Noise exposure among staff in intensive care units and the effects of unit-based noise management: a monocentric prospective longitudinal study.

BACKGROUND: Intensive care units (ICUs) are often too noisy, exceeding 70-80 dBA, which can have negative effects on staff. The corresponding recommendation of the World Health Organization (average sound pressure level below 35 dBA) is often not achieved. To date there is a lack of intervention studies examining the extent to which unit-based noise management in ICUs contributes to a reduction in noise exposure for the staff. The study therefore aims to provide answers to 1) how unit-based noise management sustainably reduces the subjective noise exposure among staff, and 2) how this intervention affects other noise-related topics. METHODS: We performed a monocentric prospective longitudinal study with three measurement points in a German university hospital in three ICUs. We collected data from different healthcare professionals and other professional groups between October 2021 and August 2022 using an online questionnaire. Data were analyzed using descriptive and inference statistics. RESULTS: A total of n = 179 participants took part in the surveys. The majority of participants were nurses or pediatric nurses. Most participants worked more than 75% full-time equivalent. Staff on the three ICUs reported high levels of noise exposure. No significant changes in noise exposure over time were observed. Participants were already aware of the topic and believed that a behavior change could positively influence the noise environment. CONCLUSIONS: This study provides an initial insight into how a unit-based noise management could contribute to a reduction in the subjective noise exposure among staff in ICUs. The results of this study highlight the importance of this topic. Future studies should aim to research aspects of adherence and their facilitators or barriers, which promote the sustained implementation of noise-reducing measures by staff. TRIAL REGISTRATION: German Clinical Trials Register (DRKS): DRKS00025835; Date of registration: 12.08.2021.

Nutritional support during the hospital stay is cost-effective for preventing adverse outcomes in patients with cancer.

Objective: Among patients with cancer, malnutrition remains common and is a key challenge in oncology practice today. A prior study from our group revealed that malnourished cancer inpatients who got nutritional treatment (intervention group) had lower mortality and improved functional and quality of life outcomes compared to inpatients without nutritional support (control group). Our present analysis aimed to determine whether the improved patient recovery by nutritional support was paralleled by cost-effectiveness of this nutritional care. Methods: We analyzed hospital costs and health outcomes in patients with cancer, using a Markov simulation model with daily cycles to analyze the economic impact of nutritional support in malnourished inpatients with malignancies. We compared results for a nutritional intervention group and a control group across a 30-day timeframe. Five health states were designated (malnourished but stable, complications, intensive care unit (ICU) admission, discharge, death). Costs for the different health states were based on publicly available data for the Swiss medical system. Total patient cost categories included in-hospital nutrition, days spent in the normal ward, days in the ICU, and medical complications. Results: Total per-patient costs for in-hospital supportive nutrition was Swiss francs (CHF) 129. Across a 30-day post-admission interval, our model determined average overall costs of care of CHF 46,420 per-patient in the intervention group versus CHF 43,711 in the control group-a difference of CHF 2,709 per patient. Modeled results showed a cost of CHF 1,788 to prevent one major complication, CHF 4,464 to prevent one day in the ICU, and CHF 3,345 to prevent one death. Recovery benefits of nutritional care were thus paralleled by cost-effectiveness of this care. Conclusion: In-hospital nutritional support for oncology patients at nutritional risk is a low-cost intervention that has both clinical and financial benefits.

Economic Evaluation of Individualized Nutritional Support for Hospitalized Patients with Chronic Heart Failure.

Background Malnutrition is a highly prevalent risk factor in hospitalized patients with chronic heart failure (CHF). A recent randomized trial found lower mortality and improved health outcomes when CHF patients with nutritional risk received individualized nutritional treatment. Objective To estimate the cost-effectiveness of individualized nutritional support in hospitalized patients with CHF. Methods This analysis used data from CHF patients at risk of malnutrition (N = 645) who were part of the Effect of Early Nutritional Therapy on Frailty, Functional Outcomes and Recovery of Undernourished Medical Inpatients Trial (EFFORT). Study patients with CHF were randomized into (i) an intervention group (individualized nutritional support to reach energy, protein, and micronutrient goals) or (ii) a control group (receiving standard hospital food). We used a Markov model with daily cycles (over a 6-month interval) to estimate hospital costs and health outcomes in the comparator groups, thus modeling cost-effectiveness ratios of nutritional interventions. Results With nutritional support, the modeled total additional cost over the 6-month interval was 15,159 Swiss Francs (SF). With an additional 5.77 life days, the overall incremental cost-effectiveness ratio for nutritional support vs. no nutritional support was 2625 SF per life day gained. In terms of complications, patients receiving nutritional support had a cost savings of 6214 SF and an additional 4.11 life days without complications, yielding an incremental cost-effectiveness ratio for avoided complications of 1513 SF per life day gained. Conclusions On the basis of a Markov model, this economic analysis found that in-hospital nutritional support for CHF patients increased life expectancy at an acceptable incremental cost-effectiveness ratio.

