RESUMO
BACKGROUND: Changes in the regulatory context enable faster approval of transformative medicines. They also lead to health technology assessment (HTA) agencies having to make decisions with less evidence. In response, HTA agencies have also initiated forms of conditional approval. When the evidence base for a new oncology treatment leaves substantial uncertainty, the new Cancer Drugs Fund allows the National Institute for Heath and Care Excellence to give the manufacturer two options: (1) offer a low price based on conservative assumptions and obtain immediate approval ("stick") or (2) wait until the evidence base has further matured before finalizing a potentially higher agreed price ("twist"). OBJECTIVES: The purpose of this article is to explain how, using the theoretical framework of the expected value of sample information, simulation methods can help inform a manufacturer's decisions when faced with the option to stick or twist. METHODS: We first summarize a general model to help frame the manufacturer's negotiating strategy. We then use a motivating case study, based on a hypothetical immunotherapy, to illustrate how manufacturers can use simulation methods to robustly characterize the uncertainty inherent to further data collection and incorporate this uncertainty within their decision making. RESULTS: Our approach allows us to estimate the commercial value of generating additional data (the difference between the estimated net present value of stick and twist). We test the sensitivity of the results to different assumptions via scenario analyses. CONCLUSIONS: This article shows that simulation methods can be used to help pharmaceutical managers make informed strategic decisions in contexts of uncertainty.
Assuntos
Antineoplásicos Imunológicos/economia , Antineoplásicos Imunológicos/uso terapêutico , Orçamentos , Contratos/economia , Tomada de Decisões , Técnicas de Apoio para a Decisão , Aprovação de Drogas/economia , Custos de Medicamentos , Desenvolvimento de Medicamentos/economia , Negociação , Avaliação da Tecnologia Biomédica/economia , Antineoplásicos Imunológicos/efeitos adversos , Simulação por Computador , Análise Custo-Benefício , Alocação de Recursos para a Atenção à Saúde/economia , Humanos , Modelos Econômicos , Modelos Estatísticos , Formulação de Políticas , Resultado do Tratamento , IncertezaRESUMO
OBJECTIVES: Suboptimal compliance and failure to persist with drug treatments are important determinants of therapeutic nonresponse and are of potential economic significance. The present article aims to describe the methodologies that may be appropriate for integrating noncompliance and nonpersistence in economic evaluations. METHODS: MEDLINE and NHS-EED were searched for economic evaluations published in the period between 1997 and 2005. Articles were included if they explored the dependence of cost-effectiveness results on varying levels of some form of compliance-related measure. The different methodologies used were reviewed and articles were appraised critically. Alternative methodological approaches are proposed, illustrated by an example of the impact of different persistence rates on a treatment's cost-effectiveness. RESULTS: Ten articles were selected for inclusion. These were generally scant on detail relating to how compliance/persistence was assessed and what the impact was on health outcomes. The methods used included Markov models and decision analyses. Markov models allow for persistence to be included directly in the analysis, as patients transit during each cycle. Net-benefit regression models are well suited for analyzing prospective and retrospective studies where patient-level data are available, whereas discrete event simulations have the potential to offer more flexibility. CONCLUSIONS: Compliance and/or persistence are not included routinely in pharmacoeconomic analyses, despite their potential impact. Where compliance and/or persistence are included, a lack of methodological rigor and consistency in definitions often limits the usefulness of the analyses. The analytical techniques discussed in this article should serve as a basis for developing guidelines on appropriate methodology.
