scholarly journals Periviable Breech Delivery Decision Analysis

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Makayla Kirksey ◽  
Brownsyne Tucker Edmonds
Keyword(s):  
Maternal Morbidity ◽  
Mode Of Delivery ◽  
Sensitivity Analyses ◽  
Extensive Literature ◽  
Health State ◽  
Health States ◽  
Severe Morbidity ◽  
Breech Delivery ◽  
Risk Estimates ◽  
Life Years

Background/Objective: The optimal mode of delivery (MOD) for malpresentation in periviable deliveries (22-24 weeks), remains a source of debate. Neonatal and maternal complications can arise from both vaginal (VD) and cesarean delivery (CD), and the threat of maternal morbidity extends to subsequent pregnancies. It has been difficult to compare these risks while counseling patients about MOD options, so we sought to create a decision tree that maps probable outcomes associated with breech deliveries at 23- and 24-weeks’ gestation, as well as complications posed for subsequent pregnancies.     Methods: An extensive literature review was conducted to identify risk estimates of periviable maternal and neonatal outcomes, along with elective repeat CD (ERCD) and trial of labor after cesarean (TOLAC) for subsequent pregnancies. Probabilities were inputted into TreeAge software, starting with primary maternal health states that may result from CD and VD – “death”, “hysterectomy”, or “no hysterectomy”, followed by the probability of neonatal health states– “death”, “severe morbidity”, or “no severe morbidity”. The likelihood of placenta previa or normal placenta was considered for subsequent pregnancies. We factored in the possibility of ERCD or TOLAC and the associated maternal and neonatal risks for each.      Results: Final design of the tree is complete and risk estimates have been inputted. Primary analysis and sensitivity analyses are planned for August 2021. Ultimately, we will also be able to use measured utility values to calculate quality adjusted life years (QALYs) for each health state.      Conclusion and Clinical Impact: Whether CD or VD is optimal for breech presentation in periviable delivery is influenced by a complex array of factors, including future reproductive plans and maternal values related to potential neonatal and maternal morbidity and mortality. Quantifying risks associated with each MOD will aid providers in their efforts to help families make informed decisions and reduce morbidity across the reproductive lifespan.  

scholarly journals Cost-effectiveness of Chloride-liberal versus Chloriderestrictive Intravenous Fluids among Patients Hospitalized in the United States

10.36469/9829 ◽  
2016 ◽  
Vol 4 (1) ◽  
pp. 90-102
Author(s):  
Louise Perrault ◽  
Dilip Makhija ◽  
Idal Beer ◽  
Suzanne Laplante ◽  
Sergio Iannazzo ◽  
...  
Keyword(s):  
Cost Effectiveness ◽  
Decision Tree ◽  
Markov Model ◽  
The United States ◽  
Sensitivity Analyses ◽  
Major Surgery ◽  
Health State ◽  
Health States ◽  
Life Years ◽  
The Us

Background: Patients developing acute kidney injury (AKI) during critical illness or major surgery are at risk for renal sequelae such as costly and invasive acute renal replacement therapy (RRT) and chronic dialysis (CD). Rates of renal injury may be reduced with use of chloride-restrictive intravenous (IV) resuscitation fluids instead of chloride-liberal fluids. Objectives: To compare the cost-effectiveness of chloride-restrictive versus chloride-liberal crystalloid fluids used during fluid resuscitation or for the maintenance of hydration among patients hospitalized in the US for critical illnesses or major surgery. Methods: Clinical outcomes and costs for a simulated patient cohort (starting age 60 years) receiving either chloride-restrictive or chloride-liberal crystalloids were estimated using a decision tree for the first 90-day period after IV fluid initiation followed by a Markov model over the remainder of the cohort lifespan. Outcomes modeled in the decision tree were AKI development, recovery from AKI, progression to acute RRT, progression to CD, and death. Health states included in the Markov model were dialysis free without prior AKI, dialysis-free following AKI, CD, and death. Estimates of clinical parameters were taken from a recent meta-analysis, other published studies, and the US Renal Data System. Direct healthcare costs (in 2015 USD) were included for IV fluids, RRT, and CD. US-normalized health-state utilities were used to calculate quality-adjusted life years (QALYs). Results: In the cohort of 100 patients, AKI was predicted to develop in the first 90 days in 36 patients receiving chloride-liberal crystalloids versus 22 receiving chloride-restrictive crystalloids. Higher costs of chloride-restrictive crystalloids were offset by savings from avoided renal adverse events. Chloride-liberal crystalloids were dominant over chloride-restrictive crystalloids, gaining 93.5 life-years and 81.4 QALYs while saving $298 576 over the cohort lifespan. One-way sensitivity analyses indicated results were most sensitive to the relative risk for AKI development and relatively insensitive to fluid cost. In probabilistic sensitivity analyses with 1000 iterations, chloride-restrictive crystalloids were dominant in 94.7% of iterations, with incremental cost-effectiveness ratios below $50 000/QALY in 99.6%. Conclusions: This analysis predicts improved patient survival and fewer renal complications with chloriderestrictive IV fluids, yielding net savings versus chloride-liberal fluids. Results require confirmation in adequately powered head-to-head randomized trials.

