Efficace, FabioGiesinger, Johannes M.Cella, DavidCottone, Francesco...
5页
查看更多>>摘要：Objectives: Incomplete reporting of key information on patient-reported outcomes (PROs) in randomized controlled trials (RCTs) in oncology has been highlighted repeatedly as a major barrier to the use of study findings in clinical practice. We investigated whether the quality of reporting of PRO data in cancer RCTs has improved over the last 15 years. Methods: We identified all cancer RCTs with PRO endpoints conducted across the most prevalent solid tumor types worldwide published between 2004 and 2019. The quality of PRO reporting was assessed using the International Society for Quality of Life Research recommended standards, which include important aspects related to assessment methodology, statistical analyses, and interpretation of data. Results: We assessed a total of 631 cancer RCTs in breast (n =187), lung (n =131), prostate (n = 120), colorectal (n = 107), and gynecological (n = 86) cancer. We observed a higher adherence to the International Society for Quality of Life Research reporting criteria in the more recently published studies. In a multivariable linear regression analysis, we observed a statistically significant improvement in the quality of PRO reporting over time (P,.001), and this relationship was independent of other measured confounding factors, such as sample size and study sponsorship. Overall, the quality of PRO reporting was higher for studies published after the publication of the Consolidated Standards of Reporting Trials-PRO Extension. Conclusions: The quality of PRO reporting in cancer RCTs published in the last 15 years has improved significantly. Our findings are encouraging because better reporting of PRO results may translate into a greater impact of study findings on real world practice.
查看更多>>摘要：Objectives: Studies face challenges with missing 5-level EQ-5D (EQ-5D-5L) data, often because of the need for longitudinal EQ-5D-5L data collection. There is a dearth of validated methodologies for dealing with missing EQ-5D-5L data in the literature. This study, for the first time, examined the possibility of using retrospectively collected EQ-5D-5L data as proxies for the missing data. Methods: Participants who had prospectively completed a 3rd month postdischarge EQ-5D-5L instrument (in-the-moment collection) were randomly interviewed to respond to a 2nd "retrospective collection" of their 3rd month EQ-5D-5L at 6th, 9th, or 12th month after hospital discharge. A longitudinal single imputation was also used to assess the relative performance of retrospective collection compared with the longitudinal single imputation. Concordances between the in the-moment, retrospective, and imputed measures were assessed using intraclass correlation coefficients and weighted kappa statistics. Results: Considerable agreement was observed on the basis of weighted kappa (range 0.72-0.95) between the mobility, self care, and usual activities dimensions of EQ-5D-5L collected in-the-moment and retrospectively. Concordance based on intraclass correlation coefficients was good to excellent (range 0.79-0.81) for utility indices computed, and excellent (range 0.93-0.96) for quality-adjusted life-years computed using in-the-moment compared with retrospective EQ-5D-5L. The longitudinal single imputation did not perform as well as the retrospective collection method. Conclusions: This study demonstrates that retrospective collection of EQ-5D-5L has high concordance with "in-the-moment" EQ-5D-5L and could be a valid and attractive alternative for data imputation when longitudinally collected EQ-5D-5L data are missing. Future studies examining this method for other disease areas and populations are required to provide more generalizable evidence.
查看更多>>摘要：Objectives: Low-value clinical practices have been identified as one of the most important areas of excess healthcare spending. Nevertheless, there is a knowledge gap on the scale of this problem in injury care. We aimed to identify clinical practice guideline (CPG) recommendations pertaining to low-value injury care, estimate how frequently they are used in practice, and evaluate interhospital variations in their use. Methods: We identified low-value clinical practices from internationally recognized CPGs. We conducted a retrospective cohort study using data from a Canadian trauma system (2014-2019) to calculate frequencies and assess interhospital variations. Results: We identified 29 low-value practices. Fourteen could be measured using trauma registry data. The 3 low-value clinical practices with the highest absolute and relative frequencies were computed tomography (CT) in adults with minor head injury (n = 5591, 24%), cervical spine CT (n = 2742, 31%), and whole-body CT in minor or single-system trauma (n = 530, 32%). We observed high interhospital variation for decompressive craniectomy in diffuse traumatic brain injury. Frequencies and interhospital variations were low for magnetic resonance imaging, intracranial pressure monitoring, inferior vena cava filter use, and surgical management of blunt abdominal injuries. Conclusions: We observed evidence of poor adherence to CPG recommendations on low-value CT imaging and high practice variation for decompressive craniectomy. Results suggest that adherence to recommendations for the 10 other low-value practices is high. These data can be used to advance the research agenda on low-value injury care and inform the development of interventions targeting reductions in healthcare overuse in this population.
