Medical Decision Making最新文献

ObjectivesBayesian multiparameter evidence synthesis (B-MPES) can improve the reliability of long-term survival extrapolations by leveraging registry data. We extended the B-MPES framework to also incorporate historical trial data and examined the impact of alternative external information sources on predictions from early data cuts for a trial in metastatic non-small-cell lung cancer (mNSCLC).MethodsB-MPES models were fitted to survival data from the phase III CheckMate 9LA study of nivolumab plus ipilimumab plus 2 cycles of chemotherapy (NIVO+IPI+CHEMO, v. 4 cycles of CHEMO) in first-line mNSCLC, with 1 y of minimum follow-up. Trial observations were supplemented by registry data from the Surveillance, Epidemiology, and End Results program, general population data, and, optionally, historical trial data with extended follow-up for first-line NIVO+IPI (v. CHEMO) and/or second-line NIVO monotherapy in advanced NSCLC, via estimated 1-y conditional survival. Predictions from the 3 alternative B-MPES models were compared with those from standard parametric models (SPMs).ResultsB-MPES models better anticipated the emergent survival plateau with NIVO+IPI+CHEMO that was apparent in the 4-y data cut compared with SPMs, for which short-term extrapolations in both treatment arms were overly conservative. However, the B-MPES model incorporating NIVO+IPI data slightly overestimated 4-y NIVO+IPI+CHEMO survival owing to a confounding effect on estimated hazards that could not be accounted for a priori until later data cuts of CheckMate 9LA. Extrapolations were relatively robust to the choice of external data sources provided that the prior data had been adjusted to attenuate confounding.ConclusionsIncorporating historical trial data into survival models can improve the plausibility and interpretability of lifetime extrapolations for studies of novel therapies in metastatic cancers when data are immature, and B-MPES provides an appealing method for this purpose.HighlightsLeveraging historical trial data with extended follow-up to extrapolate survival from early study data cuts in a Bayesian evidence synthesis framework can realize anticipated longer-term effects that are characteristic of a novel therapy or class thereof.Using moderately confounded external data sources can improve the reliability of survival extrapolations from B-MPES models provided that the prior information is adjusted and rescaled appropriately, but it is essential to rationalize the implicit assumptions surrounding longer-term treatment effects in the current study.B-MPES models are an attractive option to conduct informed lifetime survival extrapolations based on transparent clinical assumptions via leveraging multiple external data sources, but model flexibility and a priori confidence in external data must be specified carefully to avoid overfitting.

BackgroundThe Australian National Bowel Cancer Screening Program (NBCSP), which provides 2-yearly screening to people aged 50 to 74 y, had a phased rollout from 2006 and was fully implemented in 2020. To measure the effectiveness of the NBCSP accounting for age-specific trends, we aimed to develop a novel integrative method to project colorectal cancer (CRC) incidence rates from 2006 to 2045 in the absence of the NBCSP (referred to as "no-NBCSP projections") while addressing the challenge of complex age-specific trends in CRC incidence.MethodsWe constructed a new dataset by replacing the observed data for NBCSP-eligible individuals aged 50 to 74 y with intermediate projections based on pre-NBCSP data from 1982 to 2005. We compared the no-NBCSP CRC incidence projected using a standard age-period-cohort (APC) model, age-stratified APC models, and the integrative modeling approach.ResultsThe integrative modeling approach captured complex age-specific trends better than the standard and age-stratified APC models did. Without the NBCSP, the overall CRC incidence rates would be expected to decline from 2005 to 2025, followed by increases from 2026 to 2045. The incidence rates for those aged <50 y would be projected to continue increasing to 2045, and an increase in incidence rates for older age groups would be projected to occur from 2020 for ages 50 to 54 y, from 2030 for ages 65 to 74 y, and from 2035 for ages 75 y and older.ConclusionsThese no-NBCSP projections provide a counterfactual benchmark against which to measure the impact of the NBCSP on CRC incidence in Australia, and they have been used as new calibration targets for a simulation model of CRC and screening in Australia. The methods developed here could be used to generate comparators to assess the impact of other public health interventions.HighlightsWe constructed counterfactual projections of colorectal cancer (CRC) incidence rates in the absence of the National Bowel Cancer Screening Program (no-NBCSP projections).To do this, we developed a new integrative modeling approach to capture complex age-specific colorectal cancer incidence trends.These no-NBCSP projections provide a counterfactual benchmark against which to measure the impact of the NBCSP on CRC incidence in Australia.These projections stress the need for ongoing assessment of the starting age for the NBCSP, to tackle the increasing incidence for people younger than 50 y.

