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Gupta DM, Barnes J, Qin F, Kapphahn K, Hornbacker K, Blayney DW, Kunz PL. Computing the Cost of Care per Patient per Day for Patients With Metastatic Neuroendocrine Neoplasms. JCO Oncol Pract 2024; 20:203-211. [PMID: 38096469 PMCID: PMC10911580 DOI: 10.1200/op.23.00433] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2023] [Revised: 09/28/2023] [Accepted: 11/02/2023] [Indexed: 02/15/2024] Open
Abstract
PURPOSE Patients with well-differentiated, low-grade metastatic neuroendocrine neoplasms (NENs) usually have a long median survival and require complex, expensive care over many years at multidisciplinary centers. The cost burden for patients and institutions serves as a barrier to care. Understanding the drivers of these costs and whether intense monitoring adds value will help to optimize value-based care. METHODS We adapted the cost of care per patient per day (CCPD) validated methodology to measure cost while accounting for varying follow-up duration. We queried the Stanford NEN Database, which aggregates data from the electronic health record and other electronic sources, to study patients with metastatic NENs receiving regular care at Stanford. Current Procedural Terminology codes for services incurred during the monitoring period for each patient were mapped to the corresponding cost conversion factor and date in the Medicare fee schedule. RESULTS Two hundred two patients between 2010 and 2017 were studied with a mean CCPD of $119.11 in US dollars (USD); NEN-specific systemic therapy made up 55% of this cost. Somatostatin analogs were the costliest systemic therapy. Systemic therapy was the driver of cost differences among patients with various primary tumor types, stage of disease, tumor differentiation and grade, and functional hormone status. Patients in the most expensive CCPD group did not have a significant survival benefit (P = .66). CONCLUSION The CCPD methodology was effective in studying cancer care value in NENs. Systemic therapy, specifically somatostatin analogs, was the primary driver of cost, and intense monitoring and higher-cost care did not improve survival outcomes.
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Affiliation(s)
- Divya M. Gupta
- Northwestern University, Feinberg School of Medicine, Chicago, IL
| | - James Barnes
- University of Washington School of Medicine, Seattle,WA
| | - FeiFei Qin
- Stanford University School of Medicine, Stanford, CA
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White BE, Mujica-Mota R, Snowsill T, Gamper EM, Srirajaskanthan R, Ramage JK. Evaluating cost-effectiveness in the management of neuroendocrine neoplasms. Rev Endocr Metab Disord 2021; 22:647-663. [PMID: 33155118 PMCID: PMC8346405 DOI: 10.1007/s11154-020-09608-y] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/14/2020] [Indexed: 10/27/2022]
Abstract
The rapid evolution of novel, costly therapies for neuroendocrine neoplasia (NEN) warrants formal high-quality cost-effectiveness evaluation. Costs of individual investigations and therapies are high; and examples are presented. We aimed to review the last ten years of standalone health economic evaluations in NEN. Comparing to published standards, EMBASE, Cochrane library, Database of Abstracts of Reviews of Effects (DARE), NHS Economic Evaluation Database and the Health Technology Assessment (HTA) Database were searched for health economic evaluations (HEEs) in NEN published between 2010 and October 2019. Of 12 economic evaluations, 11 considered exclusively pharmacological treatment (3 studies of SSAs, 7 studies of sunitinib, everolimus and/or 177Lu-DOTATATE and 1 study of telotristat ethyl) and 1 compared surgery with intraarterial therapy. 7 studies of pharmacological treatment had placebo or best supportive care as the only comparator. There remains a paucity of economic evaluations in NEN with the majority industry funded. Most HEEs reviewed did not meet published health economic criteria used to assess quality. Lack of cost data collected from patient populations remains a significant factor in HEEs where clinical expert opinion is still often substituted. Further research utilizing high-quality effectiveness data and rigorous applied health economic analysis is needed.
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Affiliation(s)
- B E White
- Department of Gastroenterology, Basingstoke and North Hampshire Hospital, Hampshire Hospitals NHS Foundation Trust, Hampshire, UK
- Kings Health Partners Neuroendocrine Tumour Centre of Excellence, London, UK
| | - R Mujica-Mota
- Department of Health Economics, University of Leeds, Leeds, UK
| | - T Snowsill
- Department of Health Economics, University of Exeter, Exeter, UK
| | - E M Gamper
- Innsbruck Institute of Patient-centered Outcome Research (IIPCOR), Innsbruck, Austria
| | - R Srirajaskanthan
- Kings Health Partners Neuroendocrine Tumour Centre of Excellence, London, UK
| | - J K Ramage
- Department of Gastroenterology, Basingstoke and North Hampshire Hospital, Hampshire Hospitals NHS Foundation Trust, Hampshire, UK.
- Kings Health Partners Neuroendocrine Tumour Centre of Excellence, London, UK.
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Hagendijk ME, van der Schans S, Boersma C, Postma MJ, van der Pol S. Economic evaluation of orphan drug Lutetium-Octreotate vs. Octreotide long-acting release for patients with an advanced midgut neuroendocrine tumour in the Netherlands. THE EUROPEAN JOURNAL OF HEALTH ECONOMICS : HEPAC : HEALTH ECONOMICS IN PREVENTION AND CARE 2021; 22:991-999. [PMID: 33829344 PMCID: PMC8275500 DOI: 10.1007/s10198-021-01303-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 12/11/2020] [Accepted: 03/26/2021] [Indexed: 06/12/2023]
Abstract
OBJECTIVES Multiple studies showed positive effects of Lutetium-Octreotate (LO) treatment in neuroendocrine tumours. LO has been used in the Netherlands since the 1980s and recently received the orphan status shortly after the acquisition by Novartis. Since then, the official list price has increased sixfold. From a value-based pricing perspective, we analysed the impact of the increase in price on the incremental cost-effectiveness ratio (ICER) of LO treatment compared to optimal best supportive care, a high dose of Octreotide long-acting release (O-LAR), using the clinical data of the NETTER-1 trial. METHODS A Markov model was developed to evaluate the costs per quality-adjusted life-year (QALY) for LO treatment compared to O-LAR from the healthcare perspective. A scenario analysis was conducted to compare the cost-effectiveness with the initial and increased price level of the LO-treatment. RESULTS At the increased price level, the cost-effectiveness analysis rendered a deterministic ICER of €53,500 per QALY, while at the initial pricing, the ICER was €19,000 per QALY. The probabilistic sensitivity analysis (PSA) showed that LO had a high probability of being cost-effective at both the increased and initial price level, considering a cost-effectiveness threshold of €80,000. CONCLUSIONS Even at the increased price level, LO treatment can still be considered cost-effective using the applicable Dutch willingness-to-pay threshold of 80,000 euro per QALY. Considering the public scrutiny in relation to this price increase, these outcomes raise the question whether traditional cost-effectiveness methods are sufficient in fully capturing the societal acceptance of prices of new medicines.
