A Comparison of Preference-Based, Generic and Disease-Specific Health-Related Quality of Life in Pediatric Inflammatory Bowel Disease.

Objective: Generic preference-based HRQOL assessments used expressly for economic evaluation have not been examined in pediatric Crohn's disease (CD) and ulcerative colitis (UC). The objective was to further assess the construct validity of preference-based HRQOL measures in pediatric IBD by comparing the Child Health Utility 9 Dimensions (CHU9D) and Health Utilities Index (HUI) to the disease-specific IMPACT-III and to the generic PedsQL in children with CD and with UC. Methods: The CHU9D, HUI, IMPACT-III and/or PedsQL were administered to Canadian children aged 6 to 18 years with CD and UC. CHU9D total and domain utilities were calculated using adult and youth tariffs. HUI total and attribute utilities were determined for the HUI2 and HUI3. Total scores for IMPACT-III and PedsQL were determined. Spearman correlations were calculated between generic preference-based utilities and the IMPACT-III and PedsQL scores. Results: The questionnaires were administered to 157 children with CD and 73 children with UC. Moderate to strong correlations were observed between the CHU9D, HUI2, HUI3 and the disease-specific IMPACT-III or generic PedsQL. As hypothesized, domains with similar constructs demonstrated stronger correlations, such as the Pain and Well-being domains. Conclusions: While all questionnaires were moderately correlated with the IMPACT-III and PedsQL questionnaires, the CHU9D using youth tariffs and the HUI3 were most strongly correlated and would be suitable choices to generate health utilities for children with CD or UC for the purpose of economic evaluation of treatments in pediatric IBD.

A comparison of the Child Health Utility 9D and the Health Utilities Index for estimating health utilities in pediatric inflammatory bowel disease.

PURPOSE: Health utilities are challenging to ascertain in children and have not been studied in pediatric Crohn's disease (CD) and ulcerative colitis (UC). The objective was to assess discriminative validity by comparing utilities elicited using the Child Health Utility-9 Dimension (CHU9D) to the Health Utilities Index (HUI) across multiple disease activity scales in pediatric UC and CD. METHODS: Preference-based instruments were administered to 188 children with CD and 83 children with UC aged 6 to 18 years. Utilities were calculated using CHU9D adult and youth tariffs, and HUI2 and HUI3 algorithms in children with inactive (quiescent) and active (mild, moderate, and severe) disease. Differences between instruments, tariff sets and disease activity categories and were tested statistically. RESULTS: In CD and UC, all instruments detected significantly higher utilities for inactive compared to active disease (p < 0.05). Mean utilities for quiescent disease ranged from 0.810 (SD 0.169) to 0.916 (SD 0.121) in CD and from 0.766 (SD 0.208) to 0.871 (SD 0.186) in UC across instruments. Active disease mean utilities ranged from 0.694 (SD 0.212) to 0.837 (SD 0.168) in CD and from 0.654 (SD 0.226) to 0.800 (SD 0.128) in UC. CONCLUSION: CHU9D and HUI discriminated between levels of disease activity in CD and UC regardless of the clinical scale used, with the CHU9D youth tariff most often displaying the lowest utilities for worse health states. Distinct utilities for different IBD disease activity states can be used in health state transition models evaluating the cost-effectiveness of treatments for pediatric CD and UC.

Infliximab Pricing in International Economic Evaluations in Inflammatory Bowel Disease to Inform Biologic and Biosimilar Access Policies: A Systematic Review.

