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1.
Pediatr Blood Cancer ; 69(4): e29493, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35038214

RESUMO

Sickle cell disease (SCD) patients are at high risk of central nervous system (CNS) complications and may experience significant morbidity. The study was conducted to describe the comprehensive burden of SCD-related CNS complications and to identify patient-reported outcome (PRO) instruments for future research. The review included 32 studies published from January 2000 to 2020, evaluating humanistic and economic outcomes. Twenty-three studies reported humanistic outcomes, 16 of which measured cognitive function using Wechsler Intelligence Scales. A meta-analysis was conducted, finding full-scale intelligence quotient (IQ) was significantly lower in: overt stroke versus controls: -12.6 (p < .001); silent cerebral infarct (SCI) versus controls: -5.7 (p < .001); overt stroke versus SCI: -9.4 (p = .008); and any event versus controls: -7.6 (p < .001). This review quantified the cognitive deficits associated with CNS complications in pediatric SCD populations and highlights the need for improved prevention/treatment. As PRO evidence was limited, we discussed areas for future research.


Assuntos
Anemia Falciforme , Acidente Vascular Cerebral , Sistema Nervoso Central , Infarto Cerebral , Criança , Humanos , Testes de Inteligência , Acidente Vascular Cerebral/etiologia
2.
J Med Econ ; 27(1): 1253-1266, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39361016

RESUMO

AIMS: Economic studies have found that public support of basic medical research provides important long-term benefits. In response to suggestions that private pharmaceutical research and development (R&D) funding could be totally replaced by public funding, we investigate the economic implications of such a substitution in funding roles that maintain the recent pace of pharmaceutical innovation. MATERIALS AND METHODS: Total lifecycle R&D costs were estimated using the latest available R&D expenditures per novel molecule entering clinical trials, likelihood of approval, pre-clinical and post-approval expenditures, using a published survey and a review of publicly available financial accounts from US-listed multinational developers. This estimate was then stratified by the average number of annual FDA approvals to estimate total costs of R&D funding born by the private sector. RESULTS: We find total lifecycle R&D costs were US$2.83 billion per approved medicine. Estimated uncapitalized costs to replace private R&D funding for one year of FDA approvals were $139.6 billion. These additional costs are equivalent to 302% of the entire National Institute for Health 2022 budget of $46.2 billion, and around 25 times NIH's estimated annual $5.6 billion currently dedicated to clinical research trials for pharmaceuticals. Further assessing the policy proposition through a literature review, we found little evidence for improvements in economic efficiency via public funding substitution, while there may be additional challenges including asymmetric information, adverse selection, yardstick competition, hold-up, under-rewarding of incremental innovation and political rent-seeking. LIMITATIONS: Our calculations may undervalue full replacement costs, by excluding non-R&D expenses for manufacturing, distribution, or financing. CONCLUSIONS: The bulk of investment in R&D is underwritten by the private sector. Political discourse portraying the NIH as the central force in bringing a new drug to market may underappreciate the pivotal role of private at-risk capital. Replacing such investment while maintaining the current innovation output in terms of approved therapies would necessitate substantial increases in taxpayer financing.


Assuntos
Setor Privado , Setor Público , Setor Público/economia , Setor Privado/economia , Estados Unidos , Humanos , Indústria Farmacêutica/economia , Apoio à Pesquisa como Assunto , Aprovação de Drogas , Pesquisa Biomédica/economia , Financiamento Governamental , Análise Custo-Benefício
3.
Adv Ther ; 39(4): 1678-1696, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35157216