查看更多>>摘要：Objectives: To estimate the lifetime health and economic outcomes of selecting active surveillance (AS), radical prostatectomy (RP), or radiation therapy (RT) as initial management for low-or favorable-risk localized prostate cancer. Methods: A discrete-event simulation model was developed using evidence from published randomized trials. Health outcomes were measured in life-years and quality-adjusted life-years (QALYs). Costs were included from a public payer perspective in Australian dollars. Outcomes were discounted at 5% over a lifetime horizon. Probabilistic and scenario analyses quantified parameter and structural uncertainty. Results: A total of 60% of patients in the AS arm eventually received radical treatment (surgery or radiotherapy) compared with 90% for RP and 91% for RT. Although AS resulted in fewer treatment-related complications, it led to increased clinical progression (AS 40.7%, RP 17.6%, RT 19.9%) and metastatic disease (AS 13.4%, RP 6.1%, RT 7.0%). QALYs were 10.88 for AS, 11.10 for RP, and 11.13 for RT. Total costs were A$17 912 for AS, A$15 609 for RP, and A$15 118 for RT. At a willingness to pay of A$20 000/QALY, RT had a 61.4% chance of being cost-effective compared to 38.5% for RP and 0.1% for AS. Conclusions: Although AS resulted in fewer and delayed treatment-related complications, it was not found to be a cost-effective strategy for favorable-risk localized prostate cancer over a lifetime horizon because of an increase in the number of patients developing metastatic disease. RT was the dominant strategy yielding higher QALYs at lower cost although differences compared with RP were small.
查看更多>>摘要：Objectives: Real option value (ROV) is created when a drug enables a patient to live long enough to benefit from a future innovation. Few studies have quantified ROV in the real world. We aimed to estimate the ex post ROV for ipilimumab in metastatic melanoma using real-world data (RWD). Methods: We developed a framework for calculating ROV using RWD, accounting for the health gain in the standard therapy arm and the uptake of future innovations. A Markov model was developed to estimate the quality-adjusted life-years (QALYs) gained with ipilimumab compared with chemotherapy for patients with or without subsequent cancer immunotherapy (CIT). A nationwide electronic health record-derived, deidentified database was used to estimate survival and uptake of CIT. Results: The incremental QALYs gained for ipilimumab compared with chemotherapy without subsequent CIT were 1.74. With subsequent CIT, the incremental QALYs compared with chemotherapy increased by 0.92, 0.60, 0.33, 0.18, 0.10, and 0.02 when CIT became available 0, 3, 6, 9, 12, and 24 months after the initiation of first-line treatment, respectively. The results were most sensitive to the survival benefit of ipilimumab, the survival benefit of subsequent CIT, and the uptake of CIT. Conclusions: This is the first study to estimate ex post ROV using RWD. The ex post ROV was between 1% and 54% of conventional value for patients who received a diagnosis within 2 years before CIT availability. Further studies are needed to understand ROV in other disease areas, particularly those with longer survival times.
查看更多>>摘要：Objective: Early and accurate diagnosis of hip fractures minimizes morbidity and mortality. Although current guidelines favor magnetic resonance imaging (MRI) for the diagnosis of occult hip fractures, a new technology called dual-energy computed tomography (DECT) seems an effective alternative. This article investigates a potentially cost-effective strategy for the diagnosis of occult hip fractures in older adults in Singapore. Methods: A decision tree model was developed to compare costs from a payer's perspective and outcomes in terms of quality adjusted life-years (QALYs) of different imaging strategies for diagnosing occult hip fracture, comparing MRI with DECT supplementing single-energy computed tomography (SECT) and SECT alone. Model inputs were obtained from local sources where available. Sensitivity analyses are performed to test the robustness of the results. Results: The MRI strategy was dominated by the DECT strategy, whereas DECT supplementing SECT provided 0.30 more QALYs at an incremental cost of SGD106.41 with an incremental cost-effectiveness ratio of SGD352.52 per QALY relative to SECT alone. DECT seemed a cost-effective strategy at a willingness-to-pay threshold of SGD50 000 per QALY. Conclusion: DECT supplementing SECT is a cost-effective imaging strategy to diagnose occult hip fractures among older adults in Singapore and should be included in clinical pathways to expedite timely treatment and considered for reimbursement schemes.
Hao, ShuangKarlsson, AndreasHeintz, EmelieElfstrom, K. Miriam...
10页
查看更多>>摘要：Objective: This study aimed to assess the cost-effectiveness of magnetic resonance imaging (MRI) with combinations of targeted biopsy (TBx) and systematic biopsy (SBx) for early prostate cancer detection in Sweden. Methods: A cost-utility analysis was conducted from a lifetime societal perspective using a microsimulation model. Five strategies included no screening and quadrennial screening for men aged 55 to 69 years using SBx alone, TBx on positive MRI (MRI + TBx), combined TBx/SBx on positive MRI (MRI + TBx/SBx), and SBx on negative MRI with TBx/SBx on positive MRI (MRI - SBx, MRI + TBx/SBx). Test characteristics were based on a recent Cochrane review. We predicted the number of biopsies, costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios. Results: The screening strategies were classified in Sweden as high costs per QALY gained compared with no screening. Using MRI + TBx and MRI + TBx/SBx reduced the number of biopsy episodes across a lifetime by approximately 40% compared with SBx alone. Both strategies showed strong dominance over SBx alone and MRI - SBx, MRI + TBx. Compared with MRI + TBx, the MRI + TBx/SBx strategy had an incremental cost-effectiveness ratio of more than euro 200 000 per QALY gained, which was classified in Sweden as a very high cost. These predictions were robust in the probabilistic sensitivity analysis. Limitations included generalizability of the model assumptions and uncertainty regarding the health-state values and study heterogeneity from the Cochrane review. Conclusions: MRI + TBx and MRI + TBx/SBx showed strong dominance over alternative screening strategies. MRI + TBx resulted in similar or marginally lower gains in QALYs and lower costs than MRI + TBx/SBx. MRI + TBx was considered the optimal choice among the screening strategies.
