RESUMO
Pharmacogenetic testing in the United Kingdom's National Health Service (NHS) has historically been reactive in nature, undertaken in the context of single gene-drug relationships in specialist settings. Using a discrete choice experiment we aimed to identify healthcare professional preferences for development of a pharmacogenetic testing service in primary care in the NHS. Respondents, representing two professions groups (general practitioners or pharmacists), completed one of two survey versions, asking them to select their preferred pharmacogenetic testing service in the context of a presentation of low mood or joint pain. Responses from 235 individuals were included. All respondents preferred pharmacogenetic testing over no testing, though preference heterogeneity was identified. Both professional groups, but especially GPs, were highly sensitive to service design, with uptake varying depending on the service offered. This study demonstrates uptake of a pharmacogenetic testing service is impacted by service design and highlights key areas which should be prioritised within future initiatives.
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Clínicos Gerais , Farmacêuticos , Testes Farmacogenômicos , Atenção Primária à Saúde , Humanos , Testes Farmacogenômicos/métodos , Masculino , Feminino , Reino Unido , Adulto , Pessoa de Meia-Idade , Atitude do Pessoal de Saúde , Inquéritos e Questionários , Comportamento de Escolha , Farmacogenética/métodosRESUMO
AIMS: Genetic testing can be used to improve the safety and effectiveness of commonly prescribed medicines-a concept known as pharmacogenetics. This study aimed to quantify members of the UK public's preferences for a pharmacogenetic service to be delivered in primary care in the National Health Service. METHODS: Members of the UK population were surveyed via an online panel company. Respondents completed 1 of 2 survey versions, asking respondents to select their preferred pharmacogenetic testing service in the context of a presentation of low mood or pain. A conditional logit model was estimated, before the best functional form for the dataset was identified. Preference heterogeneity was identified via latent class analysis. Coefficients from the final selected models were used to estimate uptake in the context of different hypothetical pharmacogenetic services. RESULTS: Responses from 1993 individuals were included in the analysis. There were no differences observed in preference between the 2 clinical scenarios. Conditional logit analysis, using maximum likelihood estimation, indicated that respondents preferred to have noninvasive tests and wanted their data to be shared between different healthcare organizations to guide future prescribing. There was a preference for regional over national data sharing initiatives, and respondents preferred to have access to their data. Predicted uptake varied considerably, ranging from 51% to >99%, depending on design of the service. CONCLUSION: This study identifies public preferences for a pharmacogenetic testing service and demonstrates how predicted uptake can be impacted by relatively minor adaptations. This highlights areas for prioritization during development of future pharmacogenetic services.
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Testes Farmacogenômicos , Medicina Estatal , Humanos , Testes Farmacogenômicos/métodos , Masculino , Feminino , Reino Unido , Adulto , Pessoa de Meia-Idade , Idoso , Inquéritos e Questionários , Adulto Jovem , Preferência do Paciente , Adolescente , Comportamento de Escolha , Farmacogenética , Atenção Primária à SaúdeRESUMO
Developments in next-generation sequencing technologies have driven the clinical application of diagnostic tests that interrogate the whole genome, which offer the chance to diagnose rare inherited diseases or inform the targeting of therapies. New genomic diagnostic tests compete with traditional approaches to diagnosis, including the genetic testing of single genes and other clinical strategies, for finite health-care budgets. In this context, decision analytic model-based cost-effectiveness analysis is a useful method to help evaluate the costs versus consequences of introducing new health-care interventions. This Perspective presents key methodological, technical, practical and organizational challenges that must be considered by decision-makers responsible for the allocation of health-care resources to obtain robust and timely information about the relative cost-effectiveness of the increasing numbers of emerging genomic tests.