Assuntos
Técnicas de Apoio para a Decisão , Tratamento Farmacológico/economia , Farmacoeconomia/estatística & dados numéricos , Cooperação do Paciente , Análise Custo-Benefício/estatística & dados numéricos , Humanos , Cadeias de Markov , Modelos Econométricos , Análise de RegressãoRESUMO
OBJECTIVE: To assess both the health-related quality of life (HR-QOL) and the economic value of erythropoietin treatment in chemotherapy-related anaemia using direct utility elicitation and discrete choice experiment (DCE) methods from a societal perspective in the UK. METHODS: The time trade-off (TTO) method was employed to obtain utility values suitable for the calculation of QALYs for no, mild, moderate and severe anaemia. Health-state descriptions were developed using the Functional Assessment of Cancer Therapy - Anaemia (FACT-AN) subscale and the EQ-5D questionnaires, and were validated by clinical experts and patients. In addition, a DCE was implemented to elicit preferences for various anaemia treatment scenarios. The DCE analysis comprised important aspects of treatment identified from a literature review and by consultation with expert clinicians and cancer patients. The DCE included cost as an attribute in order to elicit willingness-to-pay (WTP) values (pound, 2004 values). The two methods were applied in the same cross-sectional sample of 110 lay people. Face-to-face interviews were conducted between February and March 2004. RESULTS: The mean utility scores were 0.86 (standard error [SE] 0.014) for the no-anaemia state, and 0.78 (SE 0.016), 0.61 (SE 0.020) and 0.48 (SE 0.020) for the mild, moderate and severe anaemia states, respectively. The DCE results revealed the following preferences as significant predictors of choice: higher level of relief from fatigue, lower duration of administration, subcutaneous/intravenous administration versus cannula injection, GP versus hospital location, lower risk of infection or allergic reactions and lower cost per month to the patient. Attribute levels were valued higher for recombinant erythropoietin than for blood transfusion; this is reflected in an incremental welfare value of 368 pounds (95% CI 318, 419). CONCLUSIONS: The results highlight a societal view that the severity of chemotherapy-related anaemia will significantly affect cancer patients' HR-QOL. The DCE survey shows that the public value favourably the attributes of treatment with recombinant erythropoietin, and indicates a likely patient preference for treatment with recombinant erythropoietin over blood transfusion.
Assuntos
Anemia/tratamento farmacológico , Eritropoetina/uso terapêutico , Qualidade de Vida , Adolescente , Adulto , Idoso , Anemia/induzido quimicamente , Anemia/economia , Análise Custo-Benefício/métodos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Eritropoetina/economia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes , Inquéritos e Questionários , Reino UnidoRESUMO
BACKGROUND: Sub optimal levels of compliance and persistence with bisphosphonates are potentially compromising the reduction of post menopausal osteoporotic (PMO) fracture risk. METHODS: A structured literature search (1990-2006) was performed to identify primary research studies evaluating the relationship between compliance and persistence with bisphosphonates and post menopausal osteoporotic (PMO) fracture risk in clinical practice. Search criteria were: bisphosphonates; osteoporosis/osteopenia in postmenopausal women; all types of fractures; compliance and persistence. RESULTS: Only two retrospective studies using prescription databases have specifically evaluated bisphosphonates.A cohort study tracking 35,537 women reported that in those with a Medication Possession Ratio (MPR) of > or =80% over 24 months the risk of fracture was lower than in those with an MPR of <80% (8.5% v 10.7%, p < 0.001, Relative Risk Reduction (RRR) 21%). In women who persisted with treatment (refill gap <30 days) the risk of fracture was also lower (7.7% v 10.3%, p < 0.001, RRR 29%).A nested case control study reported that 12 months persistence (refill gap <50% previous prescription (Rx) length) was associated with a 26% reduced risk of fracture (p < 0.05) and 24 months with a 32% reduced risk (p < 0.05). Four other studies, not specific to bisphosphonates, reported that compliance > or =12 months decreased fracture risk by approximately 25%. CONCLUSION: Sub optimal compliance and persistence with bisphosphonates is not providing the best possible protection against the risk of PMO fracture, however, more research is needed to delineate this relationship in clinical practice.