A Cost Impact Analysis of clonoSEQ® as a Valid and CE-Certified Minimal Residual Disease (MRD) Diagnostic Compared to No MRD Testing in Multiple Myeloma in Germany.

INTRODUCTION: The measurement of minimal residual disease (MRD) with clonoSEQ® can be used in the assessment of B-cell lymphoid tumor burden throughout treatment with accuracy, sensitivity and standardization when compared to traditional cytomorphology. With the approval of novel treatments, standardized MRD assessment with improved performance is increasingly important. The aim of this analysis is to estimate the cost-effectiveness of MRD testing with clonoSEQ® compared to no MRD testing for patients with multiple myeloma (MM) on maintenance therapy in Germany. METHODS: The cost impact of clonoSEQ® was analyzed from the German statutory insurance perspective. Clinical data were derived from the literature and expert opinions. Cost input was utilized based on publicly available data and literature. Patients in the MRD arm were tested every 6 months. The deterministic Markov model consists of six health states, and every patient begins at the start of maintenance. Included therapies are lenalidomide for maintenance and carfilzomib, lenalidomide and dexamethasone for relapse. RESULTS: For a time horizon of 10 years, the deterministic cost impact analysis shows total cost of €279,483 for patients using clonoSEQ® in comparison to €356,623 for simulated patients without MRD testing. The main drivers of the cost differences are saved cost of drug holiday. The savings per patient in 1 year are €18,396. Savings after 3 years are €69,991 per patient. Savings after 10 years are €77,140 per patient. CONCLUSIONS: Based on the underlying model, clonoSEQ® can support German health insurance funds to use high-cost drugs more efficiently in the treatment of myeloma.

Cost savings associated with nutritional support in medical inpatients: an economic model based on data from a systematic review of randomised trials.

BACKGROUND AND AIMS: Nutritional support improves clinical outcomes during hospitalisation as well as after discharge. Recently, a systematic review of 27 randomised, controlled trials showed that nutritional support was associated with lower rates of hospital readmissions and improved survival. In the present economic modelling study, we sought to determine whether in-hospital nutritional support would also return economic benefits. METHODS: The current economic model applied cost estimates to the outcome results from our recent systematic review of hospitalised patients. In the underlying meta-analysis, a total of 27 trials (n=6803 patients) were included. To calculate the economic impact of nutritional support, a Markov model was developed using transitions between relevant health states. Costs were estimated accounting for length of stay in a general hospital ward, hospital-acquired infections, readmissions and nutritional support. Six-month mortality was also considered. The estimated daily per-patient cost for in-hospital nutrition was US$6.23. RESULTS: Overall costs of care within the model timeframe of 6 months averaged US$63 227 per patient in the intervention group versus US$66 045 in the control group, which corresponds to per patient cost savings of US$2818. These cost savings were mainly due to reduced infection rate and shorter lengths of stay. We also calculated the costs to prevent a hospital-acquired infection and a non-elective readmission, that is, US$820 and US$733, respectively. The incremental cost per life-day gained was -US$1149 with 2.53 additional days. The sensitivity analyses for cost per quality-adjusted life day provided support for the original findings. CONCLUSIONS: For medical inpatients who are malnourished or at nutritional risk, our findings showed that in-hospital nutritional support is a cost-effective way to reduce risk for readmissions, lower the frequency of hospital-associated infections, and improve survival rates.

Economic evaluation of individualized nutritional support in medical inpatients: Secondary analysis of the EFFORT trial.

BACKGROUND & AIMS: Existing guidelines support the importance of nutritional interventions for medical inpatients at malnutrition risk to alleviate the impact of malnutrition on outcomes. While recent studies have reported positive effects of nutritional support on health outcomes, limited evidence exists on whether in-hospital nutritional support also results in economic advantages. We report the results of the economic evaluation of EFFORT-a pragmatic, investigator-initiated, open-label, multicenter trial. METHODS: A total of 2028 medical inpatients at nutritional risk were randomly assigned to receive individualized nutritional support to reach protein and energy goals (intervention group; n = 1015) or standard hospital food (control group; n = 1013). To calculate the economic impact of nutritional support, a Markov model was developed with relevant health states. Costs were estimated for days in normal hospital ward and in the Intensive Care Unit (ICU), hospital-acquired complications, and nutritional support. We used a Euro conversion rate of 0.93216 Euro for 1 Swiss Franc (CHF). RESULTS: The estimated per-patient cost was CHF90 (83.78 €) for the in-hospital nutritional support and CHF283.85 (264.23 €) when also considering dietitian consultation time. Overall costs of care within 30 days of admission averaged CHF29,263 (27,240 €) per-patient in the intervention group versus CHF29,477 (27,439 €) in the control group resulting in per-patient cost savings of CHF214 (199 €). Per-patient cost savings was CHF19.56 (18.21 €) when also accounting for dietician costs (full cost analysis). These cost savings were mainly due to reduced ICU length of stay and fewer complications. We also calculated costs to prevent adverse outcomes, which were CHF276 (256 €) for one severe complication, CHF2,675 (2490 €) for one day in ICU, and CHF7,975 (7423 €) for one death. For the full cost analysis, these numbers were CHF872 (811 €), CHF8,459 (7874 €) and CHF25,219 (23,475 €). Sensitivity analyses confirmed the original findings. CONCLUSIONS: Our evaluation demonstrates that in-hospital nutritional support for medical inpatients is a highly cost-effective intervention to reduce risks for ICU admissions and hospital-associated complications, while improving patient survival. The positive clinical and economic benefits of nutritional support in at-risk medical inpatients calls for comprehensive nutrition programs, including malnutrition screening, consultation, and nutritional support. TRIAL REGISTRATION: ClinicalTrials.gov number, NCT02517476.

