Non-ignorable missing covariate data in survival analysis: a case-study of an International Breast Cancer Study Group trial

Summary.  Non-ignorable missing data, a serious problem in both clinical trials and observational studies, can lead to biased inferences. Quality-of-life measures have become increasingly popular in clinical trials. However, these measures are often incompletely observed, and investigators may suspect that missing quality-of-life data are likely to be non-ignorable. Although several recent references have addressed missing covariates in survival analysis, they all required the assumption that missingness is at random or that all covariates are discrete. We present a method for estimating the parameters in the Cox proportional hazards model when missing covariates may be non-ignorable and continuous or discrete. Our method is useful in reducing the bias and improving efficiency in the presence of missing data. The methodology clearly specifies assumptions about the missing data mechanism and, through sensitivity analysis, helps investigators to understand the potential effect of missing data on study results.     

Statistics for weighing benefits and harms in a proposed genetic substudy of a randomized cancer prevention trial

Summary.  When evaluating potential interventions for cancer prevention, it is necessary to compare benefits and harms. With new study designs, new statistical approaches may be needed to facilitate this comparison. A case in point arose in a proposed genetic substudy of a randomized trial of tamoxifen versus placebo in asymptomatic women who were at high risk for breast cancer. Although the randomized trial showed that tamoxifen substantially reduced the risk of breast cancer, the harms from tamoxifen were serious and some were life threaten-ing. In hopes of finding a subset of women with inherited risk genes who derive greater bene-fits from tamoxifen, we proposed a nested case–control study to test some trial subjects for various genes and new statistical methods to extrapolate benefits and harms to the general population. An important design question is whether or not the study should target common low penetrance genes. Our calculations show that useful results are only likely with rare high penetrance genes.     

Real nonparametric regression using complex wavelets

Summary.  Wavelet shrinkage is an effective nonparametric regression technique, especially when the underlying curve has irregular features such as spikes or discontinuities. The basic idea is simple: take the discrete wavelet transform of data consisting of a signal corrupted by noise; shrink or remove the wavelet coefficients to remove the noise; then invert the discrete wavelet transform to form an estimate of the true underlying curve. Various researchers have proposed increasingly sophisticated methods of doing this by using real-valued wavelets. Complex-valued wavelets exist but are rarely used. We propose two new complex-valued wavelet shrinkage techniques: one based on multiwavelet style shrinkage and the other using Bayesian methods. Extensive simulations show that our methods almost always give significantly more accurate estimates than methods based on real-valued wavelets. Further, our multiwavelet style shrinkage method is both simpler and dramatically faster than its competitors. To understand the excellent performance of this method we present a new risk bound on its hard thresholded coefficients.     

Struggles with Time: the careers of parents with adult sons and daughters with learning disabilities

The experiences of parents with adult offspring with learning disability and the meanings their parental careers have for them, has been the subject of very little empirical research. In this paper we describe and examine some of the features that gave shape and meaning to the day to day lives of parents of 33 co-resident adults with learning disabilities. Their accounts of their situations revealed that 'time' was a factor of some importance. Participants suggested that socialisation into the parental role was one that continued over the life course. In addition, they also felt that the services they received were based upon an inadequate and too narrow an understanding of how they experienced 'time'. The data reveal that both 'over time' and 'in time', parents struggled to maintain a set of aspirations for a typical life. The data show that for many parents there was a slow accommodation to the constraints of service provision and, as a result, their needs for service support became less extensive.     

Unjust Freedom: The Ethics of Client Self-Determination in Runaway Youth Shelters

Client self-determination has been called the most confounding and professionally debilitating concept of all the intellectual principles under-girding social work (Rothman, 1989). Identifying the appropriate parameters of client self-determination is a particularly acute problem for social workers employed by runaway and homeless youth shelters where minors are making adult decisions free from parental guidance. We examine the ethical dimensions of practice with minor clients in runaway shelters by arguing that a conflict exists between the liberty-based principle of self-determination and the justice-based notion of client competency. We analyze the conflict by using minimal distributive justice as the organizing principle of social work practice. We conclude that client self-determination in runaway shelters should be restricted and that presuming client competence violates the basic value tenets of the profession.     

Strong convergence rates of probabilistic integrators for ordinary differential equations

Probabilistic integration of a continuous dynamical system is a way of systematically introducing discretisation error, at scales no larger than errors introduced by standard numerical discretisation, in order to enable thorough exploration of possible responses of the system to inputs. It is thus a potentially useful approach in a number of applications such as forward uncertainty quantification, inverse problems, and data assimilation. We extend the convergence analysis of probabilistic integrators for deterministic ordinary differential equations, as proposed by Conrad et al. (Stat Comput 27(4):1065–1082, 2017. https://doi.org/10.1007/s11222-016-9671-0), to establish mean-square convergence in the uniform norm on discrete- or continuous-time solutions under relaxed regularity assumptions on the driving vector fields and their induced flows. Specifically, we show that randomised high-order integrators for globally Lipschitz flows and randomised Euler integrators for dissipative vector fields with polynomially bounded local Lipschitz constants all have the same mean-square convergence rate as their deterministic counterparts, provided that the variance of the integration noise is not of higher order than the corresponding deterministic integrator. These and similar results are proven for probabilistic integrators where the random perturbations may be state-dependent, non-Gaussian, or non-centred random variables.