A review and validation of overall survival extrapolation in health technology assessments of cancer immunotherapy by the National Institute for Health and Care Excellence: how did the initial best estimate compare to trial data subsequently made available?

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.     

Economic progress and skill obsolescence with network effects

Summary. We construct an OLG model with network effects to examine skill obsolescence when individuals can choose technological vintages. In the absence of transfer payments, some regions of the parameter space have unique stationary equilibria, others have unique cyclical equilibria, and others have multiple stationary equilibria. All equilibria are Pareto efficient. However, rat race equilibria can exist in which all agents currently alive prefer a slower rate of progress than occurs in equilibrium. When contemporaneous transfers are allowed, equilibria are unique everywhere, but a cycle still exists, and a rat race can still arise in equilibrium. Allowing intertemporal transfers (debt) ensures that all equilibria are stationary. In the relevant parameter range, the introduction of debt can eliminate cycles and increase the long-run growth rate. No rat race equilibria exist when debt is allowed.Received: 3 January 2002, Revised: 3 June 2004, JEL Classification Numbers: 041, J24, O33. Correspondence to: Ian P. KingEarly versions of this paper were presented at the West Coast Macro Workshop, the Mid-West Macro Meetings, the Canadian Macroeconomics Study Group Meetings, and the Society for Economic Dynamics Meetings. We would like to thank V. V. Chari, Merwan Engineer, Don Ferguson, John Hillas, John Knowles, Dan Peled, Dan Usher, Linda Welling and Julian Wright for helpful comments. We are especially grateful to an anonymous referee for some very useful and substantive comments.     

Assessing the impact of patent infringement on new product sales

In order to assess the impact of patent infringement on the growth of a new product, a model is developed through the intervention model development processes of Box-Jenkins and Box-Tiao. Physical interpretations of model parameters and determination of associated damages suggest that the model can provide a sound basis for analyzing patent infringement disputes.     

Regulatory Uncertainty and Share Price Volatility: the English and Welsh Water Industry’s Periodic Price Review

This paper models the London stock markets response to the 1994 Periodic Review of prices in the English and Welsh water industry using both GARCH and stochastic volatility models. The results indicate that a significant reduction in the volatility of share prices for eight of the ten water and sewerage companies followed the announcement of revised industry price-caps. Investor expectations adjusted rapidly, reflecting confidence in the credibility and political sustainability of the settlement.     

The relationship between performance appraisal criterion specificity and statistical evidence of discrimination

Plaintiffs' expert witnesses in EEO cases involving performance appraisals often claim that adverse impact is a result of the type of rating format used. Their theory is that more specific rating criteria will lead to lessened adverse impact. We tested that theory by comparing data from a simple category‐based rating system against data from a standards‐based Work Planning and Review appraisal system with over 248,000 performance appraisals of state employees. Using logistic regression and statistical definitions of prima facie discrimination, we found no support for the hypothesis that adverse impact is materially affected by criterion specificity. © 2003 Wiley Periodicals, Inc.     

The effect of rule 12b-1 on bond fund expense ratios

This paper presents empirical evidence that bond mutual funds which have adopted the use of 12b-1 fees have not achieved the goal of lowering expense ratios. Using a model specific to bond funds, as opposed to generic models used in previous studies on equity funds, the analysis confirms that the 12b-1 fee is an additional cost borne by shareholders of the fund without any additional benefit. However, this cost as a percent of the net asset value of the fund has decreased from 1991 through 1994. This reduction coincides with the submission of a proposed rule change by the National Association of Security Dealers concerning maximum sales charges imposed by mutual funds on December 28, 1990 and the implementation of limits on 12b-1 fees which became effective in July of 1993.     

CONSTRUING ORGANIZATIONAL TEXTURE IN YOUNG ENTREPRENEURIAL FIRMS

In a young entrepreneurial firm, two developmental processes are identified. One reflects the emergence of a social network whilst the other reflects the emergence of a task domain. The concept of ‘organizational dialogue’ is introduced to describe the action strategies through which these two processes are connected. The resulting textures may critically be examined to produce ‘process’ knowledge. It is argued that organizational theory can benefit from more work of this kind.     

Macroeconomic forecasting using structural factor analysis

The use of a small number of underlying factors to summarize the information from a much larger set of information variables is one of the new frontiers in forecasting. In prior work, the estimated factors have not usually had a structural interpretation and the factors have not been chosen on a theoretical basis. In this paper we propose several variants of a general structural factor forecasting model, and use these to forecast certain key macroeconomic variables. We make the choice of factors more structurally meaningful by estimating factors from subsets of information variables, where these variables can be assigned to subsets on the basis of economic theory. We compare the forecasting performance of the structural factor forecasting model with that of a univariate AR model, a standard VAR model, and some non-structural factor forecasting models. The results suggest that our structural factor forecasting model performs significantly better in forecasting real activity variables, especially at short horizons.     

Restructuring materiel management functions: a method for prioritizing changes and reducing costs

The success of any manager depends highly on the ability to seize on opportunities that will achieve the organization's goals. Hospitals are currently searching for ways to reduce costs while maintaining or enhancing the quality of services. Quality services are increasingly being defined as those that are most responsive to customer needs. It is important, as hospital management restructures materiel systems or methods of operation for reduced costs, to focus on the user departments as the customers. The consolidation of materiel management activity should not be seen as a loss of control at the user department level. Instead it can be seen as a new way of providing service with higher quality. User departments should see concrete benefits on a weekly basis, including reduced time spent on materiel management functions; increased planning of purchasing, inventory, and distribution functions; and assistance in meeting restricted supply budgets.