'Polyphonic' welfare: Luhmann's systems theory applied to modern social work

This article applies a series of concepts from Niklas Luhmann's systems theory in an analysis of modern welfare organisations. The point of departure is that social help in late modern welfare states has become 'polycentric' in that 'help' is today being defined by various different agents: public, voluntary and private care providers. Empirically, this article investigates re-housing work with homeless people, a kind of social work which involves several different welfare organisations. The case study shows how these organisations define themselves by making internal constructions of their surroundings, and how their self-enclosed nature creates a certain 'insensitivity' towards one another. How to coordinate and translate within this 'polyphony' of incomparable observations and values represents a major managerial challenge for present-day social workers.     

Principal stratum strategy: Potential role in drug development

A randomized trial allows estimation of the causal effect of an intervention compared to a control in the overall population and in subpopulations defined by baseline characteristics. Often, however, clinical questions also arise regarding the treatment effect in subpopulations of patients, which would experience clinical or disease related events post-randomization. Events that occur after treatment initiation and potentially affect the interpretation or the existence of the measurements are called intercurrent events in the ICH E9(R1) guideline. If the intercurrent event is a consequence of treatment, randomization alone is no longer sufficient to meaningfully estimate the treatment effect. Analyses comparing the subgroups of patients without the intercurrent events for intervention and control will not estimate a causal effect. This is well known, but post-hoc analyses of this kind are commonly performed in drug development. An alternative approach is the principal stratum strategy, which classifies subjects according to their potential occurrence of an intercurrent event on both study arms. We illustrate with examples that questions formulated through principal strata occur naturally in drug development and argue that approaching these questions with the ICH E9(R1) estimand framework has the potential to lead to more transparent assumptions as well as more adequate analyses and conclusions. In addition, we provide an overview of assumptions required for estimation of effects in principal strata. Most of these assumptions are unverifiable and should hence be based on solid scientific understanding. Sensitivity analyses are needed to assess robustness of conclusions.     

Integrating phase 2 into phase 3 based on an intermediate endpoint while accounting for a cure proportion—With an application to the design of a clinical trial in acute myeloid leukemia

For a trial with primary endpoint overall survival for a molecule with curative potential, statistical methods that rely on the proportional hazards assumption may underestimate the power and the time to final analysis. We show how a cure proportion model can be used to get the necessary number of events and appropriate timing via simulation. If phase 1 results for the new drug are exceptional and/or the medical need in the target population is high, a phase 3 trial might be initiated after phase 1. Building in a futility interim analysis into such a pivotal trial may mitigate the uncertainty of moving directly to phase 3. However, if cure is possible, overall survival might not be mature enough at the interim to support a futility decision. We propose to base this decision on an intermediate endpoint that is sufficiently associated with survival. Planning for such an interim can be interpreted as making a randomized phase 2 trial a part of the pivotal trial: If stopped at the interim, the trial data would be analyzed, and a decision on a subsequent phase 3 trial would be made. If the trial continues at the interim, then the phase 3 trial is already underway. To select a futility boundary, a mechanistic simulation model that connects the intermediate endpoint and survival is proposed. We illustrate how this approach was used to design a pivotal randomized trial in acute myeloid leukemia and discuss historical data that informed the simulation model and operational challenges when implementing it.     

Quantification of follow-up time in oncology clinical trials with a time-to-event endpoint: Asking the right questions

For the analysis of a time-to-event endpoint in a single-arm or randomized clinical trial it is generally perceived that interpretation of a given estimate of the survival function, or the comparison between two groups, hinges on some quantification of the amount of follow-up. Typically, a median of some loosely defined quantity is reported. However, whatever median is reported, is typically not answering the question(s) trialists actually have in terms of follow-up quantification. In this paper, inspired by the estimand framework, we formulate a comprehensive list of relevant scientific questions that trialists have when reporting time-to-event data. We illustrate how these questions should be answered, and that reference to an unclearly defined follow-up quantity is not needed at all. In drug development, key decisions are made based on randomized controlled trials, and we therefore also discuss relevant scientific questions not only when looking at a time-to-event endpoint in one group, but also for comparisons. We find that different thinking about some of the relevant scientific questions around follow-up is required depending on whether a proportional hazards assumption can be made or other patterns of survival functions are anticipated, for example, delayed separation, crossing survival functions, or the potential for cure. We conclude the paper with practical recommendations.     

The right tool for the job: problems and solutions in visualizing sociological theory

The visualization of social theory is an important part of the development and communication of our theoretical ideas. While most theorists use figures of some kind, few if any have formal training, or guiding rules or principles for the representation of theory. This has often led to poor visualization efforts, and the visual culture of sociology continues to lag behind the natural sciences. The intent of this paper is to serve as a practical and empirically aided guide for social theorists, by providing insights surrounding the cognitive and perceptual properties of certain elements and figures. Through these properties we identify four major problems in theory visualization: vagueness, reduction, unwanted spatial inferences and unwanted metaphorical inferences. We offer solutions to these problems, and to improving theory visualization more generally. Our hope is that this paper will serve as a resource for more thoughtful and informed visualization for practicing social theorists.     

