Indirect and Direct Mapping of the Cancer-Specific EORTC QLQ-C30 onto EQ-5D-5L Utility Scores.

OBJECTIVE: The aim of this study was to develop a response mapping algorithm to predict EQ-5D-5L utilities from European Organisation for Research and Treatment Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) scores and compare performance with direct mapping approaches to identify the best performing algorithm. METHODS: The Multi-Instrument Comparison dataset contains responses to both the EQ-5D-5L and QLQ-C30 questionnaires from 692 individuals with a broad range of cancers. Response mapping was conducted, fitting ordered logistic regressions to predict response levels for each of the five EQ-5D dimensions and utilities were predicted using the US and Japanese EQ-5D-5L value sets to test the algorithm performance. Various direct mapping models were fitted: ordinary least squares, tobit, two-part (TPM), adjusted limited dependent variable mixture and beta mixture models. Model assessment and recommendations regarding the best mapping algorithm was based on goodness-of-fit statistics, predictive ability (measures of error, distribution of predicted utilities) and in sample cross-validation. RESULTS: The response mapping model performed well in terms of predictive ability and measurement error using the US or Japanese value set, with mean absolute error ranging from 0.0708 to 0.0988, and comparably to the TPM, which was the best performing direct algorithm. CONCLUSION: The developed mapping algorithms enable the prediction of EQ-5D-5L utilities from QLQ-C30 scores when EQ-5D-5L data have not been directly collected in clinical trials. The response mapping model offers the possibility of predicting EQ-5D-5L utility values using any national value set and can be generalised to multiple countries and oncology settings.

Quality of Life in Wilson's Disease: A Systematic Literature Review.

Background: Wilson's disease (WD) is a rare inherited genetic disorder characterized by the progressive accumulation of copper in the brain, liver, and other major organ systems. To date, there have been no comprehensive studies synthesizing evidence pertaining to the quality of life (QOL) in WD. Objective: We conducted a systematic literature review to identify and synthesize the evidence on QOL in patients with WD. Methods: To address this gap in the literature, we conducted a systematic literature review in MEDLINE and EMBASE to identify observational studies and clinical trials reporting QOL outcomes among people living with WD. Results: A total of 442 publications were identified, 41 publications were eligible for full-text screening, and 7 articles, representing 7 studies, met all inclusion criteria. QOL questionnaires used across studies included the 12-Item Short Form Health Survey Questionnaire (version 1) (SF-12) (n=2), the 36-Item Short Form Health Survey Questionnaire (version 1) (SF-36) (n=3), Global Assessment Scale (GAS) (n=1), and World Health Organization QOL brief questionnaire (WHO-QOL-BREF) (n=1). Overall, the pattern in QOL from most studies demonstrated a worse QOL in WD patients compared with the general population, a deterioration in QOL for patients presenting with neurologic symptoms, and more frequent psychiatric symptoms compared with the ones with hepatic symptoms. Discussion: Although our understanding of the underlying pathophysiology of WD has advanced, and novel therapeutics are on the horizon, our understanding of how WD affects overall QOL remains limited. Evidence from this review demonstrates the substantial heterogeneity in reporting outcomes pertaining to the QOL associated with WD. These differences may be attributable to the fact that QOL is not typically assessed and the lack of a standardized method for assessing QOL in WD. Conclusion: This review demonstrates a need for more up-to-date studies with larger sample sizes to further evaluate QOL in patients with WD. The study also demonstrates the need for a WD-specific instrument to measure the QOL in WD patients.

Core outcome set measurement for future clinical trials in acute myeloid leukemia: the HARMONY study protocol using a multi-stakeholder consensus-based Delphi process and a final consensus meeting.