Obinutuzumab and Chlorambucil Versus Chlorambucil Monotherapy for Treatment of Previously Untreated Chronic Lymphocytic Leukemia Where Fludarabine-Based Chemotherapy Is Considered Inappropriate: A Canadian Cost-Utility Analysis

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1288-1288 ◽  
Author(s):  
Heather Cameron ◽  
Melissa Thompson ◽  
John-Paul Marino ◽  
Michael Duong ◽  
Ursula Becker ◽  
...  
Keyword(s):  
Incremental Cost ◽  
Transition Probabilities ◽  
Cost Effective ◽  
Cost Utility ◽  
Lymphocytic Leukemia ◽  
Sensitivity Analyses ◽  
Health State ◽  
Utility Analysis ◽  
Health States ◽  
Life Years

Abstract BACKGROUND: In Canada, treatment options are limited for patients with chronic lymphocytic leukemia (CLL) where fludarabine-based regimens are considered inappropriate. For these patients, chlorambucil monotherapy is considered a standard treatment option. Obinutuzumab is a novel recombinant humanized and glycoengineered Type II anti-CD20 monoclonal antibody of the IgG1 isotype. Clinical data demonstrate that first line therapy with obinutuzumab + chlorambucil can improve progression-free survival (PFS) compared with chlorambucil alone in CLL patients ineligible for fludarabine-based chemotherapy (29.9 vs. 11.1 months; HR 0.18 (95% CI [0.14; 0.24]), p<0.0001). (Goede et al., 2014; Roche. Data on file; May 2014). Obinutuzumab + chlorambucil also demonstrated an overall survival (OS) benefit versus chlorambucil alone (HR for death, 0.47; 95% CI, 0.29 to 0.76; P=0.0014). (Goede et al., 2014; Roche. Data on file; May 2014). We conducted a cost-effectiveness and cost-utility analysis of obinutuzumab + chlorambucil versus chlorambucil monotherapy from a Canadian healthcare perspective. METHODS: A Markov model was created to estimate the cost-utility of the treatment with obinutuzumab + chlorambucil versus chlorambucil monotherapy over a ten-year time horizon in previously untreated CLL patients ineligible for fludarabine-based chemotherapy. The model simulated patients moving through three health states: “progression-free”, “progression”, and “death”, with all patients beginning in the progression-free state. The progression-free state was divided into sub health states; progression-free with therapy, and progression-free without therapy. Each health state was associated with a utility value and direct medical costs. (Roche. Data on file; April 2014) Transition probabilities from the progression-free health state to the progression state were determined by PFS collected in the CLL11 trial for obinutuzumab + chlorambucil and chlorambucil monotherapy arms (Roche. Data on file; May 2014). Patients who experienced disease progression transitioned to the progression health state where they received second-line therapy and ongoing supportive care. Transition probabilities from the progression-free health state to death were determined based on the treatment specific death rates observed in CLL11. Due to the lack of mature OS data from CLL11 the transition probabilities from the progressed health state to death were determined based on data from the CLL5 trial (Eichhorst et al., 2009). Resource use and costs were estimated using Canadian sources ($CAD 2014), and both costs and outcomes were discounted at 5% annually. The stability of model results was tested using one-way and probabilistic sensitivity analyses. RESULTS: Treatment with obinutuzumab + chlorambucil produced more life years and quality adjusted life years (QALYs) than treatment with chlorambucil alone. The incremental cost was $35,330 for an incremental life years gain (LYG) of 1.038 and an incremental QALY gain of 0.975 (Table 1). These result in an incremental cost per LYG ratio of $34,028 and an incremental cost per QALY gained of $36,246. The results of one-way sensitivity analyses indicated that the model was robust to changes in model inputs, with the most impactful parameters being time horizon, assumptions regarding survival, treatment duration, and exclusion of second-line therapies. A probabilistic sensitivity analysis resulted in a mean ICER of $35,370, with obinutuzumab + chlorambucil having a 94.3% chance of being cost-effective at a willingness to pay threshold of $50,000/QALY, and a 100% chance of being cost-effective at a willingness to pay threshold of $100,000/QALY and $150,000/QALY. Abstract 1288. Table 1. Ten year cost-effectiveness results Treatment Total Costs Total LYs Total QALYs Incremental Costs Incremental LYs Incremental QALYs Cost per LYG Cost per QALY Chlorambucil $22,417 3.971 2.546 Obinutuzumab + Chlorambucil $57,747 5.009 3.521 $35,330 1.038 0.975 $34,028 $36,246 CONCLUSIONS: The results of this analysis demonstrated that improvements in PFS and OS with obinutuzumab + chlorambucil translate into longer term gains in LYs and QALYs. From a Canadian healthcare perspective, first line treatment of CLL patients ineligible for fludarabine based therapies with obinutuzumab + chlorambucil is cost-effective with a cost-utility ratio of $36,246/QALY. Disclosures Cameron: Cornerstone Research Group: Employment. Thompson:Cornerstone Research Group: Employment. Marino:2Hoffmann-La Roche Limited : Employment. Duong:2Hoffmann-La Roche Limited : Employment. Becker:Roche: Employment. Wiesner:4Genentech, Inc. A Member of the Roche Group: Employment.

