Background: Validation of overall survival (OS) extrapolations of immune-checkpoint inhibitors (ICIs) during the National Institute for Health and Care Excellence (NICE) Single Technology Assessment (STA) process is limited due to data still maturing at the time of submission. Inaccurate extrapolation may lead to inappropriate decision-making. The availability of more mature trial data facilitates a retrospective analysis of the plausibility and validity of initial extrapolations. This study compares these extrapolations to subsequently available longer-term data.
Methods: A systematic search of completed NICE appraisals of ICIs from March 2000 to December 2017 was performed. A targeted search was also undertaken to procure published OS data from the pivotal clinical trials for each identified STA made available post-submission to NICE. Initial Kaplan-Meier curves and associated extrapolations from NICE documentation were extracted to compare the accuracy of OS projections versus the most mature data.
Results: The review identified 11 STAs, of which 10 provided OS data upon submission to NICE. The extrapolations undertaken considered parametric or piecewise survival models. Additional data cut-offs provided a mean of 18 months of OS beyond the end of the original data. Initial extrapolations typically under-estimated OS from the most mature data cut-off by 0.4–2.7%, depending on the choice of assessment method and use of the manufacturer- or ERG-preferred extrapolation.
Conclusion: Long-term extrapolation of OS is required for NICE STAs based on initial immature OS data. The results of this study demonstrate that the initial OS extrapolations employed by manufacturers and ERGs generally predicted OS reasonably well when compared to more mature data (when available), although on average they appeared to underestimate OS. This review and validation shows that, while the choice of OS extrapolation is uncertain, the methods adopted are generally aligned with later-published follow-up data and appear appropriate for informing HTA decisions. 相似文献
Motivated by problems of coordination failure in organizations, we examine how overcoming coordination failure and maintaining
coordination depend on the ability of individuals to observe others’ choices. Subjects’ payoffs depend on coordinating at
high effort levels in a weak-link game. Treatments vary along two dimensions. First, subjects either start with low financial
incentives for coordination, which typically leads to coordination failure, and then are switched to higher incentives or
start with high incentives, which usually yield effective coordination, and are switched to low incentives. Second, as the
key treatment variable, subjects either observe the effort levels chosen by all individuals in their experimental group (full
feedback) or observe only the minimum effort (limited feedback). We find three primary results: (1) When starting from coordination
failure the use of full feedback improves subjects’ ability to overcome coordination failure, (2) When starting with good
coordination the use of full feedback has no effect on subjects’ ability to avoid slipping into coordination failure, and
(3) History-dependence, defined as dependence of current effort levels on past incentives, is strengthened by the use of full
feedback.
Electronic Supplementary Material Supplementary material is available in the online version of this article at
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JEL Classification C92, D23, J31, L23, M52 相似文献
Land exploitation, as an important strategy to mitigate farmland loss and stabilize grain production, has been adopted to compensate farmland loss due to rapid urbanization in China. Bounded by the limited capacity and obvious spatial variations of national farmland reserves, it is essential to arrange land exploitation activities timely and reasonably. In this study, we propose an indicator for the status of regional land exploitation, the Exploitation Degree, to facilitate an overview of land exploitation programs in China at both provincial and prefectural levels based on project data from 2006 to 2012. To further our understanding of the regional features of land exploitation activities, we employ the Lasso model to identify and quantitatively assess influencing factors on land exploitation. Our study shows that: (1) contemporary land exploitation practices in China are significantly inconsistent across exploitable farmland reserves. Some areas are greatly over-exploited and such irrational land exploitation has been persistent; (2) related national land plans designed to guide land exploitation efforts centered on resource-rich regions and critical areas do not function as intended. Therefore, we suggest that Chinas land exploitation policy shall be improved by reconsidering the orientation of land exploitation policy, coordinating land exploitation activities with productivity improvements and eco-system protection, and enhancing the power and scope of the plans in controlling and guiding land resource management. 相似文献
The organizational literature has considered complexity as an important factor influencing organizations. More recently, the degree of dissemination of temporary organizations (TOs) increased and today TOs can be found in almost every industry. This corresponds to an augmenting treatment in the literature where TOs are often described as appropriate means to cope with complexity. Yet, few empirical studies to date have analyzed the effects of complexity on the success of TOs. This paper considers three prevalent types of complexity (structural, task, temporal) and integrates two factors (relationship quality, transparency) which are hypothesized to mediate the influence of complexity on the efficiency and effectiveness of TOs. We test the hypothesis using a sample of knowledge-intensive consulting projects. The results show that TOs possess a high degree of “complexity resistance” and are therefore particularly suited for solving unique and complex problems. Of the three types of complexity considered, only structural complexity significantly influences efficiency and effectiveness of TOs. Relationship quality and transparency act as mediators on this effect and can be used to mitigate negative effects of complexity. 相似文献
We establish dynamic game models in a low-carbon supply chain consisting of a single manufacturer and a single retailer with social preference. This study investigates the complex dynamic characteristics of pricing decision and carbon abatement strategy in the supply chain and focuses on the impact of the retailer's social preference on pricing decision, carbon emission abatement strategy, profits, supply chain coordination, and complexity of dynamic models. We find that adjustment parameters of pricing and carbon emission abatement should be maintained in a certain range; otherwise, the system will be unstable and even chaotic through period double bifurcation or wave shape chaos. A higher social preference of the retailer is always beneficial to carbon abatement and the manufacturer and helps maintain the stability of the supply chain system. However, the impact on the long-term profitability of the supply chain is related to the state of the system. Compared with the setting of a centralized decision, the optimal carbon abatement strategy and supply chain profit in a decentralized decision are always less than those in a centralized setting, regardless of whether the retailer has social preference. Therefore, a side-payment self-executing contract is designed to coordinate the supply chain and achieve Pareto improvement. The coordination mechanism proposed in this study not only leads to Pareto improvement but also increases the stability of the supply chain system. Finally, this study enlightens management in operating a low-carbon supply chain. 相似文献
We study how the predictive power of level-k models changes as we perturb the classical beauty contest setting along two dimensions: the strength of the coordination motive and the information symmetry. We use a variation of the Morris and Shin (2002) model as the unified framework for our study, and find that the predictive power of level-k models varies considerably along these two dimensions. Level-k models are successful in predicting subject behavior in settings with symmetric information and a strong coordination motive. Their predictive power weakens significantly when either private information is introduced or the importance of the coordination motive is decreased. 相似文献