BACKGROUND: Acute myeloid leukemia (AML) is the most common acute leukemia in adults and has an unacceptably low cure rate. In recent years, a number of new treatment strategies and compounds were developed for the treatment of AML. There were several randomized controlled clinical trials with the objective to improve patients' management and patients' outcome in AML. Unfortunately, these trials are not always directly comparable since they do not measure the same outcomes, and currently there are no core outcome sets that can be used to guide outcome selection and harmonization in this disease area. The HARMONY (Healthcare Alliance for Resourceful Medicine Offensive against Neoplasms in Hematology) Alliance is a public-private European network established in 2017 and currently includes 53 partners and 32 associated members from 22 countries. Amongst many other goals of the HARMONY Alliance, Work Package 2 focuses on defining outcomes that are relevant to each hematological malignancy. Accordingly, this pilot study will be performed to define a core outcome set in AML. METHODS: The pilot study will use a three-round Delphi survey and a final consensus meeting to define a core outcome set. Participants will be recruited from different stakeholder groups, including patients, clinicians, regulators and members of the European Federation of Pharmaceutical Industries and Associations. At the pre-Delphi stage, a literature research was conducted followed by several semi-structured interviews of clinical public and private key opinion leaders. Subsequently, the preliminary outcome list was discussed in several multi-stakeholder face-to-face meetings. The Delphi survey will reduce the preliminary outcome list to essential core outcomes. After completion of the last Delphi round, a final face-to-face meeting is planned to achieve consensus about the core outcome set in AML. DISCUSSION: As part of the HARMONY Alliance, the pilot Delphi aims to define a core outcome set in AML on the basis of a multi-stakeholder consensus. Such a core outcome set will help to allow consistent comparison of future clinical trials and real-world evidence research and ensures that appropriate outcomes valued by a range of stakeholders are measured within future trials.

Patient-reported outcome measures in studies of myelodysplastic syndromes and acute myeloid leukemia: Literature review and landscape analysis.

OBJECTIVES: This study aims to describe the use of patient-reported outcome measures (PROMs) in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) studies and the PROMs landscape. METHODS: A comprehensive literature review was performed in Medline/Embase (since 2000) and ClinicalTrials.gov (since 2013) to identify PROMs used in MDS and AML clinical studies. Additionally, PROMs included in approved drug labels since 2000 were reviewed. RESULTS: Overall, 112 different PROMs were used in 168 published MDS studies and 152 PROMs were used in 172 AML studies. From ClinicalTrials.gov, 16 different PROMs were used in 22 ongoing registered studies in MDS, and 24 were reported in 41 AML studies. The most frequently used PROMs were cancer-specific (eg, EORTC QLQ-C30, FACT-An) or generic (SF-36, EQ-5D) instruments, whereas MDS- and AML-specific instruments (eg, QUALMS and QOL-E in MDS; FACT-Leu and EORTC QLQ-Leu in AML) were used in a minority of studies. Two EMA-approved drugs for MDS included PROMs in their label. EORTC QLQ-C30 is by far the most frequently used cancer-specific PROM in both MDS and AML studies. CONCLUSIONS: This research indicated an underuse of AML/MDS-specific PROMs for these two indications in clinical studies and labeling claims. However, AML/MDS-specific instruments in development might be considered in future studies.

Identification, Review, and Use of Health State Utilities in Cost-Effectiveness Models: An ISPOR Good Practices for Outcomes Research Task Force Report.

Cost-effectiveness models that present results in terms of cost per quality-adjusted life-year for health technologies are used to inform policy decisions in many parts of the world. Health state utilities (HSUs) are required to calculate the quality-adjusted life-years. Even when clinical studies assessing the effectiveness of health technologies collect data on HSUs to populate a cost-effectiveness model, which rarely happens, analysts typically need to identify at least some additional HSUs from alternative sources. When possible, HSUs are identified by a systematic review of the literature, but, again, this rarely happens. In 2014, ISPOR established a Good Practices for Outcome Research Task Force to address the use of HSUs in cost-effectiveness models. This task force report provides recommendations for researchers who identify, review, and synthesize HSUs for use in cost-effectiveness models; analysts who use the results in models; and reviewers who critically appraise the suitability and validity of the HSUs selected for use in models. The associated Minimum Reporting Standards of Systematic Review of Utilities for Cost-Effectiveness checklist created by the task force provides criteria to judge the appropriateness of the HSUs selected for use in cost-effectiveness models and is suitable for use in different international settings.

Trial exclusion criteria and their impact on the estimation of antipsychotic drugs effect: A case study using the SOHO database.

