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.     

Anmerkungen zur Publikation „Möglichkeiten und Probleme des Einsatzes postalischer Befragungen“ von Karl-Heinz Reuband in der Kzfss 2001, 2, S. 307–333

Reuband’s article purports to report empirical results that seem to contradict the widely held view of mail surveys. This assertion is made possible only by an unclear statement of hypotheses and a selective perception of the literature. The data analysis is based on techniques from the 1960s and 1970s; modern methods are not even mentioned. Although all the results reported in the article are based on local surveys conducted by a university institute, these are generalized to national surveys in general. The main points of this critique are methodological: careless literature review, lack of concrete hypotheses, inefficient data analysis and generalizations without empirical foundation.     

Determinanten regelkonformen Verhaltens am beispiel des Strassenverkehrs

The main role of traffic police enforcement can be seen as preventing road users from committing offences, which can be related to road crashes and injuries. As the operating principle underlying the impact of police enforcement a deterrence effect has been discussed repeatedly, whereas from a sociological perspective the importance of “Norm Internalisation” has been emphasised. Thus, the present paper aims at comparing the influence of “Norm Internalisation” and the variables constituting the deterrence effect on the compliance with rules in road traffic. Based on a secondary analysis of data from a project on behavioural determinants of police surveillance carried out by the “Institute of Applied Transport and Tourism Research” (IVT) on behalf of the Federal Highway Research Institute (BASt) an operationalisation of the construct “General Norm Orientation” is developed. In several subsequent steps of statistical analysis patterns of correlations with variables from Opp’s “Theory of Law Obedience” are revealed. Results show a sufficiently high internal consistency (α = 0,82) of the scale “General Norm Orientation” and significant correlations with variables from Opp’s theory. The directions of these correlations are as expected and confirmed by multivariate analyses. Results are discussed with respect to their implications for influencing road users’ behaviours.     

Cohabitation and commitment: partnership plans of young men and women

Popular commentators on marriage and the family often interpret the increase in heterosexual couples living together without marrying as reduced willingness to create and honour life‐long partnerships. Survey and in‐depth interviews with samples of 20–29 year olds living in an urban area of Scotland finds little support for the postulated link between growing cohabitation and a weakened sense of commitment to long‐term arrangements. Most of the cohabiting couples strongly stressed their ‘commitment’. Socially acceptable vocabularies of motive undoubtedly influenced answers but interviews helped to explore deeper meanings. Many respondents’ views were consistent with previous research predictions of a weakening sense of any added value of marriage. At the same time, some respondents continued to stress the social significance of the distinction between marriage and cohabitation, consistent with research interpreting cohabitation as a ‘try and see’ strategy part‐way to the perceived full commitment of marriage. The notion that ‘marriage is better for children’ continued to have support among respondents. While, on average, cohabiting couples had lower incomes and poorer employment situations than married couples, only very extreme adverse circumstances were presented as making marriage ‘too risky’. Pregnancy‐provoked cohabitation was not always in this category. Cohabitation was maintained because marriage would ‘make no difference’ or because they ‘had not yet got round to’ marriage. Most respondents were more wary of attempting to schedule or plan in their personal life than in other domains and cohabitees’ attitudes to partnership, including their generally ‘committed’ approach, do not explain the known greater vulnerability of this group to dissolution.     

Beate Krais (Hg.): An der Spitze. Von Eliten und herrschenden Klassen

Ohne Zusammenfassung     

‚The Good, the Bad, and the Ugly‘

According to the most influential contribution of recent years to the comparative study of advanced welfare states, Esping-Andersen’s ’Three Worlds of Welfare Capitalism‘, the welfare state basically comes in three variants: as a social-democratic, a conservative, or as a liberal regime. Yet, at a closer look, in particular the ’conservative‘ regime-type represents a highly problematic category. The article claims that the major problems of Esping-Andersen’s typology and theory originate from his sole focus on the class conflict and his neglect of the religious cleavage. Major theoretical contradictions and empirical puzzles of his approach can be solved if we take not only the impact of the catholic social doctrine on the development of the welfare state into account, but consider also the influence of social protestantism, especially that of protestant dissent and of protestant non-conformism. The paper substantiates this claim with data for the early formative period of the welfare state (1890–1920) as well as for the high-time of the welfare state from the 1960s to the 1990s.     

Spatial Variations in Church Burnings: The Social Ecology of Victimized Communities in the South*

Abstract In recent years, church burnings in the South have attracted a great deal of attention. Many commentators have charged that they are a product of strained race relations throughout the South, and particularly of severe racial tensions in Southern rural areas. In this study we evaluate these claims. We begin by mapping the spatial coordinates of recorded church burnings from 1990 to 1997, and find that church arsons indeed are concentrated in the South. Church burnings, however, are a more urban phenomenon than popular media accounts would suggest. Our analysis then explores the influence of contextual factors (population and locale, racial composition and inequality, so‐cioeconomic conditions, local religious ecology, and patterns of reported crime) on church burnings in counties located in the study region. Logistic regression models confirm that church arsons are most likely to occur in small metropolitan statistical areas (MSAs) and non‐MSA counties containing a city of at least 10,000 residents. Church burnings also are especially likely in counties with a higher percentage of black residents, a larger number of churches relative to the rest of the state, and a higher arson rate. We conclude by discussing the implications of these findings for future research and public policy.     

Generationswechsel im Management ost- und westdeutscher Unternehmen

Currently, in the top-management of German enterprises a generational shift is taking place. The paper looks at the consequences of this change concerning the future of the ‘German model of capitalism’. Are the managers of the new generation still holding on to the traditional German management culture or are they orienting themselves more strongly towards the US-American shareholder-value model? In order to clarify this question, the existing empirical results of management research are systematically evaluated. According to the results of this analysis we are not going to face a far-reaching Americanization of the management culture. However, under the pressure of globalization a significant differentiation between management culture in large enterprises on the one hand and management culture in small and medium-sized enterprises on the other hand occurs. While managers of large enterprises adopt elements of the American management model to a great degree, German management seems to become even more accentuated in the culture of small and medium-sized enterprises. In the context of this recent development existing differences between the management in Eastern and Western German enterprises dissolve along with the alternation of generations.