Assuntos
Difosfonatos/uso terapêutico , Fraturas Ósseas/epidemiologia , Osteoporose Pós-Menopausa/tratamento farmacológico , Osteoporose Pós-Menopausa/epidemiologia , Cooperação do Paciente/estatística & dados numéricos , Fraturas Ósseas/prevenção & controle , Humanos , Osteoporose Pós-Menopausa/psicologia , Fatores de RiscoRESUMO
OBJECTIVES: The aim of this study was to determine the effect of dose frequency on compliance and persistence with bisphosphonate therapy in postmenopausal women and to compare findings from 3 different health care systems. METHODS: Three independently performed retrospective cohort analyses were performed using observational data sources. In the United States, bisphosphonate-naive postmenopausal women were identified from a database providing information on health plan prescription drug claims; in the United Kingdom and France, bisphosphonate-naive postmenopausal women were identified from a database of medical records supplied by general practice physicians. The women were grouped into 2 cohorts: those who were initiated on a weekly regimen of alendronate 70 mg or risedronate 35 mg and those initiated on a daily regimen of alendronate 5 or 10 mg or risedronate 5 mg. Compliance was measured in terms of the medication possession ratio (MPR), which was defined as the proportion of days in the 12-month follow-up period for which patients were covered by prescriptions for bisphosphonates. Persistence was measured as the number of days from the date of the index prescription to the last day of prescription coverage within the followup period. Women were classified as nonpersistent if the gap between prescriptions was > 30 days. RESULTS: The study included 2741 postmenopausal women with osteoporosis from the United States, 7567 from the United Kingdom, and 5332 from France. The mean (SD) age of the women was 73.0, 71.7, and 69.7 years in the 3 countries, respectively. The overall MPR was 61% in the United States, 74% in the United Kingdom, and 58% in France. In all 3 countries, women on a weekly regimen had a significantly greater MPR than women on a daily regimen (69% vs 58%, respectively, in the United States; 76% vs 64% in the United Kingdom; and 59% vs 53% in France; all, P < 0.001). Women on a weekly regimen of bisphosphonates persisted with treatment significantly longer than women on a daily regimen (227 vs 185 days, respectively, in the United States; 249 vs 208 in the United Kingdom; and 179 vs 155 in France; all, P < 0.001). A significantly greater proportion of the women on a weekly regimen persisted with treatment for 12 months compared with those on a daily regimen (44% vs 32%, respectively, in the United States; 52% vs 40% in the United Kingdom; and 51% vs 44% in France; all, P < 0.001). CONCLUSIONS: In all 3 countries, postmenopausal women prescribed a weekly regimen of bisphosphonates had significantly greater rates of compliance than women prescribed a daily regimen, and they persisted longer with treatment. However, compliance and persistence rates were suboptimal for both regimens.
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Difosfonatos/uso terapêutico , Osteoporose/tratamento farmacológico , Cooperação do Paciente , Pós-Menopausa , Estudos de Coortes , Feminino , França , Humanos , Reino Unido , Estados UnidosRESUMO
BACKGROUND: Bisphosphonates are currently among the most effective therapies for the treatment of osteoporosis and provide one of the mainstays of treatment in the UK. However studies in several countries have all reported sub-optimal compliance and persistence with treatment. OBJECTIVE: To examine the impact of dosing frequency on compliance and persistence with bisphosphonates in the UK. METHODS: Three UK General Practitioner sourced databases, the General Practice Research Database (GPRD), IMS Disease Analyzer (MEDIPLUS) and the Doctors Independent Network Database (DIN-LINK) were used to identify bisphosphonate naïve postmenopausal women. In each of the three retrospective analyses women were grouped into weekly or daily cohorts and followed for 12 months from an initial prescription. Compliance was measured as a Medication Possession Ratio (MPR), defined as the proportion of days for which patients had prescription coverage. Persistence was measured as the number of continuous days of treatment from the initial prescription to the end of the last prescription issued in the follow-up period. RESULTS: GPRD, MEDIPLUS and DIN-LINK provided access to 7567, 5962 and 1801 women, respectively. All three analyses consistently demonstrated that those on weekly regimens had a higher MPR than those on daily regimens (GPRD 76.2%, CI(95%,) 75.4-77.0 vs. 63.5%, CI(95%) 61.2-65.8, MEDIPLUS 70.3%, CI(95%) 69.3-71.2 vs. 56.3%, CI(95%) 53.8-58.9, DIN-LINK 59.5%, CI(95%) 59.4-59.6 vs. 46.3%, CI(95%) 45.9-46.7) (p < 0.0001) and persisted longer with treatment (GPRD 249, CI(95%) 246-253 vs. 208, CI(95%) 199-217, MEDIPLUS 228, CI(95%) 224-231 vs. 186, CI(95%,) 176-196, DIN-LINK 235, CI(95%) 234-236 vs. 189, CI(95%) 187-191) days respectively), (p < 0.0001). CONCLUSIONS: Although this study only provided an indirect measure of medication usage, it demonstrated that a less frequent dosing regimen significantly improved levels of both compliance and persistence; however, even on weekly regimens bisphosphonate usage remains sub-optimal thereby reducing the clinical benefits.