RESUMO

INTRODUCTION: Tazemetostat is an enhancer of zeste homolog 2 (EZH2) inhibitor recommended for patients with relapsed/refractory (R/R) follicular lymphoma (FL) after demonstrating single-agent, antitumor activity in patients with wild-type or mutant EZH2. The phosphoinositide 3-kinase (PI3K) inhibitors idelalisib, copanlisib, umbralisib and (formerly) duvelisib are indicated for third-line, fourth-line, and later (3L/4L+) treatment of R/R FL. The objective of this analysis was to provide an indirect treatment comparison of tazemetostat with each PI3K inhibitor for 3L/4L+ R/R FL treatment. METHODS: A systematic literature review was conducted to identify trials for idelalisib (DELTA), duvelisib (DYNAMO), copanlisib (CHRONOS-1 Part B), and umbralisib (UNITY-NHL) in 3L+ R/R FL. Matching-adjusted indirect comparisons were conducted by weighting tazemetostat individual patient data with available baseline characteristics from each comparator trial: age, Eastern Cooperative Oncology Group performance status, disease stage, histology, prior treatment lines, prior stem cell therapy, progression within 24 months, and refractory status to last therapy. Only the tazemetostat trial included patients with grade 3b or transformed FL, or recorded EZH2 mutation status. Primary safety outcomes included risk of grade ≥ 3 treatment-emergent adverse events (TEAEs); primary efficacy outcomes included objective response rate (ORR). RESULTS: Matched patients treated with tazemetostat had lower relative risk (RR) for all grouped safety outcomes, including any grade ≥ 3 TEAEs, compared with idelalisib (RR = 0.45), duvelisib (RR = 0.35), copanlisib (RR = 0.37), and umbralisib (RR = 0.65; all, p < 0.01), any serious TEAE, and any TEAE leading to dose reduction, drug discontinuation, or interruption. The ORR was not significantly different for tazemetostat versus other treatments (idelalisib 43% vs 56%, p = 0.16; duvelisib 48% vs 47%, p = 0.91; copanlisib 49% vs 61%, p = 0.11; and umbralisib 57% vs 47%, p = 0.10). CONCLUSIONS: In this statistically adjusted comparison, tazemetostat was associated with lower RR for safety outcomes versus idelalisib, duvelisib, copanlisib, and umbralisib, while achieving similar efficacy outcomes.


Assuntos
Linfoma Folicular , Fosfatidilinositol 3-Quinases , Benzamidas , Compostos de Bifenilo , Pré-Escolar , Compostos Heterocíclicos de 4 ou mais Anéis , Humanos , Isoquinolinas , Linfoma Folicular/tratamento farmacológico , Linfoma Folicular/genética , Linfoma Folicular/patologia , Morfolinas , Recidiva Local de Neoplasia/tratamento farmacológico , Fosfatidilinositol 3-Quinases/uso terapêutico , Purinas , Piridonas , Pirimidinas , Quinazolinas , Quinazolinonas , Risco
4.
J Med Econ ; 25(1): 817-825, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35593483

RESUMO

AIMS: Use of comprehensive genomic profiling (CGP) in metastatic colorectal cancer (mCRC) is limited. We estimated impacts of expanded 1 L CGP, using the Tempus xT test, on detection of actionable alterations and testing budgets in a modeled US health plan over two-years. MATERIALS AND METHODS: A decision analytic model was developed to estimate the impact of replacing 20% of usual testing (a mix of CGP and non-CGP) with Tempus xT CGP. Actionable alterations for matched treatments or clinical trial included KRAS, NRAS, RAF, BRAF, deficient mismatch repair (dMMR)/microsatellite instability (MSI), NTRK, RET, EGFR, HER2, MET, PIK3CA and POLE1. Costs included initial and repeat testing, physician-associated and administrative costs. RESULTS: In a hypothetical five-million-member plan, 50% Medicare and 50% commercial, 1,112 new cases of mCRC were expected per year. Of these, 566 (51%) would undergo 1 L molecular testing, with 55 re-tested upon progression. Based on current testing rates, there were an expected 521 missed opportunities for genomically informed treatment (47% of new cases), with 442 missed due to lack of testing and 79 due to testing without CGP. Replacing 20% of usual testing with Tempus xT CGP was associated with up to a $0.003 per member per month testing cost increase (net total cost of $202,102 for the five-million-member plan) and 15.5 additional patients with an opportunity for genomically informed care (12.7 patients for treatment and 2.8 for clinical trial). The testing total cost (initial test, repeat test, biopsy and physician services, and administrative cost) to put one additional patient with mCRC on matched therapy or matched clinical trial was estimated to be $13,005. Number needed to test to identify one actionable alteration with Tempus xT CGP versus usual testing was 7.8 patients. LIMITATIONS: Conservative assumptions were made for inputs with limited evidence. Based on high concordance rates with dMMR/MSI status, tumor mutational burden (TMB) status was not calculated separately. CONCLUSIONS: Replacing 20% of usual testing with Tempus xT CGP was associated with a small incremental testing cost and can identify meaningfully more actionable alterations.