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Affiliation(s)
- Marije E Hagendijk
- Departments of Economics, Econometrics and Finance, Faculty of Economics and Business, University of Groningen, Groningen, The Netherlands.
- Coronel Institute of Occupational Health and Research Center for Insurance Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam Public Health Research Institute, Amsterdam, The Netherlands.
| | - Simon van der Schans
- Department of Health Sciences, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
- Fair Medicine Foundation, Amsterdam, The Netherlands
| | - Cornelis Boersma
- Department of Health Sciences, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
- Faculty of Management Sciences, Open University, Heerlen, The Netherlands
| | - Maarten J Postma
- Departments of Economics, Econometrics and Finance, Faculty of Economics and Business, University of Groningen, Groningen, The Netherlands
- Department of Health Sciences, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
- Institute of Science in Healthy Aging and Healthcare (SHARE), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Simon van der Pol
- Department of Health Sciences, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
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Froelich MF, Schnitzer ML, Holzgreve A, Gassert FG, Gresser E, Overhoff D, Schwarze V, Fabritius MP, Nörenberg D, von Münchhausen N, Hokamp NG, Auernhammer CJ, Ilhan H, Todica A, Rübenthaler J. Cost-Effectiveness Analysis of 68Ga DOTA-TATE PET/CT, 111In-Pentetreotide SPECT/CT and CT for Diagnostic Workup of Neuroendocrine Tumors. Diagnostics (Basel) 2021; 11:diagnostics11020334. [PMID: 33670457 PMCID: PMC7922846 DOI: 10.3390/diagnostics11020334] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Revised: 02/11/2021] [Accepted: 02/15/2021] [Indexed: 02/06/2023] Open
Abstract
Neuroendocrine tumors (NETs) are relatively rare neoplasms arising from the hormone-producing neuroendocrine system that can occur in various organs such as pancreas, small bowel, stomach and lung. As the majority of these tumors express somatostatin receptors (SSR) on their cell membrane, utilization of SSR analogs in nuclear medicine is a promising, but relatively costly approach for detection and localization. The aim of this study was to analyze the cost-effectiveness of 68Ga-DOTA-TATE PET/CT (Gallium-68 DOTA-TATE Positron emission tomography/computed tomography) compared to 111In-pentetreotide SPECT/CT (Indium-111 pentetreotide Single Photon emission computed tomography/computed tomography) and to CT (computed tomography) alone in detection of NETs. A decision model on the basis of Markov simulations evaluated lifetime costs and quality-adjusted life years (QALYs) related to either a CT, SPECT/CT or PET/CT. Model input parameters were obtained from publicized research projects. The analysis is grounded on the US healthcare system. Deterministic sensitivity analysis of diagnostic parameters and probabilistic sensitivity analysis predicated on a Monte Carlo simulation with 30,000 reiterations was executed. The willingness-to-pay (WTP) was determined to be $ 100,000/QALY. In the base-case investigation, PET/CT ended up with total costs of $88,003.07 with an efficacy of 4.179, whereas CT ended up with total costs of $88,894.71 with an efficacy of 4.165. SPECT/CT ended up with total costs of $89,973.34 with an efficacy of 4.158. Therefore, the strategies CT and SPECT/CT were dominated by PET/CT in the base-case scenario. In the sensitivity analyses, PET/CT remained a cost-effective strategy. This result was due to reduced therapy costs of timely detection. The additional costs of 68Ga-DOTA-TATE PET/CT when compared to CT alone are justified in the light of potential savings in therapy costs and better outcomes.
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Affiliation(s)
- Matthias Frank Froelich
- Department of Radiology and Nuclear Medicine, University Medical Center Mannheim, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany; (M.F.F.); (D.O.); (D.N.); (N.v.M.)
| | - Moritz Ludwig Schnitzer
- Department of Radiology, University Hospital, LMU Munich, Marchioninistr. 15, 81377 Munich, Germany; (M.L.S.); (E.G.); (V.S.); (M.P.F.)
- ENETS Centre of Excellence, Interdisciplinary Center of Neuroendocrine Tumors of the GastroEnteroPancreatic System (GEPNET-KUM), LMU Munich, 81377 Munich, Germany; (A.H.); (C.J.A.); (H.I.); (A.T.)
| | - Adrien Holzgreve
- ENETS Centre of Excellence, Interdisciplinary Center of Neuroendocrine Tumors of the GastroEnteroPancreatic System (GEPNET-KUM), LMU Munich, 81377 Munich, Germany; (A.H.); (C.J.A.); (H.I.); (A.T.)
- Department of Nuclear Medicine, University Hospital, LMU Munich, Marchioninistr. 15, 81377 Munich, Germany
| | - Felix Gerhard Gassert
- Department of Diagnostic and Interventional Radiology, Klinikum rechts der Isar, Technical University of Munich, Ismaninger Str. 22, 81675 Munich, Germany;
| | - Eva Gresser
- Department of Radiology, University Hospital, LMU Munich, Marchioninistr. 15, 81377 Munich, Germany; (M.L.S.); (E.G.); (V.S.); (M.P.F.)
- ENETS Centre of Excellence, Interdisciplinary Center of Neuroendocrine Tumors of the GastroEnteroPancreatic System (GEPNET-KUM), LMU Munich, 81377 Munich, Germany; (A.H.); (C.J.A.); (H.I.); (A.T.)
| | - Daniel Overhoff
- Department of Radiology and Nuclear Medicine, University Medical Center Mannheim, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany; (M.F.F.); (D.O.); (D.N.); (N.v.M.)
| | - Vincent Schwarze
- Department of Radiology, University Hospital, LMU Munich, Marchioninistr. 15, 81377 Munich, Germany; (M.L.S.); (E.G.); (V.S.); (M.P.F.)