Incidence of acquired thrombotic thrombocytopenic purpura in Germany: a hospital level study.

BACKGROUND: Acquired thrombotic thrombocytopenic Purpura (aTTP) is a life-threatening ultra-orphan disease with a reported annual incidence between 1.5 and 6.0 cases per million in Europe and mainly affecting otherwise young and healthy adults aged 40 years on average. The goal of this study was to assess the incidence of aTTP in Germany. METHODS: A systematic review was performed to determine the published evidence on the aTTP epidemiology in Germany. To obtain additional evidence on the proportion of aTTP cases within the national Thrombotic Microangiopathy (TMA) population a hospital-level study was performed, using a retrospective data collection approach. Diagnosis of aTTP was confirmed if ADAMTS13 level were < 10% and/or the medical records explicitly mentioned aTTP diagnosis. The aggregated hospital data were then projected to the national level using logistic regression techniques. RESULTS: The systematic literature search did not provide incidence estimates of aTTP in Germany. Eight centers (≈27% of the top 30 TMA hospitals) delivered data according to a predefined data collection form. On average (year 2014-2016) a total number of 172 aTTP episodes per year was projected (95% confidence interval [95%CI]: 132-212). The majority were newly diagnosed aTTP cases (n = 121; 95%CI: 105-129), and 51 were recurrent aTTP cases (95%CI: 27-84). The average annual projected incidence (year 2014-2016) of aTTP episodes was 2.10 per million inhabitants in Germany (95%CI: 1.60-2.58). CONCLUSIONS: The determined annual incidence of newly diagnosed aTTP cases and the overall annual incidence of aTTP episodes in Germany confirm the ultra-orphan character of aTTP. An external validation against international registries (France, UK and USA) shows that our findings are quite comparable with those international incidence rates.

A cost-effectiveness analysis of a hydration response technology dressing in the treatment of venous leg ulcers in the UK.

OBJECTIVE: Venous leg ulcers (VLUs) cause significant pain and suffering for patients. Additionally, they place considerable financial and service burden on the National Health Service (NHS). A large proportion of VLUs do not heal within the standard time frame of 16-24 weeks, resulting in static wounds which commonly have issues with increasing exudate production. As the NHS continues to face times of austerity, services need to find solutions to be able to reduce costs and release nursing time while maintaining standards of care. Cutimed Sorbion Sachet S, a hydration response technology dressing (HRTD), is a treatment option for the management of patients with a VLU. The objective of this study was to provide an update of the health economic analysis of HRTD in comparison with relevant comparators in the UK with current cost data. METHOD: HRTD was compared against four different dressings, Zetuvit Plus (a super absorbent polymer dressing SAP), DryMax extra (a superabsorbent dressing, SADM), KerraMax Care (superabsorbent dressing, SAKM) and Eclypse (superabsorbent dressing, SAE) from a cost-effectiveness perspective. Clinical data were derived from literature and expert opinion. Cost input was utilised based on publicly available data and literature. The average patient in the model is assumed to be 65 years with a diagnosed VLU. It is assumed that patients in the different treatment arms have the same background mortality, hence the endpoint mortality is not included in the model. The analysis is based on a deterministic Markov model derived from Harding et al. with weekly cycles. The following assumptions are made: first, all patients start in a static health state with a non-healed but non-progressing VLU. It is assumed in the model that patients wounds can transition to a deteriorating state or one where a wound is improving or could progress. Additionally, VLUs could be healed from a progressed wound (i.e. improved wound), or they could develop into a severe wound with complications (infections) to be treated in hospitals. The time frame for the analysis was fixed for one year and no re-occurence after healing was assumed to happen. RESULTS: The cost-effectiveness analysis demonstrates health economic dominance of HRDT being more effective and cost-saving against all analysed comparators. When using literature-based input values, the incrementally higher healing rates for HRDT are 11.04 months (versus SAP), 29.04 months (versus SADM), 1.68 months (versus SAKM) and 11.04 months (versus SAE). Cost savings per patient were £37.60 versus SAP, £171.68 versus SADM, £3.13 versus SAKM and £43.63 versus SAE. CONCLUSION: Clinical benefits and cost savings increase when real-life practice assumptions, based on expert opinion, are included. Based on the underlying health economic model, HRDT is more effective and less costly than other comparative products in VLUs in the UK.