Assuntos
Neoplasias Colorretais , Neoplasias Retais , Idoso , Biomarcadores Tumorais/uso terapêutico , Orçamentos , Neoplasias Colorretais/tratamento farmacológico , Genômica , Humanos , Medicare , Estados Unidos
5.
Oncotarget ; 13: 677-683, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35574216

RESUMO

PURPOSE: In the tazemetostat E7438-G000-101 trial of relapsed/refractory (R/R) follicular lymphoma (FL), apparent superior efficacy was suggested for mutant-type (MT) EZH2 versus wild-type (WT) status. However, clinical disparities might have contributed to this conclusion. This study aimed to estimate outcomes after minimizing differences in baseline characteristics. METHODS: Propensity scores for each participant with WT (n = 54) and MT (n = 45) status were generated based on the likelihood of being selected given their baseline characteristics. Participants were matched using a 1:1 nearest-neighbor approach. RESULTS: The propensity-matched sample included 56 participants (28 WT, 28 MT). Objective response rates (95% confidence interval [CI]) were 35% (22-48) in WT and 69% (55-83) in MT prior to matching and 50% (31-69) in WT and 71% (54-88) in MT after matching. Median progression-free survival values (95% CI) were 11.1 (5.4-16.7) in WT and 13.8 months (11.1-22.1) in MT prior to matching and 14.3 (11.1-∞]) and 14.8 months (10.7-∞]) in WT and MT matched groups, respectively. CONCLUSIONS: This analysis suggests that efficacy outcomes for tazemetostat observed in participants with WT EZH2 R/R FL may have been similar to those in participants with MT had the 2 cohorts been more closely matched.


Assuntos
Linfoma Folicular , Benzamidas , Compostos de Bifenilo , Humanos , Linfoma Folicular/tratamento farmacológico , Linfoma Folicular/genética , Morfolinas , Pontuação de Propensão , Piridonas
6.
J Manag Care Spec Pharm ; 27(10): 1447-1456, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34278835