- ENETS Centre of Excellence, Interdisciplinary Center of Neuroendocrine Tumors of the GastroEnteroPancreatic System (GEPNET-KUM), LMU Munich, 81377 Munich, Germany; (A.H.); (C.J.A.); (H.I.); (A.T.)
| | - Matthias Philipp Fabritius
- Department of Radiology, University Hospital, LMU Munich, Marchioninistr. 15, 81377 Munich, Germany; (M.L.S.); (E.G.); (V.S.); (M.P.F.)
- ENETS Centre of Excellence, Interdisciplinary Center of Neuroendocrine Tumors of the GastroEnteroPancreatic System (GEPNET-KUM), LMU Munich, 81377 Munich, Germany; (A.H.); (C.J.A.); (H.I.); (A.T.)
| | - Dominik Nörenberg
- Department of Radiology and Nuclear Medicine, University Medical Center Mannheim, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany; (M.F.F.); (D.O.); (D.N.); (N.v.M.)
| | - Niklas von Münchhausen
- Department of Radiology and Nuclear Medicine, University Medical Center Mannheim, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany; (M.F.F.); (D.O.); (D.N.); (N.v.M.)
| | - Nils Große Hokamp
- Institute for Diagnostic and Interventional Radiology, University Hospital Cologne, 50937 Cologne, Germany;
| | - Christoph J. Auernhammer
- ENETS Centre of Excellence, Interdisciplinary Center of Neuroendocrine Tumors of the GastroEnteroPancreatic System (GEPNET-KUM), LMU Munich, 81377 Munich, Germany; (A.H.); (C.J.A.); (H.I.); (A.T.)
- Department of Internal Medicine 4, University Hospital, LMU Munich, 81377 Munich, Germany
| | - Harun Ilhan
- ENETS Centre of Excellence, Interdisciplinary Center of Neuroendocrine Tumors of the GastroEnteroPancreatic System (GEPNET-KUM), LMU Munich, 81377 Munich, Germany; (A.H.); (C.J.A.); (H.I.); (A.T.)
- Department of Nuclear Medicine, University Hospital, LMU Munich, Marchioninistr. 15, 81377 Munich, Germany
| | - Andrei Todica
- ENETS Centre of Excellence, Interdisciplinary Center of Neuroendocrine Tumors of the GastroEnteroPancreatic System (GEPNET-KUM), LMU Munich, 81377 Munich, Germany; (A.H.); (C.J.A.); (H.I.); (A.T.)
- Department of Nuclear Medicine, University Hospital, LMU Munich, Marchioninistr. 15, 81377 Munich, Germany
| | - Johannes Rübenthaler
- Department of Radiology, University Hospital, LMU Munich, Marchioninistr. 15, 81377 Munich, Germany; (M.L.S.); (E.G.); (V.S.); (M.P.F.)
- ENETS Centre of Excellence, Interdisciplinary Center of Neuroendocrine Tumors of the GastroEnteroPancreatic System (GEPNET-KUM), LMU Munich, 81377 Munich, Germany; (A.H.); (C.J.A.); (H.I.); (A.T.)
- Correspondence:
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Watson C, Tallentire CW, Ramage JK, Srirajaskanthan R, Leeuwenkamp OR, Fountain D. Quality of life in patients with gastroenteropancreatic tumours: A systematic literature review. World J Gastroenterol 2020; 26:3686-3711. [PMID: 32742136 PMCID: PMC7366058 DOI: 10.3748/wjg.v26.i25.3686] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2020] [Revised: 06/04/2020] [Accepted: 06/16/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Gastroenteropancreatic neuroendocrine tumours (GEP-NETs) are slow-growing cancers that arise from diffuse endocrine cells in the gastrointestinal tract (GI-NETs) or the pancreas (P-NETs). They are relatively uncommon, accounting for 2% of all gastrointestinal malignancies. The usual treatment options in advanced GEP-NET patients with metastatic disease include chemotherapy, biological therapies, and peptide receptor radionuclide therapy. Understanding the impact of treatment on GEP-NET patients is paramount given the nature of the disease. Health-related quality of life (HRQoL) is increasingly important as a concept reflecting the patients’ perspective in conjunction with the disease presentation, severity and treatment.
AIM To conduct a systematic literature review to identify literature reporting HRQoL data in patients with GEP-NETs between January 1985 and November 2019.
METHODS The PRISMA guiding principles were applied. MEDLINE, Embase and the Cochrane library were searched. Data extracted from the publications included type of study, patient population data (mid-gut/hind-gut/GI-NET/P-NET), sample size, intervention/comparators, HRQoL instruments, average and data spread of overall and sub-scores, and follow-up time for data collection.
RESULTS Forty-three publications met the inclusion criteria. The heterogeneous nature of the different study populations was evident; the percentage of female participants ranged between 30%-60%, whilst average age ranged from 53.8 to 67.0 years. Eight studies investigated GI-NET patients only, six studies focused exclusively on P-NET patients and the remaining studies involved both patient populations or did not report the location of the primary tumour. The most commonly used instrument was the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (n = 28) with consistent results across studies; the GI-NET-specific module Quality of Life Questionnaire-GINET21 was used in six of these studies. A number of randomised trials demonstrated no HRQoL changes between active treatment and placebo arms. The Phase III NETTER-1 study provides the best data available for advanced GEP-NET patients; it shows that peptide receptor radionuclide therapy can significantly improve GEP-NET patients’ HRQoL.
CONCLUSION HRQoL instruments offer a means to monitor patients’ general disease condition, disease progression and their physical and mental well-being. Instruments including the commonly used European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30 and GINET21 lack, however, validation and a defined minimal clinical important difference specifically for GI-NET and P-NET patients.
