Incidence of solitary pulmonary nodules in Northeastern France: a population-based study in five regions.

BACKGROUND: The discovery of a solitary pulmonary nodule (SPN) on a chest imaging exam is of major clinical concern. However, the incidence rates of SPNs in a general population have not been estimated. The objective of this study was to provide incidence estimates of SPNs in a general population in 5 northeastern regions of France. METHODS: This population-based study was undertaken in 5 regions of northeastern France in May 2002-March 2003 and May 2004-June 2005. SPNs were identified by chest CT reports collected from all radiology centres in the study area by trained readers using a standardised procedure. All reports for patients at least 18 years old, without a previous history of cancer and showing an SPN between 1 and 3 cm, were included. RESULTS: A total of 11,705 and 20,075 chest CT reports were collected for the 2002-2003 and 2004-2005 periods, respectively. Among them, 154 and 297 reports showing a SPN were included, respectively for each period. The age-standardised incidence rate (IR) was 10.2 per 100,000 person-years (95% confidence interval 8.5-11.9) for 2002-2003 and 12.6 (11.0-14.2) for 2004-2005. From 2002 to 2005, the age-standardised IR evolved for men from 16.4 (13.2-19.6) to 17.7 (15.0-20.4) and for women from 4.9 (3.2-6.6) to 8.2 (6.4-10.0). In multivariate Poisson regression analysis, gender, age, region and period were significantly associated with incidence variation. CONCLUSIONS: This study provides reference incidence rates of SPN in France. Incidence was higher for men than women, increased with age for both gender and with time for women. Trends in smoking prevalence and improvement in radiological equipment may be related to incidence variations.

EQOFIX: a combined economic and quality-of-life study of hemophilia B treatments in France.

BACKGROUND: EQOFIX is a medicoeconomic study that analyzed the health-related quality of life (HRQoL) and costs of care of the moderate and severe forms of hemophilia B, treated on demand or by prophylaxis with either plasma-derived Factor IX (pdFIX) or recombinant FIX (rFIX). STUDY DESIGN AND METHODS: The primary objectives were evaluations of the impact of hemophilia B on HRQoL and of the costs associated with its management. The secondary objectives were evaluations of the clinical efficacy and costs of care of pdFIX and rFIX. In this observational study we included and followed for 1 year severe and moderate hemophilia B patients without inhibitor. HRQoL was evaluated through generic and disease-specific questionnaires. Information on the health resources consumed was collected every 3 months. RESULTS: The EQOFIX cohort was composed of 155 patients, including 51 children and 104 adults, with 114 having severe disease and 41 having moderate disease. The regimens were prophylactic for 61 and on demand for 94. Altogether, 78 were treated with rFIX and 77 with pdFIX. There was no difference in the QoL between the pdFIX and rFIX treatments. The extra cost of prophylaxis was €22,605 per bleeding event prevented. The consumption of FIX was 1.4-fold higher for the patients treated with rFIX than for the patients treated with pdFIX. CONCLUSION: Our findings in a cohort composed of 25% of the French population of moderate and severe hemophilia B patients show, with similar clinical and HRQoL results, that treatment with rFIX is more expensive than treatment with pdFIX.

Quality of life after the initial treatments of non-small cell lung cancer: a persistent predictor for patients' survival.

BACKGROUND: Health-related quality of life (HRQoL) before treatment may predict survival of patients with non-small-cell lung cancer (NSCLC). We investigated the predictive role of HRQoL after the initial treatments, on the survival of these patients. METHODS: A prospective multi-center study conducted in northeastern France. The SF-36 and European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire Core-30 (QLQ C-30) were mailed to patients 3 months after the end of the diagnostic process. High scores for functioning dimensions on both questionnaires indicated better QoL, and low scores for symptom dimensions on the QLQ C-30 indicated few symptoms. Cox regression modeling was used to identify predictive factors of survival. RESULTS: In total, 230 (63.5%) patients responded to the SF-36 and QLQ C-30. Before completing the questionnaires, almost 60% of patients had undergone some chemotherapy, about 10% underwent radio/chemotherapy or both and more than 30% underwent surgery or surgery plus chemo/radiotherapy. On SF-36, the highest mean score was for social functioning dimension (55.5 ± 28), and the lowest was for the physical role dimension (17.9 ± 32.2). On QLQ C-30, for the functioning dimensions, the highest mean score was for cognitive functioning (74.6 ± 25.9) and the lowest was for role functioning (47.2 ± 34.1). For symptom dimensions, the lowest score was for diarrhoea (11.5 ± 24.2) and the highest was for fatigue (59.7 ± 27.7). On multivariate analysis, high bodily pain, social functioning and general health scores (SF-36) were associated with a lower risk of death (hazard ratio 0.580; 95% confidence interval [0.400-0.840], p = 0.004; HR 0.652 [0.455-0.935], p < 0.02; HR 0.625 [0.437-0.895] respectively). Better general QoL on QLQ C-30 was related to lower risk of death (HR 0.689 [0.501-0.946], p = 0.02). CONCLUSION: Adding to previous knowledge about factors that may influence patients QoL, this study shows a persisting relationship between better perceived health in HRQoL after the initial treatment of NSCLC and better survival.