scholarly journals Valuation of the EQ-5D-3L in Russia

2021 ◽  
Author(s):  
Vitaly Omelyanovskiy ◽  
Nuriya Musina ◽  
Svetlana Ratushnyak ◽  
Tatiana Bezdenezhnykh ◽  
Vlada Fediaeva ◽  
...  
Keyword(s):  
Health Problems ◽  
Cost Utility ◽  
Economic Evaluations ◽  
Computer Assisted ◽  
Health State ◽  
Primary Analysis ◽  
Health States ◽  
Value Set ◽  
Model Combining ◽  
Life Years

Abstract Purpose The most widely used generic questionnaire to estimate the quality of life for yielding quality-adjusted life years in economic evaluations is EQ-5D. Country-specific population value sets are required to use EQ-5D in economic evaluations. The aim of this study was to establish an EQ-5D-3L value set for Russia. Methods A representative sample aged 18+ years was recruited from the Russia`s general population. Computer-assisted face–to–face interviews were conducted based on the standardized valuation protocol using EQ-Portable Valuation Technology. Population preferences were elicited utilizing both composite time trade-off (cTTO) and discrete choice experiment (DCE) techniques. To estimate the value set, a hybrid regression model combining cTTO and DCE data was used. Results A total of 300 respondents who successfully completed the interview were included in the primary analysis. 120 (40.0%) respondents reported no health problems of any dimension, and 56 (18.7%) reported moderate health problems in one dimension of the EQ‐5D‐3L. Median self-rated health using EQ‐VAS was 80 with IQR 70–90. Comparing cTTO and DCE-predicted values for 243 health states resulted in a similar pattern. This supports the use of hybrid models. The predicted value based on the preferred model for the worst health state “33333” was −0.503. Mobility dimension had the most significant impact on the utility decrement, and anxiety/depression had the lowest decrement. Conclusion Determining a Russian national value set may be considered the first step towards promoting cost-utility analysis use to increase comparability among studies and improve the transferability of healthcare decision-making in Russia.

scholarly journals Funding the New Biologics – CCOHTA Report on the Cost Effectiveness of Infliximab for Crohn’s Disease: Pearls and Pitfalls

2002 ◽  
Vol 16 (12) ◽  
pp. 877-879 ◽  
Author(s):  
John K Marshall
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Economic Analysis ◽  
Safety Data ◽  
Cost Utility ◽  
Sensitivity Analyses ◽  
State Transitions ◽  
Health State ◽  
Life Years ◽  
The Cost