Assuntos
Conservadores da Densidade Óssea/administração & dosagem , Difosfonatos/administração & dosagem , Osteoporose Pós-Menopausa/tratamento farmacológico , Cooperação do Paciente , Idoso , Bases de Dados Factuais , Esquema de Medicação , Feminino , Humanos , Reino UnidoRESUMO
The European Orphan Medicinal Products (OMP) Regulation has successfully encouraged research to develop treatments for rare diseases resulting in the authorisation of new OMPs in Europe. While decisions on OMP designation and marketing authorisation are made at the European Union level, reimbursement decisions are made at the national level. OMP value and affordability are high priority issues for policymakers and decisions regarding their pricing and funding are highly complex. There is currently no European consensus on how OMP value should be assessed and inequalities of access to OMPs have previously been observed. Against this background, policy makers in many countries are considering reforms to improve access to OMPs. This paper proposes ten principles to be considered when undertaking such reforms, from the perspective of an OMP manufacturer. We recommend the continued prioritisation of rare diseases by policymakers, an increased alignment between payer and regulatory frameworks, pricing centred on OMP value, and mechanisms to ensure long-term financial sustainability allowing a continuous and virtuous development of OMPs. Our recommendations support the development of more consistent frameworks and encourage collaboration between all stakeholders, including research-based industry, payers, clinicians, and patients.
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Política de Saúde/economia , Produção de Droga sem Interesse Comercial/economia , Custos de Medicamentos , Europa (Continente) , Humanos , Produção de Droga sem Interesse Comercial/legislação & jurisprudência , Doenças Raras/tratamento farmacológico , Doenças Raras/economiaRESUMO
Stroke prevention guidelines recommend oral anticoagulants (OAC) for atrial fibrillation (AF) patients at moderate/high risk of stroke, and antiplatelet or no therapy for those at low/moderate risk. Outcomes for AF patients receiving antiplatelet/no therapy in 'real-life' clinical practice were explored. This study compared clinical event rates (stroke/bleeding) for AF patients treated with OAC therapy, antiplatelets or no therapy in usual clinical practice to event rates in OAC-treated AF patients from optimally-monitored 'real-life' settings (anticoagulation clinics). We searched biomedical literature (1994-2010) using PubMed to identify 'real-world' studies of clinical event rates for AF patients receiving OAC therapy, antiplatelets, or no therapy; event rates were extracted for each treatment and setting. We identified 136 studies of thromboembolic events and 86 of bleeding events. Ischaemic stroke rates (30 studies) were higher for AF patients receiving no therapy (median: 4.45/100 person-years; range: 0.25-5.9) or antiplatelet-therapy (median: 4.45/100 person-years; range: 2.0-10) compared to OAC-treated patients monitored in anticoagulation clinics (median: 1.72/100 person-years; range: 0.97-2.00), or from a non-specialized setting (median 1.66/100 person-years; range: 0-4.9). Major bleeding rates (32 studies) for patients receiving antiplatelet/no therapy were similar to OAC-treated patients from both clinical settings. As in randomised clinical trials, AF patients in 'real-world' clinical practice receiving antiplatelet/no therapy have higher rates of ischaemic stroke than OAC-treated patients. Antiplatelet/no therapy was associated with similar bleeding rates to OAC therapy. Increasing utilisation of anticoagulants in clinical practice could improve patient outcomes.