Background. Policies mandating the use of lower cost biosimilars in patients with inflammatory bowel disease (IBD) have created concerns for patients who prefer their original biologic. Purpose. To inform the cost-effectiveness of biosimilar infliximab treatment in IBD by systematically reviewing the effect of infliximab price variation on cost-effectiveness for jurisdictional decision making. Data Sources. MEDLINE, Embase, Healthstar, Allied and Complementary Medicine, Joanna Briggs Institute EBP Database, International Pharmaceutical Abstracts, Health and Psychosocial Instruments, Mental Measurements Yearbook citation databases, PEDE, CEA registry, HTA agencies. Study Selection. Economic evaluations of infliximab for adult or pediatric Crohn's disease and/or ulcerative colitis published from 1998 through 2019 in which drug price was varied in sensitivity analysis were included. Data Extraction. Study characteristics, main findings, and results of drug price sensitivity analyses were extracted. Studies were critically appraised. The cost-effective price of infliximab was determined based on the stated willingness-to-pay (WTP) thresholds for each jurisdiction. Data Synthesis. Infliximab price was examined in sensitivity analysis in 31 studies. Infliximab showed favorable cost-effectiveness at a price ranging from CAD $66 to $1,260 per vial, depending on jurisdiction. A total of 18 studies (58%) demonstrated cost-effectiveness ratios above the jurisdictional WTP threshold. Limitations. Drug prices were not always reported separately, WTP thresholds varied, and funding sources were not consistently reported. Conclusion. Despite the high cost of infliximab, few economic evaluations examined price variation, limiting the ability to infer the effects of biosimilar introduction. Alternative pricing strategies and access to treatment could be considered to enable IBD patients to maintain access to their current medications. Highlights: In an effort to reduce public drug expenditures, Canadian and other jurisdictional drug plans have mandated the use of lower cost, but similarly effective, biosimilars in patients with newly diagnosed inflammatory bowel disease or require a nonmedical switch for established patients. This switch has created concerns for patients and clinicians who want to maintain the ability to make treatment decisions and remain with the original biologic.It is customary for economic evaluations to assess the robustness of results to variations in high-cost items such as medications. In the absence of economic evaluations of biosimilars, examining biologic drug price in sensitivity analysis provides insight into the cost-effectiveness of biosimilar alternatives. A total of 31 economic evaluations of infliximab for the treatment of inflammatory bowel disease varied the infliximab price in sensitivity analysis.The infliximab price deemed to be cost-effective within each study ranged from CAD $66 to CAD $1,260 per 100-mg vial. A total of 18 studies (58%) demonstrated an incremental cost-effectiveness ratio above the jurisdictional willingness-to-pay threshold. If policy decisions are based on price, then originator manufacturers could consider reducing the price or negotiating alternative pricing models to enable patients with inflammatory bowel disease to remain on their current medications.

Considerations for developing regulations for direct-to-consumer genetic testing: a scoping review using the 3-I framework.

Direct-to-consumer (DTC) genetic testing exists largely outside of any regulatory schemes, and studies providing a comprehensive overview of the ethical, social, legal, and technological considerations for regulating these types of technologies are lacking. This paper uses the 3-I framework for policy analysis to analyze the ideas, interests, and institutions relevant to policy development for DTC genetic testing in North America and internationally. A scoping review was conducted. Citation databases were searched for papers addressing the ethical, social, legal, and technological implications of DTC genetic testing; stakeholder perspectives on and experiences with DTC genetic testing; or the effect of such testing on the healthcare system. Ninety-nine publications, organizational reports, governmental documents, or pieces of legislation were included. The ideas included are autonomy, informed decision making, privacy, and clinical validity and utility. The interests discussed are those of the public and healthcare providers. The institutions included are regulatory organizations such as the Food and Drug Administration in the United States, laws governing the implementation or delivery of genetic testing in general, and legislation created to protect against genetic discrimination. This analysis clarifies the ethical, social, legal, and technological issues of DTC genetic testing regulation. This information can be used by policy makers to develop or strengthen regulations for DTC genetic testing such as requiring an assessment of the clinical validity of tests before they become publicly available, controlling how tests are marketed, and stipulating requirements for healthcare provider involvement and informed consent.

The Clinician-reported Genetic testing Utility InDEx (C-GUIDE): Preliminary evidence of validity and reliability.