The Canadian Coordinating Office for Health Technology Assessment (CCOHTA) published an economic analysis, using a Markov model, of infliximab therapy for Crohn’s disease that is refractory to other treatments. This was the first fully published economic analysis that addresses this treatment option. Health state transitions were based on data from Olmsted County, Minnesota, health state resource profiles were created using expert opinion and a number of assumptions were made when designing the model. The analysis was rigorous, the best available efficacy and safety data were used, state-of-the art sensitivity analyses were undertaken and an ‘acceptability curve‘ was constructed. The model found that infliximab was effective in increasing quality-adjusted life years when offered in a variety of protocols, but it was associated with high incremental cost utility ratios compared with usual care. The results should be interpreted, however, in view of a number of limitations. The time horizon for the analysis was short (one year), because of a lack of longer-term efficacy data, and might have led to an underestimation of the benefits from averting surgery. Because the analysis was performed from the perspective of a Canadian provincial ministry of health, only direct medical costs were considered. Patients with active Crohn’s disease are likely to incur significant indirect costs, which could be mitigated by this medication. The analysis should be updated as new data become available. Moreover, small changes in the cost of the medication could make the treatment cost effective, according to this model. Economic analyses, such as the one undertaken by the CCOHTA, cannot by themselves solve dilemmas in the allocation of limited health care resources, and other considerations must be included when formulating policy. This is especially important for patients with severe Crohn’s disease, who have significant disability and for whom few therapeutic options exist.

A quality-adjusted time without symptoms or toxicity (Q-TWiST) analysis comparing lapatinib plus capecitabine compared to capecitabine for metastatic breast cancer (MBC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 1026-1026 ◽  
Author(s):  
B. Sherrill ◽  
A. Allshouse ◽  
M. Amonkar ◽  
S. Stein
Keyword(s):  
Disease Progression ◽  
Randomized Study ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Sensitivity Analyses ◽  
Health State ◽  
Utility Analysis ◽  
Health States ◽  
Significant Difference

1026 Background: Data for this analysis is from a Phase III randomized study that was stopped early by the IDMC since a planned interim analysis demonstrated the primary endpoint had been achieved i.e. longer time to disease progression for patients taking lapatinib plus capecitabine (L+C) versus capecitabine (C) alone. The study included women with refractory advanced or ErbB2+ MBC who had received prior therapy which included anthracyclines, taxanes and trastumuzab. The Q-TWiST method was used to compare the trade-off between toxicities and delayed progression. Methods: The area under overall survival curves for each treatment group was partitioned into three health states: toxicity (TOX), time without toxicity or disease progression (TWiST), and the period until death or end of follow-up following disease progression (REL). TOX is time spent with grade ¾ adverse events (AEs) during progression-free survival (PFS) time. TWiST is the remaining time prior to progression in which no serious AEs were experienced. The utility-weighted sum of the mean health state durations was derived and treatment comparisons of Q-TWiST were made at varying combinations of the utility weights using a threshold utility analysis. Results: The ITT population included 399 subjects ages 26–83 [L+C group N=198, C group N=201]. Overall median survival was 67 weeks based on data through 3APR2006. There was not a significant difference between groups in mean duration of serious AEs prior to progression. (L+C 1.7 weeks, C 1.5 weeks). Using utility weights of 0.5 for both TOX and REL, i.e. counting 2 days of TOX or REL as 1 day of TWiST, resulted in a 7-week difference in quality-adjusted survival favoring L+C (p = 0.0013). The Q-TWiST difference was significant across an entire matrix of possible utility weights. Results were robust in sensitivity analyses including all AEs. An observed-utility analysis based on EQ-5D scores is in progress. Conclusions: The longer time to disease progression with L+C versus C was achieved without increased time with serious AEs, resulting in more quality-adjusted survival for patients. No significant financial relationships to disclose.

scholarly journals Cost-Effectiveness Analysis of Fourth- or Further-Line Ripretinib in Advanced Gastrointestinal Stromal Tumors

2021 ◽  
Vol 11 ◽  
Author(s):  
Weiting Liao ◽  
Huiqiong Xu ◽  
David Hutton ◽  
Qiuji Wu ◽  
Kexun Zhou ◽  
...  
Keyword(s):  
Overall Survival ◽  
Cost Effectiveness ◽  
Gastrointestinal Stromal Tumors ◽  
Cost Effective ◽  
Sensitivity Analyses ◽  
Health State ◽  
Lifetime Horizon ◽  
Stromal Tumors ◽  
Life Years ◽  
Health State Utilities