Cytomegalovirus exposure, immune exhaustion and cancer occurrence in renal transplant recipients.

The role of Cytomegalovirus (CMV) in carcinogenesis is controversial. We studied whether CMV may contribute to cancer occurrence in renal transplant recipients. We studied a prospective cohort of 455 consecutive patients who received a kidney transplant between January 1995 and December 2006. All cancers and types of cancers were assessed. Lymphocyte phenotype and cytokines production were analysed according to CMV status in a subset population of this cohort. Mean follow-up was 84 ± 29 months. One hundred and nineteen cancers (26.2%) occurred during the study follow-up. There was a higher cumulated incidence of cancers in CMV-exposed patients (30.4% vs. 20%; P=0.018). Mean time to cancer occurrence was shorter in CMV-exposed patients than in CMV-naïve patients (4.7 ± 2.6 vs. 6.7 ± 2.8; P = 0.001). Cox regression analysis revealed that both pretransplant CMV exposure (HR, 1.83; 95% CI, 1.17-2.88; P = 0.009) and post-transplant CMV replication (HR, 2.17; 95% CI, 1.02-4.59; P = 0.044) were risk factors for cancer. Among CD8+ T cells, exhausted T cells assessed as CD57+CD28- were expanded in CMV-exposed patients (26 ± 20 vs. 9 ± 8%; P < 0.0001), whereas CD8+CD57+IL2- cells were more frequent in CMV-exposed patients. Our results highly suggest that CMV increases the risk of cancer after transplantation.

Solitary pulmonary nodules: consequences for patient quality of life.

PURPOSE: The aim was to describe levels of health-related quality of life (HRQoL) and its determinants in patients with solitary pulmonary nodule (SPN) and to compare them with the French general population. METHODS: A prospective multicentre study of patients diagnosed with SPN, in northeastern regions of France, was carried out between 2002 and 2005. Six months after the end of diagnostic procedure, patients completed the SF-36 self-reported questionnaire (where 100 indicates high HRQoL). For a comparison, HRQoL data from a sample of the French general population collected by INSEE in 2002-2003 (n = 17,750). RESULTS: Among 171 participating patients, 39 had malignant nodules and had lesser mean scores on physical and emotional role, vitality and social functioning (-6 to -18 points) than those with nonmalignant nodule. Compared to the French general population, patients with SPN had lower scores, by 11-30 points, in all dimensions (P < 0.001). Older age and smoking history were associated with low HRQoL. CONCLUSIONS: Six months after receiving a diagnosis of SPNs, whether malignant, patients have worse HRQoL compared to the French general population. It indicates areas where physicians can help patients coping with their disease.

Assessing cancer drugs for reimbursement: methodology, relationship between effect size and medical need.