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Affiliation(s)
- Catherine Watson
- PHMR Health Economics, Pricing and Reimbursement, London NW1 8XY, United Kingdom
| | | | - John K Ramage
- Kings Health Partners NET centre, Kings College Hospital London, London SE5 9RS, United Kingdom
| | | | | | - Donna Fountain
- PHMR Health Economics, Pricing and Reimbursement, London NW1 8XY, United Kingdom
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Mujica-Mota R, Varley-Campbell J, Tikhonova I, Cooper C, Griffin E, Haasova M, Peters J, Lucherini S, Talens-Bou J, Long L, Sherriff D, Napier M, Ramage J, Hoyle M. Everolimus, lutetium-177 DOTATATE and sunitinib for advanced, unresectable or metastatic neuroendocrine tumours with disease progression: a systematic review and cost-effectiveness analysis. Health Technol Assess 2019; 22:1-326. [PMID: 30209002 DOI: 10.3310/hta22490] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Neuroendocrine tumours (NETs) are a group of heterogeneous cancers that develop in cells in the diffuse neuroendocrine system. OBJECTIVES To estimate the clinical effectiveness of three interventions [everolimus (Afinitor®; Novartis International AG, Basel, Switzerland), lutetium-177 DOTATATE (177Lu-DOTATATE) (Lutathera®; Imaging Equipment Ltd, Radstock, UK) and sunitinib (Sutent®; Pfizer Inc., New York, NY, USA)] for treating unresectable or metastatic NETs with disease progression and establish the cost-effectiveness of these interventions. DATA SOURCES The following databases were searched from inception to May 2016: MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, MEDLINE Daily, Epub Ahead of Print, EMBASE, Cochrane Central Register of Controlled Trials and Web of Science. REVIEW METHODS We systematically reviewed the clinical effectiveness and cost-effectiveness literature on everolimus, 177Lu-DOTATATE and sunitinib for treating advanced, unresectable or metastatic progressive NETs. The following NET locations were considered separately: pancreas, gastrointestinal (GI) tract and lung, and GI tract (midgut only). We wrote a survival partition cohort-based economic evaluation in Microsoft Excel® 2013 (Microsoft Corporation, Redmond, WA, USA) from the UK NHS and Personal Social Services perspective. This comprised three health states: (1) progression-free survival (PFS), (2) progressed disease and (3) death. RESULTS Three randomised controlled trials (RCTs), RADIANT-3 [RAD001 in Advanced Neuroendocrine Tumors, Third Trial; pancreatic NETs (pNETs): everolimus vs. best supportive care (BSC)], A6181111 (pNETs: sunitinib vs. BSC) and RADIANT-4 (RAD001 in Advanced Neuroendocrine Tumors, Fourth Trial; GI and lung NETs: everolimus vs. BSC), met the inclusion criteria for the clinical effectiveness systematic review. The risk of bias was low. Although the NETTER-1 (Neuroendocrine Tumors Therapy) RCT, of 177Lu-DOTATATE plus 30 mg of octreotide (Sandostatin®, Novartis) compared with 60 mg of octreotide, was excluded from the review, we nonetheless present the results of this trial, as it informs our estimate of the cost-effectiveness of 177Lu-DOTATATE. The pNETs trials consistently found that the interventions improved PFS and overall survival (OS) compared with BSC. Our indirect comparison found no significant difference in PFS between everolimus and sunitinib. Estimates of OS gain were confounded because of high rates of treatment switching. After adjustment, our indirect comparison suggested a lower, but non-significant, hazard of death for sunitinib compared with everolimus. In GI and lung NETs, everolimus significantly improved PFS compared with BSC and showed a non-significant trend towards improved OS compared with BSC. Adverse events were more commonly reported following treatment with targeted interventions than after treatment with BSC. In the base case for pNETs, assuming list prices, we estimated incremental cost-effectiveness ratios (ICERs) for everolimus compared with BSC of £45,493 per quality-adjusted life-year (QALY) and for sunitinib compared with BSC of £20,717 per QALY. These ICERs increased substantially without the adjustment for treatment switching. For GI and lung NETs, we estimated an ICER for everolimus compared with BSC of £44,557 per QALY. For GI (midgut) NETs, the ICERs were £199,233 per QALY for everolimus compared with BSC and £62,158 per QALY for a scenario analysis comparing 177Lu-DOTATATE with BSC. We judge that no treatment meets the National Institute for Health and Care Excellence's (NICE) end-of-life criteria, although we cannot rule out that sunitinib in the A6181111 trial does. LIMITATIONS A RCT with included comparators was not identified for 177Lu-DOTATATE. The indirect treatment comparison that our economic analysis was based on was of a simple Bucher type, unadjusted for any differences in the baseline characteristics across the two trials. CONCLUSIONS Given NICE's current stated range of £20,000-30,000 per QALY for the cost-effectiveness threshold, based on list prices, only sunitinib might be considered good value for money in England and Wales. FUTURE WORK Further analysis of individual patient data from RADIANT-3 would allow assessment of the robustness of our findings. The data were not made available to us by the company sponsoring the trial. STUDY REGISTRATION This study is registered as PROSPERO CRD42016041303. FUNDING The National Institute for Health Research Health Technology Assessment programme.