BackgroundThe INVICTUS trial assessed the efficacy and safety of ripretinib compared with placebo in the management of advanced gastrointestinal stromal tumors.MethodWe used a Markov model with three health states: progression-free disease, progression disease and death. We parameterized the model from time-to-event data (progression-free survival, overall survival) of ripretinib and placebo arms in the INVICTUS trial and extrapolated to a patient’s lifetime horizon. Estimates of health state utilities and costs were based on clinical trial data and the published literature. The outcomes of this model were measured in quality-adjusted life-years (QALYs), costs, and incremental cost-effectiveness ratios (ICERs). Uncertainty was tested via univariate and probabilistic sensitivity analyses.ResultsThe base-case model projected improved outcomes (by 0.29 QALYs) and additional costs (by $70,251) and yielded an ICER of $244,010/QALY gained for ripretinib versus placebo. The results were most sensitive to progression rates, the price of ripretinib, and health state utilities. The ICER was most sensitive to overall survival. When overall survival in the placebo group was lower, the ICER dropped to $127,399/QALY. The ICER dropped to $150,000/QALY when the monthly cost of ripretinib decreased to $14,057. Probabilistic sensitivity analyses revealed that ripretinib was the cost-effective therapy in 41.1% of simulations at the willingness-to-pay (WTP) threshold of $150,000.ConclusionAs the fourth- or further-line therapy in advanced gastrointestinal stromal tumors, ripretinib is not cost-effective in the US. Ripretinib would achieve its cost-effectiveness with a price discount of 56% given the present effectiveness.

scholarly journals Premedication Prior to Peg-Asparaginase Is Cost-Effective for Pediatric Leukemia Patients

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 7-7
Author(s):  
Meghan McCormick ◽  
Jillian Lapinski ◽  
Erika Friehling ◽  
Ken Smith
Keyword(s):  
High Risk ◽  
Hypersensitivity Reaction ◽  
Risk Model ◽  
Sensitivity Analyses ◽  
Health State ◽  
Pediatric Leukemia ◽  
Childhood All ◽  
Life Years ◽  
Standard Risk ◽  
Level Monitoring

Background: Asparaginase is a critical therapy component for childhood acute lymphoblastic leukemia (ALL). Hypersensitivity reactions and silent inactivation by neutralizing antibodies can lead to withholding further doses. Reactions occur in 10-20% of children receiving the commonly used, widely available pegylated asparaginase. The less immunogenic Erwinia asparaginase may allow continued administration, but requires more frequent dosing and is subject to limitations in availability. Inability to receive all recommended asparaginase doses decreases disease-free survival. Premedication with antihistamines, antipyretics and steroids decreases hypersensitivity reaction frequency, preventing the need for alternates. The cost-effectiveness of premedication strategies in childhood ALL is unclear. Methods: We used a Markov model to estimate strategy costs and quality-adjusted life years (QALYs) for two patient scenarios: a 3-year-old with standard-risk ALL receiving 2 asparaginase doses, and a 15-year-old with high-risk ALL receiving 7 asparaginase doses over a 5-year time horizon. Patients entering the model received premedication with serum asparaginase level monitoring, monitoring only, or no premedication/monitoring. Literature data were used for hypersensitivity reaction and silent inactivation risks following each asparaginase dose. Silent inactivation was not identified the non-monitoring strategy. Disease outcomes, therapy and associated additional care costs, and health state quality-of-life utilities were obtained from the literature and US databases. Evaluation took the societal perspective, with costs and effectiveness discounted at 3%/yr. Multiple sensitivity analyses were performed. Results: In both the standard-risk and high-risk analyses, premedication was the least costly strategy. In the standard-risk model, premedication with monitoring cost $4,586 less than monitoring alone, resulted in 8% fewer changes to Erwinia and 0.01 additional QALYs. It cost $1,993 less than no premedication/monitoring, resulted in 3% fewer changes and 0.08 additional QALYs. In the high-risk model, premedication cost $29,757 less than monitoring alone, resulted in 7% fewer medication changes and 0.01 fewer QALYS; thus, monitoring alone was expensive, costing &gt;$2 million/QALY gained compared to premedication and monitoring. Premedication cost $11,255 less than no premedication/monitoring, resulted in 2% fewer changes and 0.07 additional QALYs. Individual variation of all model inputs did not change the favorability of premedication and monitoring for either model. In probabilistic sensitivity analyses varying all parameters simultaneously over distributions 1000 times, premedication and monitoring was favored in &gt;86% of model iterations in both standard- and high-risk scenarios. Conclusion: Compared to other strategies, premedication use and asparaginase level monitoring in children with ALL is economically reasonable and potentially cost-saving. Disclosures No relevant conflicts of interest to declare.