Assuntos
Anticoagulantes/efeitos adversos , Fibrilação Atrial/tratamento farmacológico , Hemorragia/induzido quimicamente , Isquemia/induzido quimicamente , Inibidores da Agregação Plaquetária/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/administração & dosagem , Fibrilação Atrial/complicações , Fibrilação Atrial/epidemiologia , Fibrilação Atrial/fisiopatologia , Feminino , Hemorragia/epidemiologia , Hospitais Especializados/estatística & dados numéricos , Humanos , Isquemia/epidemiologia , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação Plaquetária/administração & dosagem , Prevalência , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de TempoRESUMO
Despite the efficacy of oral anticoagulants for stroke prevention in atrial fibrillation (AF), evidence suggests that many patients with AF who should be treated with vitamin K antagonists (VKAs) are treated with antiplatelet therapy or remain untreated. The aims of this study were to determine the proportion of patients with AF in each treatment category in clinical practice and to ascertain whether treatment is appropriate for stroke risk. An extensive search of the biomedical research published since 1994 was performed. Studies delineating the treatment of patients with AF were captured. Seventy-eight studies pertaining to the treatment of patients with AF were identified; 56 studies, containing data from 1980 to 2007, met the inclusion criteria. Over time, the use of VKA therapy for stroke prevention increased, while the proportion of untreated patients decreased; antiplatelet use remained static. Looking at the more recent data, (collected from 2000 onward), the proportion of patients receiving no therapy ranged from 4% to 48% (median 18%), antiplatelet therapy from 10% to 56% (median 30%), and VKA therapy from 9% to 86% (median 52%). Although most studies showed a decrease in the proportion of antiplatelet-treated and untreated patients with increasing stroke risk (12 of 14 studies), many patients at moderate or high risk for stroke were not treated according to guidelines. In conclusion, this review shows that up to 56% of patients with AF are treated with antiplatelet therapy, and up to 48% receive no therapy regardless of stroke risk level. This may reflect the inconvenience associated with VKA use, inadequate assessment of stroke risk, or poor adherence to treatment guidelines.
Assuntos
Fibrilação Atrial/tratamento farmacológico , Inibidores da Agregação Plaquetária/uso terapêutico , Fibrilação Atrial/complicações , Fibrilação Atrial/epidemiologia , Humanos , Incidência , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Reino Unido/epidemiologiaRESUMO
The aims of this study were to investigate trends in the incidence of diagnosed atrial fibrillation (AF), and to identify factors associated with the prescription of antithrombotics (ATs) and to identify the persistence of patients with oral anticoagulant (OAC) treatment in primary care. Data were obtained from 400 Italian primary care physicians providing information to the Health Search/Thales Database from 2001 to 2004. The age-standardised incidence of AF was: 3.9-3.0 cases, and 3.6-3.0 cases per 1,000 person-years in males and females, respectively. During the study period, 2,016 (37.2%) patients had no prescription, 1,663 (30.7%) were prescribed an antiplatelet (AP) agent, 1,440 (26.6%) were prescribed an OAC and 301 (5.5%) had both prescriptions. The date of diagnosis (p = 0.0001) affected the likelihood of receiving an OAC. AP, but not OAC, use significantly increased with a worsening stroke risk profile using the CHADS2 risk score. Older age increased the probability (p < 0.0001) of receiving an AP, but not an OAC. Approximately 42% and 24% of patients persisted with OAC treatment at one and two years, respectively, the remainder interrupted or discontinued their treatment. Underuse and discontinuation of OAC treatment is common in incident AF patients. Risk stratification only partially influences AT management.