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Testes Genéticos , Genômica , Sequenciamento de Nucleotídeos em Larga Escala , Análise Custo-Benefício , Testes Genéticos/economia , Testes Genéticos/métodos , Testes Genéticos/normas , Genômica/economia , Genômica/métodos , Genômica/normas , Sequenciamento de Nucleotídeos em Larga Escala/economia , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Sequenciamento de Nucleotídeos em Larga Escala/normas , HumanosRESUMO
BACKGROUND: Risk stratification as a routine part of the NHS Breast Screening Programme (NHSBSP) could provide a better balance of benefits and harms. We developed BC-Predict, to offer women when invited to the NHSBSP, which collects standard risk factor information; mammographic density; and in a sub-sample, a Polygenic Risk Score (PRS). METHODS: Risk prediction was estimated primarily from self-reported questionnaires and mammographic density using the Tyrer-Cuzick risk model. Women eligible for NHSBSP were recruited. BC-Predict produced risk feedback letters, inviting women at high risk (≥8% 10-year) or moderate risk (≥5-<8% 10-year) to have appointments to discuss prevention and additional screening. RESULTS: Overall uptake of BC-Predict in screening attendees was 16.9% with 2472 consenting to the study; 76.8% of those received risk feedback within the 8-week timeframe. Recruitment was 63.2% with an onsite recruiter and paper questionnaire compared to <10% with BC-Predict only (P < 0.0001). Risk appointment attendance was highest for those at high risk (40.6%); 77.5% of those opted for preventive medication. DISCUSSION: We have shown that a real-time offer of breast cancer risk information (including both mammographic density and PRS) is feasible and can be delivered in reasonable time, although uptake requires personal contact. Preventive medication uptake in women newly identified at high risk is high and could improve the cost-effectiveness of risk stratification. TRIAL REGISTRATION: Retrospectively registered with clinicaltrials.gov (NCT04359420).
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Neoplasias da Mama , Feminino , Humanos , Neoplasias da Mama/diagnóstico , Mamografia , Detecção Precoce de Câncer , Densidade da Mama , Fatores de RiscoRESUMO
OBJECTIVE: To develop EULAR points-to-consider for therapeutic drug monitoring (TDM) of biopharmaceuticals in inflammatory rheumatic and musculoskeletal diseases (RMDs). METHODS: The points-to-consider were developed in accordance with EULAR standardised operation procedures by a multidisciplinary task force from eight European countries, based on a systematic literature review and expert consensus. Level of evidence and strength of the points-to-consider were determined, and mean levels of agreement among the task force were calculated using a 10-point rating scale. RESULTS: Six overarching principles and 13 points-to-consider were formulated. The level of agreement among the task force for the overarching principles and points-to-consider ranged from 8.4 to 9.9.The overarching principles define TDM and its subtypes, and reinforce the underlying pharmacokinetic/pharmacodynamic principles, which are relevant to all biopharmaceutical classes. The points-to-consider highlight the clinical utility of the measurement and interpretation of biopharmaceutical blood concentrations and antidrug antibodies in specific clinical scenarios, including factors that influence these parameters. In general, proactive use of TDM is not recommended but reactive TDM could be considered in certain clinical situations. An important factor limiting wider adoption of TDM is the lack of both high quality trials addressing effectiveness and safety of TDM and robust economic evaluation in patients with RMDs. Future research should focus on providing this evidence, as well as on further understanding of pharmacokinetic and pharmacodynamic characteristics of biopharmaceuticals. CONCLUSION: These points-to-consider are evidence-based and consensus-based statements for the use of TDM of biopharmaceuticals in inflammatory RMDs, addressing the clinical utility of TDM.
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Produtos Biológicos , Doenças Musculoesqueléticas , Doenças Reumáticas , Humanos , Produtos Biológicos/uso terapêutico , Monitoramento de Medicamentos , Doenças Musculoesqueléticas/tratamento farmacológico , Anticorpos , Europa (Continente) , Doenças Reumáticas/tratamento farmacológicoRESUMO
OBJECTIVES: This study aimed to demonstrate how to estimate the value of health gain after patients with a multisystem disease achieve a condition-specific composite response endpoint. METHODS: Data from patients treated in routine practice with an exemplar multisystem disease (systemic lupus erythematosus) were extracted from a national register (British Isles Lupus Assessment Group Biologics Register). Two bespoke composite response endpoints (Major Clinical Response and Improvement) were developed in advance of this study. Difference-in-differences regression compared health utility values (3-level version of EQ-5D; UK tariff) over 6 months for responders and nonresponders. Bootstrapped regression estimated the incremental quality-adjusted life-years (QALYs), probability of QALY gain after achieving the response criteria, and population monetary benefit of response. RESULTS: Within the sample (n = 171), 18.2% achieved Major Clinical Response and 49.1% achieved Improvement at 6 months. Incremental health utility values were 0.0923 for Major Clinical Response and 0.0454 for Improvement. Expected incremental QALY gain at 6 months was 0.020 for Major Clinical Response and 0.012 for Improvement. Probability of QALY gain after achieving the response criteria was 77.6% for Major Clinical Response and 72.7% for Improvement. Population monetary benefit of response was £1 106 458 for Major Clinical Response and £649 134 for Improvement. CONCLUSIONS: Bespoke composite response endpoints are becoming more common to measure treatment response for multisystem diseases in trials and observational studies. Health technology assessment agencies face a growing challenge to establish whether these endpoints correspond with improved health gain. Health utility values can generate this evidence to enhance the usefulness of composite response endpoints for health technology assessment, decision making, and economic evaluation.