How Significant Are “High” Correlations Between EQ-5D Value Sets?

2018 ◽  
Vol 38 (6) ◽  
pp. 635-645 ◽  
Author(s):  
Franz Ombler ◽  
Michael Albert ◽  
Paul Hansen
Keyword(s):  
Correlation Coefficients ◽  
Cost Utility ◽  
Health State ◽  
Health States ◽  
Life Years ◽  
Significance Levels ◽  
Related Quality ◽  
Health Related ◽  
Descriptive System ◽  
Value Sets

The calculation of quality-adjusted life years, as used for cost–utility analysis, depends on the availability of value sets representing people’s preferences with respect to health-related quality of life (HRQoL). A value set consists of HRQoL index values for all health states representable by the particular descriptive system used, of which the EQ-5D (EuroQoL, 5 Dimensions) is by far the most widely used. High correlation coefficients for EQ-5D value sets derived from different samples—across countries and/or using different valuation techniques—are conventionally interpreted as evidence that the people in the respective samples have similar HRQoL preferences. However, EQ-5D value sets—for both versions of the system (EQ-5D-3L and EQ-5D-5L)—contain many inherent rankings of health state values by design. By calculating correlation coefficients for value sets created from random data, we demonstrate that “high” coefficients are artifacts of these inherent rankings, such as median Pearson’s r = 0.783 for the EQ-5D-3L and 0.850 for the EQ-5D-5L instead of zero. Therefore, high correlation coefficients do not necessarily constitute evidence of meaningful associations in terms of similar HRQoL preferences. After calculating significance levels based on our simulations—available as an online resource for other researchers—we find that many high coefficients are not as significant as conventionally interpreted, whereas other coefficients are not significant. These “high” but insignificant correlations are in fact spurious.

scholarly journals Estimating the Relative Treatment Effect and Corresponding Cost-Effectiveness Estimates of Inotuzumab Ozogamicin Vs. Blinatumomab for Adults with Philadelphia Chromosome-Negative (Ph-) Relapsed/Refractory (R/R) B-Cell Acute Lymphoblastic Leukaemia (B-ALL) in the United Kingdom (UK)

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3427-3427 ◽  
Author(s):  
Simone Critchlow ◽  
Miranda Cooper ◽  
Ilse van Oostrum ◽  
Verna L Welch ◽  
T. Alexander Russell-Smith
Keyword(s):  
Cost Effectiveness ◽  
Cost Effective ◽  
Complete Response ◽  
Health State ◽  
Health States ◽  
Term Survival ◽  
Long Term Survival ◽  
Treatment Comparison ◽  
Life Years