Reimbursement is assessed by the Transparency Commission from the Health Authority (HAS) using a medical benefit (SMR) score that gives access to reimbursement, an "improvement of medical service rendered" (ASMR) that determines the added therapeutic value, and the target population. Assessing cancer drugs for reimbursement raises the same issues as other therapeutic classes, with some key differences. Overall survival (OS) is considered by the Transparency Commission as the endpoint for assessing clinical benefit, and yet it is not an applicable primary endpoint in all types of cancer. Later lines of treatment, particularly during the development process, may make it difficult to interpret OS as the primary endpoint. Therefore, progression-free survival (PFS) for metastatic situations and disease-free survival (DFS) in adjuvant situations are wholly relevant endpoints for decisions on the reimbursement of a new cancer drug. Effect size is assessed using actuarial survival curves of the product versus the comparator, and it is difficult to summarise them into one single parameter. Results are generally interpreted based on median survival, which is fragmented because it only measures one point of the curve. The hazard ratio measures the effect of treatment throughout the duration of survival and is therefore more comprehensive in quantifying clinical benefit. Determining an effect size threshold for granting reimbursement is difficult given the diversity of cancer settings and the level of medical need, which influences assessment of the clinical relevance of the observed difference. Rapid progress in comparators (700 molecules in development) and the identification of predictive factors of efficacy (biomarkers, histology, etc.) during development may lead to different ASMR scores per population, or to the restriction of the target population to a subgroup of the marketing authorisation (MA) population in which the expected effect size is greater. To address these issues, the roundtable recommends the possibility of early scientific opinions by the office of the Transparency Commission in order to discuss comparators and the relevance of responder subgroups. It also recommends the possibility of granting a temporary ASMR, on condition of subsequent confirmation by production of data, when reimbursement appears justified in a subpopulation of the MA for which only subgroup analysis is available.

Predictive factors of tumour necrosis inhibitor treatment persistence for rheumatoid arthritis: An observational study in 8052 patients.

OBJECTIVES: To determine whether changes in ultrasonography (US) features of monosodium urate crystal deposition is associated with the number of gouty flares after stopping gout flare prophylaxis. METHODS: We performed a 1-year multicentre prospective study including patients with proven gout and US features of gout. The first phase of the study was a 6-month US follow-up after starting urate-lowering therapy (ULT) with gout flare prophylaxis. After 6 months of ULT, gout flare prophylaxis was stopped, followed by a clinical follow-up (M6 to 12) and ULT was maintained. Outcomes were the proportion of relapsing patients between M6 and M12 according to changes of US features of gout and determining a threshold decrease in tophus size according to the probability of relapse. RESULTS: We included 79 gouty patients (mean [±SD] age 61.8±14 years, 91% males, median disease duration 4 [IQR 1.5; 10] years). Among the 49 completers at M12, 23 (47%) experienced relapse. Decrease in tophus size≥50% at M6 was more frequent without than with relapse (54% vs. 26%, P=0.049). On ROC curve analysis, a threshold decrease of 50.8% in tophus size had the best sensitivity/specificity ratio to predict relapse. Probability of relapse was increased for patients with a decrease in tophus size <50% between M0 and M6 (OR 3.35 [95% confidence interval 0.98; 11.44]). CONCLUSION: A high reduction in US tophus size is associated with low probability of relapse after stopping gout prophylaxis. US follow-up may be useful for managing ULT and gout flare prophylaxis.

Does the availability of positron emission tomography modify diagnostic strategies for solitary pulmonary nodules? An observational study in France.

BACKGROUND: Previous studies showed that at the individual level, positron emission tomography (PET) has some benefits for patients and physicians in terms of cancer management and staging. We aimed to describe the benefits of (PET) in the management of solitary pulmonary nodules (SPNs) in a population level, in terms of the number of diagnostic and invasive tests performed, time to diagnosis and factors determining PET utilization. METHODS: In an observational study, we examined reports of computed tomography (CT) performed and mentioning "spherical lesion", "nodule" or synonymous terms. We found 11,515 reports in a before-PET period, 2002-2003, and 20,075 in an after-PET period, 2004-2005. Patients were followed through their physician, who was responsible for diagnostic management. RESULTS: We had complete data for 112 patients (73.7%) with new cases of SPN in the before-PET period and 250 (81.4%) in the after-PET period. Patients did not differ in mean age (64.9 vs. 64.8 years). The before-PET patients underwent a mean of 4 tests as compared with 3 tests for the after-PET patients (p = 0.08). Patients in the before-PET period had to wait 41.4 days, on average, before receiving a diagnosis as compared with 24.0 days, on average, for patients in the after-PET period who did not undergo PET (p < 0.001). In the after-PET period, 11% of patients underwent PET during the diagnostic process. A spiculated nodule was more likely to determine prescription for PET (p < 0.001). Multivariate analysis revealed that patients in both periods underwent fewer tests when PET was prescribed by general practitioners (p < 0.001) and if the nodule was not spiculated (p < 0.001). The proportion of unnecessary invasive approaches prescribed (47% vs. 49%) did not differ between the groups. CONCLUSION: In our study, 1 year after the availability of PET, the technology was not the first choice for diagnostic management of SPN. Even though we observed a tendency for reduced number of tests and mean time to diagnosis with PET, these phenomena did not fully relate to PET availability in health communities. In addition, the availability of PET in the management of SPN diagnosis did not reduce the overall rate of unnecessary invasive approaches.