Administrative risk quantification of subcutaneous and intravenous therapies in Italian centers utilizing the Failure Mode and Effects Analysis approach.

BACKGROUND: In oncology, an important parameter of safety is the potential treatment error in hospitals. The analyzed hypothesis is that of subcutaneous therapies would provide a superior safety benefit over intravenous therapies through fixed-dose administrations, when analyzed with trastuzumab and rituximab. METHODS: For the calculation of risk levels, the Failure Mode and Effect Analysis approach was applied. Within this approach, the critical treatment path is followed and risk classification for each individual step is estimated. For oncology and hematology administration, 35 different risk steps were assessed. The study was executed in 17 hematology and 16 breast cancer centers in Italy. As intravenous and subcutaneous were the only injection routes in medical available for trastuzumab and rituximab in oncology at the time of the study, these two therapies were chosen. RESULTS: When the risk classes were calculated, eight high-risk areas were identified for the administration of an intravenous therapy in hematology or oncology; 13 areas would be defined as having a median-risk classification and 14 areas as having a low-risk classification (total risk areas: n=35). When the new subcutaneous formulation would be applied, 23 different risk levels could be completely eliminated (65% reduction). Important high-risk classes such as dose calculation, preparation and package labeling, preparation of the access to the vein, pump infusion preparation, and infusion monitoring were included in the eliminations. The overall risk level for the intravenous administration was estimated to be 756 (ex-ante) and could be reduced by 70% (ex-post). The potential harm compensation for errors related to pharmacy would be decreased from eight risk classes to only three risk classes. CONCLUSION: The subcutaneous administration of trastuzumab (breast cancer) and rituximab (hematology) might lower the risk of administration and treatment errors for patients and could hence indirectly have a positive financial impact for hospitals.

Potential resource and cost saving analysis of subcutaneous versus intravenous administration for rituximab in non-Hodgkin's lymphoma and for trastuzumab in breast cancer in 17 Italian hospitals based on a systematic survey.

INTRODUCTION: Subcutaneous versions of different oncology therapies have been available for patients for a few years, yet patient-relevant and hospital benefits have not been assessed in real life. METHODS: In order to analyze the impact of subcutaneous administrations for rituximab or trastuzumab in comparison to the respective intravenous mode a primary research in Italy was executed. The study's primary objectives were to analyze the resource and cost implications from different perspectives (patient, medical staff) in the real world. The route of administration was discussed and aligned with the participating centers in order to capture all relevant therapy parts. After the successful execution of a pilot study 19 centers in six regions in Italy were recruited to participate. RESULTS: Significant time savings might be achieved with the subcutaneous mode through significantly lower patient preparation time including less time preparing the actual dosing for each individual patient. The total time difference is 3.3 hours with rituximab in hematology (non-Hodgkin's lymphoma), which adds up to 23.55 hours for a full course of treatment per patient (overall preparation time: 40.1 hours intravenous [95% confidence interval (CI): ±0.47] vs 16.6 hours subcutaneous [95% CI: ±0.2]). In early breast cancer (trastuzumab), the time saving might be 3.3 hours for the first cycle and the total time saving for patient preparation might be 17.2 hours (overall preparation time: 38.8 hours intravenous [95% CI: ±9.42] vs 21.6 hours subcutaneous [95% CI: ±9.9]). Furthermore, in both settings, the time of medical staff was reduced and could hence be used elsewhere. Finally, in case wastage was experienced with intravenous therapies, there were potential significant reductions in wastage through the subcutaneous administration (93%-100%) with cost savings of €6,057 with rituximab subcutaneous and €28,399 with trastuzumab subcutaneous administration for the full treatment course. CONCLUSION: There are significant resource and cost savings due to subcutaneous administration with rituximab and trastuzumab in Italy based on a systematic survey. With the availability of a subcutaneous use of rituximab and trastuzumab, hospitals, patients and payers in general still have the current standard of care therapies available in the approved indications for a more efficient use of time and resources.

Simulation and comparison of progression-free survival among patients with non-squamous non-small-cell lung cancer receiving sequential therapy.