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Análise Custo-Benefício , Humanos , Reino Unido , Anos de Vida Ajustados por Qualidade de VidaRESUMO
OBJECTIVES: Quantitative benefit-risk assessment (qBRA) is a structured process to evaluate the benefit-risk balance of treatment options to support decision making. The ISPOR qBRA Task Force was recently established to provide recommendations for the design, conduct, and reporting of qBRA. This report presents a hypothetical case study illustrating how to apply the Task Force's recommendations toward a qBRA to inform the benefit-risk assessment of brodalumab at the time of initial marketing approval. The qBRA evaluated 2 dosing regimens of brodalumab (210 mg or 140 mg twice weekly) compared with weight-based dosing of ustekinumab and placebo. METHODS: We followed the 5 steps recommended by the Task Force. Attributes included treatment response (≥75% improvement in Psoriasis Area and Severity Index), suicidal ideation and behavior, and infections. Performance data were drawn from pivotal clinical trials of brodalumab. The qBRA used multicriteria decision analysis and preference weights from a hypothetical discrete choice experiment. Sensitivity analyses examined the robustness of benefit-risk ranking to uncertainty in clinical effect and preference estimates, consideration of a subgroup (nail psoriasis), and the maintenance phase of treatment (52 weeks instead of 12). RESULTS: Results from this hypothetical qBRA suggest that brodalumab 210 mg had a more favorable benefit-risk profile compared with ustekinumab and placebo. Ranking of brodalumab compared with ustekinumab was dependent on brodalumab's dose. Sensitivity analyses demonstrated robustness of benefit-risk ranking to uncertainty in clinical effect and preference estimates, as well as choice of attributes and length of follow-up. CONCLUSION: This case study demonstrates how to implement the ISPOR Task Force's good practice recommendations on qBRA.
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Produtos Biológicos , Psoríase , Humanos , Ustekinumab/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Índice de Gravidade de Doença , Psoríase/tratamento farmacológico , Medição de Risco , Produtos Biológicos/uso terapêutico , Resultado do TratamentoRESUMO
Benefit-risk assessment is commonly conducted by drug and medical device developers and regulators, to evaluate and communicate issues around benefit-risk balance of medical products. Quantitative benefit-risk assessment (qBRA) is a set of techniques that incorporate explicit outcome weighting within a formal analysis to evaluate the benefit-risk balance. This report describes emerging good practices for the 5 main steps of developing qBRAs based on the multicriteria decision analysis process. First, research question formulation needs to identify the needs of decision makers and requirements for preference data and specify the role of external experts. Second, the formal analysis model should be developed by selecting benefit and safety endpoints while eliminating double counting and considering attribute value dependence. Third, preference elicitation method needs to be chosen, attributes framed appropriately within the elicitation instrument, and quality of the data should be evaluated. Fourth, analysis may need to normalize the preference weights, base-case and sensitivity analyses should be conducted, and the effect of preference heterogeneity analyzed. Finally, results should be communicated efficiently to decision makers and other stakeholders. In addition to detailed recommendations, we provide a checklist for reporting qBRAs developed through a Delphi process conducted with 34 experts.