BackgroundReal-world data can inform health care decisions by allowing the evaluation of nuanced treatment strategies. Longitudinal observational data enable the assessment of dynamic treatment regimes (DTRs), strategies that adapt treatment over time based on patient history, but require causal inference methods to address time-varying confounding. Longitudinal targeted minimum loss-based estimation (LTMLE) is a machine learning-based double-robust approach for improved causal effect estimation.MethodsWe applied LTMLE to longitudinal registry data to evaluate the impact of erythropoiesis-stimulating agents (ESAs) in the clinical management of low to intermediate-1 risk myelodysplastic syndrome (MDS). We defined DTRs based on clinically relevant decision rules (e.g., commencing treatment when the hemoglobin level falls below a threshold) and compared them to static treatment regimes (always or never giving ESAs). Outcomes include mortality and health-related quality of life measured by EQ-5D scores.ResultsThe static regime of never administering ESAs resulted in declining counterfactual EQ-5D scores and increasing mortality risk over time. In contrast, both the static regime of continuous administration of ESAs and the use of dynamic regimes improved the EQ-5D scores and tended to reduce mortality, although the mortality differences were not statistically significant.ConclusionsThe article provides a case study application of the LTMLE method to evaluate realistic treatment policies under time-varying confounding. The findings support the potential benefits of dynamic treatment strategies for the management of MDS, highlighting the importance of personalized treatment adaptation. The study contributes methodological insights into the applications of LTMLE in small-sample, long-follow-up settings relevant to health technology assessment and policy making.HighlightsThis study applies the longitudinal targeted minimum loss estimation (LTMLE) method to evaluate the causal effect of static and dynamic treatment strategies using longitudinal observational data.We demonstrate the use of the LTMLE method to assess the impact of erythropoiesis stimulating agents (ESAs) on quality of life and mortality in patients with low to intermediate-1 risk myelodysplastic syndromes.The findings suggest that patients treated under dynamic ESA treatment regimes show an improved quality of life measured by EQ-5D scores and survival compared with those treated under the static treatment regime of never administering ESAs.This study contributes to the methodological literature by showcasing the application of the LTMLE method in a small-sample, long-follow-up setting with time-varying confounding, informing health technology assessment and policy decisions.

This article critically examines the application of minimal important differences (MIDs) to health state values or utilities. The concept of MIDs aims to guide clinical and research decisions by identifying important changes in health-related quality-of-life (HRQoL) indicators. However, this cannot be used without additional information not contained within the indicator itself, so that the MID cannot be regarded as a property of the indicator. First, MIDs defined at the individual patient level cannot be meaningfully aggregated for groups without additional context. Second, any improvement in HRQoL is important for patients themselves, so decision making using an MID also requires context, such as resource costs for effecting change. Third, health state values incorporate a measure of importance according to patient preferences, so the only change that is unimportant is zero. Calculating and reporting MIDs for health state values is not only unhelpful but also misleading.HighlightsThe minimal important difference (MID) for health-related quality of life and patient-reported outcome measures is widely used but arguably is not only of limited use but also usually misleading because it lacks context-specific meaning.MIDs for individuals cannot be aggregated without judgments about the distribution of outcomes over patient groups, and quality-of-life indicators need context; thus, the MID cannot be regarded as a property of an indicator.Quality-of-life indicators that generate health state values or utilities incorporate importance based on patient preferences, so the only unimportant change is zero.Published research into MIDs for health state values is unhelpful and even misleading.

BackgroundIndividuals commonly want diagnostic testing even after being informed the test is clinically unbeneficial and has risks. These preferences are poorly understood but may relate to beliefs that any testing information is valuable. To explore this, we examined Australian adults' attitudes toward finding harmless abnormalities using diagnostic tests and the broader beliefs related to these attitudes.MethodsData collected via survey were analyzed using mixed methods. Free text explaining attitudes to finding harmless abnormalities were analyzed using comparative content and interpretative analyses. Associations between attitudes to finding harmless abnormalities and broader beliefs and demographics were analyzed using regression.ResultsAlmost three-fifths of 655 participants considered it valuable to identify harmless abnormalities using tests. Qualitative analyses showed this attitude was driven by beliefs that identification would provide psychological reassurance, valuable biodata, and enable monitoring and management of the harmless abnormalities. These beliefs were underpinned by a skepticism that abnormalities can ever be harmless and by a range of beliefs about the broader value of diagnostic testing. Participants with negative attitudes to identifying harmless abnormalities were concerned about resultant anxiety and unnecessary health interventions. Regression showed that positive attitudes to identifying harmless abnormalities were associated with greater confidence in doctors, lesser concerns about overtreatment, and a stronger desire to know as much about their bodies as possible as well as with several demographic variables.Conclusions and ImplicationsOur study explores why people seek diagnostic tests that they know lack obvious clinical benefits. It identifies broader beliefs and psychological factors that profoundly influence testing choices. This knowledge will help overcome the limitations of existing strategies to explain the risks of tests to patients and the public.HighlightsFindings help explain why facts showing that particular diagnostic tests are ineffective or harmful fail to dissuade many Australians from seeking those tests.Many Australians value diagnostic testing for perceived reassurance, understanding one's body, and use in medical decision making.Many are skeptical that identifying incidentalomas is harmful, and are confident they can avoid unnecessarily treating them.Messages about testing risks should focus on broader beliefs and respond to psychological factors that undermine the effect of risk/benefit information.