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Affiliation(s)
- Ruben Mujica-Mota
- Peninsula Technology Assessment Group (PenTAG), University of Exeter, Exeter, UK
| | - Jo Varley-Campbell
- Peninsula Technology Assessment Group (PenTAG), University of Exeter, Exeter, UK
| | - Irina Tikhonova
- Peninsula Technology Assessment Group (PenTAG), University of Exeter, Exeter, UK
| | - Chris Cooper
- Peninsula Technology Assessment Group (PenTAG), University of Exeter, Exeter, UK
| | - Ed Griffin
- Peninsula Technology Assessment Group (PenTAG), University of Exeter, Exeter, UK
| | - Marcela Haasova
- Peninsula Technology Assessment Group (PenTAG), University of Exeter, Exeter, UK
| | - Jaime Peters
- Peninsula Technology Assessment Group (PenTAG), University of Exeter, Exeter, UK
| | - Stefano Lucherini
- Peninsula Technology Assessment Group (PenTAG), University of Exeter, Exeter, UK
| | - Juan Talens-Bou
- Peninsula Technology Assessment Group (PenTAG), University of Exeter, Exeter, UK
| | - Linda Long
- Peninsula Technology Assessment Group (PenTAG), University of Exeter, Exeter, UK
| | - David Sherriff
- Plymouth Oncology Centre, Plymouth Hospitals NHS Trust, Plymouth, UK
| | - Mark Napier
- Exeter Oncology Centre, Royal Devon & Exeter NHS Foundation Trust, Exeter, UK
| | - John Ramage
- Neuroendocrine Tumour Service, King's College Hospital NHS Foundation Trust, London, UK
| | - Martin Hoyle
- Peninsula Technology Assessment Group (PenTAG), University of Exeter, Exeter, UK
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Grande E, Díaz Á, López C, Munarriz J, Reina JJ, Vera R, Bernárdez B, Aller J, Capdevila J, Garcia-Carbonero R, Jimenez Fonseca P, Trapero-Bertran M. Economics of gastroenteropancreatic neuroendocrine tumors: a systematic review. Ther Adv Endocrinol Metab 2019; 10:2042018819828217. [PMID: 30815246 PMCID: PMC6381439 DOI: 10.1177/2042018819828217] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2018] [Accepted: 01/13/2019] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND Despite current interest, enthusiasm and progress in the development of therapies for gastroenteropancreatic (GEP) neuroendocrine tumors (NETs), there are substantial gaps in the published literature regarding cost-of-illness analyses, economic evaluation and budget impact analyses. Compounding the issue is that data on resource utilization and cost-effectiveness of different diagnostic and therapeutic modalities for GEP-NETs are scarce. METHODS A systematic review on the economic impact of GEP-NETs was carried out using four databases: EMBASE, PubMed, the National Health Service Economic Evaluation Database and Cochrane review. Fully published articles from January 2000 to May 2017, in English and Spanish, were included. All articles that satisfied the inclusion criteria were included in the systematic review; summary descriptive statistics were used to describe the methodological characteristics. RESULTS The 14 studies selected included cost-of-illness analyses (n = 4), economic evaluations (n = 7) and budget impact analyses (n = 3). Almost all studies were performed in the United States. Healthcare costs for patients with NETs included medication, outpatient visits, hospitalizations, and check-ups/tests. Reducing adverse events is an area where cost savings could be achieved; however, there was not enough evidence on the cost impact of adverse events. CONCLUSION There is a lack of data related to resource utilization in the field of GEP-NETs. Therefore, cost-effectiveness and budget impact studies of existing and emerging treatments are urgently needed to help the decision-making process for patients with NETs.
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Affiliation(s)
- Enrique Grande
- Department of Medical Oncology, Hospital Universitario Ramón y Cajal, Madrid, Spain
| | - Ángel Díaz
- Department of Medical Oncology, Hospital Universitario Clínico San Carlos, Madrid, Spain
| | - Carlos López
- Department of Medical Oncology, Hospital Universitario Marqués de Valdecilla, Santander, Spain
| | - Javier Munarriz
- Department of Medical Oncology, Hospital Provincial de Castellón, Castellón, Spain
| | - Juan-José Reina
- Department of Medical Oncology, Hospital Virgen Macarena, Sevilla, Spain
| | - Ruth Vera
- Department of Medical Oncology, Complejo Hospitalario de Navarra, Pamplona, Spain
| | - Beatriz Bernárdez
- Department of Pharmacy, Complejo Hospitalario Universitario de Santiago, Santiago de Compostela, Spain
| | - Javier Aller
- Department of Endocrinology, Hospital Universitario Puerta de Hierro, Madrid, Spain
| | - Jaume Capdevila
- Vall d’Hebron University Hospital, Vall d’Hebron Institute of Oncology (VHIO), Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Rocio Garcia-Carbonero
- Oncology Department, Hospital Universitario 12 de Octubre, IIS imas12, UCM, CNIO, CIBERONC, Madrid, Spain
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Wagner M, Samaha D, Cuervo J, Patel H, Martinez M, O'Neil WM, Jimenez-Fonseca P. Applying Reflective Multicriteria Decision Analysis (MCDA) to Patient-Clinician Shared Decision-Making on the Management of Gastroenteropancreatic Neuroendocrine Tumors (GEP-NET) in the Spanish Context. Adv Ther 2018; 35:1215-1231. [PMID: 29987525 PMCID: PMC6096971 DOI: 10.1007/s12325-018-0745-6] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2018] [Indexed: 12/18/2022]
Abstract
Introduction Unresectable, well-differentiated nonfunctioning gastroenteropancreatic neuroendocrine tumors (GEP-NETs) can be monitored (watchful waiting, WW) or treated with systemic therapy such as somatostatin analogues (SSAs) to delay progression. We applied a reflective multicriteria decision analysis (MCDA) shared-decision framework (previously developed for the USA) to explore what matters to Spanish patients and clinicians considering GEP-NET treatment options. Methods The EVIDEM-derived framework was updated and adapted to the Spanish context. During a Chatham House session, five patients and six physicians assigned criteria weights using hierarchical point allocation and direct rating scale (alternative analysis). Informed by synthesized evidence embedded in the framework, participants scored how each criterion favored SSA treatment (reference case lanreotide) or WW and shared insights and knowledge. Weights and scores were combined into value contributions (norm. weight × score/5), which were added across criteria to derive the relative benefit–risk balance (RBRB, scale − 1 to + 1). Exploratory comparisons to US study findings were performed. Results Focusing on intervention outcomes (effectiveness, patient-reported, and safety), the mean RBRB favored treatment over WW (+ 0.32 ± 0.24), with the largest contributions from progression-free survival (+ 0.11 ± SD 0.07), fatal adverse events (+ 0.06 ± SD 0.08), and impact on HRQoL (+ 0.04 ± SD 0.04). Consideration of modulating criteria (type of benefit, need, costs, evidence, and feasibility) increased the RBRB to + 0.50 ± 0.14, with type of therapeutic benefit (+ 0.10 ± SD 0.08) and quality of evidence (+ 0.08 ± SD 0.06) contributing most towards treatment. Alternative weighting yielded similar results. Results were broadly comparable to those derived from the US study. Conclusion The multicriteria framework helped Spanish patients and clinicians identify and express what matters to them. The approach is transferable across decision-making contexts. Funding IPSEN Pharma. Electronic supplementary material The online version of this article (10.1007/s12325-018-0745-6) contains supplementary material, which is available to authorized users.
