RESUMO
Background: Clinical guidelines commonly recommend preventative treatments for people above a risk threshold. Therefore, decision-makers must have faith in risk prediction tools and model-based cost-effectiveness analyses for people at different levels of risk. Two problems that arise are inadequate handling of competing risks of death and failing to account for direct treatment disutility (i.e. the hassle of taking treatments). We explored these issues using two case studies: primary prevention of cardiovascular disease using statins and osteoporotic fracture using bisphosphonates. Objectives: Externally validate three risk prediction tools [QRISK®3, QRISK®-Lifetime, QFracture-2012 (ClinRisk Ltd, Leeds, UK)]; derive and internally validate new risk prediction tools for cardiovascular disease [competing mortality risk model with Charlson Comorbidity Index (CRISK-CCI)] and fracture (CFracture), accounting for competing-cause death; quantify direct treatment disutility for statins and bisphosphonates; and examine the effect of competing risks and direct treatment disutility on the cost-effectiveness of preventative treatments. Design, participants, main outcome measures, data sources: Discrimination and calibration of risk prediction models (Clinical Practice Research Datalink participants: aged 25-84 years for cardiovascular disease and aged 30-99 years for fractures); direct treatment disutility was elicited in online stated-preference surveys (people with/people without experience of statins/bisphosphonates); costs and quality-adjusted life-years were determined from decision-analytic modelling (updated models used in National Institute for Health and Care Excellence decision-making). Results: CRISK-CCI has excellent discrimination, similar to that of QRISK3 (Harrell's c = 0.864 vs. 0.865, respectively, for women; and 0.819 vs. 0.834, respectively, for men). CRISK-CCI has systematically better calibration, although both models overpredict in high-risk subgroups. People recommended for treatment (10-year risk of ≥ 10%) are younger when using QRISK-Lifetime than when using QRISK3, and have fewer observed events in a 10-year follow-up (4.0% vs. 11.9%, respectively, for women; and 4.3% vs. 10.8%, respectively, for men). QFracture-2012 underpredicts fractures, owing to under-ascertainment of events in its derivation. However, there is major overprediction among people aged 85-99 years and/or with multiple long-term conditions. CFracture is better calibrated, although it also overpredicts among older people. In a time trade-off exercise (n = 879), statins exhibited direct treatment disutility of 0.034; for bisphosphonates, it was greater, at 0.067. Inconvenience also influenced preferences in best-worst scaling (n = 631). Updated cost-effectiveness analysis generates more quality-adjusted life-years among people with below-average cardiovascular risk and fewer among people with above-average risk. If people experience disutility when taking statins, the cardiovascular risk threshold at which benefits outweigh harms rises with age (≥ 8% 10-year risk at 40 years of age; ≥ 38% 10-year risk at 80 years of age). Assuming that everyone experiences population-average direct treatment disutility with oral bisphosphonates, treatment is net harmful at all levels of risk. Limitations: Treating data as missing at random is a strong assumption in risk prediction model derivation. Disentangling the effect of statins from secular trends in cardiovascular disease in the previous two decades is challenging. Validating lifetime risk prediction is impossible without using very historical data. Respondents to our stated-preference survey may not be representative of the population. There is no consensus on which direct treatment disutilities should be used for cost-effectiveness analyses. Not all the inputs to the cost-effectiveness models could be updated. Conclusions: Ignoring competing mortality in risk prediction overestimates the risk of cardiovascular events and fracture, especially among older people and those with multimorbidity. Adjustment for competing risk does not meaningfully alter cost-effectiveness of these preventative interventions, but direct treatment disutility is measurable and has the potential to alter the balance of benefits and harms. We argue that this is best addressed in individual-level shared decision-making. Study registration: This study is registered as PROSPERO CRD42021249959. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme (NIHR award ref: 15/12/22) and is published in full in Health and Social Care Delivery Research; Vol. 12, No. 4. See the NIHR Funding and Awards website for further award information.
