Can the EVIDEM Framework Tackle Issues Raised by Evaluating Treatments for Rare Diseases: Analysis of Issues and Policies, and Context-Specific Adaptation.

BACKGROUND: The multiplicity of issues, including uncertainty and ethical dilemmas, and policies involved in appraising interventions for rare diseases suggests that multicriteria decision analysis (MCDA) based on a holistic definition of value is uniquely suited for this purpose. The objective of this study was to analyze and further develop a comprehensive MCDA framework (EVIDEM) to address rare disease issues and policies, while maintaining its applicability across disease areas. METHODS: Specific issues and policies for rare diseases were identified through literature review. Ethical and methodological foundations of the EVIDEM framework v3.0 were systematically analyzed from the perspective of these issues, and policies and modifications of the framework were performed accordingly to ensure their integration. RESULTS: Analysis showed that the framework integrates ethical dilemmas and issues inherent to appraising interventions for rare diseases but required further integration of specific aspects. Modification thus included the addition of subcriteria to further differentiate disease severity, disease-specific treatment outcomes, and economic consequences of interventions for rare diseases. Scoring scales were further developed to include negative scales for all comparative criteria. A methodology was established to incorporate context-specific population priorities and policies, such as those for rare diseases, into the quantitative part of the framework. This design allows making more explicit trade-offs between competing ethical positions of fairness (prioritization of those who are worst off), the goal of benefiting as many people as possible, the imperative to help, and wise use of knowledge and resources. It also allows addressing variability in institutional policies regarding prioritization of specific disease areas, in addition to existing uncertainty analysis available from EVIDEM. CONCLUSION: The adapted framework measures value in its widest sense, while being responsive to rare disease issues and policies. It provides an operationalizable platform to integrate values, competing ethical dilemmas, and uncertainty in appraising healthcare interventions.

United States-based practice patterns and resource utilization in advanced neuroendocrine tumor treatment.

AIM: To assess advanced neuroendocrine tumor (NET) treatment patterns and resource utilization by tumor progression stage and tumor site in the United States. METHODS: United States Physicians meeting eligibility criteria were provided with online data extraction forms to collect patient chart data on recent NET patients. Resource utilization and treatment pattern data were collected over a baseline period (after diagnosis and before tumor progression), as well as initial and secondary progression periods, with progression defined according to measureable radiographic evidence of tumor progression. Resource categories used in the analysis include: Treatments (e.g., surgery, chemotherapy, radiotherapy, targeted therapies), hospitalizations and physician visits, diagnostic tests (biomarkers, imaging, laboratory tests). Comparisons between categories of resource utilization and tumor progression status were examined using univariate (by tumor site) and multivariate analyses (across all tumor sites). RESULTS: Fifty-five physicians were included in the study and completed online data extraction forms using the charts of 110 patients. The physician sample showed a relatively even distribution for those affiliated with academic versus community hospitals (46% vs 55%). Forty (36.3%) patients were reported to have pancreatic NET (pNET), while 70 (63.6%) patients had gastrointestinal tract (GI)/Lung as the primary NET site. Univariate analysis showed the proportion of patients hospitalized increased from 32.7% during baseline to 42.1% in the progression stages. While surgeries were performed at similar proportions overall at baseline and progression, pNET patients, were more likely than GI/Lung NET patients to have undergone surgery during the baseline (33.3% vs 25.0%) and any progression periods (26.7% vs 23.4%). While peptide-receptor radionuclide and targeted therapy utilization was low across NET types and tumor stages, GI/Lung types exhibited greater utilization of these technologies compared to pNET. Chemotherapy utilization was also greater among GI/Lung types. Multivariate analysis results demonstrated that patients in first progression period were over 3 times more likely to receive chemotherapy when compared to baseline (odds ratio: 3.31; 95%CI: 1.46-7.48, P = 0.0041). Further, progression was associated with a greater likelihood of having a study physician visit [relative risk (RR): 1.54; 95%CI: 1.10-2.17, P = 0.0117], and an increased frequency of other physician visits (RR: 1.84; 95%CI: 1.10-3.10, P = 0.0211). CONCLUSION: Resource utilization in advanced NET in the United States is significant overall and data suggests progression has an impact on resource utilization regardless of NET tumor site.

Key issues in addressing the clinical and humanistic burden of short bowel syndrome in the US.

