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 majorization comparison of apportionment methods in proportional representation

From the inception of the proportional representation movement it has been an issue whether larger parties are favored at the expense of smaller parties in one apportionment of seats as compared to another apportionment. A number of methods have been proposed and are used in countries with a proportional representation system. These apportionment methods exhibit a regularity of order, as discussed in the present paper, that captures the preferential treatment of larger versus smaller parties. This order, namely majorization, permits the comparison of seat allocations in two apportionments. For divisor methods, we show that one method is majorized by another method if and only if their signpost ratios are increasing. This criterion is satisfied for the divisor methods with power-mean rounding, and for the divisor methods with stationary rounding. Majorization places the five traditional apportionment methods in the order as they are known to favor larger parties over smaller parties: Adams, Dean, Hill, Webster, and Jefferson. Received: 5 August 2000/Accepted: 24 October 2001     

Territorial Modernity and Public Space: Lessons from the Politics of Water Conflict Along the US/Canadian Border

Conflict over water resources is a major problem throughout the world. This essay describes the long-standing and often successful effort to insulate decisions on how to allot water among contending users, and how to reduce water pollution along a 5000-mile international border. The effort has been fraught with political and scientific complexity. Yet, after more than 90 years of experience, it provides a model that other nations are beginning to examine as relevant to their own efforts to find solutions.     

Binding the Generations: Household Formation Patterns among Vietnamese Refugees1

Much of the analysis of refugee and immigrant adaptation has stressed the interaction of prior experience with the requirements of life in a new country. For refugees, that interaction has often been jarring because of the after‐effects of their flight and their relative inability to prepare for a new life in a new country. Yet refugees have often done rather well in economic terms in that new country. The reasons for that relative success have been phrased in cultural terms (e.g., the predisposition toward education) and in general socioeconomic terms (e.g., refugees as educated and skilled). This article examines a set of factors that lie between these customary cultural and socioeconomic categories. Specifically, the paper examines key features of household formation among Vietnamese refugees. An examination of historical data from southern Vietnam indicates patterns in household formation that appear durable over time yet are not shared across the breadth of Vietnam and cannot thus be viewed as “cultural” in the usual sense. A comparison of the historical data with recent national survey data on refugees in the United States indicates that these patterns continue among Vietnamese refugees and are ‐ as compared to other refugees ‐ distinctive to them. These patterns of household formation provide Vietnamese refugees with important options in adaptation to a new country.     

The Persistent Problem of Colorism: Skin Tone, Status, and Inequality

Colorism is a persistent problem for people of color in the USA. Colorism, or skin color stratification, is a process that privileges light-skinned people of color over dark in areas such as income, education, housing, and the marriage market. This essay describes the experiences of African Americans, Latinos, and Asian Americans with regard to skin color. Research demonstrates that light-skinned people have clear advantages in these areas, even when controlling for other background variables. However, dark-skinned people of color are typically regarded as more ethnically authentic or legitimate than light-skinned people. Colorism is directly related to the larger system of racism in the USA and around the world. The color complex is also exported around the globe, in part through US media images, and helps to sustain the multibillion-dollar skin bleaching and cosmetic surgery industries.