OBJECTIVES: To explore the impact upon estimation of drug effect as a result of applying exclusion criteria in randomized-controlled trials (RCT) measuring the efficacy of antipsychotics (AP) in schizophrenia. METHODS: Three characteristics which may act as effect-modifiers of AP, while also common exclusion criteria in RCTs, were identified through literature review: schizophrenia duration, substance use disorder and poor adherence. The SOHO cohort was used to estimate the effect of initiating antipsychotic drugs "A", "B" or "C" (pooled) upon symptom evolution at 3months from baseline (CGI-S scale). "Estimated effectiveness" and "estimated efficacy" were drawn from the "SOHO" and "RCT-like" (patients with none of the above-listed exclusion criteria) samples, respectively. Effect-modification and impact of each exclusion criterion on AP effect estimates were explored using non-adjusted statistics. RESULTS: The "SOHO sample" included 8250 patients initiating drug A, B or C at baseline, whose AP "estimated effectiveness" was ΔCGI-S=-0.78 (95% CI=-0.80, -0.76). The "RCT-like" sub-sample included 5348 (65%) patients whose AP "estimated efficacy" was ΔCGI-S=-0.73 (95% CI=-0.75, -0.70). Patients with short illness duration (≤3years since first AP; n=2436) experienced significant symptom improvement (ΔCGI-S=-0.89; 95%CI=-0.93, -0.85) compared to patients with duration >3years (mean ΔCGI-S=-0.73; 95%CI=-0.76, -0.71). Excluding patients with short illness duration led to a change in AP effect estimates but this was not the case for substance use disorder or poor adherence. CONCLUSION: Using certain exclusion criteria in RCTs may impact the drug's effect estimate, particularly when exclusion criteria are AP effect-modifiers representing frequent characteristics among patients with schizophrenia.

Cost-effectiveness of vedolizumab compared with infliximab, adalimumab, and golimumab in patients with ulcerative colitis in the United Kingdom.

OBJECTIVE: To examine the clinical and economic impact of vedolizumab compared with infliximab, adalimumab, and golimumab in the treatment of moderately to severely active ulcerative colitis (UC) in the United Kingdom (UK). METHODS: A decision analytic model in Microsoft Excel was used to compare vedolizumab with other biologic treatments (infliximab, adalimumab, and golimumab) for the treatment of biologic-naïve patients with UC in the UK. Efficacy data were obtained from a network meta-analysis using placebo as the common comparator. Other inputs (e.g., unit costs, adverse-event disutilities, probability of surgery, mortality) were obtained from published literature. Costs were presented in 2012/2013 British pounds. Outcomes included quality-adjusted life-years (QALYs). Costs and outcomes were discounted by 3.5% per year. Incremental cost-effectiveness ratios were presented for vedolizumab compared with other biologics. Univariate and multivariate probabilistic sensitivity analyses were conducted to assess model robustness to parameter uncertainty. RESULTS: The model predicted that anti-tumour necrosis factor-naïve patients on vedolizumab would accrue more QALY than patients on other biologics. The incremental results suggest that vedolizumab is a cost-effective treatment compared with adalimumab (incremental cost-effectiveness ratio of £22,735/QALY) and dominant compared with infliximab and golimumab. Sensitivity analyses suggest that results are most sensitive to treatment response and transition probabilities. However, vedolizumab is cost-effective irrespective of variation in any of the input parameters. CONCLUSIONS: Our model predicted that treatment with vedolizumab improves QALY, increases time in remission and response, and is a cost-effective treatment option compared with all other biologics for biologic-naïve patients with moderately to severely active UC.

Cost-effectiveness of vedolizumab compared with conventional therapy for ulcerative colitis patients in the UK.