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Lista de Checagem , Tomada de Decisão Clínica , Humanos , Medição de Risco , Tomada de DecisõesRESUMO
OBJECTIVE: To investigate the association between chronic pelvic pain (CPP) and pelvic vein incompetence (PVI) or pelvic varices. DESIGN: Case-control study. SETTING: Gynaecology and vascular surgery services in two teaching hospitals in north-west England. SAMPLE: A total of 328 premenopausal women (aged 18-54 years), comprising 164 women with CPP and 164 matched controls with no history of CPP. METHODS: Symptom and quality-of-life questionnaires and transvaginal duplex ultrasound for PVI and pelvic varices. MAIN OUTCOME MEASURES: Venous reflux of >0.7 s in the ovarian or internal iliac veins (primary outcome) and presence of pelvic varices (secondary outcome). Statistical analysis compared the prevalence of PVI between women with and without CPP using the two-sided chi-square test. Logistic regression was used to compare the odds of having PVI and pelvic varices between women with and without CPP. RESULTS: Pelvic vein incompetence was found on transvaginal duplex ultrasound in 101/162 (62%) women with CPP, compared with 30/164 (19%) asymptomatic controls (OR 6.79, 95% CI 4.11-11.47, p < 0.001). Forty-three of 164 (27%) women with CPP had pelvic varices compared with three of 164 (2%) asymptomatic women (OR 18.9, 95% CI 5.73-62.7, p < 0.001). CONCLUSIONS: There was a significant association between PVI, as detected by transvaginal duplex imaging, and CPP. Pelvic varices were strongly associated with CPP and were infrequently seen in control patients. These results justify further evaluation of PVI and its treatment in well-designed research.
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Dor Crônica , Varizes , Insuficiência Venosa , Humanos , Feminino , Masculino , Estudos de Casos e Controles , Insuficiência Venosa/complicações , Insuficiência Venosa/diagnóstico por imagem , Insuficiência Venosa/epidemiologia , Dor Pélvica/epidemiologia , Dor Pélvica/etiologia , Varizes/complicações , Varizes/diagnóstico por imagem , Varizes/epidemiologia , Veia Ilíaca , Dor Crônica/epidemiologia , Dor Crônica/etiologiaRESUMO
OBJECTIVE: To investigate the effectiveness of transvenous occlusion of incompetent pelvic veins in women presenting with chronic pelvic pain (CPP) in improving symptoms and quality of life. DESIGN: Patient-blinded randomised controlled trial with objective outcome measures. Results were analysed on an intention-to-treat basis. SETTING: Gynaecology and Vascular Surgery Services of two teaching hospitals in northwest England. POPULATION: Sixty women aged 18-54 years presenting with CPP after exclusion of other pathology, and who were found to have pelvic vein incompetence. METHODS: Participants were randomised and assigned to contrast venography alone or contrast venography plus transvenous occlusion of the incompetent pelvic veins. MAIN OUTCOME MEASURE: The primary outcome was change in pain score measured using the short-form McGill Pain Score (SF-MPQ) and the Visual Analogue Score (VAS) recorded at 12 months post-randomisation. Secondary outcomes included quality of life using the EQ-5D instrument, symptomatic improvement and procedure-related complications. RESULTS: Sixty participants were randomised to transvenous occlusion of incompetent pelvic veins or venography only. At 12 months, median pain scored 2 (3-10) in the intervention group versus 9 (5-22) in controls (p = 0.016). Pain on the VAS scored 15 (0-3) versus 53 (20-71), respectively (p = 0.002). Median EQ-5D improved after intervention from 0.79 (0.74-0.84) to 0.84 (0.79-1.00; p = 0.008) over 12 months. No major complications were reported. CONCLUSION: Transvenous occlusion of pelvic vein incompetence reduced pain scores, improved quality of life and diminished symptom burden with no major reported complications. TRIAL REGISTRATION: ISRCTN 15091500.
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Pelve , Qualidade de Vida , Humanos , Feminino , Resultado do Tratamento , Dor Pélvica/etiologia , Dor Pélvica/terapia , InglaterraRESUMO
Introducing precision medicine strategies into routine practice will require robust economic evidence. Decision-makers need to understand the value of a precision medicine strategy compared with alternative ways to treat patients. This chapter describes health economic analysis techniques that are needed to generate this evidence. The value of any precision medicine strategy can be demonstrated early to inform evidence generation and improve the likelihood of translation into routine practice. Advances in health economic analysis techniques are also explained and their relevance to precision medicine is highlighted. Ensuring that constraints on delivery are resolved to increase uptake and implementation will improve the value of a new precision medicine strategy. Empirical methods to quantify stakeholders' preferences can be effective to inform the design of a precision medicine intervention or service delivery model. A range of techniques to generate relevant economic evidence are now available to support the development and translation of precision medicine into routine practice. This economic evidence is essential to inform resource allocation decisions and will enable patients to benefit from cost-effective precision medicine strategies in the future.