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Affiliation(s)
| | | | | | | | | | | | - Paula Jimenez-Fonseca
- Department of Medical Oncology, Hospital Universitario Central de Asturias, Oviedo, Spain
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Lee L, Ito T, Jensen RT. Everolimus in the treatment of neuroendocrine tumors: efficacy, side-effects, resistance, and factors affecting its place in the treatment sequence. Expert Opin Pharmacother 2018; 19:909-928. [PMID: 29757017 PMCID: PMC6064188 DOI: 10.1080/14656566.2018.1476492] [Citation(s) in RCA: 66] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Since the initial approval of everolimus in 2011, there have been a number of important changes in therapeutic/diagnostic modalities as well as classification/staging systems of neuroendocrine tumors (NETs), which can significantly impact the use of everolimus in patients with advanced NETs. Areas covered: The efficacy of everolimus monotherapy and combination therapy demonstrated in clinical studies involving patients with advanced NETs are reviewed. Several factors affecting everolimus use are described including: the development and routine use of NET classification/staging systems; widespread use of molecular imaging modalities; side effects; drug resistance; and the availability of other treatment options. Furthermore, the current position of everolimus in the treatment approach is discussed, taking into account the recommendations from the recent guidelines. Expert opinion: Although everolimus demonstrated its high efficacy and tolerability in the RADIANT trials and other clinical studies, there still remain a number of controversies related to everolimus treatment in the management of NETs. The synergistic anti-growth effect of other agents in combination with everolimus or its effect on overall survival have not been established. The appropriate order of the use of everolimus in the treatment of advanced NETs still remains unclear, which needs to be defined in further studies and will be addressed in the new guidelines.
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Affiliation(s)
- Lingaku Lee
- Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, 20892-1804,USA
| | - Tetsuhide Ito
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, International University of Health and Welfare, 3-6-45 Momochihama, Sawara-Ku, Fukuoka 814-0001, Japan
| | - Robert T. Jensen
- Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, 20892-1804,USA
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Wagner M, Samaha D, Khoury H, O'Neil WM, Lavoie L, Bennetts L, Badgley D, Gabriel S, Berthon A, Dolan J, Kulke MH, Goetghebeur M. Development of a Framework Based on Reflective MCDA to Support Patient-Clinician Shared Decision-Making: The Case of the Management of Gastroenteropancreatic Neuroendocrine Tumors (GEP-NET) in the United States. Adv Ther 2018; 35:81-99. [PMID: 29270780 PMCID: PMC5778190 DOI: 10.1007/s12325-017-0653-1] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2017] [Indexed: 01/15/2023]
Abstract
Introduction Well- or moderately differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are often slow-growing, and some patients with unresectable, asymptomatic, non-functioning tumors may face the choice between watchful waiting (WW), or somatostatin analogues (SSA) to delay progression. We developed a comprehensive multi-criteria decision analysis (MCDA) framework to help patients and physicians clarify their values and preferences, consider each decision criterion, and support communication and shared decision-making. Methods The framework was adapted from a generic MCDA framework (EVIDEM) with patient and clinician input. During a workshop, patients and clinicians expressed their individual values and preferences (criteria weights) and, on the basis of two scenarios (treatment vs WW; SSA-1 [lanreotide] vs SSA-2 [octreotide]) with evidence from a literature review, expressed how consideration of each criterion would impact their decision in favor of either option (score), and shared their knowledge and insights verbally and in writing. Results The framework included benefit-risk criteria and modulating factors, such as disease severity, quality of evidence, costs, and constraints. Overall and progression-free survival being most important, criteria weights ranged widely, highlighting variations in individual values and the need to share them. Scoring and considering each criterion prompted a rich exchange of perspectives and uncovered individual assumptions and interpretations. At the group level, type of benefit, disease severity, effectiveness, and quality of evidence favored treatment; cost aspects favored WW (scenario 1). For scenario 2, most criteria did not favor either option. Conclusions Patients and clinicians consider many aspects in decision-making. The MCDA framework provided a common interpretive frame to structure this complexity, support individual reflection, and share perspectives. Funding Ipsen Pharma. Electronic supplementary material The online version of this article (10.1007/s12325-017-0653-1) contains supplementary material, which is available to authorized users.
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11
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Neuzillet C, de Mestier L, Rousseau B, Mir O, Hebbar M, Kocher HM, Ruszniewski P, Tournigand C. Unravelling the pharmacologic opportunities and future directions for targeted therapies in gastro-intestinal cancers part 2: Neuroendocrine tumours, hepatocellular carcinoma, and gastro-intestinal stromal tumours. Pharmacol Ther 2017; 181:49-75. [PMID: 28723416 DOI: 10.1016/j.pharmthera.2017.07.006] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Until the 1990s, cytotoxic chemotherapy has been the cornerstone of medical therapy for gastrointestinal (GI) cancers. Better understanding of the cancer cell molecular biology has led to the therapeutic revolution of targeted therapies, i.e. monoclonal antibodies or small molecule inhibitors directed against proteins that are specifically overexpressed or mutated in cancer cells. These agents, being more specific to cancer cells, were expected to be less toxic than conventional cytotoxic agents. However, their effects have sometimes been disappointing, due to intrinsic or acquired resistance mechanisms, or to an activity restricted to some tumour settings, illustrating the importance of patient selection and early identification of predictive biomarkers of response to these therapies. Targeted agents have provided clinical benefit in many GI cancer types. Particularly, some GI tumours are considered chemoresistant and targeted therapies have offered a new therapeutic base for their management. Hence, somatostatin receptor-directed strategies, sorafenib, and imatinib have revolutioned the management of neuroendocrine tumours (NET), hepatocellular carcinoma (HCC), and gastrointestinal stromal tumours (GIST), respectively, and are now used as first-line treatment in many patients affected by these tumours. However, these agents face problems of resistances and identification of predictive biomarkers from imaging and/or biology. We propose a comprehensive two-part review providing a panoramic approach of the successes and failures of targeted agents in GI cancers to unravel the pharmacologic opportunities and future directions for these agents in GI oncology. In this second part, we will focus on NET, HCC, and GIST, whose treatment relies primarily on targeted therapies.