Cost effectiveness of high-dose chemotherapy with autologous stem cell support as initial treatment of aggressive non-Hodgkin's lymphoma.

The GOELAMS 072 study showed that first-line high-dose chemotherapy (HDT) with peripheral blood stem cell transplant (PBSCT) support was superior to the standard chemotherapy regimen (cyclophosphamide, doxorubicin, vincristine and prednisone; CHOP) in adults with aggressive non-Hodgkin's lymphoma (NHL). The aim of the study was to evaluate the pharmacoeconomic profile of HDT with PBSCT support relative to standard CHOP therapy as first-line treatment in adults with aggressive NHL. We performed a cost-effectiveness analysis from the French Public Health Insurance perspective, restricted to hospital costs (euro, year 2008 values). The clinical effectiveness criterion was censured overall survival (OS) difference after a median follow-up of 4 years for the entire cohort. A total of 197 patients were included (CHOP, n = 99; HDT, n = 98). Uncertainty was assessed using non-parametric bootstrap simulations and various scenario analyses. Five-year OS did not differ significantly between groups for the entire cohort. Nevertheless, subgroup analyses appeared to be more relevant for decision making: among patients with a high-intermediate risk according to the age-adjusted International Prognostic Index (IPI), HDT yielded a significantly higher 5-year OS than CHOP (74% vs 44%; p = 0.001). Among these patients, the mean censured OS survival, adjusted for time discounting and quality of life (QOL), increased with HDT by 1.20 years (95% CI 1.19, 1.21). The cost per life-year saved with HDT was estimated as euro34 315 (95% CI 32 683, 35 947) in this subgroup. Results suggested that HDT with PBSCT support might be considered a cost-effective strategy among patients with high-intermediate-risk NHL according to the age-adjusted IPI. Its place and its cost effectiveness potential versus, or in combination with, rituximab still need further research.

Management of SPN in France. Pathways for definitive diagnosis of solitary pulmonary nodule: a multicentre study in 18 French districts.

BACKGROUND: The process of diagnosis and management of solitary pulmonary nodules (SPNs) between 1 and 3 cm is not standardized. This multicentre study investigated how diagnosis of newly discovered SPNs is managed in routine practice. METHODS: We examined 11,515 radiology reports of patients undergoing chest computed tomography (CT) at all 76 radiology centres in 18 French administrative districts covering 8,220,000 people. Information on diagnostic procedures and treatment administered from discovery to definitive diagnosis of SPN was collected prospectively. RESULTS: We identified 152 cases of newly diagnosed SPNs. Follow-up was complete for 112 patients. The median number of diagnostic tests was 4 and the mean time to diagnosis was 41.4 days. Marked variability was observed in the sequence of diagnostic tests, and 8 diagnostic pathways were identified. Patients' characteristics and radiological features of SPNs influenced the number of tests performed. Referral by specialist, history of smoking and spiculated SPN predicted the performance of at least one invasive procedure (P < 0.01). Definitive diagnosis was a malignant disease in 30 patients (26%). CONCLUSION: The diagnosis of SPN is a complex process that physicians approach in markedly different ways. Implementing practice guidelines for managing the diagnosis of SPN requires clarification.

Relative added value: what are the tools to evaluate it?