PURPOSE: Demonstrating the clinical utility of genetic testing is fundamental to clinical adoption and reimbursement, but standardized definitions and measurement strategies for this construct do not exist. The Clinician-reported Genetic testing Utility InDEx (C-GUIDE) offers a novel measure to fill this gap. This study assessed its validity and inter-rater reliability. METHODS: Genetics professionals completed C-GUIDE after disclosure of test results to patients. Construct validity was assessed using regression analysis to measure associations between C-GUIDE and global item scores as well as potentially explanatory variables. Inter-rater reliability was assessed by administering a vignette-based survey to genetics professionals and calculating Krippendorff's α. RESULTS: On average, a 1-point increase in the global item score was associated with an increase of 3.0 in the C-GUIDE score (P < .001). Compared with diagnostic results, partially/potentially diagnostic and nondiagnostic results were associated with a reduction in C-GUIDE score of 9.5 (P < .001) and 10.2 (P < .001), respectively. Across 19 vignettes, Krippendorff's α was 0.68 (95% CI: 0.63-0.72). CONCLUSION: C-GUIDE showed acceptable validity and inter-rater reliability. Although further evaluation is required, C-GUIDE version 1.2 can be useful as a standardized approach to assess the clinical utility of genetic testing.

Imputing missing patient-level data and propensity score matching in cost-effectiveness analysis in Crohn's disease.

OBJECTIVES: The effect of imputing missing data followed by propensity score analysis on the incremental cost-effectiveness ratio (ICER) in a cost-effectiveness analysis is unknown. The objective was to compare alternative approaches in grouping data following imputation and prior to calculating propensity scores for use in economic evaluation. METHODS: Patient-level data from an observational study of 573 children with Crohn's disease were used in a microsimulation model to determine the incremental cost of early anti-tumor necrosis factor-α treatment compared to standard care per remission week gained. Multiple imputation of a missing covariate followed by propensity score matching to create comparator groups was approached in two ways. The Within approach calculated propensity scores on each imputed dataset separately, while the Across method averaged propensity scores to create one matched population resulting in multiple sets of health state transition probabilities. RESULTS: The incremental cost per remission week gained ranged from CAD$2,236 to CAD$12,464 (mean CAD$4,266) with Within datasets and was CAD$4,679 per remission week gained with the Across dataset. CONCLUSION: Imputation of missing patient-level data and propensity score analysis increases methodological uncertainty in cost-effectiveness analysis. The present study indicated that the Across approach may be less cumbersome, and slightly reduce bias and variance.

An Assessment of the Validity and Reliability of the Pediatric Child Health Utility 9D in Children with Inflammatory Bowel Disease.

Health utilities relevant to children are lacking, compromising health funding and policy decisions for children. The Child Health Utility 9D (CHU9D) is a recently developed preference-based health utility instrument designed for use in children. The objective was to examine the validity of the CHU9D in a cohort of 285 Canadian children aged 6.5 to 18 years of age with Crohn's disease (CD) and ulcerative colitis (UC), (collectively inflammatory bowel disease (IBD)). The correlation and agreement between paired CHU9D and Health Utility Index (HUI) assessments were determined with Spearman coefficients and Bland-Altman levels of agreement. Total and domain utilities were calculated for the CHU9D using Australian adult and youth tariffs. Algorithms for HUI2 and HUI3 were used. Domain correlations were determined between domains with expected overlap between instruments. In CD and in UC, correlations between CHU9D, HUI2, and HUI3 utilities ranged between 0.62 to 0.67 and 0.67 to 0.69, respectively (p < 0.05). CHU9D utilities were lower using youth tariffs compared to adult tariffs. A large range in health utilities suggested a heterogeneous quality of life. The CHU9D is a good option for preference-based utility measurement in pediatric IBD. Additional research is required to derive pediatric tariffs to conduct economic evaluation in children.