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Medicina de Precisão , Humanos , Análise Custo-BenefícioRESUMO
OBJECTIVES: To identify barriers to the use of nailfold capillaroscopy as a diagnostic tool for patients presenting with Raynaud's phenomenon in UK rheumatology centres and to obtain rheumatologists' views on a proposed internet-based standardized system for clinical reporting of nailfold capillaroscopy images. METHODS: An online survey was developed using expert opinion from clinicians, scientists and health service researchers. The survey was piloted and sent to UK-based rheumatologists using established electronic mailing lists between October 2020 and March 2021. Survey data were analysed using descriptive statistics. RESULTS: A total of 104 rheumatologists representing rheumatology centres across the UK responded to the survey. Wide variations in terms of workloads and practices were described. Thirty-four (33%) respondents reported using nailfold capillaroscopy only at their own centre, 33 (32%) referred to other centres, 9 (9%) did both and 28 (27%) did not use capillaroscopy at all. Of the 43 respondents using capillaroscopy on site, 25 (58%) used either a dermatoscope or universal serial bus microscope and 9 (21%) used videocapillaroscopy. Among the 61 respondents not undertaking capillaroscopy on site, barriers included lack of equipment (85%), lack of experience in acquiring images (69%) and lack of expertise in interpreting images (67%). Sixty-six respondents (63%) expressed interest in an internet-based, standardized automated system for reporting images. CONCLUSION: Most UK rheumatologists currently do not perform nailfold capillaroscopy on site. An internet-based nailfold capillaroscopy system for use with low-cost microscopes as well as with videocapillaroscopy could help increase uptake of capillaroscopy and thereby facilitate early diagnosis of SSc across the UK.
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Doença de Raynaud , Escleroderma Sistêmico , Humanos , Angioscopia Microscópica/métodos , Reumatologistas , Doença de Raynaud/diagnóstico , Inquéritos e Questionários , Reino Unido , Unhas/diagnóstico por imagem , CapilaresRESUMO
BACKGROUND: The use of indoor tanning devices causes melanoma and other skin cancers with resulting morbidity, mortality and increased healthcare costs. Policymakers require robust economic evidence to inform decisions about a possible ban of such devices to mitigate these burdens. OBJECTIVES: To assess the health costs and consequences of introducing a policy-based intervention across England to ban commercial indoor tanning with an accompanying public information campaign. METHODS: A cost-effectiveness analysis, adopting a healthcare system perspective, was conducted using a decision model to track a national cohort of 18-year-olds over a lifetime time horizon. A nationwide ban on commercial indoor tanning combined with a public information campaign (the policy-based intervention) was compared with the status quo of availability of commercial indoor tanning. The expected costs (currency, GBP; price year, 2019) and quality-adjusted life-years (QALYs) were calculated. Net monetary benefit (NMB) (net benefit measured in cost compared with an accepted threshold) and net health benefit (NHB) (net gain in QALYs compared with an accepted threshold) of implementation were calculated. A probabilistic sensitivity analysis was used to calculate the probability that the intervention was cost-effective. RESULTS: Compared with the current situation, a ban on commercial indoor tanning combined with a public information campaign would result in 1206 avoided cases of melanoma, 207 fewer melanoma deaths and 3987 averted cases of keratinocyte cancers over the lifetime of all 18-year-olds (n = 618 873) living in England in 2019. An additional 497 QALYs would be realized along with healthcare cost-savings of £697 858. This intervention would result in an NMB of £10.6m and an NHB of 530 QALYS. Multiple sensitivity analyses confirmed the robustness of the findings. At a cost-effectiveness threshold of £20 000, there is a 99% likelihood of this policy-based intervention being cost-effective. CONCLUSIONS: The implementation of a ban on commercial indoor tanning across England with an accompanying public information campaign would be an effective use of healthcare resources.
