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      Cost-Effectiveness of Inotuzumab Ozogamicin Compared to Standard of Care Chemotherapy for Treating Relapsed or Refractory Acute Lymphoblastic Leukaemia Patients in Norway and Sweden

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          Abstract

          Objective

          The aim was to estimate the cost-effectiveness of inotuzumab ozogamicin (InO) versus standard of care chemotherapy (SoC) for adults with relapsed or refractory B cell acute lymphoblastic leukaemia (R/R ALL) in Sweden and Norway, and compare this to evaluations made by the health technology assessment (HTA) authorities Tandvårds- och läkemedelsförmånsverket (TLV) and the Norwegian Medicines Agency (NoMA).

          Materials and methods

          A partitioned survival model was developed to determine incremental cost-effectiveness ratios (ICERs) for InO versus SoC. Parametric survival models were fit to overall survival and progression-free survival Kaplan-Meier data from the INO-VATE ALL phase III trial. Two base cases were run using (1) Swedish and (2) Norwegian inputs (costs and discount rates). Core clinical inputs and utilities did not differ between countries. Analyses were then conducted to reflect the preferred assumptions of TLV and NoMA. Univariate and multivariate sensitivity analyses were performed.

          Results

          The base case deterministic ICERs for InO versus SoC were €16,219/quality-adjusted life years (QALY) in Sweden (probabilistic €19,415) and €44,405/QALY in Norway (probabilistic €47,305). The ICERs using our model but applying the preferred assumptions of TLV or NoMA were €74,061/QALY (probabilistic €77,484) and €59,391/QALY (probabilistic €63,632), respectively. Differences between our base cases and the ICERs with TLV and NoMA settings were mainly explained by the exclusion of productivity costs and use of pooled post-haematopoietic stem-cell transplant (post-HSCT) survival in Sweden and use of higher HSCT costs in Norway. All ICERs remained below the approximated willingness-to-pay thresholds. The probability of InO being cost-effective ranged from 77 to 99% versus SoC.

          Conclusions

          InO can likely be considered cost-effective versus SoC under our and the HTA-preferred settings.

          Supplementary Information

          The online version contains supplementary material available at 10.1007/s41669-021-00287-2.

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          Most cited references20

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          Inotuzumab Ozogamicin versus Standard Therapy for Acute Lymphoblastic Leukemia

          The prognosis for adults with relapsed acute lymphoblastic leukemia is poor. We sought to determine whether inotuzumab ozogamicin, an anti-CD22 antibody conjugated to calicheamicin, results in better outcomes in patients with relapsed or refractory acute lymphoblastic leukemia than does standard therapy.
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            Acute lymphoblastic leukaemia.

            Acute lymphoblastic leukaemia, a malignant disorder of lymphoid progenitor cells, affects both children and adults, with peak prevalence between the ages of 2 and 5 years. Steady progress in development of effective treatments has led to a cure rate of more than 80% in children, creating opportunities for innovative approaches that would preserve past gains in leukaemia-free survival while reducing the toxic side-effects of current intensive regimens. Advances in our understanding of the pathobiology of acute lymphoblastic leukaemia, fuelled by emerging molecular technologies, suggest that drugs specifically targeting the genetic defects of leukaemic cells could revolutionise management of this disease. Meanwhile, studies are underway to ascertain the precise events that take place in the genesis of acute lymphoblastic leukaemia, to enhance the clinical application of known risk factors and antileukaemic agents, and to identify treatment regimens that might boost the generally low cure rates in adults and subgroups of children with high-risk leukaemia.
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              flexsurv: A Platform for Parametric Survival Modeling in R.

              flexsurv is an R package for fully-parametric modeling of survival data. Any parametric time-to-event distribution may be fitted if the user supplies a probability density or hazard function, and ideally also their cumulative versions. Standard survival distributions are built in, including the three and four-parameter generalized gamma and F distributions. Any parameter of any distribution can be modeled as a linear or log-linear function of covariates. The package also includes the spline model of Royston and Parmar (2002), in which both baseline survival and covariate effects can be arbitrarily flexible parametric functions of time. The main model-fitting function, flexsurvreg, uses the familiar syntax of survreg from the standard survival package (Therneau 2016). Censoring or left-truncation are specified in 'Surv' objects. The models are fitted by maximizing the full log-likelihood, and estimates and confidence intervals for any function of the model parameters can be printed or plotted. flexsurv also provides functions for fitting and predicting from fully-parametric multi-state models, and connects with the mstate package (de Wreede, Fiocco, and Putter 2011). This article explains the methods and design principles of the package, giving several worked examples of its use.
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                Author and article information

                Contributors
                Alexander.Smith@pfizer.com
                Journal
                Pharmacoecon Open
                Pharmacoecon Open
                PharmacoEconomics Open
                Springer International Publishing (Cham )
                2509-4262
                2509-4254
                26 July 2021
                26 July 2021
                January 2022
                : 6
                : 1
                : 47-62
                Affiliations
                [1 ]Ingress-Health, Weena 316-318, 3012 NJ Rotterdam, The Netherlands
                [2 ]GRID grid.410513.2, ISNI 0000 0000 8800 7493, Pfizer Inc, ; New York, USA
                [3 ]Pfizer Innovations AB, Stockholm, Sweden
                [4 ]Pfizer Inc, Oslo, Norway
                Author information
                http://orcid.org/0000-0003-1445-8138
                Article
                287
                10.1007/s41669-021-00287-2
                8807767
                34309818
                fe977cb0-7a74-4a06-84e6-c4c6eea277db
                © The Author(s) 2021

                Open AccessThis article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/.

                History
                : 27 June 2021
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100004319, Pfizer;
                Categories
                Original Research Article
                Custom metadata
                © The Author(s) 2022

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