OBJECTIVES: In recent years, the treatment landscape in advanced non-squamous non-small-cell lung cancer (nsNSCLC) has changed. New therapies (e.g., bevacizumab indicated in first line) have become available and other therapies (e.g., pemetrexed in first line and second line) moved into earlier lines in the treatment paradigm. While there has been an expansion of the available treatment options, it is still a key research question which therapy sequence results in the best survival outcomes for patients with nsNSCLC. METHODS: A therapy-sequencing disease model that approximates treatment outcomes in up to five lines of treatment was developed for patients with nsNSCLC. The primary source of data for progression-free survival (PFS) and time to death was published pivotal trial data. All patients were treatment-naïve and in the PFS state, received first-line treatment with either bevacizumab-based therapy or doublet chemotherapy (including the option of pemetrexed + cisplatin). Patients would then progress to a subsequent line of therapy, remain in PFS or die. In case of progression, it was assumed that each survivor would receive a subsequent line of therapy, based on EMA licensed therapies. Weibull distribution curves were fitted to the data. RESULTS: All bevacizumab-based first-line therapy sequences analyzed achieved total PFS of around 15 months. Bevacizumab + carboplatin + paclitaxel (first line) → pemetrexed (second line) → erlotinib (third line) → docetaxel (fourth line) resulted in total mean PFS time of 15.7 months, for instance. Sequences with pemetrexed in combination with cisplatin in first line achieved total PFS times between 12.6 and 12.8 months with a slightly higher total PFS time achieved when assuming pemetrexed continuation therapy in maintenance after pemetrexed + cisplatin in first-line induction. Overall survival results followed the same trend as PFS. CONCLUSION: The model suggests that treatment-sequencing strategies starting with a bevacizumab-based combination in first line yield better survival outcomes than those starting with pemetrexed-based combinations, a result that is attributable to the possibility of one further line of treatment with first-line bevacizumab-based treatment sequences.

Evaluation of a possible predictor for Federal Joint Committee decisions on early benefit assessments according to the German act on the reform of the market for medicinal products.

OBJECTIVES: As of 1st January 2011 the German drug market is regulated by the act on the reform of the market for medicinal products (AMNOG). Since then the normal procedure for reimbursement of a new pharmaceutical is a benefit assessment by the joint federal committee (G-BA) which determines one of six additional benefit levels. METHODS: In order to evaluate a possible predictor of G-BA decisions, the 'evaluation of pharmaceutical innovations (EVITA)' score was calculated for 40 out of 63 dossiers and compared with published G-BA appraisals. RESULTS: Univariate ordinary least squares (p<0.001) and ordered logit regression (p=0.008) analyses show statistically significant correlations between EVITA scores and the G-BA additional benefit levels. Moreover, for the prediction of an additional benefit level of at least 'minor', an EVITA score cutpoint of ≥3 is associated with a sensitivity of 100% and a specificity of 80%. For the prediction of an additional benefit level of at least 'considerable', an EVITA score cutpoint of ≥7.5 is associated with a sensitivity of 100% and a specificity of 93.1%. CONCLUSION: The present investigation indicates that the EVITA score may have some potential to act as a possible predictor of G-BA decisions related to AMNOG early benefit assessments.

Health economics evidence for medical nutrition: are these interventions value for money in integrated care?

BACKGROUND: Health care decision-makers have begun to realize that medical nutrition plays an important role in the delivery of care, and it needs to be seen as a sole category within the overall health care reimbursement system to establish the value for money. Indeed, improving health through improving patients' nutrition may contribute to the cost-effectiveness and financial sustainability of health care systems. Medical nutrition is regulated by a specific bill either in Europe or in the United States, which offers specific legislations and guidelines (as provided to patients with special nutritional needs) and indications for nutritional support. Given that the efficacy of medical nutrition has been proven, one can wonder whether the heterogeneous nature of its coverage/reimbursement across countries might be due to the lack of health-related economic evidence or value-for-money of nutritional interventions. This paper aims to address this knowledge gap by performing a systematic literature review on health economics evidence regarding medical nutrition, and by summarizing the results of these publications related to the value for money of medical nutrition interventions. METHODS: A systematic literature search was initiated and executed based on a predefined search protocol following the population, intervention, comparison, and outcomes (PICO) criteria. Following the systematic literature search of recently published literature on health economics evidence regarding medical nutrition, this study aims to summarize the results of those publications that are related to the value for money of medical nutrition interventions. The evaluations were conducted by analyzing different medical nutrition according to their indications, the economic methodology or perspective adopted, the cost source and utility measures, selected efficiency measures, as well as the incremental cost-effectiveness ratio. RESULTS: A total of 225 abstracts were identified for the detailed review, and the data were entered into a data extraction sheet. For the abstracts that finally met the predefined inclusion criteria (n=53), full-text publications were obtained via PubMed, subito, or directly via each journal's Webpage for further assessment. After a detailed review of the full text articles, 34 publications have been qualified for a thorough data extraction procedure. When differentiating the resulting articles in terms of their settings, 20 studies covered inpatients, whereas 14 articles covered outpatients, including patients in community centers. When reviewing the value-for-money evaluations, the indications showed that the different results were mostly impacted by the different perspectives adopted and the comparisons that were made. In order to draw comprehensive conclusions, the results were split according to the main indications and diseases. DISCUSSION: The systematic literature search has shown that there is not only an interest in health economics and its application in medical nutrition, but that there is a lot of ongoing research in this area. Based on the underlying systematic analysis, it has been shown that medical nutrition interventions offer value for money in the different health care settings, particularly for the specific disease areas that have been pointed out. CONCLUSION: Based on the systematic literature search that was performed, it was shown that medical nutrition interventions offer value for money in the different health care settings. Although medical nutrition has been the topic of some health economic analyses, the usual willingness to pay threshold used in health care rarely was applied. Often, these products are either directly part of a lump sum in the financing system (for example, diagnosis-related groups), or they are covered as out-of-pocket payments by patients directly. More research would be necessary to better understand how medical nutrition interventions can be optimally funded by the health care system, given the clinical value they bring to patients in their recovery process.