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Melanoma , Neoplasias Cutâneas , Banho de Sol , Análise Custo-Benefício , Humanos , Melanoma/epidemiologia , Melanoma/etiologia , Melanoma/prevenção & controle , Políticas , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/etiologia , Neoplasias Cutâneas/prevenção & controle , SíndromeRESUMO
OBJECTIVES: To identify whether it is feasible to develop a mapping algorithm to predict presenteeism using multiattribute measures of health status. METHODS: Data were collected using a bespoke online survey in a purposive sample (n = 472) of working individuals with a self-reported diagnosis of Rheumatoid arthritis (RA). Survey respondents were recruited using an online panel company (ResearchNow). This study used data captured using two multiattribute measures of health status (EQ5D-5 level; SF6D) and a measure of presenteeism (WPAI, Work Productivity Activity Index). Statistical correlation between the WPAI and the two measures of health status (EQ5D-5 level; SF6D) was assessed using Spearman's rank correlation. Five regression models were estimated to quantify the relationship between WPAI and predict presenteeism using health status. The models were specified based in index and domain scores and included covariates (age; gender). Estimated and observed presenteeism were compared using tenfold cross-validation and evaluated using Root mean square error (RMSE). RESULTS: A strong and negative correlation was found between WPAI and: EQ5D-5 level and WPAI (r = - 0.64); SF6D (r =- 0.60). Two models, using ordinary least squares regression were identified as the best performing models specifying health status using: SF6D domains with age interacted with gender (RMSE = 1.7858); EQ5D-5 Level domains and age interacted with gender (RMSE = 1.7859). CONCLUSIONS: This study provides indicative evidence that two existing measures of health status (SF6D and EQ5D-5L) have a quantifiable relationship with a measure of presenteeism (WPAI) for an exemplar application of working individuals with RA. A future study should assess the external validity of the proposed mapping algorithms.
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Absenteísmo , Presenteísmo , Eficiência , Nível de Saúde , Humanos , Qualidade de Vida/psicologia , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: Non-invasive prenatal testing (NIPT) identifies the risk of abnormalities in pregnancy, potentially reducing the risk of miscarriage associated with invasive tests. This study aimed to understand the preferences of current and future mothers about the content, format and timing of information provision about NIPT. METHODS: An online discrete choice experiment was designed comprising four attributes: when in the pregnancy information is provided (4 levels); degree of detail (2 levels); information format (6 levels); cost to women for gathering information (5 levels). Respondents included women identified by an online-panel company in Sweden. The mathematical design was informed by D-efficient criteria. Choice data were analysed using uncorrelated random parameters logit and latent class models. RESULTS: One thousand Swedish women (56% current mothers) aged 18-45 years completed the survey. On average, women preferred extensive information provided at/before 9 weeks of pregnancy. There was heterogeneity in preferences about the desired format of information provision (website, mobile app or individual discussion with a midwife) in the population. CONCLUSION: Women had clear preferences about the desired content, format and timing of information provision about NIPT. It is important to tailor information provision to enable informed choices about NIPT.
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Aborto Espontâneo , Diagnóstico Pré-Natal , Comportamento de Escolha , Feminino , Humanos , Mães , Gravidez , Inquéritos e Questionários , SuéciaRESUMO
BACKGROUND: In model-based economic evaluations, the effectiveness parameter is often informed by studies with a limited duration of follow-up, requiring extrapolation of the treatment effect over a longer time horizon. Extrapolation from short-term data alone may not adequately capture uncertainty in that extrapolation. This study aimed to use structured expert elicitation to quantify uncertainty associated with extrapolation of the treatment effect observed in a clinical trial. METHODS: A structured expert elicitation exercise was conducted for an applied study of a podiatry intervention designed to reduce the rate of falls and fractures in the elderly. A bespoke web application was used to elicit experts' beliefs about two outcomes (rate of falls and odds of fracture) as probability distributions (priors), for two treatment options (intervention and treatment as usual) at multiple time points. These priors were used to derive the temporal change in the treatment effect of the intervention, to extrapolate outcomes observed in a trial. The results were compared with extrapolation without experts' priors. RESULTS: The study recruited thirty-eight experts (geriatricians, general practitioners, physiotherapists, nurses, and academics) from England and Wales. The majority of experts (32/38) believed that the treatment effect would depreciate over time and expressed greater uncertainty than that extrapolated from a trial-based outcome alone. The between-expert variation in predicted outcomes was relatively small. CONCLUSIONS: This study suggests that uncertainty in extrapolation can be informed using structured expert elicitation methods. Using structured elicitation to attach values to complex parameters requires key assumptions and simplifications to be considered.