查看更多>>摘要：Objectives: The growing focus on the value of new drugs for patients and society has led to a more differentiated notion of innovation in the context of pharmaceutical products. The goal of this article is to provide an overview of the current debate about the definition and assessment of innovation and how innovation is considered in reimbursement and pricing decisions. Methods: To compile the relevant literature, we followed a 2-step approach. First, we searched for peer-reviewed literature that deals with the definition of pharmaceutical innovation. Second, we reviewed health technology assessment (HTA) guidelines of 11 selected countries (Australia, Belgium, Canada, England, France, Germany, Italy, Japan, Norway, Sweden, and The Netherlands) regarding aspects of innovation that are currently considered as relevant by the respective HTA bodies. Results: All countries in our sample use 1 of 2 types of reward mechanism for novel drugs that they consider provide some sort of benefit. Generally, the focus is on the therapeutic benefit of a drug, whereas, depending on the exact arrangement, other aspects can also be taken into account. A reduction in side effects and aspects of treatment convenience can be invoked in some of the countries. Mostly, however, they are not considered unless they are already captured in the clinical outcomes used to measure the therapeutic benefit. Conclusion: Our review shows that although the health economic literature discusses a range of aspects on how innovation may generate value even without providing an immediate added therapeutic benefit (or on top of it), these are only selectively considered in the reviewed HTA guidelines. For most part, only the added therapeutic value is crucial when it comes to pricing and reimbursement decisions.
查看更多>>摘要：Objectives: This study provides a retrospective analysis of the recommendations of the French National Health Authority on the reimbursement and pricing of innovative drugs. Methods: The analysis includes drugs subjected to both economic and clinical evaluations in France from 2014 to 2020. Ordered logistic and quantile regressions are used to estimate the factors associated with the clinical value (SMR), the clinical added value (ASMR), and the incremental cost-utility ratio (ICUR) of innovative drugs. All variables used in the regression analyses are extracted from the Clinical and Economic Opinions for the 146 observations. Results: Regression analyses indicate that 2 of the 5 official criteria, the efficacy-adverse events balance of the drug and its function, are significantly associated with the SMR rating. The ASMR is positively associated with the disease severity, the quality-adjusted life-year (QALY) gain provided by the drug, and the validation of the ICUR in the Economic Opinion. At the first quartile of the ICUR distribution (approximately euro 50 000/QALY), higher ICUR levels are observed for drugs with a smaller target population and for drugs claimed as more innovative. Higher ICUR levels are also observed for pediatric drugs and for drugs with no therapeutic alternative at the third quartile of the distribution (approximately euro 240 000/QALY). Conclusions: Not all official criteria of the SMR are associated with actual ratings obtained. Regarding the ASMR, the results support the idea of a convergence between the 2 independent clinical and economic appraisal processes. Finally, the factors influencing the ICUR level vary across the distribution of ICUR.
Timbie, Justin W.Kim, Alice Y.Concannon, Thomas W.
7页
查看更多>>摘要：Objectives: To enhance the generalizability of the evidence it reviews, the US Food and Drug Administration (FDA) has encouraged manufacturers to expand the submission of real-world evidence (RWE). The extent to which this evidence, which is generated outside of research settings, can support decision making remains unclear. We described the current use of RWE for medical devices, assessed manufacturers' challenges in generating and using it for regulatory and coverage decisions, and identified opportunities to expand its use. Methods: We conducted 27 solo and group interviews with FDA officials and representatives of device manufacturers, payers, and health technology assessment organizations. All interviews used a semistructured protocol and were transcribed to allow thematic analysis. Results: Accessing and linking real-world data sources, identifying unique devices, capturing longitudinal data, limited staff expertise, and uncertain return on investment have hampered efforts to use real-world data. Many companies in our sample were conducting research using real-world data, but none had submitted RWE as the primary evidence supporting a premarket approval. FDA guidance was helpful, but regulatory requirements remained ambiguous and examples of successful regulatory decisions based on RWE were limited. Payers mainly used RWE to supplement experimental evidence in coverage decisions, evaluated both types of evidence in similar ways, and had concerns about the rigor of RWE. Conclusions: Technical challenges may slow efforts to generate and use RWE in the near term. Additional regulatory guidance and examples, greater use of rigorous study designs and analytic methods, and continued stakeholder engagement could accelerate the use of RWE.
NSTL
Elsevier