IntroductionIn the health technology assessment (HTA) of biologic treatments for rheumatoid arthritis (RA), there is limited randomized evidence on treatment effectiveness after first-line treatment failure. We demonstrate how real-world data (RWD) could fill this evidence gap.MethodsTarget trial emulation (TTE) minimizes biases in the causal analysis of RWD by prespecifying a protocol for a hypothetical randomized clinical trial (RCT) that would estimate the effect of interest. The application of TTE for HTA was illustrated using RWD from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis to estimate the effectiveness of rituximab versus nonbiologic therapy (NBT) after first-line biologic failure, in terms of European Alliance of Associations for Rheumatology response achievement. The effectiveness estimates from RWD were combined with RCT estimates in a meta-analysis. The pooled estimates were entered into an economic model to estimate the incremental cost-effectiveness ratio (ICER) comparing biologic versus NBT strategies.ResultsBased on RWD, rituximab was associated with higher probabilities of achieving a moderate or good response (0.215 v. 0.174) and a good response (0.090 v. 0.066) as compared with NBT. These probabilities were lower than those estimated from RCT data (moderate or good 0.650; good 0.150). The economic model estimated less time on treatment and lower costs associated with biologics when based on RWD compared with RCT data (mean £63,500 v. £70,000). This resulted in a higher ICER based on RWD compared with RCT data (mean £46,800 v. £34,700 per quality-adjusted life-year gained).ConclusionsRWD can provide supplemental evidence on treatment effectiveness where randomized evidence is limited. This can make a meaningful difference to cost-effectiveness estimates. Our results are not intended to inform current RA management.HighlightsIn health technology assessment, real-world data (RWD) can provide supplemental evidence on treatment effectiveness where there is limited randomized evidence.Target trial emulation was applied using RWD to estimate the clinical effectiveness of biologic treatment; these estimates were combined with estimates from an RCT in a meta-analysis, and the pooled estimates were entered into an economic model for rheumatoid arthritis.Treatment effect estimates based on combining RWD and RCT data were more modest compared with the effectiveness estimates from the RCT data alone, leading to a difference in the estimate of cost-effectiveness comparing biologics with nonbiologic therapy.

ObjectivesDiscrete choice experiment (DCE) methods that account for nonlinear time preferences have been tested in adult EQ-5D instruments but have yet to be tested for the valuation of EQ-5D-Y instruments. The aims of this study were to test the feasibility of using DCE methods that model nonlinear time preferences for the valuation of the EQ-5D-Y-5L as well as to explore the impact of the perspective adult respondents are asked to take.MethodsA representative Australian adult general population sample completed an online survey that included 15 DCE split triplet tasks. Depending on arm assignment, respondents were asked to imagine themselves or a 10-y-old when choosing between health states. A Bayesian efficient design was used to construct DCE tasks; the design was updated 3 times. Data were analyzed using correlated mixed logit models with exponential discounting.ResultsThere were 955 and 947 respondents in the "self" and "10-y-old" arms, respectively. When nonlinear modeling is used, there is evidence of discounting in the "self" (17%) and "10-y-old" (15%) perspective. Avoiding the experience of pain and discomfort were most important in both arms. When imagining a 10-y-old, rather than "self," respondents considered being worried, sad, or unhappy to be more important. Sensitivity analysis revealed that nonparents considered a higher number of health states to be worse than dead when imagining themselves.ConclusionsThis is the first study to use a nonlinear DCE approach in the valuation of the EQ-5D-Y-5L and in pediatric health-related quality of life more generally. Nonlinear modeling methods were found to be suitable for the valuation of the EQ-5D-Y-5L.HighlightsThere is evidence that modeling for nonlinear time preferences is suitable for the valuation of adult health-related quality of life (HRQoL). It is unknown how time preferences affect the valuation of pediatric instruments, such as the EQ-5D-Y-5L, and whether this differs when adults are asked to imagine "self" versus a "10-y-old."There was evidence of nonlinear time preferences when adult respondents value health states for a 10-y-old using a discrete choice experiment (DCE) that included a duration attribute. Perspective was a strong driver of estimating states worse than dead: 42% of health states were considered worse than dead for a 10-y-old as opposed to 26% when respondents imagined themselves.Nonlinear DCE methods are feasible for the valuation of the EQ-5D-Y-5L and have advantages compared with the use of time tradeoff in valuing child HRQoL. Future studies can test whether nonlinear modeling methods are suitable for other pediatric HRQoL instruments.