The relative added value of a drug is currently evaluated in France by the Transparency Commission (TC) of the National Health Authority (HAS), by assigning a level of Improvement in Actual Benefit (IAB). IAB is based on two parameters, efficacy and safety of the product, in a defined target population, either as compared to one or more other drugs with similar indications, or within therapeutic strategy. The items used for evaluation, including the level of clinical effect, the relevance of the comparator, the choice of comparison criteria and the methodology used (indirect comparison, non-inferiority studies, etc.), have been reviewed by the working group in Giens with regard to an analysis of the opinion on TC issued between 2004 and 2007 in several therapeutic areas First of all, this attempt at rationalisation based on the criteria used to assess the relative added value demonstrated the rareness of direct comparative data, and was followed by a discussion on the possible broadening of the evaluation criteria. The group discussed taking into account the Public Health Impact (PHI), which has now been incorporated into the assessment of Actual Benefit (AB). The group believes that PHI seems to be more related to the notion of IAB than to that of AB. Indeed, it is frequently the relative added value of a new drug that produces an impact in public health. Conversely, considering the comparative evaluation criteria of PHI, which are not systematically taken into account in IMSR (such as improvement in the health of the population, meeting a public health need or impact on the healthcare system), PHI could legitimately be included in the assessment of the relative added value of a drug. Other parameters such as compliance or impact on professional practice have been considered. Thus, the notion of relative added value, evaluated at initial registration, could be based on an expected improvement in medical service. The notion of expected medical service leads to the requirement of producing additional data in real life (post-registration studies), which would support the definitive notion of improvement in actual benefit at the time of renewed registration, while taking into account the place occupied by the drug in the therapeutic strategy.

Relative Added Value: What are the Tools to Evalue it?

The relative added value of a drug is currently evaluated in France by the Transparency Commission (TC) of the National Health Authority (HAS), by assigning a level of Improvement in Actual Benefit (IAB). IAB is based on two parameters, efficacy and safety of the product, in a defined target population, either as compared to one or more other drugs with similar indications, or within therapeutic strategy. The items used for evaluation, including the level of clinical effect, the relevance of the comparator, the choice of comparison criteria and the methodology used (indirect comparison, non-inferiority studies, etc.), have been reviewed by the working group in Giens with regard to an analysis of the opinion on TC issued between 2004 and 2007 in several therapeutic areas. First of all, this attempt at rationalisation based on the criteria used to assess the relative added value demonstrated the rareness of direct comparative data, and was followed by a discussion on the possible broadening of the evaluation criteria. The group discussed taking into account the Public Health Impact (PHI), which has now been incorporated into the assessment of Actual Benefit (AB). The group believes that PHI seems to be more related to the notion of IAB than to that of AB. Indeed, it is frequently the relative added value of a new drug that produces an impact in public health. Conversely, considering the comparative evaluation criteria of PHI, which are not systematically taken into account in IMSR (such as improvement in the health of the population, meeting a public health need or impact on the healthcare system), PHI could legitimately be included in the assessment of the relative added value of a drug. Other parameters such as compliance or impact on professional practice have been considered. Thus, the notion of relative added value, evaluated at initial registration, could be based on an expected improvement in medical service. The notion of expected medical service leads to the requirement of producing additional data in real life (post-registration studies), which would support the definitive notion of improvement in actual benefit at the time of renewed registration, while taking into account the place occupied by the drug in the therapeutic strategy.

Economic impact of simplified de Gramont regimen in first-line therapy in metastatic colorectal cancer.

The cost of chemotherapy has dramatically increased in advanced colorectal cancer patients, and the schedule of fluorouracil administration appears to be a determining factor. This retrospective study compared direct medical costs related to two different de Gramont schedules (standard vs. simplified) given in first-line chemotherapy with oxaliplatin or irinotecan. This cost-minimization analysis was performed from the French Health System perspective. Consecutive unselected patients treated in first-line therapy by LV5FU2 de Gramont with oxaliplatin (Folfox regimen) or with irinotecan (Folfiri regimen) were enrolled. Hospital and outpatient resources related to chemotherapy and adverse events were collected from 1999 to 2004 in 87 patients. Overall cost was reduced in the simplified regimen. The major factor which explained cost saving was the lower need for admissions for chemotherapy. Amount of cost saving depended on the method for assessing hospital stay. In patients treated by the Folfox regimen the per diem and DRG methods found cost savings of Euro 1,997 and Euro 5,982 according to studied schedules; in patients treated by Folfiri regimen cost savings of Euro 4,773 and Euro 7,274 were observed, respectively. In addition, travel costs were also reduced by simplified regimens. The robustness of our results was showed by one-way sensitivity analyses. These findings demonstrate that the simplified de Gramont schedule reduces costs of current first-line chemotherapy in advanced colorectal cancer. Interestingly, our study showed several differences in costs between two costing approaches of hospital stay: average per diem and DRG costs. These results suggested that standard regimen may be considered a profitable strategy from the hospital perspective. The opposition between health system perspective and hospital perspective is worth examining and may affect daily practices. In conclusion, our study shows that the simplified de Gramont schedule in combination with oxaliplatin or irinotecan is an attractive option from the French Health System perspective. This safe and less costly regimen must compared to alternative options such as oral fluoropyrimidines.