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Affiliation(s)
- Cindy Neuzillet
- INSERM UMR1149, Beaujon University Hospital (Assistance Publique-Hôpitaux de Paris, AP-HP), Paris 7 Diderot University, 100 Boulevard du Général Leclerc, 92110 Clichy, France; Department of Medical Oncology, Henri Mondor University Hospital (AP-HP), Paris Est Créteil University (UPEC), 51 Avenue du Maréchal de Lattre de Tassigny, 94010 Créteil, France; Tumour Biology Laboratory, Barts Cancer Institute, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, United Kingdom; Barts and The London HPB Centre, The Royal London Hospital, Whitechapel, London E1 1BB, United Kingdom.
| | - Louis de Mestier
- INSERM UMR1149, Beaujon University Hospital (Assistance Publique-Hôpitaux de Paris, AP-HP), Paris 7 Diderot University, 100 Boulevard du Général Leclerc, 92110 Clichy, France; Department of Gastroenterology and Pancreatology, Beaujon University Hospital (AP-HP), Paris 7 Diderot University, 100 Boulevard du Général Leclerc, 92110 Clichy, France
| | - Benoît Rousseau
- Department of Medical Oncology, Henri Mondor University Hospital (AP-HP), Paris Est Créteil University (UPEC), 51 Avenue du Maréchal de Lattre de Tassigny, 94010 Créteil, France; Institut Mondor de Recherche Biomédicale, INSERM UMR955 Team 18, Paris Est Créteil University (UPEC), 51 Avenue du Maréchal de Lattre de Tassigny, 94010 Créteil, France
| | - Olivier Mir
- Department of Cancer Medicine - Sarcoma Group, Department of Early Drug Development (DITEP) - Phase 1 Unit, Gustave Roussy Cancer Campus, University of Paris Sud, 114, Rue Edouard Vaillant, 94800 Villejuif, France
| | - Mohamed Hebbar
- Department of Medical Oncology, Lille University Hospital, 1, Rue Polonovski, 59037 Lille, France
| | - Hemant M Kocher
- Tumour Biology Laboratory, Barts Cancer Institute, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, United Kingdom; Barts and The London HPB Centre, The Royal London Hospital, Whitechapel, London E1 1BB, United Kingdom
| | - Philippe Ruszniewski
- INSERM UMR1149, Beaujon University Hospital (Assistance Publique-Hôpitaux de Paris, AP-HP), Paris 7 Diderot University, 100 Boulevard du Général Leclerc, 92110 Clichy, France
| | - Christophe Tournigand
- Department of Medical Oncology, Henri Mondor University Hospital (AP-HP), Paris Est Créteil University (UPEC), 51 Avenue du Maréchal de Lattre de Tassigny, 94010 Créteil, France
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Rivera F, Valladares M, Gea S, López-Martínez N. Cost-effectiveness analysis in the Spanish setting of the PEAK trial of panitumumab plus mFOLFOX6 compared with bevacizumab plus mFOLFOX6 for first-line treatment of patients with wild-type RAS metastatic colorectal cancer. J Med Econ 2017; 20:574-584. [PMID: 28107090 DOI: 10.1080/13696998.2017.1285780] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
OBJECTIVE To assess the cost-effectiveness of panitumumab in combination with mFOLFOX6 (oxaliplatin, 5-fluorouracil, and leucovorin) vs bevacizumab in combination with mFOLFOX6 as first-line treatment of patients with wild-type RAS metastatic colorectal cancer (mCRC) in Spain. METHODS A semi-Markov model was developed including the following health states: Progression free; Progressive disease: Treat with best supportive care; Progressive disease: Treat with subsequent active therapy; Attempted resection of metastases; Disease free after metastases resection; Progressive disease: after resection and relapse; and Death. Parametric survival analyses of patient-level progression free survival and overall survival data from the PEAK Phase II clinical trial were used to estimate health state transitions. Additional data from the PEAK trial were considered for the dose and duration of therapy, the use of subsequent therapy, the occurrence of adverse events, and the incidence and probability of time to metastasis resection. Utility weightings were calculated from patient-level data from panitumumab trials evaluating first-, second-, and third-line treatments. The study was performed from the Spanish National Health System (NHS) perspective including only direct costs. A life-time horizon was applied. Probabilistic sensitivity analyses and scenario sensitivity analyses were performed to assess the robustness of the model. RESULTS Based on the PEAK trial, which demonstrated greater efficacy of panitumumab vs bevacizumab, both in combination with mFOLFOX6 first-line in wild-type RAS mCRC patients, the estimated incremental cost per life-year gained was €16,567 and the estimated incremental cost per quality-adjusted life year gained was €22,794. The sensitivity analyses showed the model was robust to alternative parameters and assumptions. LIMITATIONS The analysis was based on a simulation model and, therefore, the results should be interpreted cautiously. CONCLUSIONS Based on the PEAK Phase II clinical trial and taking into account Spanish costs, the results of the analysis showed that first-line treatment of mCRC with panitumumab + mFOLFOX6 could be considered a cost-effective option compared with bevacizumab + mFOLFOX6 for the Spanish NHS.
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Affiliation(s)
- Fernando Rivera
- a Hospital Universitario Marqués de Valdecilla , Santander , Spain
| | | | - Salvador Gea
- c Unidad de Farmacoeconomía e Investigación de Resultados en Salud, AMGEN , S . A. , Barcelona , Spain
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Basuroy R, Sarker D, Quaglia A, Srirajaskanthan R, Ramage J. Personalized medicine for gastroenteropancreatic neuroendocrine tumors: a distant dream? INTERNATIONAL JOURNAL OF ENDOCRINE ONCOLOGY 2015. [DOI: 10.2217/ije.15.9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Neuroendocrine tumors are heterogeneous cancers that can present with advanced disease. Treatment stratification is often based on limited characterization of tumor behavior from histological grade and imaging assessments. Personalized medicine strategies focus on tailoring therapy through characterization of cancer pathways and the development of biomarkers. This review article explores the current personalized medicine landscape in gastroenteropancreatic neuroendocrine tumors, from tissue and circulating biomarkers development through to tumor heterogeneity and reimbursement issues.