BACKGROUND: The purpose of this analysis was to provide a concise report of the literature on the burden of intestinal failure associated with short bowel syndrome (SBS-IF) in adults, focused on clinical and humanistic issues important to clinicians and payers. SCOPE: A literature search was performed using the National Library of Medicine PubMed database ( http://www.ncbi.nlm.nih.gov/pubmed ) with the search term 'short bowel syndrome' limited to adult populations and English-language reports published from January 1, 1965, to January 18, 2013. Citations were assessed for relevance and excluded articles focused on single case studies, colon fermentation, absorption of medications with PN/IV, surgical technique, mesenteric artery complications/surgery, and transplantation focus. Additional hand searches were performed using the terms 'short bowel syndrome' AND 'cost', and 'home parenteral nutrition' AND 'cost', along with the exclusion criteria described above. FINDINGS: Despite advances in management in recent decades, SBS-IF continues to carry a high burden of morbidity and mortality. In the absence of sufficient intestinal adaptation following resection, many patients remain dependent on long-term parenteral nutrition and/or intravenous fluids (PN/IV). Although potentially life saving, PN/IV is costly, invasive, and associated with numerous complications and deleterious effects on health and quality of life. Surgical interventions, especially intestinal transplantation, are costly and are associated with substantial morbidity and high mortality. New therapies, which show promise in promoting intestinal rehabilitation and reducing dependence on PN/IV therapy, are the subject of active research. CONCLUSIONS: Overall, the available literature suggests that although SBS-IF affects a relatively small population, the clinical and humanistic burden is significant, and there is an unmet need for effective therapeutic options that target the underlying problem of inadequate absorptive capacity of the remaining intestine. Consequently, many patients with SBS-IF remain dependent on long-term PN/IV support, adding to the burden imposed by the underlying disorder.

International practice patterns and resource utilization in the treatment of neuroendocrine tumors.

OBJECTIVES: This study compared resource use and practice patterns in patients with advanced neuroendocrine tumors (NETs) on disease progression, across countries, and by tumor type. METHODS: Physicians in the United States, United Kingdom, Germany, France, Brazil, and Italy completed data extraction forms to extract chart data of patients with NET relating to health care resource utilization and treatment practice. Data were assessed in a cross-sectional manner, by country, and by NET subtype. Univariate and multivariate analyses were performed to compare categories of resource use by disease progression status. RESULTS: A total of 197 physicians provided data on 394 patients. Overall resource utilization was high across tumor types, countries, and progression. Nearly half of all patients received chemotherapy (49%); moreover, high rates of hospitalization (65%), surgery (47%), and use of somatostatin analog (77%) were observed, with lower rates of peptide receptor radionuclide therapy (10%) and targeted therapies (6%). These patterns were consistent across gastrointestinal tract/lung NET and pancreatic NET. However, a certain variation in resource utilization was observed across countries. Disease progression was associated with increasing utilization of chemotherapy, hospitalization, and targeted therapy. CONCLUSIONS: Advanced NET is associated with significant resource use across subtypes and countries, and resource utilization is likely to increase on disease progression. There remains an unmet need for therapeutic options after disease progression.

An adjusted indirect comparison of everolimus and sorafenib therapy in sunitinib-refractory metastatic renal cell carcinoma patients using repeated matched samples.

OBJECTIVE: To date, no trial data exist comparing treatment outcomes for everolimus versus sorafenib. The current analysis indirectly compares the overall survival (OS) benefit of everolimus and sorafenib as second-line treatment options. RESEARCH DESIGN AND METHODS: A single-arm sorafenib study is selected as a basis to match an everolimus sunitinib-refractory subpopulation of the RECORD-1 trial. Only patients with clear cell histology are included. An adjusted matching approach is taken where 1000 repeated random samples matched to the sorafenib population on risk score distribution are produced, and a 95% CI around the mean of all sampled median OS is generated. MAIN OUTCOME MEASURES: The main outcome measures include adjusted median OS and progression-free survival. RESULTS: In all, 45 clear cell histology sorafenib patients and 1000 samples of N=41 sunitinib-refractory everolimus patients are considered for analysis. After adjusted matching, the estimated median OS benefit is 32.0 [corrected] weeks (95% CI: 22, 64) and 81.5 weeks (95% CI:78, 86) for sorafenib and everolimus patients, respectively. CONCLUSION: Results suggest that sunitinib-refractory metastatic renal cell carcinoma patients treated with everolimus may experience significantly improved OS outcomes compared to those treated with sorafenib. However, because this is not a randomized controlled trial, the results should be interpreted as those from an observational study.