Inference and Decision Making for 21st-Century Drug Development and Approval

ABSTRACT

The cost and time of pharmaceutical drug development continue to grow at rates that many say are unsustainable. These trends have enormous impact on what treatments get to patients, when they get them and how they are used. The statistical framework for supporting decisions in regulated clinical development of new medicines has followed a traditional path of frequentist methodology. Trials using hypothesis tests of “no treatment effect” are done routinely, and the p-value < 0.05 is often the determinant of what constitutes a “successful” trial. Many drugs fail in clinical development, adding to the cost of new medicines, and some evidence points blame at the deficiencies of the frequentist paradigm. An unknown number effective medicines may have been abandoned because trials were declared “unsuccessful” due to a p-value exceeding 0.05. Recently, the Bayesian paradigm has shown utility in the clinical drug development process for its probability-based inference. We argue for a Bayesian approach that employs data from other trials as a “prior” for Phase 3 trials so that synthesized evidence across trials can be utilized to compute probability statements that are valuable for understanding the magnitude of treatment effect. Such a Bayesian paradigm provides a promising framework for improving statistical inference and regulatory decision making.     

A critical evaluation of the commodification thesis

A recurring theme across the social sciences is that non‐capitalist production is disappearing albeit slowly and unevenly, and is being replaced by a commodified economy in which goods and services are produced by capitalist firms for a profit under conditions of market exchange. In this paper, however, I evaluate critically this commodification thesis. Even in the heartland of commoditisation ‐ the advanced economies. Large economic spaces are identified where alternative economic relations and motives prevail. Rather than view them as leftovers of pre‐capitalist formations, this paper argues that they are the result of both the contradictions inherent in the structural shifts associated with the pursuit of commodification as well as the existence of‘cultures of resistance’, As such, they are viewed as 'spaces of hope’which highlight the demonstrable construction and practice of alternative social relations and logic's of work outside profit‐motivated market‐oriented exchange.     

Secondary analysis of dangerousness among death sentenced capital murderers

The theory of incapacitation involves reducing an offender's ability or capacity to commit further crimes. Capital punishment accomplishes this goal. An executed murderer never murders again. However, we do not execute all murderers, only capital murderers. This policy produces several research questions. Do capital murderers present a special risk to society? Are capital murderers more likely to murder or commit other violent crimes again than other murderers or the average citizen? To answer these questions, many states require a prediction of future dangerousness of a newly convicted murderer. To what extent has the judgment of future dangerousness matched actuarial data of subsequent murders and serious crimes? Using a secondary analysis, this investigation attempted to assemble available data of postconviction dangerousness of death sentenced capital murderers to create a more comprehensive actuarial account of subsequent dangerousness and to present the data in a common format used by the Federal Bureau of Investigation and the Bureau of Justice Statistics. Across 14 studies identified with relevant data, there were 13 instances of subsequent murder and 462 serious crime or prison rule violations.     

Book review

Stewart, J., Econometrics. (Philip Man, London, 1991.) Pp. viii + 331. $27.95.     

Evaluation: Stakeholder-focused Criteria

Identifying and selecting suitable criteria is an important consideration in evaluating the performance of public sector organizations. Which criteria are chosen, and how they are weighted, will depend largely on the perspective being taken; different stakeholders (for example, clients, providers or commissioners) are likely to emphasize different criteria. In this paper a number of criteria are identified and an argument is developed to indicate which criteria are likely to be valued by various stakeholders. Furthermore, a number of approaches and mechanisms for evaluation are identified and the links between these, the criteria appropriate to them and the various stakeholders are made explicit. Finally, the issue of politics and the distribution of power between the stakeholders is addressed with a call for greater explicitness in using and balancing criteria (for example, as between professionals and the intended beneficiaries of services). In this way, while recognizing the inherent political nature of performance evaluation, the planning and implementation of services may be improved by a more mutually informed approach to evaluation.     

Calculating the total vote where the district magnitude is greater than one: A test of some algorithms using British local election data

Electoral analysis using aggregate data relies on the availability of accurate voting statistics. One vital piece of information, often missing from official electoral returns, particularly British local government elections, is the total number of valid ballot papers. This figure is essential for the calculation of electoral turnout. When voters have a single vote and official information about the number of ballot papers issued is missing, a figure for the total vote can still be derived. However, local elections in Britain frequently use a system of multiple-member wards, where voters have as many votes as there are seats to be filled. In such cases, calculating the total vote and, hence, the turnout does present a real problem. It cannot be assumed that all voters will use their full quota of votes or that voters will cast a ballot in favour of a single party. This paper develops and tests diff erent algorithms for calculating the total vote in such circumstances. We conclude that the accuracy of an algorithm is closely related to the structure of party competition. The findings of this paper have a number of important implications. First, the difficulties in calculating the turnout in multiple-member wards are identified. This will inform the debate about public participation in the local electoral process. Second, the method for deriving a figure for the total vote has an important bearing on a number of other statistics widely employed in electoral analysis.