Testing for ordered failure rates under general progressive censoring

For exponentially distributed failure times under general progressive censoring schemes, testing procedures for ordered failure rates are proposed using the likelihood ratio principle. Constrained maximum likelihood estimators of the failure rates are found. The asymptotic distributions of the test statistics are shown to be mixtures of chi-square distributions. When testing the equality of the failure rates, a simulation study shows that the proposed test with restricted alternative has improved power over the usual chi-square statistic with an unrestricted alternative. The proposed methods are illustrated using data of survival times of patients with squamous carcinoma of the oropharynx.     

A Bayesian method of sample size determination with practical applications

Summary.  The problem motivating the paper is the determination of sample size in clinical trials under normal likelihoods and at the substantive testing stage of a financial audit where normality is not an appropriate assumption. A combination of analytical and simulation-based techniques within the Bayesian framework is proposed. The framework accommodates two different prior distributions: one is the general purpose fitting prior distribution that is used in Bayesian analysis and the other is the expert subjective prior distribution, the sampling prior which is believed to generate the parameter values which in turn generate the data. We obtain many theoretical results and one key result is that typical non-informative prior distributions lead to very small sample sizes. In contrast, a very informative prior distribution may either lead to a very small or a very large sample size depending on the location of the centre of the prior distribution and the hypothesized value of the parameter. The methods that are developed are quite general and can be applied to other sample size determination problems. Some numerical illustrations which bring out many other aspects of the optimum sample size are given.     

A theory of age exclusion through closure: ‘Chronological age’ to ‘clinical need’

In an approach, I term ‘age exclusion through closure,’ I describe the exclusion of older people, from the workforce, and from hospital-based continuing care in Britain. Nineteenth century socioeconomic changes—the introduction of workplace technology, social surveys, the New Poor Law, and workhouse isolation, culminated in workforce exclusion on the grounds of chronological age. In the 20th century, the Poor Law ‘therapy’/‘succour’ divide, was recast in the Welfare State ‘health’/‘social care’ divide. Socioeconomic changes—the rising cost of health care, demographic change, the development of geriatric medicine, and economic restructuring, have served to allocatively ration ‘continuing care’ at this interface through the criteria of ‘clinical need.’ To conclude, age has become forged to clinical need, to become a formidable force of exclusion and exploitation perpetuating Poor Law closure between those ‘able’ and ‘unable’ to work, and creating a consequent ‘process of subordination’ within Welfare State capitalism.     

Some large trial properties of minimum likelihood allocation

The method of minimum likelihood allocation (MLA) for allocating subjects to treatments in a clinical trial amounts to checking at each stage which allocation would lead an outside observer to find the least evidence of a relationship between treatment and factors of prognostic significance, assuming that the observer would use a linear exponential model. One advantage of MLA is that results from game theory and likelihood theory can be used to prove it has desirable long run properties. Two of these demonstrated here are (1) ‘consistency’, in the sense that the average likelihood ratio which measures design imbalance tends to zero, and (2) ‘efficiency’ in the sense that the variance estimates of treatment effects will tend to be minimized in the long run.     

Indications for,and timing of,planned caesarean section: A systematic analysis of clinical guidelines

BackgroundThere has been a worldwide rise in planned caesarean sections over recent decades, with significant variations in practice between hospitals and countries. Guidelines are known to influence clinical decision-making and, potentially, unwarranted clinical variation. The aim of this study was to review guidelines for recommendations in relation to the timing and indications for planned caesarean section as well as recommendations around the process of decision-making.MethodA systematic search of national and international English-language guidelines published between 2008 and 2018 was undertaken. Guidelines were reviewed, assessed in terms of quality and extracted independently by two reviewers.FindingsIn total, 49 guidelines of varying quality were included. There was consistency between the guidelines in potential indications for caesarean section, although guidelines vary in terms of the level of detail. There was substantial variation in timing of birth, for example recommended timing of caesarean section for women with uncomplicated placenta praevia is between 36 and 39 weeks depending on the guideline. Only 11 guidelines provided detailed guidance on shared decision-making. In general, national-level guidelines from Australia, and overseas, received higher quality ratings than regional guidelines.ConclusionThe majority of guidelines, regardless of their quality, provide very limited information to guide shared decision-making or the timing of planned caesarean section, two of the most vital aspects of guidance. National guidelines were generally of better quality than regional ones, suggesting these should be used as a template where possible and emphasis placed on improving national guidelines and minimising intra-country, regional, variability of guidelines.     