Health economic analyses in medical nutrition: a systematic literature review.

BACKGROUND: Medical nutrition is a specific nutrition category either covering specific dietary needs and/or nutrient deficiency in patients or feeding patients unable to eat normally. Medical nutrition is regulated by a specific bill in Europe and in the US, with specific legislation and guidelines, and is provided to patients with special nutritional needs and indications for nutrition support. Therefore, medical nutrition products are delivered by medical prescription and supervised by health care professionals. Although these products have existed for more than 2 decades, health economic evidence of medical nutrition interventions is scarce. This research assesses the current published health economic evidence for medical nutrition by performing a systematic literature review related to health economic analysis of medical nutrition. METHODS: A systematic literature search was done using standard literature databases, including PubMed, the Health Technology Assessment Database, and the National Health Service Economic Evaluation Database. Additionally, a free web-based search was conducted using the same search terms utilized in the systematic database search. The clinical background and basis of the analysis, health economic design, and results were extracted from the papers finally selected. The Drummond checklist was used to validate the quality of health economic modeling studies and the AMSTAR (A Measurement Tool to Assess Systematic Reviews) checklist was used for published systematic reviews. RESULTS: Fifty-three papers were identified and obtained via PubMed, or directly via journal webpages for further assessment. Thirty-two papers were finally included in a thorough data extraction procedure, including those identified by a "gray literature search" utilizing the Google search engine and cross-reference searches. Results regarding content of the studies showed that malnutrition was the underlying clinical condition in most cases (32%). In addition, gastrointestinal disorders (eg, surgery, cancer) were often analyzed. In terms of settings, 56% of papers covered inpatients, whereas 14 papers (44%) captured outpatients, including patients in community centers. Interestingly, in comparison with the papers identified overall, very few health economic models were found. Most of the articles were modeling analyses and economic trials in different design settings. Overall, only eight health economic models were published and were validated applying the Drummond checklist. In summary, most of the models included were carried out to quite a high standard, although some areas were identified for further improvement. Of the two systematic health economic reviews identified, one achieved the highest quality score when applying the AMSTAR checklist. CONCLUSION: The reasons for finding only a few modeling studies but quite a large number of clinical trials with health economic endpoints, might be different. Until recently, health economics has not been required for reimbursement or coverage decisions concerning medical nutrition interventions. Further, there might be specifics of medical nutrition which might not allow easy modeling and consequently explain the limited uptake so far. The health economic data on medical nutrition generated and published is quite ample. However, it has been primarily based on database analysis and clinical studies. Only a few modeling analyses have been carried out, indicating a need for further research to understand the specifics of medical nutrition and their applicability for health economic modeling.

Free drugs in clinical trials and their potential cost saving impact on the National Health Service: a retrospective cost analysis in Italy.

BACKGROUND: The cost of new anti-cancer drugs has dramatically increased in recent years, and countermeasures are required in order to limit pharmaceutical expenses. Sponsored clinical trials that provide drugs free of charge may be a useful tool in order to reduce drug costs. The aim of this analysis is to evaluate the effect of clinical trials on pharmaceutical expenditure savings. METHODS: We evaluated the cost of drugs administered in clinical practice and in clinical trials (considering only the standard regimens that were administered also in clinical practice) in 2010 at the Lung Cancer Unit of the National Institute for Cancer Research in Genoa, Italy. The cost of drugs was calculated on the price charged at our Institute in 2010. The supposed cost of experimental treatment replacing standard therapy was converted in the cost of the treatments that would have been chosen in clinical practice, considering histology, line of treatment and number of administered cycles. RESULTS: From 1/1/2010 to 12/31/2010, 196 patients affected by lung cancer or pleural mesothelioma were treated. 152 patients (78%) received treatment in clinical practice or in non-sponsored trials (18 patients in 4 trials), while 44 (22%) were treated in one of the 12 sponsored clinical trials recruiting in 2010. Globally, 606 cycles of treatment would have been administered to patients, of which 436 (72%) were administered in clinical practice or in non-sponsored trials and 170 (28%) were administered in pharmaceutical company sponsored clinical trials. The overall cost of those anti-neoplastic drugs, based on the prices charged at our Institute in 2010, was €799 803. The cost of drugs administered in clinical practice or in non-sponsored trials was €556 649 (70%), whereas the cost of standard drugs administered in clinical trials was €243 154 (30%). The grants provided by pharmaceutical companies were evaluated and amounted to €235 965. CONCLUSIONS: The participation in sponsored clinical trials in which drugs are provided free of charge offers substantial cost savings for the National Health Service; moreover, the grants received for each enrolled patient produced additional income.