RESUMO

BACKGROUND: Promacta (eltrombopag; EPAG) and Nplate (romiplostim; ROMI) have not been compared in head-to-head trials for treatment of chronic immune thrombocytopenia (cITP); however, indirect treatment comparisons have indicated similar efficacy and safety outcomes, and the drugs are generally accepted as therapeutic alternatives. OBJECTIVE: To determine which of the 2 therapies would result in the lowest overall cost from a US health plan perspective, under the assumption of equivalent clinical efficacy and safety. METHODS: A cost-minimization model was developed in Microsoft Excel. The model incorporated only costs that differ between the treatments, including drug acquisition, administration, and monitoring costs, over a 52-week horizon. Average dosing for EPAG and ROMI was taken from the long-term EXTEND trial and from a published metaanalysis of 14 clinical trials, respectively. ROMI is injectable and EPAG is oral, so only ROMI had administration costs. The model assumed patients used 25 mg EPAG tablets and the 250 µg vial size of ROMI. ROMI wastage was included in drug acquisition costs by rounding up average dose to the nearest whole vial. Monitoring requirements were determined from US prescribing information, with platelet monitoring assumed equal, and hepatic panel testing every 4 weeks for EPAG. The model was adjustable to commercial, Medicare, and Medicaid plan perspectives, with optional inclusion of drug wastage, monitoring, or administration costs. RESULTS: The base case used a commercial plan perspective, with average dosing of 51.5 mg/day for EPAG and 4.20 µg/kg/week for ROMI. The analysis found a cost difference per treated patient of $64,770 in favor of EPAG on an annual basis. Breakdown by unique costs for EPAG included drug-acquisition cost of $123,135 and monitoring cost of $705. Breakdown by unique costs for ROMI included drug-acquisition cost of $183,234, with wastage of $63,179 and administration cost of $5,377. Based on a hypothetical commercial plan with 1 million members and an estimated 11 patients with cITP receiving ROMI, potential annual savings for switching all patients from ROMI to EPAG is $712,473 or $0.06 per member per month. EPAG remained the less costly option for all plan types and assumptions. A sensitivity analysis found that the result was most sensitive to drug pricing and wastage inputs. CONCLUSIONS: Because of lower drug-acquisition costs (including drug wastage) and administration costs, treatment of cITP with EPAG is associated with a lower net cost per patient than ROMI. DISCLOSURES: This study was funded by Novartis Pharmaceuticals Corporation. Proudman, Lucas, and Nellesen are employees of Analysis Group, Inc., which received funding from Novartis Pharmaceuticals Corporation to conduct this study. Patwardhan was employed by Novartis Pharmaceuticals Corporation at the time of this study; Allen is an employee of Novartis. This research was presented as an e-poster at the AMCP 2020 Virtual, April 2020.


Assuntos
Benzoatos/economia , Doença Crônica/economia , Hidrazinas/economia , Pirazóis/economia , Proteínas Recombinantes de Fusão/economia , Trombocitopenia/tratamento farmacológico , Trombopoetina/economia , Adolescente , Adulto , Controle de Custos , Custos de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Receptores Fc , Estados Unidos , Adulto Jovem
7.
JAMA Netw Open ; 3(11): e2025866, 2020 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-33201235

RESUMO

Importance: With the approval of avapritinib for adults with unresectable or metastatic gastrointestinal stromal tumors (GISTs) harboring a platelet-derived growth factor receptor alpha (PDGFRA) exon 18 variant, including PDGFRA D842V variants, and National Comprehensive Cancer Network guideline recommendations as an option for patients with GIST after third-line treatment, it is important to estimate the potential financial implications of avapritinib on a payer's budget. Objective: To estimate the budget impact associated with the introduction of avapritinib to a formulary for metastatic or unresectable GISTs in patients with a PDGFRA exon 18 variant or after 3 or more previous treatments from the perspective of a US health plan. Design, Setting, and Participants: For this economic evaluation, a 3-year budget impact model was developed in March 2020, incorporating costs for drug acquisition, testing, monitoring, adverse events, and postprogression treatment. The model assumed that avapritinib introduction would be associated with increased PDGFRA testing rates from the current 49% to 69%. The health plan population was assumed to be mixed 69% commercial, 22% Medicare, and 9% Medicaid. Base case assumptions included a GIST incidence rate of 9.6 diagnoses per million people, a metastatic PDGFRA exon 18 mutation rate of 1.9%, and progression rate from first-line to fourth-line treatment of 17%. Exposures: The model compared scenarios with and without avapritinib in a formulary. Main Outcomes and Measures: Annual, total, and per member per month (PMPM) budget impact. Results: In a hypothetical 1-million member plan, fewer than 0.1 new patients with a PDGFRA exon 18 variant per year and 1.2 patients receiving fourth-line therapy per year were eligible for treatment. With avapritinib available, the total increase in costs in year 3 for all eligible adult patients with a PDGFRA exon 18 variant was $46 875, or $0.004 PMPM. For patients undergoing fourth-line treatment, the total increase in costs in year 3 was $69 182, or $0.006 PMPM. The combined total budget impact in year 3 was $115 604, or $0.010 PMPM, including an offset of $3607 in postprogression costs avoided or delayed. The higher rates of molecular testing resulted in a minimal incremental testing cost of $453 in year 3. Conclusions and Relevance: These results suggest that adoption of avapritinib as a treatment option would have a minimal budget impact to a hypothetical US health plan. This would be primarily attributable to the small eligible patient population and cost offsets from reduced or delayed postprogression costs.