Treatment effect quantification for time‐to‐event endpoints–Estimands,analysis strategies,and beyond

A draft addendum to ICH E9 has been released for public consultation in August 2017. The addendum focuses on two topics particularly relevant for randomized confirmatory clinical trials: estimands and sensitivity analyses. The need to amend ICH E9 grew out of the realization of a lack of alignment between the objectives of a clinical trial stated in the protocol and the accompanying quantification of the “treatment effect” reported in a regulatory submission. We embed time‐to‐event endpoints in the estimand framework and discuss how the four estimand attributes described in the addendum apply to time‐to‐event endpoints. We point out that if the proportional hazards assumption is not met, the estimand targeted by the most prevalent methods used to analyze time‐to‐event endpoints, logrank test, and Cox regression depends on the censoring distribution. We discuss for a large randomized clinical trial how the analyses for the primary and secondary endpoints as well as the sensitivity analyses actually performed in the trial can be seen in the context of the addendum. To the best of our knowledge, this is the first attempt to do so for a trial with a time‐to‐event endpoint. Questions that remain open with the addendum for time‐to‐event endpoints and beyond are formulated, and recommendations for planning of future trials are given. We hope that this will provide a contribution to developing a common framework based on the final version of the addendum that can be applied to design, protocols, statistical analysis plans, and clinical study reports in the future.     

Perceived racial discrimination, depression, and coping: a study of Southeast Asian refugees in Canada.

Using data obtained from personal interviews with 647 Southeast Asian refugees in Canada, this study tests hypotheses regarding both the association between perceived racial discrimination and depression, and the roles of coping and ethnic identity in conditioning the nature of the discrimination-depression relation. Refugees who reported that they had experienced racial discrimination had higher depression levels than their counterparts who reported no such experiences. Responding to discrimination through confrontation was not significantly associated with depression. Study findings support the effectiveness of forbearance in diminishing the strength of the association between discrimination and depression. The moderating effect of forbearance was conditioned by the level of ethnic identity: The beneficial effect of forbearance was significantly greater among those holding stronger ethnic identification. Cultural and situational interpretations of the findings are presented.     

Bayesian predictive power: choice of prior and some recommendations for its use as probability of success in drug development

Bayesian predictive power, the expectation of the power function with respect to a prior distribution for the true underlying effect size, is routinely used in drug development to quantify the probability of success of a clinical trial. Choosing the prior is crucial for the properties and interpretability of Bayesian predictive power. We review recommendations on the choice of prior for Bayesian predictive power and explore its features as a function of the prior. The density of power values induced by a given prior is derived analytically and its shape characterized. We find that for a typical clinical trial scenario, this density has a u‐shape very similar, but not equal, to a β‐distribution. Alternative priors are discussed, and practical recommendations to assess the sensitivity of Bayesian predictive power to its input parameters are provided. Copyright © 2016 John Wiley & Sons, Ltd.     

Estimands in hematologic oncology trials

The estimand framework included in the addendum to the ICH E9 guideline facilitates discussions to ensure alignment between the key question of interest, the analysis, and interpretation. Therapeutic knowledge and drug mechanism play a crucial role in determining the strategy and defining the estimand for clinical trial designs. Clinical trials in patients with hematological malignancies often present unique challenges for trial design due to complexity of treatment options and existence of potential curative but highly risky procedures, for example, stem cell transplant or treatment sequence across different phases (induction, consolidation, maintenance). Here, we illustrate how to apply the estimand framework in hematological clinical trials and how the estimand framework can address potential difficulties in trial result interpretation. This paper is a result of a cross-industry collaboration to connect the International Conference on Harmonisation (ICH) E9 addendum concepts to applications. Three randomized phase 3 trials will be used to consider common challenges including intercurrent events in hematologic oncology trials to illustrate different scientific questions and the consequences of the estimand choice for trial design, data collection, analysis, and interpretation. Template language for describing estimand in both study protocols and statistical analysis plans is suggested for statisticians' reference.     

Searching for therapies,seeking for hope: transnational cancer care in Asia

ABSTRACT

This paper is about transnational cancer care in Asia. People with terminal diseases such as cancer increasingly escape devastating prognosis of their local regimes of clinical diagnostic truth by traveling to destinations where medicine is more advanced, yet affordable for them, and hence offers a broader scope for hope. The paper suggests that transnational cancer care provides an instructive case of the enormous geographical disparities in the availability of therapies and how this, combined with economies of hope and the marketization of health care, affects patients and their family caregivers. The primary contribution of the paper is the introduction of the concept of relational subjectivities to the health mobilities literature. The findings presented proof that the concept provides a fruitful analytical lens, yielding not only fresh empirical insights but prompting re-conceptualizations of medical travel itself as hopeful, yet risky transnational acts of family care.