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Fraturas Ósseas , Avaliação da Tecnologia Biomédica , Idoso , Análise Custo-Benefício , Prova Pericial/métodos , Humanos , IncertezaRESUMO
BACKGROUND: There is an emerging interest in using automated approaches to enable the incidental identification of vertebral fragility fractures (VFFs) on existing medical images visualising the spine. AIM: To quantify values, and the degree of uncertainty associated with them, for the incidental identification of VFFs from computed tomography (CT) scans in current practice. METHODS: An expert elicitation exercise was conducted to generate point estimates and measures of uncertainty for four values representing the probability of: VFF being correctly reported by the radiologist; the absence of VFF being correctly assessed by the radiologist; being referred for management when a VFF is identified; having a dual-energy X-ray absorptiometry (DXA) scan after general practitioner (GP) referral. Data from a sample of seven experts in the diagnosis and management of people with VFFs were pooled using mathematical aggregation. RESULTS: The estimated mean values for each probability parameter were: VFF being correctly reported by the radiologist = 0.25 (standard deviation (SD): 0.21); absence of VFF being correctly assessed by the radiologist = 0.89 (0.10); being referred for management when a VFF is identified by the radiologist = 0.15 (0.12); having a DXA scan after GP referral = 0.66 (0.28). DISCUSSION: These estimates could be used to facilitate the subsequent early economic evaluation of potential new approaches to improve the health outcomes of people with VFFs. CONCLUSION: In the absence of epidemiological studies, this study produced point estimates and measures of uncertainty for key parameters needed to describe current pathways for the incidental diagnosis of VFFs.
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Osteoporose , Fraturas por Osteoporose , Fraturas da Coluna Vertebral , Absorciometria de Fóton/métodos , Densidade Óssea , Humanos , Osteoporose/complicações , Osteoporose/diagnóstico por imagem , Fraturas da Coluna Vertebral/complicações , Fraturas da Coluna Vertebral/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Reino UnidoRESUMO
BACKGROUND: For reasons unclear, some stored red blood cells (RBCs) have low hemolysis, while others have high hemolysis, which impacts quality consistency. To identify variables that influence hemolysis, routine quality control (QC) data for 42-days-stored RBCs with corresponding donor information were analyzed. STUDY DESIGN AND METHODS: RBC QC and donor data were obtained from a national blood supplier. Regression models and analyses were performed on total cohort stratified by donor sex and by high hemolysis (≥90th percentile) vs control (<90th percentile) samples, including matching. RESULTS: Data included 1734 leukoreduced RBCs (822 female, 912 male), processed by buffy coat-poor or whole blood filtration methods. Male RBCs had larger volume, hemoglobin content, and higher hemolysis than female RBCs (median hemolysis, 0.24% vs 0.21%; all P < .0001). Multivariable regression identified increased body mass index (BMI) and RBC variables were associated with higher hemolysis (P < .0001), along with older female age and buffy coat-poor processing method (P < .002). Logistic regression models comparing the high and control hemolysis subsets, matched for RBC component variables and processing method, identified overweight-obese BMI (>27 kg/m2 ) in males remained the single donor-related variable associated with higher hemolysis (P < .0001); odds ratio, 3 (95% confidence interval [CI], 1.3-6.7), increasing to 4 (95% CI, 1.8-8.6) for obese males (BMI > 30 kg/m2 ). Female donor obesity and older age trended toward higher hemolysis. CONCLUSION: Donor BMI, sex, and female age influence the level of hemolysis of 42-days-stored RBCs. Other factors, not identified in this study, also influence the level of hemolysis.