Introduction: Inotuzumab ozogamicin (InO), is a novel anti-CD22 antibody-calicheamicin conjugate approved in R/R B-ALL due to its high hematologic remission rate (81%) based on the phase 3 INO-VATE trial comparing to investigators choice (IC). The TOWER trial demonstrated the efficacy and safety of blinatumomab (Blina) for treatment of Ph- B-ALL versus IC. The relative effectiveness of InO versus Blina was investigated by applying indirect treatment comparison (ITC) methods. A UK-based cost-effectiveness model (CEM) submitted to the Scottish Medicines Consortium (SMC) explored the impact of treatment differences with regard to mean life years (LY) gained and quality-adjusted life years (QALY). Methods: As R/R ALL is a terminal disease if left untreated, achievement of complete response/complete response with incomplete count recovery (CR/CRi) in conjunction with stem cell transplant (SCT) is essential for long-term survival. The three most important outcomes related to treatment are thus the level of response determined by CR/CRi, the rate of SCT, and overall survival (OS). Without potentially curative therapy such as SCT, there is no evidence to suggest long-term survival is possible. Therefore, to compare InO to Blina, comparisons of these outcomes were explored using patient-level data from the INO-VATE ALL trial and aggregate data from the TOWER trial. The CEM structure contained four health states categorising patients based on 'No CR/CRi & no SCT', 'CR/CRi and no SCT' and patients receiving SCT ('SCT/Post SCT') - with progression-free survival (PFS) and OS modelled within these states. States were clinically validated as relevant to treatment of the disease. Death was the fourth health state. Different methods were incorporated to allocate Blina patients to the respective health-states. For levels of response (CR/CRi) and SCT a matching-adjusted indirect comparison (MAIC) and a Bucher ITC were explored. As CR/CRi and SCT rates are not mutually exclusive, a multinomial ITC was also conducted. Once allocated into respective health states, OS and PFS were modelled. Three ITC methods were used to compare OS; a simulated treatment comparison (STC), MAIC and a standard network meta-analysis. In the absence of PFS data for Blina, PFS was assumed to have the same relative treatment effect as OS. Quality of life data within the model for the 'No CR/CRi & no SCT' and 'CR/CRi and no SCT' were informed from InO trial data, while SCT quality of life was informed from the literature with time-varying utilities. Costs were incorporated from a UK perspective using 2017 sources and were those submitted to the SMC. Results were annually discounted at 3.5%. Results: Health state proportions for Ph- InO patients were used as the basis to estimate corresponding Blina proportions and show 49.3% of patients treated with InO reach SCT. With higher odds for CR/CRi and SCT for InO, the ITC results consistently indicate Blina leads to lower proportions of patients receiving SCT (19.1-22.5%) and CR/CRi (25.2-33.3%). ITCs comparing OS outcomes for InO versus blinatumomab show negligible differences between treatments, consistently across the three methods. All combinations of the various methods were explored using the list price for both treatments. The results of the CEM ranged from 0.91-1.14 incremental QALYs for InO versus Blina, while LYs ranged from 2.03-2.59 resulting from higher rates of SCT. The incremental cost-effectiveness ratio (ICER) ranged from £3,700 to £7,010 for InO versus Blina. Extensive scenario analysis indicates that InO is a cost-effective option compared to Blina at a willingness to pay threshold of £20,000 per QALY. The SMC recommended InO as a cost-effective use of resources citing an ICER of £6,754 in the CEM when using the MAIC; InO was associated with a mean survival gain of &gt;29 months over Blina corresponding to this ICER. Conclusions: Outcomes from the ITC indicate that InO provides patients with a greater probability of achieving CR/CRi and/or receiving a subsequent SCT versus Blina. As CR/CRi followed by SCT are essential for long-term survival and potential cure, the mean OS gain in the model cited in the SMC recommendation is intuitive as it aligns with the superior CR/CRi and SCT odds ratios associated with InO. Further research is required to determine the long-term PFS and OS following SCT in R/R B-ALL, beyond what can be reliably captured within clinical trials. Disclosures Critchlow: BresMed Health Solutions Ltd.: Consultancy. Cooper:BresMed Health Solutions Ltd.: Consultancy. van Oostrum:Ingress Health: Employment; Pfizer: Consultancy; Merck: Consultancy; Janssen: Consultancy; AstraZeneca: Consultancy. Welch:Pfizer Inc: Employment, Equity Ownership. Russell-Smith:Pfizer: Employment, Equity Ownership.

scholarly journals Conducting a Time Trade-Off Study Alongside a Clinical Trial: A Case Study and Recommendations

2018 ◽  
Vol 3 (1) ◽  
pp. 5-20 ◽  
Author(s):  
Jing Shen ◽  
Sarah Hill ◽  
David Mott ◽  
Matthew Breckons ◽  
Luke Vale ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Health State ◽  
Health States ◽  
Trade Off ◽  
Life Years ◽  
Related Quality ◽  
Health Related ◽  
Health State Utilities

Abstract Time trade-off (TTO) is an established method in health economics to elicit and value individuals’ preferences for different health states. These preferences are expressed in the form of health-state utilities that are typically used to measure health-related quality of life and calculate quality-adjusted life-years in an economic evaluation. The TTO approach to directly elicit health-state utilities is particularly valuable when generic instruments (e.g. EQ-5D) may not fully capture changes in utility in a clinical trial. However, there is limited guidance on how a TTO study should be conducted alongside a clinical trial despite it being a valuable tool. We present an account of the design and development of a TTO study within a clinical trial as a case study. We describe the development of materials needed for the TTO interviews, the piloting of the TTO materials and interview process, and recommendations for future TTO studies. This paper provides a practical guide and reference for future applications of the TTO method alongside a clinical trial.

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