OBJECTIVE: To examine the clinical and economic impact of vedolizumab compared with conventional therapy in the treatment of moderately-to-severely active ulcerative colitis (UC) in the UK based on results of the GEMINI I trial. METHODS: A decision-analytic model in Microsoft Excel was used to compare vedolizumab with conventional therapy (aminosalicylates, corticosteroids, immunomodulators) for the treatment of patients with UC in the UK. We considered the following three populations: the overall intent-to-treat population from the GEMINI I trial, patients naïve to anti-TNF therapy, and those who had failed anti-TNF-therapy. Population characteristics and efficacy data were obtained from the GEMINI I trial. Other inputs (eg, unit costs, probability of surgery, mortality) were obtained from published literature. Time horizon was a lifetime horizon, with costs and outcomes discounted by 3.5% per year. One-way and probabilistic sensitivity analyses were conducted to measure the impact of parameter uncertainty. RESULTS: Vedolizumab had incremental cost-effectiveness ratios of £4,095/quality-adjusted life-year (QALY), £4,423/QALY, and £5,972/QALY compared with conventional therapy in the intent-to-treat, anti-TNF-naïve, and anti-TNF-failure populations, respectively. Patients on vedolizumab accrued more QALYs while incurring more costs than patients on conventional therapy. The sensitivity analyses showed that the results were most sensitive to induction response and transition probabilities for each treatment. CONCLUSION: The results suggest that vedolizumab results in more QALYs and may be a cost-effective treatment option compared with conventional therapy for both anti-TNF-naïve and anti-TNF-failure patients with moderately-to-severely active UC.

Current recommendations on the estimation of transition probabilities in Markov cohort models for use in health care decision-making: a targeted literature review.

OBJECTIVE: Although Markov cohort models represent one of the most common forms of decision-analytic models used in health care decision-making, correct implementation of such models requires reliable estimation of transition probabilities. This study sought to identify consensus statements or guidelines that detail how such transition probability matrices should be estimated. METHODS: A literature review was performed to identify relevant publications in the following databases: Medline, Embase, the Cochrane Library, and PubMed. Electronic searches were supplemented by manual-searches of health technology assessment (HTA) websites in Australia, Belgium, Canada, France, Germany, Ireland, Norway, Portugal, Sweden, and the UK. One reviewer assessed studies for eligibility. RESULTS: Of the 1,931 citations identified in the electronic searches, no studies met the inclusion criteria for full-text review, and no guidelines on transition probabilities in Markov models were identified. Manual-searching of the websites of HTA agencies identified ten guidelines on economic evaluations (Australia, Belgium, Canada, France, Germany, Ireland, Norway, Portugal, Sweden, and UK). All identified guidelines provided general guidance on how to develop economic models, but none provided guidance on the calculation of transition probabilities. One relevant publication was identified following review of the reference lists of HTA agency guidelines: the International Society for Pharmacoeconomics and Outcomes Research taskforce guidance. This provided limited guidance on the use of rates and probabilities. CONCLUSIONS: There is limited formal guidance available on the estimation of transition probabilities for use in decision-analytic models. Given the increasing importance of cost-effectiveness analysis in the decision-making processes of HTA bodies and other medical decision-makers, there is a need for additional guidance to inform a more consistent approach to decision-analytic modeling. Further research should be done to develop more detailed guidelines on the estimation of transition probabilities.

A Review of Generic Preference-Based Measures for Use in Cost-Effectiveness Models.

Generic preference-based measures (GPBMs) of health are used to obtain the quality adjustment weight required to calculate the quality-adjusted life year in health economic models. GPBMs have been developed to use across different interventions and medical conditions and typically consist of a self-complete patient questionnaire, a health state classification system, and preference weights for all states defined by the classification system. Of the six main GPBMs, the three most frequently used are the Health Utilities Index version 3, the EuroQol 5 dimensions (3 and 5 levels), and the Short Form 6 dimensions. There are considerable differences in GPBMs in terms of the content and size of descriptive systems (i.e. the numbers of dimensions of health and levels of severity within these), the methods of valuation [e.g. time trade-off (TTO), standard gamble (SG)], and the populations (e.g. general population, patients) used to value the health states within the descriptive systems. Although GPBMs are anchored at 1 (full health) and 0 (dead), they produce different health state utility values when completed by the same patient. Considerations when selecting a measure for use in a clinical trial include practicality, reliability, validity and responsiveness. Requirements of reimbursement agencies may impose additional restrictions on suitable measures for use in economic evaluations, such as the valuation technique (TTO, SG) or the source of values (general public vs. patients).

International Regulations and Recommendations for Utility Data for Health Technology Assessment.

