What constitutes best supportive care in the treatment of advanced non-small cell lung cancer patients?--Results from the lung cancer economics and outcomes research (LUCEOR) study.

BACKGROUND: A significant proportion of advanced non-small cell lung cancer (NSCLC) patients receive supportive treatments to manage disease-related symptoms either separately or combined with systemic anti-cancer therapy (SACT). This supportive treatment is commonly referred to as best supportive care (BSC). Definition of BSC in clinical trials and its description in published comparative and real-life NSCLC studies is limited. The lack of a consensus BSC definition makes detailed evaluations of clinical trials and comparisons between clinical trials problematic. METHODS: Data were collected as part of the lung cancer economics and outcomes research (LUCEOR) study. Information on treatment and treatment outcomes from deceased stage IIIb/IV NSCLC patients across ten countries was retrospectively collected from medical records. BSC was defined as the best care available as judged by the attending physicians. RESULTS: A total of 1327 patients' data were analyzed. Of those, 774/1327 (58%), 316/631 (50%), 123/259 (47%), 25/56 (45%) and 15/26 (58%) were administered treatment defined as BSC with first, second, third, fourth and fifth-line SACT respectively. In total, 346/678 (51%), 149/335 (45%), 86/176 (49%), 11/28 (39%) and 13/25 (52%) of patients were administered treatment defined as BSC in the end-of-life setting after finishing first, second, third, fourth and fifth-line SACT respectively. BSC therapies could be grouped into 24 different categories. The most common elements did not vary substantially whether given with SACT (irrespective of treatment line), in the end-of-life setting, or between countries. The commonest categories of BSC were narcotic and non-narcotic analgesics, corticosteroids and gastrointestinal medication. CONCLUSION: There were no major differences in what constituted BSC. BSC included in all instances narcotic and non-narcotic analgesics, corticosteroids and gastrointestinal medication. To our knowledge this is the first study attempting to describe BSC in routine clinical practice. This study's results could help define a practical, up to date, evidence-based definition of BSC.

Treatment patterns, use of resources, and costs of advanced non-small-cell lung cancer patients in Spain: results from a Delphi panel

INTRODUCTION: Approximately 80-85% of lung cancer patients are diagnosed with non-small-cell lung cancer (NSCLC), of which 50% of patients present with advanced or metastatic disease. The objective of this study was to describe treatment patterns, use of resources and costs associated with treating advanced or metastatic NSCLC patients in Spain. METHODS: A two-round Delphi consensus panel of clinical experts was carried out to describe local clinical patterns based on treatment algorithms from SEOM and ASCO treatment guidelines. The panel consisted of 19 oncologists and 1 hospital pharmacist, who were asked during the first round to define therapeutic pathways for NSCLC by the patients' performance status, age and histology; to quantify the use of resources associated with the preparation and administration of anticancer pharmacotherapy; management of adverse events associated with anticancer pharmacotherapy; and best supportive care (BSC). The second round was used to try to reduce the variability of responses in some questions and to further describe differences between intravenous and oral therapy. 2009 unit costs were applied to the use of resources described by the clinical experts. The perspective of the study was from the Spanish National Healthcare System. RESULTS: Performance status guided therapy decision and led to differences in costs. Patients with a performance status of 0-2 were expected to receive anticancer pharmacotherapy while patients with a performance status of 3-4 received BSC including analgesics and corticosteroids. Anticancer pharmacotherapies containing cisplatin or carboplatin were used preferably in first-line treatment, while the usual second- and third-line treatments were docetaxel, erlotinib or pemetrexed monotherapy. The importance of the cost of anticancer pharmacotherapy as a proportion of total healthcare costs was higher for combination therapies containing bevacizumab or pemetrexed. The anticancer pharmacotherapies associated with adverse events like febrile neutropenia or infection increased the total treatment cost. Administration costs were more relevant in regimens containing cisplatin and were low for orally administered therapies. The total cost per patient with advanced or metastatic NSCLC from starting anticancer therapy until death was estimated to be between €11,301 and €32,754 depending on the number of treatment lines received. CONCLUSIONS: In the treatment of advanced or metastatic NSCLC, healthcare costs are impacted by line of treatment, patient performance status, type of administration of therapy and adverse event management (AU)

Cost-effectiveness of licensed treatment options for restless legs syndrome in the UK and Sweden.