Before offering a medicine to prevent disease, prescribers must expect it to do more good than harm. This balance depends on how likely it is that the person will develop the disease we want to prevent. But people might first die for other reasons. We call this a 'competing risk'. In most cases, the mathematical tools we use to estimate the chance of developing a disease do not account for competing risks. Another problem is that, when weighing up the benefits and harms of medicines, we ignore the hassle they cause patients, even when they do not cause side effects. We used two examples: statins to prevent heart disease and bisphosphonates to prevent fractures. First, we assessed if existing tools get predictions wrong by not accounting for competing risks. We found that they exaggerate the chance of heart attacks and strokes. However, the exaggeration is greatest among people who would clearly benefit from preventative treatment. So it may not change treatment decisions much. The fracture prediction tool we studied was very inaccurate, exaggerating risk among older people, but underestimating risk among younger people. We made a new fracture risk prediction tool. It gave better predictions, but it was still inaccurate for people aged > 85 years and those with several health problems. Next, we asked people questions designed to put a number on the hassle that statins and bisphosphonates cause. Most people thought that taking either is inconvenient, but the hassle factor for bisphosphonates is bigger. Finally, we updated the mathematical models that the National Institute for Health and Care Excellence used when recommending statins and bisphosphonates. We worked out if competing risks and the hassle of taking medicines make a difference to results. Statins remain a good idea for almost everyone, unless they really hate the idea of taking them. But bisphosphonates would do more harm than good for anyone who agrees with the hassle factor we found.
Assuntos
Doenças Cardiovasculares , Inibidores de Hidroximetilglutaril-CoA Redutases , Fraturas por Osteoporose , Masculino , Humanos , Feminino , Idoso , Fraturas por Osteoporose/epidemiologia , Análise de Custo-Efetividade , Doenças Cardiovasculares/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Difosfonatos/uso terapêuticoRESUMO
PURPOSE: Evaluating interventions for cardiovascular disease (CVD) requires estimates of its effect on utility. We aimed to 1) systematically review utility estimates for CVDs published since 2013 and 2) critically appraise UK-relevant estimates and calculate corresponding baseline utility multipliers. METHODS: We searched MEDLINE and Embase (April 22, 2021) using CVD and utility terms. We screened results for primary studies reporting utility distributions for people with experience of heart failure, myocardial infarction, peripheral arterial disease, stable angina, stroke, transient ischemic attack, or unstable angina. We extracted characteristics from studies included. For UK estimates based on the EuroQoL 5-dimension (EQ-5D) measure, we assessed risk of bias and applicability to a decision-analytic model, pooled arms/time points as appropriate, and estimated baseline utility multipliers using predicted utility for age- and sex- matched populations without CVD. We sought utility sources from directly applicable studies with low risk of bias, prioritizing plausibility of severity ordering in our base-case model and highest population ascertainment in a sensitivity analysis. RESULTS: Most of the 403 studies identified used EQ-5D (n = 217) and most assessed Organisation for Economic Co-operation and Development populations (n = 262), although measures and countries varied widely. UK studies using EQ-5D (n = 29) produced very heterogeneous baseline utility multipliers for each type of CVD, precluding meta-analysis and implying different possible severity orderings. We could find sources that provided a plausible ordering of utilities while adequately representing health states. CONCLUSIONS: We cataloged international CVD utility estimates and calculated UK-relevant baseline utility multipliers. Modelers should consider unreported sources of heterogeneity, such as population differences, when selecting utility evidence from reviews. HIGHLIGHTS: Published systematic reviews have summarized estimates of utility associated with cardiovascular disease published up to 2013.We 1) reviewed utility estimates for 7 types of cardiovascular disease published since 2013, 2) critically appraised UK-relevant studies, and 3) estimated the effect of each cardiovascular disease on baseline utility.Our review 1) recommends a consistent and reliable set of baseline utility multipliers for 7 types of cardiovascular disease and 2) provides systematically identified reference information for researchers seeking utility evidence for their own context.
Assuntos
Doenças Cardiovasculares , Técnicas de Apoio para a Decisão , Humanos , Reino Unido , Qualidade de Vida , Anos de Vida Ajustados por Qualidade de VidaRESUMO
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.
Assuntos
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
Prior to 2011 legislation prohibiting children from using commercial sunbeds, the prevalence of sunbed use in 15- to 17-year-olds in some areas in England was as high as 50%. Despite significant decreases since 2011, children today still practice indoor tanning. We estimated current sunbed use in 11- to 17-year-olds in England, the number of available commercial sunbed units, and the associated cost of a 'buy-back' scheme to remove commercial sunbeds under a potential future policy to ban sunbeds. We undertook a calibration approach based on published prevalence rates in English adults and other sources. Internet searches were undertaken to estimate the number of sunbed providers in Greater Manchester, then we extrapolated this to England. Estimated mean prevalence of sunbed use was 0.6% for 11- to 14-year-olds and 2.5% for 15- to 17-year-olds, equating to 62,130 children using sunbeds in England. A predicted 2958 premises and 17,865 sunbeds exist nationally and a 'buy-back' scheme would cost approximately GBP 21.7 million. Public health concerns remain greatest for 11- to 17-year-olds who are particularly vulnerable to developing skin cancers after high ultraviolet exposure.