Recommendations and guidelines for the collection, generation, source and usage of utility data for health technology assessment (HTA) vary across different countries, with no international consensus. Many international agencies generate their own guidelines providing details on their preferred methods for HTA submissions, and there is variability in both what they recommend and the clarity and amount of detail provided in their guidelines. This article provides an overview of international regulations and recommendations for utility data in HTA for a selection of key HTA countries: Australia, Canada, France, Germany, the Netherlands, Spain (Catalonia), Sweden and the UK (England/Wales and Scotland). International guidelines are typically clear and detailed for the selection of countries assessed regarding the source description of health states (e.g. generic preference-based measure) and who should provide preference weights for these health states (e.g. general population for own country). Many guidelines specify the use of off-the-shelf generic preference-based measures, and some further specify a measure, such as EQ-5D. However, international guidelines are either unclear or lack detailed guidance regarding the collection (e.g. patients report own health), source (e.g. clinical trial) and usage (e.g. adjusting for comorbidities) of utility values. It is argued that there is a need for transparent and detailed international guidelines on utility data recommendations to provide decision makers with the best possible evidence. Where this is not possible it is recommended that best practice should be used to inform the collection, source and usage of utility values in HTA.

Oncology drugs for orphan indications: how are HTA processes evolving for this specific drug category?

Orphan drugs (ODs) are intended for the diagnosis, prevention, or treatment of rare diseases. Many cancer subtypes, including all childhood cancers, are defined as rare diseases, and over one-third of ODs are now intended to treat oncology indications. However, market access for oncology ODs is becoming increasingly challenging; ODs are prone to significant uncertainty around their cost-effectiveness, while payers must balance the need for these vital innovations with growing sensitivity to rising costs. The objective of this review was to evaluate different mechanisms that have been introduced to facilitate patient access to oncology ODs in five different countries (Australia, Canada, England, France, and Sweden), using eight oncology ODs and non-orphan oncology drugs as examples of their application. A targeted literature review of health technology assessment (HTA) agency websites was undertaken to identify country-specific guidance and HTA documentation for recently evaluated oncology ODs and non-orphan oncology drugs. None of these countries were found to have explicit HTA criteria for the assessment of ODs, and therefore, oncology ODs are assessed through the usual HTA process. However, distinct and additional processes are adopted to facilitate access to oncology ODs. Review of eight case-study drugs showed that these additional assessment processes were rarely used, and decisions were largely driven by proving cost-effectiveness using standard incremental cost-effectiveness ratio (ICER) thresholds. The predominant implication arising from this study is that application of standard HTA criteria to oncology ODs in many countries fails to take into account any uncertainties around their clinical- and cost-effectiveness, resulting in disparities in HTA reimbursement decisions based on differences in addressing or accepting uncertainty. In order to address this issue, HTA agencies should adopt a more flexible approach to cost-effectiveness, as typified by the Tandvårds-och Läkemedelsförmånsverket in Sweden, which takes into account the small patient numbers involved, limited budget impact, and high unmet medical needs.

The "Efficacy-Effectiveness Gap": Historical Background and Current Conceptualization.

BACKGROUND: The concept of the "efficacy-effectiveness gap" (EEG) has started to challenge confidence in decisions made for drugs when based on randomized controlled trials alone. Launched by the Innovative Medicines Initiative, the GetReal project aims to improve understanding of how to reconcile evidence to support efficacy and effectiveness and at proposing operational solutions. OBJECTIVES: The objectives of the present narrative review were 1) to understand the historical background in which the concept of the EEG has emerged and 2) to describe the conceptualization of EEG. METHODS: A focused literature review was conducted across the gray literature and articles published in English reporting insights on the EEG concept. The identification of different "paradigms" was performed by simple inductive analysis of the documents' content. RESULTS: The literature on the EEG falls into three major paradigms, in which EEG is related to 1) real-life characteristics of the health care system; 2) the method used to measure the drug's effect; and 3) a complex interaction between the drug's biological effect and contextual factors. CONCLUSIONS: The third paradigm provides an opportunity to look beyond any dichotomy between "standardized" versus "real-life" characteristics of the health care system and study designs. Namely, future research will determine whether the identification of these contextual factors can help to best design randomized controlled trials that provide better estimates of drugs' effectiveness.

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.

Cost-effectiveness analysis of immune-modulating nutritional support for gastrointestinal cancer patients.