OBJECTIVE: To estimate the cost-effectiveness of pramipexole versus no treatment and ropinirole in moderate to very severe idiopathic restless legs syndrome (RLS) in the UK and Sweden. METHODS: A Markov model was developed using clinical trial data for pramipexole and ropinirole. Model health states were based on the International RLS Study Group Rating Scale (IRLS) scores. Health states were: no (IRLS 0), mild (IRLS 1-14), moderate (IRLS 15-24), severe (IRLS 25-34), very severe RLS (IRLS 35-40) and death. Patients entered the model with an IRLS score > 15 matching the trial inclusion criteria of the pramipexole trials. Resource use and utilities were based on trial data, literature, a patient survey and a panel of physicians from the UK and Sweden in the absence of published information. A healthcare sector perspective was taken for the UK and a societal perspective for Sweden using 2004-2005 unit costs. The base case analysis took a 1-year timeframe. RESULTS: In the UK the incremental cost per quality-adjusted life year (QALY) for pramipexole was 3349 pounds sterling versus no treatment and a cost-saving of 92 pounds sterling against ropinirole. In Sweden, pramipexole produced cost-savings of Swedish Krona (SEK) 2381 (176 pounds sterling) versus no treatment and SEK 3564 (264 pounds sterling) against ropinirole. QALY gains in both countries were 0.095 versus no treatment and 0.007 versus ropinirole. Results compare well with UK cost-effectiveness thresholds of 20,000 pounds sterling/30,000 pounds sterling per QALY and are cost-saving for Sweden. One-way and probabilistic sensitivity analyses showed results to be robust. CONCLUSIONS: Pramipexole is cost-effective compared to no treatment and ropinirole for patients with moderate to very severe RLS.

Meta-analysis of the efficacy and tolerability of pramipexole versus ropinirole in the treatment of restless legs syndrome.

OBJECTIVE: In the absence of comparative trials a meta-analysis was performed to compare the efficacy and tolerability of the non-ergot derived dopamine agonists, pramipexole and ropinirole, in restless legs syndrome (RLS). METHODS: Frequentist fixed and random-effects models were pre-specified for the direct comparisons and a Bayesian approach for the indirect comparison. Efficacy outcomes included the mean change from baseline in the International RLS Study Group Rating Scale (IRLS) score and the percentage of responders on the clinical global impressions - improvement scale (CGI-I). Safety outcomes included the incidence of withdrawal and adverse events. RESULTS: The direct meta-analysis confirmed superior efficacy for both treatments versus placebo for the IRLS (pramipexole: -5.45; 95% CI: -7.70; -3.20; ropinirole: -3.16; 95% CI: -4.26; -2.05) and the CGI-I (pramipexole: OR=2.98; 95% CI: 2.08; 4.26; ropinirole: OR=1.99; 95% CI: 1.52; 2.60). Placebo comparisons showed a significantly higher incidence of nausea for pramipexole (p<0.01), whereas nausea, vomiting, dizziness, and somnolence were significantly higher for ropinirole (all p<0.01). The indirect comparison showed with a probability of > or = 95%, a superior reduction in the mean IRLS score (-2.33; 95% credibility interval [CrI]: -4.23; -0.41), higher CGI-I response rate (OR=1.50; 95% CrI: 0.97; 2.32) and significantly lower incidence of nausea, vomiting, and dizziness for pramipexole compared to ropinirole. CONCLUSION: Differences in efficacy and tolerability favouring pramipexole over ropinirole can be observed. These findings should be further confirmed in head-to-head clinical trials.

Burden of illness imposed by severe sepsis in Switzerland.

OBJECTIVE: This study aims to determine the burden of illness imposed by severe sepsis in Switzerland by evaluating the direct and indirect patient-related costs for critically ill patients with severe sepsis. METHODS: In order to estimate the direct costs a retrospective analysis was undertaken using records from 61 adult patients treated in three intensive care units (ICUs) in three different University hospitals in Switzerland, in 2001. Resource use was determined by a bottom up approach and valued using centre-specific unit costs for medication, nutrition, blood products, disposables and official tariffs for laboratory and microbiology analysis, diagnostic services, and clinical procedures. By adding centre-specific personnel and basic bed (hotel) costs total direct costs in the ICU were calculated. Indirect costs resulting from unfitness for work, early retirement, and premature death were calculated using official Swiss statistics for the years 1998-2000. RESULTS: The mean total direct costs for a severely septic patient are CHF 41,790 (+/- 33,222 CHF) or CHF 3244 (+/- 757 CHF) per day. Nonsurvivors cause significantly higher costs than survivors (CHF 45,956 vs. CHF 37,759, p <0.001). The total intensive care costs in Switzerland due to severe sepsis amount to CHF 146-355 million. Indirect costs were estimated to range from CHF 347 to 844 million (predominantly due to premature death). Consequently the burden of illness of severe sepsis can be estimated to range from CHF 493 to 1199 million per year in Switzerland (1 CHF = 0.662 Euro in 2001). CONCLUSION: Patients suffering from severe sepsis in Switzerland have a high mortality rate and spend a prolonged time in the ICU, leading to high direct and indirect costs. Particularly productivity losses due to premature death represent a considerable burden to the Swiss society.