Impact of medical practices on the costs of management of rheumatoid arthritis by anti-TNFalpha biological therapy in France.

UNLABELLED: When the anti-TNFalpha drugs first came onto the market, their high price was the subject of much debate. Moreover, we must add the costs associated with their administration to the purchase price. Variations in medical practices may be the source of substantial variations in these costs. OBJECTIVE: To compare the costs involved with the use of infliximab and etanercept in the treatment of rheumatoid arthritis (RA) and to study the impact of variations in medical practices on them. METHODS: A pragmatic cost minimization analysis was conducted from the payer's perspective to compare the costs of administration, that is, the direct medical costs, of the first two available anti-TNFalpha agents: infliximab and etanercept. Records of 60 patients from three university hospital rheumatology departments were reviewed retrospectively for a 52-week period. This analysis considered the following costs: purchase costs for the drugs and for any co-prescribed disease-modifying drugs, inpatient or outpatient administration, medical follow-up and the transportation costs associated with treatment that were reimbursed by the French health insurance system. Costs that did not differ between the two products were excluded (work-up for inclusion, etc.). RESULTS: Data were collected for 58 patients, 30 treated with infliximab and 28 with etanercept. Patients' mean age was 52 years; 81% were women. RA had first developed on average 15 years earlier; the disease was positive for rheumatoid factors in 68% of cases and erosive in 93%. The total average annual cost of administration did not differ for infliximab and etanercept: 19,469 and 19,619 , respectively (P=0.56). The mean costs of administration nonetheless varied considerably between the three hospital centers: from 16,566 to 24,313 for infliximab (P<0.0001) and from 16,069 to 24,383 for etanercept (P<0.0001). CONCLUSION: The financial burden of biological treatments for RA is strongly influenced by the substantial heterogeneity in medical practices.

Infliximab continuation rates in patients with rheumatoid arthritis in everyday practice.

UNLABELLED: Infliximab is a major breakthrough in the management of rheumatoid arthritis (RA). We evaluated infliximab continuation rates and reasons for discontinuation in patients with RA. PATIENTS AND METHODS: We studied patients with RA started on infliximab at any time between March 2000 and December 2002, under the conditions of everyday practice (as opposed to clinical trial settings), as recommended by the French marketing license (3 mg/kg as an intravenous infusion at weeks 0, 2, and 6 then at 8-week intervals). The number of infliximab infusions, side effects, and nonresponse rates was recorded. The Kaplan-Meier method was used to evaluate treatment continuation. Reasons for discontinuation were studied. RESULTS: We included 41 patients, with a mean age of 54 years, a mean RA duration of 9 years, and a mean of three previous disease-modifying antirheumatic drug treatments. The total number of infliximab infusions was 461 with a mean of 10.8 per patient and a mean follow-up under treatment of 15.3 months. The proportions of patients still on infliximab were 82%, 74%, and 67% after 6, 12, and 24 months, respectively. The main reasons for discontinuation were escape phenomenon (n = 6, 42.8% of discontinuations) and allergy (n = 3); in one case each, the reason was primary ineffectiveness, severe infection, plans to start a pregnancy, poor compliance, and unavailability for follow-up. There were 59 recorded episodes of side effects, with a profile similar to that in the literature and in postmarketing databases. CONCLUSION: The infliximab continuation rate in everyday practice in patients with RA (67% after 2 years) was consistent with published data and with the results of controlled trials.

Use of a decision analysis model to assess the medicoeconomic implications of FDG PET imaging in diagnosing a solitary pulmonary nodule.