Assuntos
Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/epidemiologia , Prescrições de Medicamentos/estatística & dados numéricos , Fibrinolíticos/uso terapêutico , Atenção Primária à Saúde , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Fibrilação Atrial/diagnóstico , Feminino , Humanos , Incidência , Itália , Masculino , Conduta do Tratamento Medicamentoso , Pessoa de Meia-Idade , Cooperação do Paciente , Estudos Retrospectivos , Fatores de RiscoRESUMO
BACKGROUND: Atrial fibrillation is associated with substantial mortality and morbidity from stroke and thromboembolism. Despite an efficacious oral anticoagulation therapy (warfarin), atrial fibrillation patients at high risk for stroke are often under-treated. This systematic review compares current treatment practices for stroke prevention in atrial fibrillation with published guidelines. METHODS: Literature searches (1997-2008) identified 98 studies concerning current treatment practices for stroke prevention in atrial fibrillation. The percentage of patients eligible for oral anticoagulation due to elevated stroke risk was compared with the percentage treated. Under-treatment was defined as treatment of <70% of high-risk patients. RESULTS: Of 54 studies that reported stroke risk levels and the percentage of patients treated, most showed underuse of oral anticoagulants for high-risk patients. From 29 studies of patients with prior stroke/transient ischemic attack who should all receive oral anticoagulation according to published guidelines, 25 studies reported under-treatment, with 21 of 29 studies reporting oral anticoagulation treatment levels below 60% (range 19%-81.3%). Subjects with a CHADS(2) (congestive heart failure, hypertension, age >75 years, diabetes mellitus, and prior stroke or transient ischemic attack) score >or=2 also were suboptimally treated, with 7 of 9 studies reporting treatment levels below 70% (range 39%-92.3%). Studies (21 of 54) using other stroke risk stratification schemes differ in the criteria they use to designate patients as "high risk," such that direct comparison is not possible. CONCLUSIONS: This systematic review demonstrates the underuse of oral anticoagulation therapy for real-world atrial fibrillation patients with an elevated risk of stroke, highlighting the need for improved therapies for stroke prevention in atrial fibrillation.
Assuntos
Anticoagulantes/administração & dosagem , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Acidente Vascular Cerebral/prevenção & controle , Tromboembolia/prevenção & controle , Administração Oral , Anticoagulantes/uso terapêutico , HumanosRESUMO
A review was undertaken to identify relevant and appropriate heath-utility estimates for patients with atrial fibrillation who had stroke and to appraise them against the published requirements for several countries' Health Technology Assessment agencies: Australia (Pharmaceutical Benefits Advisory Committee), Canada (Common Drug Review), England and Wales (NICE), Germany (Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen), Scotland (Scottish Medicines Consortium) and Sweden (Tandvårds-och läkemedelsförmånsverket). National agencies have created guidelines to support economic evaluations for their own countries but these guidelines differ. It may be more appropriate for agencies to be concerned primarily with the methodological quality of studies that report utilities rather than identifying local values. As such, we recommend some steps that could be considered when assessing the quality of utility studies in a systematic review or meta-analysis. These steps include considering the methods of utility estimation, model needs, generalizability, sample size and the use of large databases. This may, thus, facilitate consistent and rational Health Technology Assessment decision making.
Assuntos
Modelos Econômicos , Qualidade de Vida , Mecanismo de Reembolso , Fibrilação Atrial/economia , Fibrilação Atrial/terapia , Tomada de Decisões , Guias como Assunto , Humanos , Anos de Vida Ajustados por Qualidade de Vida , Acidente Vascular Cerebral/economia , Acidente Vascular Cerebral/terapia , Avaliação da Tecnologia Biomédica/métodosRESUMO
OBJECTIVE: To determine direct costs associated with a blood transfusion session in two hospital settings. RESEARCH DESIGN AND METHODS: The study was conducted in two United Kingdom hospital sites during April 2004. Transfusion sessions for patients receiving units of red blood cells within either haematology or oncology departments were followed using time and motion techniques to measure the direct costs. Other data were collected from the centres to calculate the cost of disposables, blood wastage and blood bank machines. RESULTS: Total mean staff cost per transfusion of 2 units was 37.24 pounds sterling (9.68 pounds sterling for blood bank and 27.56 pounds sterling for ward procedures). The mean cost of disposables was 13.25 pounds sterling and the mean cost for blood products was 287.56 pounds sterling. The mean cost of wastage was 11.86 pounds sterling per transfusion. After including other derived costs, such as hospital stay, the mean cost for a transfusion of 2 units of blood was estimated to be 546.12 pounds sterling. CONCLUSION: This study estimates the cost of an average blood transfusion of 2 units to be 546.12 pounds sterling. It should be noted that significant indirect costs, such as those incurred by patients, their carers and societal costs, have not been considered. Against the background of finite blood resources and other factors such as patient quality of life, blood transfusion may not represent the best choice for patient care. Alternative treatments should be considered.