Assuntos
Antineoplásicos/economia , Neoplasias Gastrointestinais/tratamento farmacológico , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Programas de Assistência Gerenciada/economia , Pirazóis/economia , Pirróis/economia , Triazinas/economia , Antineoplásicos/uso terapêutico , Orçamentos , Análise Custo-Benefício , Formulários Farmacêuticos como Assunto , Neoplasias Gastrointestinais/patologia , Tumores do Estroma Gastrointestinal/genética , Tumores do Estroma Gastrointestinal/patologia , Tumores do Estroma Gastrointestinal/secundário , Humanos , Mesilato de Imatinib/economia , Mesilato de Imatinib/uso terapêutico , Indazóis , Medicaid , Medicare , Técnicas de Diagnóstico Molecular/economia , Compostos de Fenilureia/economia , Compostos de Fenilureia/uso terapêutico , Pirazóis/uso terapêutico , Piridinas/economia , Piridinas/uso terapêutico , Pirimidinas/economia , Pirimidinas/uso terapêutico , Pirróis/uso terapêutico , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/genética , Sulfonamidas/economia , Sulfonamidas/uso terapêutico , Sunitinibe/economia , Sunitinibe/uso terapêutico , Falha de Tratamento , Triazinas/uso terapêutico , Estados Unidos
8.
PLoS One ; 15(1): e0226895, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31940319

RESUMO

OBJECTIVE: To estimate healthcare expenditures that could be impacted by advanced diagnostic testing for patients hospitalized with meningitis or encephalitis. METHODS: Patients hospitalized with meningitis (N = 23,933) or encephalitis (N = 7,858) in the U.S. were identified in the 2010-2014 Truven Health MarketScan Commercial Claims and Encounters Database using ICD-9-CM diagnostic codes. The database included an average of 40.8 million commercially insured enrollees under age 65 per year. Clinical, demographic and healthcare utilization criteria were used to identify patient subgroups early in their episode who were at risk to have high inpatient expenditures. Healthcare expenditures of patients within each subgroup were bifurcated: those expenditures that remained five days after the patient could be classified into the subgroup versus those that had occurred previously. RESULTS: The hospitalization episode rate per 100,000 enrollee-years for meningitis was 13.0 (95% CI: 12.9-13.2) and for encephalitis was 4.3 (95% CI: 4.2-4.4), with mean inpatient expenditures of $36,891 (SD = $92,636) and $60,181 (SD = $130,276), respectively. If advanced diagnostic testing had been administered on the day that a patient could be classified into a subgroup, then a test with a five-day turnaround time could impact the following mean inpatient expenditures that remained by subgroup for patients with meningitis or encephalitis, respectively: had a neurosurgical procedure ($83,337 and $56,020), had an ICU stay ($34,221 and $46,051), had HIV-1 infection or a previous organ transplant ($37,702 and $62,222), were age <1 year ($35,371 and $52,812), or had a hospital length of stay >2 days ($18,325 and $30,244). DISCUSSION: Inpatient expenditures for patients hospitalized with meningitis or encephalitis were substantial and varied widely. Patient subgroups who had high healthcare expenditures could be identified early in their stay, raising the potential for advanced diagnostic testing to lower these expenditures.


Assuntos
Encefalite/diagnóstico , Encefalite/economia , Gastos em Saúde/estatística & dados numéricos , Hospitalização , Meningite/diagnóstico , Meningite/economia , Adulto , Criança , Pré-Escolar , Encefalite/terapia , Feminino , Humanos , Lactente , Recém-Nascido , Seguro Saúde , Masculino , Meningite/terapia , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
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