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Doadores de Sangue , Preservação de Sangue , Índice de Massa Corporal , Eritrócitos/citologia , Hemólise , Sobrepeso/sangue , Adolescente , Adulto , Fatores Etários , Idoso , Doadores de Sangue/estatística & dados numéricos , Feminino , Humanos , Procedimentos de Redução de Leucócitos/métodos , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Controle de Qualidade , Estudos Retrospectivos , Fatores Sexuais , Adulto JovemRESUMO
BACKGROUND: In principle, risk-stratification as a routine part of the NHS Breast Screening Programme (NHSBSP) should produce a better balance of benefits and harms. The main benefit is the offer of NICE-approved more frequent screening and/ or chemoprevention for women who are at increased risk, but are unaware of this. We have developed BC-Predict, to be offered to women when invited to NHSBSP which collects information on risk factors (self-reported information on family history and hormone-related factors via questionnaire; mammographic density; and in a sub-sample, Single Nucleotide Polymorphisms). BC-Predict produces risk feedback letters, inviting women at high risk (≥8% 10-year) or moderate risk (≥5 to < 8% 10-year) to have discussion of prevention and early detection options at Family History, Risk and Prevention Clinics. Despite the promise of systems such as BC-Predict, there are still too many uncertainties for a fully-powered definitive trial to be appropriate or ethical. The present research aims to identify these key uncertainties regarding the feasibility of integrating BC-Predict into the NHSBSP. Key objectives of the present research are to quantify important potential benefits and harms, and identify key drivers of the relative cost-effectiveness of embedding BC-Predict into NHSBSP. METHODS: A non-randomised fully counterbalanced study design will be used, to include approximately equal numbers of women offered NHSBSP (n = 18,700) and BC-Predict (n = 18,700) from selected screening sites (n = 7). In the initial 8-month time period, women eligible for NHSBSP will be offered BC-Predict in four screening sites. Three screening sites will offer women usual NHSBSP. In the following 8-months the study sites offering usual NHSBSP switch to BC-Predict and vice versa. Key potential benefits including uptake of risk consultations, chemoprevention and additional screening will be obtained for both groups. Key potential harms such as increased anxiety will be obtained via self-report questionnaires, with embedded qualitative process analysis. A decision-analytic model-based cost-effectiveness analysis will identify the key uncertainties underpinning the relative cost-effectiveness of embedding BC-Predict into NHSBSP. DISCUSSION: We will assess the feasibility of integrating BC-Predict into the NHSBSP, and identify the main uncertainties for a definitive evaluation of the clinical and cost-effectiveness of BC-Predict. TRIAL REGISTRATION: Retrospectively registered with clinicaltrials.gov (NCT04359420).
Assuntos
Ansiedade/diagnóstico , Neoplasias da Mama/prevenção & controle , Análise Custo-Benefício , Detecção Precoce de Câncer/métodos , Programas de Rastreamento/métodos , Adolescente , Adulto , Ansiedade/epidemiologia , Ansiedade/etiologia , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/economia , Neoplasias da Mama/epidemiologia , Criança , Ensaios Clínicos como Assunto , Detecção Precoce de Câncer/economia , Detecção Precoce de Câncer/psicologia , Estudos de Viabilidade , Feminino , Implementação de Plano de Saúde/economia , Implementação de Plano de Saúde/organização & administração , Humanos , Programas de Rastreamento/economia , Programas de Rastreamento/organização & administração , Programas de Rastreamento/psicologia , Anamnese , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Avaliação de Programas e Projetos de Saúde , Medição de Risco/economia , Medição de Risco/métodos , Autorrelato/estatística & dados numéricos , Medicina Estatal/economia , Medicina Estatal/organização & administração , Reino Unido/epidemiologia , Adulto JovemRESUMO
Precision medicine is a dynamic area embracing a diverse and increasing type of approaches that allow the targeting of new medicines, screening programs or preventive healthcare strategies, which include the use of biologic markers or complex tests driven by algorithms also potentially taking account of patient preferences. The International Society for Pharmacoeconomics and Outcome Research expanded its current work around precision medicine to (1) describe the evolving paradigm of precision medicine with examples of current and evolving applications, (2) describe key stakeholders perspectives on the value of precision medicine in their respective domains, and (3) define the core factors that should be considered in a value assessment framework for precision medicine. With the ultimate goal of improving health of well-defined patient groups, precision medicine will affect all stakeholders in the healthcare system at multiple levels spanning the individual perspective to the societal perspective. For an efficient, timely and practical precision medicine value assessment framework, it will be important to address these multiple perspectives through building consensus among the stakeholders for robust procedures and measures of value aspects, including performance of precision mechanism; aligned reimbursement processes of precision mechanism and subsequent treatment; transparent expectations for evidence requirements and study designs adequately matched to the intended use of the precision mechanism and to the smaller target patient populations; recognizing the potential range of value-generation such as ruling-in and ruling-out decisions.