Cost-effectiveness and Clinical Outcomes of Early Anti-Tumor Necrosis Factor-α Intervention in Pediatric Crohn's Disease.

BACKGROUND: Anti-tumor necrosis factor-α (anti-TNF-α) treatments are increasingly used to treat pediatric Crohn's disease, even without a prior trial of immunomodulators, but the cost-effectiveness of such treatment algorithms has not been formally examined. Drug plan decision-makers require evidence of cost-effectiveness to inform funding decisions. The objective was to assess the incremental cost-effectiveness of early intervention with anti-TNF-α treatment vs a conventional step-up strategy per steroid-free remission-week gained from public health care and societal payer perspectives over 3 years. METHODS: A probabilistic microsimulation model was constructed for children with newly diagnosed moderate to severe Crohn's disease receiving anti-TNF-α treatment and concomitant treatments within the first 3 months of diagnosis compared with children receiving standard care consisting of steroids and/or immunomodulators with the possibility of anti-TNF-α treatment after 3 months of diagnosis. A North American multicenter observational study with 360 patients provided input into clinical outcomes and health care resource use. RESULTS: Early intervention with anti-TNF-α treatment was more costly, with an incremental cost of CAD$31,112 (95% confidence interval [CI], $2939-$91,715), and more effective, with 11.3 more weeks in steroid-free remission (95% CI, 10.6-11.6) compared with standard care, resulting in an incremental cost per steroid-free remission-week gained of CAD$2756 from an Ontario public health care perspective and CAD$2968 from a societal perspective. The incremental cost-effectiveness ratio was sensitive to the price of infliximab. CONCLUSIONS: The results suggest that although early anti-TNF-α was not cost-effective, it was clinically beneficial. These findings, along with other randomized controlled trial evidence, may inform formulary decision-making.

The 3-I framework: a framework for developing public policies regarding pharmacogenomics (PGx) testing in Canada.

The 3-I framework of analyzing the ideas, interests, and institutions around a topic has been used by political scientists to guide public policy development. In Canada, there is a lack of policy governing pharmacogenomics (PGx) testing compared to other developed nations. The goal of this study was to use the 3-I framework, a policy development tool, and apply it to PGx testing to identify and analyze areas where current policy is limited and challenges exist in bringing PGx testing into wide-spread clinical practice in Canada. A scoping review of the literature was conducted to determine the extent and challenges of PGx policy implementation at federal and provincial levels. Based on the 3-I analysis, contentious ideas related to PGx are (i) genetic discrimination, (ii) informed consent, (iii) the lack of knowledge about PGx in health care, (iv) the value of PGx testing, (v) the roles of health care workers in the coordination of PGx services, and (vi) confidentiality and privacy. The 3-I framework is a useful tool for policy makers, and applying it to PGx policy development is a new approach in Canadian genomics. Policy makers at every organizational level can use this analysis to help develop targeted PGx policies.

Cost-Effectiveness Analysis Comparing Pre-diagnosis Autism Spectrum Disorder (ASD)-Targeted Intervention with Ontario's Autism Intervention Program.

Novel management strategies for autism spectrum disorder (ASD) propose providing interventions before diagnosis. We performed a cost-effectiveness analysis comparing the costs and dependency-free life years (DFLYs) generated by pre-diagnosis intensive Early Start Denver Model (ESDM-I); pre-diagnosis parent-delivered ESDM (ESDM-PD); and the Ontario Status Quo (SQ). The analyses took government and societal perspectives to age 65. We assigned probabilities of Independent, Semi-dependent or Dependent living based on projected IQ. Costs per person (in Canadian dollars) were ascribed to each living setting. From a government perspective, the ESDM-PD produced an additional 0.17 DFLYs for $8600 less than SQ. From a societal perspective, the ESDM-I produced an additional 0.53 DFLYs for $45,000 less than SQ. Pre-diagnosis interventions targeting ASD symptoms warrant further investigation.