Effects of erlotinib first-line maintenance therapy versus placebo on the health-related quality of life of patients with metastatic non-small-cell lung cancer.

INTRODUCTION: Maintenance therapy can delay progression and prolong survival in metastatic non-small-cell lung cancer (mNSCLC). As treatment for mNSCLC is non-curative, its impact on patient health-related quality of life (HRQoL) is an important consideration. SATURN (Sequential Tarceva in Unresectable NSCLC) was a randomised, double-blind, placebo-controlled, multicentre study investigating the impact of erlotinib maintenance therapy on HRQoL in patients with locally advanced or recurrent NSCLC. PATIENTS AND METHODS: Eligible patients who had previously completed four cycles of platinum-based chemotherapy were randomised 1:1 to receive erlotinib 150 mg/day or placebo until disease progression, unacceptable toxicity or death. Patient HRQoL was assessed using the Functional Assessment of Cancer Therapy-Lung questionnaire, in terms of time to symptom progression (TSP), time to deterioration (TTD) in Trial Outcome Index (TOI) and TTD. Exploratory analysis was based on time to analgesia and appearance of key symptoms (pain, cough and dyspnoea). RESULTS: Compared with placebo, erlotinib maintenance therapy prolonged progression-free and overall survival by 41% and 23%, respectively. At baseline, HRQoL measures were comparable between the two treatment groups. Maintenance therapy with erlotinib did not impact on deterioration in HRQoL: TSP (hazard ratio [HR]=0.91 [95% confidence interval (CI) 0.74-1.12]; n=785), TTD in TOI (HR=1.06 [95% CI 0.87-1.31]; n=781) and TTD in HRQoL (HR=0.96 [95% CI 0.79-1.16]; n=776). Time to pain and time to analgesic use were significantly delayed in patients receiving erlotinib compared with placebo (HR=0.61 [95% CI 0.42-0.88]; p=0.0080 and HR=0.66 [95% CI 0.46-0.94]; p=0.0199, respectively). A non-significant trend towards delayed time to cough and time to dyspnoea (HR=0.77 [95% CI 0.49-1.21] and HR=0.75 [95% CI 0.48-1.17], respectively) was also observed. CONCLUSIONS: Erlotinib maintenance therapy significantly extends progression-free survival without compromising patient HRQoL in comparison with placebo, with some improvement in symptoms.

Maintenance erlotinib in advanced nonsmall cell lung cancer: cost-effectiveness in EGFR wild-type across Europe.

BACKGROUND: First-line maintenance erlotinib in patients with locally advanced or metastatic nonsmall cell lung cancer (NSCLC) has demonstrated significant overall survival and progression-free survival benefits compared with best supportive care plus placebo, irrespective of epidermal growth factor receptor (EGFR) status (SATURN trial). The cost-effectiveness of first-line maintenance erlotinib in the overall SATURN population has been assessed and published recently, but analyses according to EGFR mutation status have not been performed yet, which was the rationale for assessing the cost-effectiveness of first-line maintenance erlotinib specifically in EGFR wild-type metastatic NSCLC. METHODS: The incremental cost per life-year gained of first-line maintenance erlotinib compared with best supportive care in patients with EGFR wild-type stable metastatic NSCLC was assessed for five European countries (the United Kingdom, Germany, France, Spain, and Italy) with an area-under-the-curve model consisting of three health states (progression-free survival, progressive disease, death). Log-logistic survival functions were fitted to Phase III patient-level data (SATURN) to model progression-free survival and overall survival. The first-line maintenance erlotinib therapy cost (modeled for time to treatment cessation), medication cost in later lines, and cost for the treatment of adverse events were included. Deterministic and probabilistic sensitivity analyses using Monte Carlo simulation (1000 iterations) were performed. RESULTS: According to the model simulations, first-line maintenance erlotinib compared with best supportive care in EGFR wild-type stable metastatic NSCLC resulted in 4.57 months of life gained (17.82 months for erlotinib versus 13.24 months for best supportive care) and 1.14 months of life without progression gained (erlotinib 4.29 versus best supportive care 3.15), and incremental total costs of erlotinib from €7897 (UK) to €9580 (Germany). The corresponding mean incremental cost per life-year gained of erlotinib ranged between €20,711 (UK) and €25,124 (Germany). Sensitivity analyses confirmed these results. CONCLUSION: First-line erlotinib maintenance treatment is cost-effective compared with best supportive care in EGFR wild-type stable metastatic NSCLC, irrespective of the country setting.