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Affiliation(s)
- Ron Basuroy
- ENETS Neuroendocrine Centre of Excellence, Institute of Liver studies, King's College Hospital, London, SE5 9RS, UK
| | - Debashis Sarker
- ENETS Neuroendocrine Centre of Excellence, Institute of Liver studies, King's College Hospital, London, SE5 9RS, UK
- Department of Research Oncology, Division of Cancer Studies, King's College London, Strand, WC2R 2LS, UK
| | - Alberto Quaglia
- ENETS Neuroendocrine Centre of Excellence, Institute of Liver studies, King's College Hospital, London, SE5 9RS, UK
- Histopathology Department, Institute of Liver Studies, King's College Hospital, London, SE5 9RS, UK
| | - Rajaventhan Srirajaskanthan
- ENETS Neuroendocrine Centre of Excellence, Institute of Liver studies, King's College Hospital, London, SE5 9RS, UK
- Gastroenterology Department, University Hospital Lewisham, London, SE13 6LH, UK
| | - John Ramage
- ENETS Neuroendocrine Centre of Excellence, Institute of Liver studies, King's College Hospital, London, SE5 9RS, UK
- Gastroenterology Department, Hampshire Hospitals NHS Trust, Hampshire, RG24 9NA, UK
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Levy JF, Meek PD, Rosenberg MA. US-Based Drug Cost Parameter Estimation for Economic Evaluations. Med Decis Making 2014; 35:622-32. [PMID: 25532826 DOI: 10.1177/0272989x14563987] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2014] [Accepted: 11/08/2014] [Indexed: 12/13/2022]
Abstract
INTRODUCTION In the United States, more than 10% of national health expenditures are for prescription drugs. Assessing drug costs in US economic evaluation studies is not consistent, as the true acquisition cost of a drug is not known by decision modelers. Current US practice focuses on identifying one reasonable drug cost and imposing some distributional assumption to assess uncertainty. METHODS We propose a set of Rules based on current pharmacy practice that account for the heterogeneity of drug product costs. The set of products derived from our Rules, and their associated costs, form an empirical distribution that can be used for more realistic sensitivity analyses and create transparency in drug cost parameter computation. The Rules specify an algorithmic process to select clinically equivalent drug products that reduce pill burden, use an appropriate package size, and assume uniform weighting of substitutable products. Three diverse examples show derived empirical distributions and are compared with previously reported cost estimates. RESULTS The shapes of the empirical distributions among the 3 drugs differ dramatically, including multiple modes and different variation. Previously published estimates differed from the means of the empirical distributions. Published ranges for sensitivity analyses did not cover the ranges of the empirical distributions. In one example using lisinopril, the empirical mean cost of substitutable products was $444 (range = $23-$953) as compared with a published estimate of $305 (range = $51-$523). CONCLUSIONS Our Rules create a simple and transparent approach to creating cost estimates of drug products and assessing their variability. The approach is easily modified to include a subset of, or different weighting for, substitutable products. The derived empirical distribution is easily incorporated into 1-way or probabilistic sensitivity analyses.
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Affiliation(s)
- Joseph F Levy
- University of Wisconsin-Madison Department of Population Health Sciences, Madison, WI, USA (JFL)
| | - Patrick D Meek
- Albany College of Pharmacy and Health Sciences Department of Pharmacy, Research Institute for Health Outcomes, Albany, NY, USA (PDM)
| | - Marjorie A Rosenberg
- University of Wisconsin-Madison Department of Actuarial Science, Risk Management and Insurance and Department of Biostatistics and Medical Informatics, Madison, WI, USA (MAR)
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Smieliauskas F, Chien CR, Shen C, Geynisman DM, Shih YCT. Cost-effectiveness analyses of targeted oral anti-cancer drugs: a systematic review. PHARMACOECONOMICS 2014; 32:651-680. [PMID: 24821281 DOI: 10.1007/s40273-014-0160-z] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/03/2023]
Abstract
BACKGROUND Over the last 15 years, a paradigm shift in oncology has led to the approval of dozens of targeted oral anti-cancer medications (OAMs), which have become the standard of care for certain cancers. While more convenient for patients than infused drugs, the possibility of non-adherence and the frequently high costs of targeted OAMs have proven controversial. OBJECTIVE Our objective was to perform the first comprehensive review of cost-effectiveness analyses (CEAs) of targeted OAMs. METHODS A literature search in PubMed, The Cochrane Library, and the Health Technology Assessment (HTA) reports published by the National Institute for Health Research HTA Programme in the UK was performed, covering articles published in the 5 years prior to 30 September 2013. Our inclusion criteria were peer-reviewed English-language full-text original research articles with a primary focus on CEA related to targeted OAMs. We categorized these articles by treatment setting (i.e. cancer site/type, line of therapy, and treatment and comparator) and synthesized information from the articles into summary tables. RESULTS We identified 41 CEAs covering nine of the 18 targeted OAMs approved by the US FDA as of December 2012. These medications were studied in seven cancers, most often as second-line therapy for advanced-stage patients. In over half of treatment settings where a targeted OAM was compared with treatment that was not a targeted OAM, targeted OAMs were considered cost effective. Limitations in interpreting these findings include the risk of bias due to author conflicts of interest, cross-country variation, and difficulties in generalizing clinical trial evidence to community practice. CONCLUSIONS Several types of cost-effectiveness studies remain under-represented in the literature on targeted OAMs, including those for follow-on indications approved after the initial indication for a drug and for off-label indications, head-to-head comparisons of targeted OAMs with other targeted OAMs and targeted intravenous therapies, and studies that adopt a perspective other than the payer's. Keeping up with the increasing number of approved targeted OAMs will also prove an important challenge for economic evaluation.
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Sharma J, Duque M, Saif MW. Emerging therapies and latest development in the treatment of unresectable pancreatic neuroendocrine tumors: an update for clinicians. Therap Adv Gastroenterol 2013; 6:474-90. [PMID: 24179483 PMCID: PMC3808571 DOI: 10.1177/1756283x13498808] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Pancreatic neuroendocrine tumors (pNETs) differ in their clinical behavior, presentation and prognosis based on their initial histological features and disease stage. While small resectable tumors can be treated surgically, metastatic and locally advanced disease carries a significant mortality and treatment options have been limited in terms of their efficacy. Streptozocin-based regimens were the only agents available before but recent advances have improved the armamentarium to treat pNETs. Newer chemotherapeutic agents such as temozolomide, somatostatin analogs and targeted therapies including everolimus and sunitinib are now available to treat these tumors. Several combination regimens with targeted therapies and newer agents such as pazopanib are being developed and tested in ongoing trials.
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Affiliation(s)
- Jaya Sharma
- Tufts University School of Medicine, Tufts Medical Center, Boston, MA, USA
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Lee K. Introducing the JME special issue on cost-effectiveness analyses. J Med Econ 2012; 15 Suppl 1:1-2. [PMID: 23163333 DOI: 10.3111/13696998.2012.745993] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
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