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.     

Risk Modeling of Interdependent Complex Systems of Systems: Theory and Practice

The emergence of the complexity characterizing our systems of systems (SoS) requires a reevaluation of the way we model, assess, manage, communicate, and analyze the risk thereto. Current models for risk analysis of emergent complex SoS are insufficient because too often they rely on the same risk functions and models used for single systems. These models commonly fail to incorporate the complexity derived from the networks of interdependencies and interconnectedness (I–I) characterizing SoS. There is a need to reevaluate currently practiced risk analysis to respond to this reality by examining, and thus comprehending, what makes emergent SoS complex. The key to evaluating the risk to SoS lies in understanding the genesis of characterizing I–I of systems manifested through shared states and other essential entities within and among the systems that constitute SoS. The term “essential entities” includes shared decisions, resources, functions, policies, decisionmakers, stakeholders, organizational setups, and others. This undertaking can be accomplished by building on state‐space theory, which is fundamental to systems engineering and process control. This article presents a theoretical and analytical framework for modeling the risk to SoS with two case studies performed with the MITRE Corporation and demonstrates the pivotal contributions made by shared states and other essential entities to modeling and analysis of the risk to complex SoS. A third case study highlights the multifarious representations of SoS, which require harmonizing the risk analysis process currently applied to single systems when applied to complex SoS.     

朱熹和孟子解读舜之“怨慕”的不同逻辑

对于舜之“怨慕”,朱熹作出了不同于孟子的解读。这是基于心学、理学内在逻辑的不同。孟子作为私学之儒,和孔子一样,是主张士君子的阳刚人格的,并且从性向善的人性论出发,协调义与利、公与私的关系,而以君臣父子关系都属对待关系;依此,将舜之“怨慕”解读为舜对父母的既怨又慕。朱熹则作为官学之儒,以所谓“气质之性”协调理学先驱荀子的性向恶论,以二歧化思维把天地之性、天理绝对化,以公去私,视君臣父子关系则为下对上的绝对服从关系;依此解读,舜之“怨”只能是自怨。     

需求率受推广努力水平影响的新能源汽车租赁系统协调契约

考虑由新能源汽车租赁企业和政府组成的二级系统，在需求率为随机且与推广努力水平相关的市场环境下，建立了新能源汽车租赁企业和政府之间的博弈模型，探讨了分散决策、集中决策、收益共享与成本共担契约下的最优车队配置和推广努力水平，并对三种情形下的最优决策进行了比较和分析。研究结果表明：在分散决策情况下无法实现系统协调，通过引入成本共担与收益共享组合契约，当契约参数满足一定条件时，该组合契约模型不仅可以实现系统协调而且可以使系统成员达到帕累托改进。最后通过算例分析，验证了模型了可靠性和有效性。     

Professional blinders? The novel as an eye-opener in organizational analysis

ABSTRACT

Scholarly textbooks often follow a logic where suitable empirical cases are selected to illustrate the theoretical and analytical points that we as scholars want to make. But what would happen if we would do the opposite: build a textbook on a novel written by a novelist for such purpose and let the theories explain the actions and emotions of fictional characters? In this article, we share and reflect upon our experiences of co-authoring a textbook in organization theory together with a professional novelist. We argue that the novel can function as an eye-opener in organizational analysis, forcing us to look beyond more static and rationalistic perspectives on organizations as well as the stereotypes of such. We build and relate our experiences to the growing literature about using fiction in scholarly work and discuss the potential of such genre-bending work when we bring in flesh and blood into the analyses.     

Transnational policy entrepreneurs and the cultivation of influence: individuals,organizations and their networks

ABSTRACT

The ‘policy entrepreneur’ concept arises from the Multiple Streams’ theory of agenda setting in Policy Studies. Through conceptual stretching’, the concept is extended to global policy dynamics. Unlike ‘advocacy networks’ and ‘norm entrepreneurs’, the discussion addresses the strategies of ‘insider’ or ‘near-governmental’ non-state actors. The analysis advances the policy entrepreneur concept in three directions. First, the discussion develops the transnational dimensions of this activity through a case study of International Crisis Group. Second, rather than focusing on charismatic individuals, the discussion emphasizes the importance of organizational resources and reputations for policy entrepreneurship and access into international policy communities. Organizations maintain momentum behind policy solutions and pressures for change over the long term when individuals retire or depart for other positions. Third, the discussion outlines four distinct entrepreneur strategies and techniques that both individuals and organizations cultivate and deploy to enhance their power and persuasion in global policy processes and politics.     

How do countries choose their monetary policy frameworks?

This paper investigates the determinants of countries’ choices of monetary policy framework. A brief narrative focused on groupings of countries motivates an econometric analysis which draws on previous work on the determinants of exchange rate regimes, bringing in standard factors as well as the trade networks of potential anchor currency blocs and the financial market depth that are emphasised in the narrative. The model turns out to be able to predict three quarters of countries’ choices, and there is no obvious systematic pattern in the errors. The results have important implications for how countries should choose their monetary policy frameworks.     

Enterprising? Disabled? The status and potential for disabled people’s microenterprise in South Korea

This article explores the position, potential and scope for self-employment and microenterprise for disabled South Koreans. The chronic barriers experienced in disabled people gaining paid work suggest that self-employment and enterprise might offer a good alternative to paid work. The self-determined nature of running a microenterprise has been shown to connect with disabled people who may not conform to standardised notions of body and brain that underpin many mainstream work contexts. Despite this promise, several barriers continue to beset disabled people’s access to micro-enterprise activity; barriers ranging from Confucian precepts, to employment protections that are geared largely towards paid employment and to the lack of training, finance and business support for disabled people starting up and sustaining microenterprise in Korea. The extension of legal protections, meaningful start-up subsidies, better business support and bridges between paid work and microenterprise are all seen as important policy correctives that would better support disabled people.     

The disembedded digital economy: Social protection for new economy employment in China

This research focuses upon employment in the new economy, exploring labour protection and social protection in the digital age in China. Through an empirical survey conducted in three Chinese cities, social insurance and the labour rights of employees in the digital economic sector, such as gig employment, e-commerce, and various other forms of online employment, have been examined in-depth. This study reveals new regulatory loopholes in the digital labour market, which have substantially eroded the basis of social policy arrangements in China, “softening” participation in social insurance branches and compliance with labour regulations remarkably. Drawing upon the theoretical concepts of Polanyi on embeddedness and disembeddedness, we argue that the digital employment sector in China has been increasingly disembedded from social institutions and social control. The new configuration in the digital field of social policy requires novel conceptual models and institutional settings to cope with increasing social risks in virtual spaces.     

Journey towards independent living: a grounded theory investigation of leaving the care of Girls & Boys Town,South Africa

The journey out of care and towards independent living is a challenge for many care-leavers. There has been little research into the social processes involved in this care-leaving journey. This paper presents the results of a grounded theory investigation into the care-leaving journeys of nine young men who had, several years previously, been in the care of Girls & Boys Town in South Africa. Working from a resilience perspective, with an ecological emphasis, four central social processes emerged that together explain the care-leaving experiences of the participants. These processes are striving for authentic belonging; networking people for goal attainment; contextualised responsiveness and building hopeful and tenacious self-confidence. These four processes are located within contextual boundaries and at the social environmental interface. The paper presents these processes in detail, drawing on selected narratives of the participants and integrated with additional theory. It is hoped that this paper may contribute to theory building concerning care-leaving processes and enhance youth care practices for youth in care and leaving care.