Bayesian hierarchical joint modeling using skew-normal/independent distributions

The multiple longitudinal outcomes collected in many clinical trials are often analyzed by multilevel item response theory (MLIRT) models. The normality assumption for the continuous outcomes in the MLIRT models can be violated due to skewness and/or outliers. Moreover, patients’ follow-up may be stopped by some terminal events (e.g., death or dropout), which are dependent on the multiple longitudinal outcomes. We proposed a joint modeling framework based on the MLIRT model to account for three data features: skewness, outliers, and dependent censoring. Our method development was motivated by a clinical study for Parkinson’s disease.     

Are Private Interests Clouding the Peer-Review Process of the WHO Bulletin? A Case Study

Readers’ trust on the medical literature has been eroded, and journal editors and some editorial boards are taking measures to ensure that authors fully and accurately report research findings and disclose conflicts of interest. This article describes a case study in which the papers editor of the World Health Organization (WHO) Bulletin influenced the content of an article that had been approved by the external reviewers. The editor objected to the publication of the large price differentials of the new molecular entities (NMEs) across the Latin American countries where they had been tested and the limited added therapeutic value of the NMEs that had been assessed by independent drug bulletins. This article summarizes the exchanges with WHO staff and posits the hypothesis that the WHO Bulletin might be affected by the shifts in WHO financing. Several authors have raised concern about the impact of financial conflicts of interest in WHO activities in the field of nutrition, intellectual property, and in the emergency response to the flu pandemic. Moreover, it has been reported that powerful WHO contributors pressured WHO into revising its publication policy. This is the first time that authors question if these conflicts of interest are also affecting the editorial independence of the WHO Bulletin.     

A Hybrid Geometric Phase II/III Clinical Trial Design based on Treatment Failure Time and Toxicity

The problem of comparing several experimental treatments to a standard arises frequently in medical research. Various multi-stage randomized phase II/III designs have been proposed that select one or more promising experimental treatments and compare them to the standard while controlling overall Type I and Type II error rates. This paper addresses phase II/III settings where the joint goals are to increase the average time to treatment failure and control the probability of toxicity while accounting for patient heterogeneity. We are motivated by the desire to construct a feasible design for a trial of four chemotherapy combinations for treating a family of rare pediatric brain tumors. We present a hybrid two-stage design based on two-dimensional treatment effect parameters. A targeted parameter set is constructed from elicited parameter pairs considered to be equally desirable. Bayesian regression models for failure time and the probability of toxicity as functions of treatment and prognostic covariates are used to define two-dimensional covariate-adjusted treatment effect parameter sets. Decisions at each stage of the trial are based on the ratio of posterior probabilities of the alternative and null covariate-adjusted parameter sets. Design parameters are chosen to minimize expected sample size subject to frequentist error constraints. The design is illustrated by application to the brain tumor trial.     

Teaching Clinical Social Work Skills Entirely Online: A Case Example

While numerous disciplines have eagerly embraced innovative educational technology, many social work educators have not been among early adopters. Social work's focus on the human connection and hands‐on practice skills can seem antithetical to technology‐mediated education. Nevertheless, social work programs are implementing distance learning and Internet‐mediated courses, and some schools are offering entire social work courses online. Leading the way in this regard is the Florida State University College of Social Work, which has developed and implemented the first CSWE‐accredited, entirely online Master of Social Work program. The purpose of this paper is to describe the development, design, and implementation of one skills‐based clinical course in this program, with the goal of sharing information in a way that will further the discussion of the risks and benefits of online education as well as provide guidance for educators who may be interested in developing a skills‐based online course in the future.     

The Clinical Aspects of Case Management and its Role in Graduate Field Education

In graduate social work education, faculty advisors together with practice instructors can improve social work students' skills to link the practical aspects of ‘work responsibilities’ to the clinical underpinnings of case management. Often students are taught the direct services (case management) with a view solely focused on the practical aspects of care, and this curtails the students' opportunity to learn the clinical interventions that exist in all components of social work: to identify, understand and apply clinical dynamics to presenting problems. The authors discuss their work in addressing case management from a clinical perspective with MSW students and recommendations for its inclusion in graduate social work programs.