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.     

The Antecedents of Middle Managers' Strategic Contribution: The Case of a Professional Bureaucracy

abstract    Our study contributes towards a burgeoning literature that argues organizational performance is heavily influenced by what happens in the middle of the organization, rather than at the top. Examining the UK National Health Service, our study develops the work of Floyd and Wooldridge (1992 , 1994 , 1997 , 2000 ). It utilizes role theory to conceptualize changing experiences of middle managers in organizations as a role transition. Associated with this are problems of role conflict and role ambiguity ( Biddle, 1979 , 1986 ; Biddle and Thomas, 1966 ; Kahn et al., 1964 , 1966 ). Our study illustrates that there are limiting factors to a more strategic role for middle managers associated with the professional bureaucracy context. However, role conflict and ambiguity can be mediated by a socialization process, which values incoming identity and personal characteristics ( Van Maanen and Schein, 1979 ).     

Chance Constrained Programming Formulations for Stochastic Characterizations of Efficiency and Dominance in DEA

Pareto-Koopmans efficiency in Data Envelopment Analysis (DEA) is extended to stochastic inputs and outputs via probabilistic input-output vector comparisons in a given empirical production (possibility) set. In contrast to other approaches which have used Chance Constrained Programming formulations in DEA, the emphasis here is on joint chance constraints. An assumption of arbitrary but known probability distributions leads to the P-Model of chance constrained programming. A necessary condition for a DMU to be stochastically efficient and a sufficient condition for a DMU to be non-stochastically efficient are provided. Deterministic equivalents using the zero order decision rules of chance constrained programming and multivariate normal distributions take the form of an extended version of the additive model of DEA. Contacts are also maintained with all of the other presently available deterministic DEA models in the form of easily identified extensions which can be used to formalize the treatment of efficiency when stochastic elements are present.     

The rationality and efficacy of decisions under uncertainty and the value of an experiment

Summary A decision maker faces a known prior distribution over payoff relevant states. We compare the expected utility of this individual under two scenarios. In the first, the decision maker makes a choice without further information. In the second, the decision maker has access to an experiment before choosing an action. However, the decision maker does not know the true joint distribution over states and messages. The value of the experiment as measured by the difference in the two utility levels can be negative as well as positive. We give a condition which is necessary and sufficient for the experiment to be valuable in our sense, for any decision problem.An earlier version of this paper was circulated under the title Noisy Bayes Updating and the Value of Information. We have gained from the comments of Stephen Coate, John Geanakoplos, Larry Samuelson, Timothy Van Zandt and seminar participants at Harvard Business School, Princeton, Boston University, the international conference on game theory at Stony Brook 1992 and the Winter meeting of the Econometric Society at Anaheim 1993. The first author received support for this project from NSF grant #SES-9308515 and a University of Pennsylvania Research Foundation Grant.     

Time to default in the UK mortgage market

This paper employs duration analysis to investigate the timing of default in the UK mortgage market. Our analysis is performed on an ex ante basis, in that our explanatory variables are available to mortgage lenders when the loan is first made. We estimate both standard Weibull distributions and generalizations of the Weibull that permit non-monotonic hazard functions. The models fit the data well, suggesting that we have captured the major sources of variation in duration. We find that ‘cash flow’ variables, such as salary and interest rate paid, play the largest role. Surprisingly, loan-to-value ratios are either insignificant or influence default times in a counter-intuitive direction.     

Observability and overcoming coordination failure in organizations: An experimental study

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 . JEL Classification C92, D23, J31, L23, M52     

Bioenergy Crop Production in the United States: Potential Quantities, Land Use Changes, and Economic Impacts on the Agricultural Sector

The U.S. Departments of Agriculture and Energyjointly analyzed the economic potential for,and impacts of, large-scale bioenergy cropproduction in the United States. Anagricultural sector model (POLYSYS) wasmodified to include three potential bioenergycrops (switchgrass, hybrid poplar, and willow). At farmgate prices of US $2.44/GJ, anestimated 17 million hectares of bioenergycrops, annually yielding 171 million dry Mg ofbiomass, could potentially be produced at aprofit greater than existing agricultural usesfor the land. The estimate assumes highproductivity management practices are permittedon Conservation Reserve Program lands. Traditional crops prices are estimated toincrease 9 to 14 percent above baseline pricesand farm income increases annually by US $6.0billion above baseline.At farmgate prices of US $1.83/GJ, anestimated 7.9 million hectares of bioenergycrops, annually yielding 55 million dry Mg ofbiomass, could potentially be produced at aprofit greater than existing agricultural usesfor the land. The estimate assumes managementpractices intended to achieve highenvironmental benefits on Conservation ReserveProgram lands. Traditional crops prices areestimated to increase 4 to 9 percent abovebaseline prices and farm income increasesannually by US $2.8 billion above baseline.     

The role of (non-)transparency in a currency crisis model

This paper extends the work by Morris and Shin (Am. Econom. Rev. 88 (1998) 587-597) where multiple equilibria in the self-fulfilling currency attack models can be reduced to a unique equilibrium when agents observe fundamentals privately with small errors. We find that under a more general specification with realistic parameters, noisy private observations are generally insufficient to prevent the multiplicity of equilibria. The pivotal role played by the transparency of fundamentals/policies in currency crisis is also examined. Surprisingly, transparency may trigger rather than eliminate currency crises when fundamentals are relatively healthy. Our results may be relevant to research in other coordination problems.     

Some Determinants of Property Crime: Economic Factors Influence Criminal Behavior But Cannot Completely Explain the Syndrome

Abstract . An empirical analysis of the property crimes, robbery, burglary and larceny, is presented for all 120 counties in Kentucky. While this analysis is based on an economic model of crime, certain sociological and legal variables are included as well in the system of equations. Overall, the empirical results support prior studies’findings with the exception that a quadratic relationship is found to exist between urbanization and each of the property crimes. Furthermore, neither the economic nor the non economic influences measured appear more important for affecting crime rates. Specifically, results indicate that the level of poverty, the degree of tourism, the presence of police, the unemployment rate and the apprehension rate all affect property crimes. In contrast, the length of sentence, the degree of industrialization, the level of public assistance payments and the proportion of youth in the county have no affect on property crime rates in these areas.