This study assessed the use of positron emission tomography (PET) in identifying and diagnosing solitary pulmonary nodules (SPNs). For this a decision analysis model was constructed, and three alternatives were compared: wait and watch (WW), PET and anatomical computed tomography (PET), and CT plus PET (CT+PET). Transition probabilities were estimated from published data and consultations with experts. Costs of diagnosis were derived from the French reimbursement scale, and treatment costs from a national hospital database of diagnosis-related groups. The base case was defined as a 65-year-old male smoker with a 2-cm SPN and an associated high risk of malignancy of 43%. Evaluation criteria included incremental cost-effectiveness ratios and the proportion of unnecessary operations avoided in patients without malignant SPN. For the base case WW was the least effective and cheapest strategy. CT+PET was more effective and presented lower incremental cost-effectiveness ratio (3,022 per life-year gained). It also was superior to PET in cost-effectiveness terms and resulted in 4.3% fewer unnecessary resections of benign SPN than did PET. Risk profile analyses performed on SPN malignancy risk showed that CT + PET remains the most cost-effective strategy in the range of 5.7-87%, and that WW is more cost-effective in the range of 0.3-5.0%. CT+PET is thus cost-effective in detecting malignant SPN in patients with a risk of malignity of at least 5.7% and may avoid inappropriate resections of benign SPN. These findings support the attempts to introduce a larger number of PETs in France for SPN diagnosis.

Cost Effectiveness of Cardioprotective Strategies in Patients with Aggressive Non-Hodgkin's Lymphoma.

OBJECTIVE: The cardiotoxicity of anthracyclines remains a key problem in patients with aggressive non-Hodgkin's lymphoma (NHL). With regard to the actual long-term prognosis of aggressive NHL, the development of cardioprotective strategies is mandatory for these patients. A cost-effectiveness analysis was carried out to determine the potential economic profile of dexrazoxane or liposome-encapsulated doxorubicin in patients with aggressive NHL treated with a CHOP regimen (cyclophosphamide, doxorubicin, vincristine, prednisone) as first-line therapy. METHODS: A decision-analysis model described clinical events and economic consequences for theoretical patients who were to receive eight consecutive cycles of a CHOP regimen containing 50 mg/m(2) of doxorubicin as first-line chemotherapy. The timeframe of the model was the patient's lifetime. The probabilities were related to the cumulative dose of doxorubicin and age. The study was carried out from the perspective of the French healthcare system. Patients entered the model at 'choose' node: no cardioprotection versus cardioprotection with dexrazoxane or liposome-encapsulated doxorubicin. The model was based on a retrospective epidemiological study and on published data. The clinical end-point was life expectancy. Direct medical costs related to the cardioprotection and the treatment of congestive heart failure were considered. Monetary values for French prices in the year 2002 were used. Several univariate sensitivity analyses were carried out with varying clinical and economic parameters. RESULTS: Per 100 patients, the two cardioprotective strategies provided similar benefits that were estimated as 24.5 and 13.4 life-years in 60- and 40-year-old patients, respectively. The cost per life-year saved with dexrazoxane was estimated as euro6931 and euro15 599 in 60- and 40-year-old patients, respectively, and euro22 940 and euro44 982, respectively, with liposome-encapsulated doxorubicin. Several sensitivity analyses showed the robustness of the model. CONCLUSION: The results suggest the potential clinical and economic usefulness of cardioprotective therapies in patients with aggressive NHL. Prospective studies are needed to confirm these findings.

Quality assessment of economic evaluation studies in pediatric surgery: a systematic review.

PURPOSE: To assess economic evaluation studies (EES) in pediatric surgery and to identify potential factors associated with high-quality studies. METHODS: A systematic review of the literature using PubMed and Cochrane databases was conducted to identify EES in pediatric surgery published between 1 June 1993 and 30 June 2013. Assessment criteria are derived from the Drummond checklist. A high quality study was defined as a Drummond score ≥7. Logistic regression analysis was used to determine factors associated with high quality studies. RESULTS: 119 studies were included. 43.7% (n=52) of studies were full EES. Cost-effectiveness analysis was the most frequent (61.5%) type of full EES. Only 31.6% of studies had a Drummond score ≥7 and 73% of these were full EES. The factors associated with high quality were identification of costs (OR: 14.08; 95% CI: 3.38-100; p<0.001), estimation of utility value (OR: 8.13; 95% CI: 2.02-43.47; p=0.005) and study funding (OR: 3.50; 95% CI: 1.27-10.10; p=0.02). CONCLUSION: This review shows that the number and the quality of EES are low despite the increasing number of studies published in recent years. In the current context of budget constraints, our results should encourage pediatric surgeons to focus more on EES.