SCI caused by Candida non-albicans species have been reported. Resistance to fluconazole and azoles in general is not uncommon for non-albicans species. Despite guidelines recommending initial treatment with broad-spectrum antifungals such as echinocandins with subsequent switch to fluconazole if isolates are sensitive (de-escalation strategy), fluconazole is still the preferred first-line antifungal (escalation) in many clinical practice settings. After diagnosis of the pathogen, the initial therapy with fluconazole is switched to a broad-spectrum antifungal if a non-albicans is identified. METHODS:The cost-effectiveness of initial treatment with micafungin (de-escalation) vs fluconazole (escalation) in patients with SCI was estimated using decision analysis based on clinical and microbiological data from pertinent studies. The model horizon was 42 days, and was extrapolated to cover a lifetime horizon. All costs were analyzed from the UK NHS perspective. Several assumptions were taken to address uncertainties; the limitations of these assumptions are discussed in the article. RESULTS:In patients with fluconazole-resistant isolates, initial treatment with micafungin avoids 30% more deaths and successfully treats 23% more patients than initial treatment with fluconazole, with cost savings of £1621 per treated patient. In the overall SCI population, de-escalation results in 1.2% fewer deaths at a marginal cost of £740 per patient. Over a lifetime horizon, the incremental cost-effectiveness of de-escalation vs escalation was £15,522 per life-year and £25,673 per QALY. CONCLUSIONS:De-escalation from micafungin may improve clinical outcomes and overall survival, particularly among patients with fluconazole-resistant Candida strains. De-escalation from initial treatment with micafungin is a cost-effective alternative to escalation from a UK NHS perspective, with a differential cost per QALY below the 'willingness-to-pay' threshold of £30,000.

Paliperidone palmitate has demonstrated non-inferior efficacy to risperidone long acting injectable (LAI) for the treatment of schizophrenia in previous studies. The objective of this analysis was to assess the cost effectiveness of paliperidone palmitate relative to risperidone LAI, based on the cost-utility analysis described in the current NICE Guidelines for the Management of Schizophrenia. The analysis was undertaken from the perspective of NHS Wales and was submitted to the All Wales Medicines Strategy Group for evaluation. A decision-analytic Markov model was developed to estimate the cost-utility of paliperidone palmitate relative to risperidone LAI. The model adopted an annual cycle length. Patients who entered the model initiated either paliperidone palmitate or risperidone LAI and could subsequently transition between five health states during each annual cycle. AEs associated with each intervention were derived from literature. Utility values were derived from a community-based study, using trade-off technique to elicit HRQoL for schizophrenia according to frequency of injections. Resource use data was sourced from the NICE core model/guidelines, Welsh clinical experts, and a UK Delphi panel. Unit costs were derived from the British National Formulary, NHS reference costs, and the Personal Social Services Research Unit reports. Costs and outcomes were evaluated over a 10-year horizon, and discounted at 3.5%. Results were presented as incremental costs/QALY. Uncertainty was addressed via deterministic and probabilistic sensitivity analyses. The base case analyses demonstrated that paliperidone palmitate would incur lower costs (-£3,773) and generate more quality adjusted life years (QALYs) (+0.13) than risperidone LAI. This indicated that paliperidone palmitate ‘dominated’ risperidone LAI. Extensive scenario/sensitivity analyses confirmed the robustness of the results Compared with risperidone LAI, paliperidone palmitate is a cost-effective therapy for the treatment of schizophrenia in adult patients in NHS Wales.

BACKGROUND:Hereditary angioedema (HAE) is a rare but serious disease marked by swelling attacks in the extremities, face, trunk, airway, or abdominal areas that can be spontaneous or the result of trauma and other triggers. It can be life-threatening due to the risk of asphyxiation. While there have been major advancements in our understanding of the immunogenetics of HAE, there are significant gaps in the literature regarding understanding of the humanistic and economic impact of the disease, particularly in Europe. The purpose of the HAE Burden of Illness Study-Europe (HAE-BOIS-Europe), the development and methodology of which is described here, is to better understand the management and impact of HAE from the patient perspective in Europe.METHODS/DESIGN:This is a cross-sectional study in which retrospective data were also collected being conducted in Denmark, Germany and Spain. The study is open to patients ages 12 and older with a diagnosis of HAE-I or HAE-II. Data collection includes: (i) a survey on individuals' health care resource use, direct and indirect medical costs, impact on work and school, treatment satisfaction, and emotional functioning (via the Hospital Anxiety and Depression Scale); and (ii) one-on-one interviews to collect detailed descriptive data and patient testimonials on the impact of HAE on patients' health-related quality of life.DISCUSSION:The present manuscript describes the development and plans for implementing a multi-country European study with the aim of characterizing the humanistic and economic burden of HAE from the patient perspective. This study will help raise awareness of HAE as a rare but debilitating condition with wide-ranging impacts.

Hereditary angioedema due to C1 inhibitor deficiency (HAE) is a rare but serious disease marked by swelling attacks in various areas of the body. The HAE Burden of Illness Study-Europe (HAE-BOIS-Europe) addresses the gaps in our knowledge of the humanistic and economic impact of HAE in Europe. We report the economic results. This cross-sectional study was conducted in Spain (ES), Denmark (DK), and Germany (DE), and was open to patients aged ≥12 years, with a diagnosis of HAE-I or HAE-II. Data collection included a survey on individuals' direct and indirect resource utilization, and the impact of HAE on work, school and other activities. A total of 186 patients participated. From 84-100% across countries reported having medication at home to treat attacks, although 48%, 25%, and 23% in ES, DK, and DE, respectively, still received care at a treatment facility or saw a physician for their most recent attack; 21%, 18%, and 0%, respectively, visited an emergency department. On a 0.0-10.0 (higher worse) rating scale of the impact of the attack on ability to perform daily activities, patients reported a mean score of 5.0; this did not vary significantly by site of attack. Overall, 24% of patients missed time from work/school during the most recent attack, missing a mean of 2.9 days, and 29% missed time from work/school between attacks over the past 6 months, missing a median of 2.0 days. Overall, 59% required carer help over the past 6 months, with a corresponding detriment to the carers' work and/or leisure time. Overall, 48% of patients reported that HAE has hindered their career and/or educational advancement. The HAE-BOIS-Europe survey has highlighted the substantial economic burden of HAE, which encompasses medical resource use, impact on productivity for both patients and carers, and detrimental effects on education and careers.