BACKGROUND & AIM: Immune-modulating nutritional formula containing arginine, omega-3 fatty acids and nucleotides has been demonstrated to decrease complications and length of stay in surgical patients. This study aims at assessing the impact of immune-modulating formula on hospital costs in gastrointestinal cancer surgical patients in Switzerland. METHOD: Based on a previously published meta-analysis, the relative risks of overall and infectious complications with immune-modulating versus standard nutrition formula were computed. Swiss hospital costs of patients undergoing gastrointestinal cancer surgery were retrieved. A method was developed to compute the patients' severity level, not taking into account the complications from the surgery. Incremental costs of complications were computed for both treatment groups, and sensitivity analyses were carried out. RESULTS: Relative risk of complications with pre-, peri- and post-operative use of immune-modulating formula was 0.69 (95%CI 0.58-0.83), 0.62 (95%CI 0.53-0.73) and 0.73 (95%CI 0.35-0.96) respectively. The estimated average contribution of complications to the cost of stay was CHF 14,949 (€10,901) per patient (95%CI 10,712-19,186), independently of case's severity. Based on this cost, immune-modulating nutritional support decreased costs of hospital stay by CHF 1638 to CHF 2488 per patient (€1195-€1814). Net hospital savings were present for baseline complications rates as low as 5%. CONCLUSION: Immune-modulating nutritional solution is a cost-saving intervention in gastrointestinal cancer patients. The additional cost of immune-modulating formula are more than offset by savings associated with decreased treatment of complications.

Early enteral nutrition in critical illness: a full economic analysis using US costs.

PURPOSE: Although published meta-analyses demonstrate patient survival may be improved if enteral nutrition (EN) is provided to critically ill patients within 24 hours of injury or admission to the intensive care unit (ICU), these publications did not investigate the impact of early EN on measures of health care resource consumption and total costs. MATERIALS AND METHODS: From the perspective of the US acute care hospital system, a cost-effectiveness analysis was undertaken based on a large-scale Monte Carlo simulation (N = 1,000,000 trials) of a 1,000-patient stochastic model, developed using clinical outcomes and measures of resource consumption reported by published meta-analyses combined with cost distributions obtained from the published literature. The mean cost differences between early EN and standard care, along with respective 95% confidence intervals, were obtained using the percentile method. RESULTS AND CONCLUSION: THE PROVISION OF EARLY EN TO CRITICALLY ILL PATIENTS IS A DOMINANT TECHNOLOGY: Patient survival is significantly improved and total costs of care reduced meaningfully. Under conservative assumptions, the total costs of acute hospital care were reduced by US$14,462 per patient (95% confidence interval US$5,464 to US$23,669). These results were robust, with all sensitivity analyses demonstrating significant savings attributable to the use of early EN, including sensitivity analysis conducted using European cost data.

Immunonutrition for patients undergoing elective surgery for gastrointestinal cancer: impact on hospital costs.

BACKGROUND: Oral or enteral dietary supplementation with arginine, omega 3 fatty acids and nucleotides (known as immunonutrition) significantly improve outcomes in patients undergoing elective surgery. The objective of the study was to determine the impact on hospital costs of immunonutrition formulas used in patients undergoing elective surgery for gastrointestinal cancer. METHODS: US hospital costs of stay with and without surgical infectious complications, and average cost per day in the hospital for patients undergoing elective surgery for gastrointestinal cancer were estimated using data from the Healthcare Cost and Utilization Project's 2008 Nationwide Inpatient Sample. These costs were then used to estimate the impact of perioperative immunonutrition on hospital costs using estimates of reduction in infectious complications or length of stay from a meta-analysis of clinical trials in patients undergoing elective surgery for gastrointestinal cancer. Sensitivity of the results to changes in baseline complication rates or length of stay was tested. RESULTS: From the meta-analysis estimates, use of immunonutrition resulted in savings per patient of $3,300 with costs based on reduction in infectious complication rates or $6,000 with costs based on length of hospital stay. Cost savings per patient were present for baseline complication rates above 3.5% or when baseline length of stay and infectious complication rates were reduced to reflect recent US data for those with upper and lower GI elective cancer surgery (range, $1,200 to $6,300). CONCLUSIONS: Use of immunonutrition for patients undergoing elective surgery for gastrointestinal cancer is an effective and cost-saving intervention.