Societal savings in patients with advanced non-squamous non-small-cell lung cancer receiving bevacizumab-based versus non-bevacizumab-based treatments in France, Germany, Italy, and Spain.

BACKGROUND: The purpose of this study was to investigate the savings accrued using bevacizumab-based treatment for non-small-cell lung cancer from the societal perspective, taking only public costs into account, in France, Germany, Italy, and Spain. METHODS: Societal costs were estimated by collecting and analyzing labor costs, carer costs, sickness benefits, disability benefits, and home care benefits. Cost inputs were derived from publicly available databases or from the published literature. Expert opinion was only used if no other source was available. Efficacy data from two randomized clinical trials were used. The time horizon in the health economic model was lifetime. Efficacy and costs were discounted by 3.5%. All main model parameters were tested in deterministic and probabilistic sensitivity analyses. RESULTS: Mean incremental savings to society per patient ranged from €2277 in Italy to €4461 in Germany. The results were most sensitive to the change in proportion of patients working fulltime and the proportion of patients who were able to return to work. CONCLUSION: This analysis shows that bevacizumab-based treatment in non-small-cell lung cancer is associated with more savings to society compared to standard chemotherapy in terms of increased productivity and decreased social benefits paid to patients who are able to work in France, Germany, Italy, and Spain.

Cost comparison of second-line treatment options for late stage non-small-cell lung cancer: cost analysis for Italy.

BACKGROUND: Lung cancer is the leading cause of cancer deaths worldwide (1.38 million cancer deaths, 18.2% of the total) and of cancer morbidity (1.61 million new cases, 12.7% of all new cancers). Currently only three second-line non-small-cell lung cancer (NSCLC) pharmacotherapies are licensed in the European Union: the chemotherapies pemetrexed and docetaxel and the epidermal growth factor receptor tyrosine kinase inhibitor erlotinib. These therapy alternatives have shown a comparable efficacy (survival benefit). In the past, cost comparisons showed that erlotinib was less costly compared to docetaxel, which in turn is cheaper than pemetrexed. Nowadays erlotinib (and docetaxel) are still less expensive than pemetrexed; but docetaxel lost patent protection (basic compound patent) at the end of 2010, so docetaxel drug costs have decreased rapidly and the question remains whether erlotinib is still the least costly therapy alternative in second-line NSCLC. MATERIAL AND METHODS: Italy was selected for base case analysis to compare the total therapy costs, estimated by combining country-specific drug costs, administration costs, and adverse event costs of erlotinib and generic docetaxel in second-line NSCLC therapy. Sensitivity analyses on central input parameters have been performed. RESULTS: The total costs of treating one patient with erlotinib therapy of €5121 are lower than the docetaxel costs of €6699 for the Italian health care setting. Although the drug costs of erlotinib are higher than generic docetaxel (incremental €3770): the costs of intravenous chemotherapy administration (incremental -€4510), and the costs of adverse event therapy (incremental -€837) lead to higher total therapy costs for docetaxel compared to the epidermal growth factor receptor tyrosine kinase inhibitor therapy erlotinib. CONCLUSION: The cost comparison findings for Italy show that erlotinib is still the less costly therapy alternative in second-line NSCLC. These results were robust to changes of central input parameters and robust to further potential price decreases for docetaxel.

Cross-market cost-effectiveness analysis of erlotinib as first-line maintenance treatment for patients with stable non-small cell lung cancer.

BACKGROUND: Platinum-doublet, first-line treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) is limited to 4-6 cycles. An alternative strategy used to prolong the duration of first-line treatment and extend survival in metastatic NSCLC is first-line maintenance therapy. Erlotinib was approved for first-line maintenance in a stable disease population following results from a randomized, controlled Phase III trial comparing erlotinib with best supportive care. We aimed to estimate the incremental cost-effectiveness of erlotinib 150 mg/day versus best supportive care when used as first-line maintenance therapy for patients with locally advanced or metastatic NSCLC and stable disease. METHODS: An economic decision model was developed using patient-level data for progression-free survival and overall survival from the SATURN (SequentiAl Tarceva in UnResectable NSCLC) study. An area under the curve model was developed; all patients entered the model in the progression-free survival health state and, after each month, moved to progression or death. A time horizon of 5 years was used. The model was conducted from the perspective of national health care payers in France, Germany, and Italy. Probabilistic sensitivity analyses were performed. RESULTS: Treatment with erlotinib in first-line maintenance resulted in a mean life expectancy of 1.39 years in all countries, compared with a mean 1.11 years with best supportive care, which represents 0.28 life-years (3.4 life-months) gained with erlotinib versus best supportive care. In the base-case analysis, the cost per life-year gained was €39,783, €46,931, and €27,885 in France, Germany, and Italy, respectively. CONCLUSION: Erlotinib is a cost-effective treatment option when used as first-line maintenance therapy for locally advanced or metastatic NSCLC.