On Causal Inferences for Personalized Medicine: How Hidden Causal Assumptions Led to Erroneous Causal Claims About the D-Value

Abstract

Personalized medicine asks if a new treatment will help a particular patient, rather than if it improves the average response in a population. Without a causal model to distinguish these questions, interpretational mistakes arise. These mistakes are seen in an article by Demidenko that recommends the “D-value,” which is the probability that a randomly chosen person from the new-treatment group has a higher value for the outcome than a randomly chosen person from the control-treatment group. The abstract states “The D-value has a clear interpretation as the proportion of patients who get worse after the treatment” with similar assertions appearing later. We show these statements are incorrect because they require assumptions about the potential outcomes which are neither testable in randomized experiments nor plausible in general. The D-value will not equal the proportion of patients who get worse after treatment if (as expected) those outcomes are correlated. Independence of potential outcomes is unrealistic and eliminates any personalized treatment effects; with dependence, the D-value can even imply treatment is better than control even though most patients are harmed by the treatment. Thus, D-values are misleading for personalized medicine. To prevent misunderstandings, we advise incorporating causal models into basic statistics education.     

Black adolescents' racial discrimination and suicide behaviors: Testing perceived school safety as a protective moderator

The current study examined associations between Black adolescents' (M_age = 15.55, SD = 1.23) racial discrimination and suicide behaviors (i.e., suicide ideation, suicide plan, and suicide attempts), and whether perceived school safety was a protective moderator. Furthermore, we tested gender differences in relations, which were not significant. Racial discrimination predicted greater suicide behaviors, and school safety informed less suicide behaviors. School safety moderated the relation between discrimination and suicide plan, such that at low school safety, discrimination predicted having a suicide plan but was not significant at high school safety. Furthermore, school safety moderated the relation between discrimination and suicide attempts. At low school safety, discrimination predicted more suicide attempts, but was not significant at high school safety.     

Estimation of a common mean vector in bivariate meta-analysis under the FGM copula

We propose a bivariate Farlie–Gumbel–Morgenstern (FGM) copula model for bivariate meta-analysis, and develop a maximum likelihood estimator for the common mean vector. With the aid of novel mathematical identities for the FGM copula, we derive the expression of the Fisher information matrix. We also derive an approximation formula for the Fisher information matrix, which is accurate and easy to compute. Based on the theory of independent but not identically distributed (i.n.i.d.) samples, we examine the asymptotic properties of the estimator. Simulation studies are given to demonstrate the performance of the proposed method, and a real data analysis is provided to illustrate the method.     

A non-inferiority test for diagnostic accuracy in the absence of the golden standard test based on the paired partial areas under receiver operating characteristic curves

Non-inferiority tests are often measured for the diagnostic accuracy in medical research. The area under the receiver operating characteristic (ROC) curve is a familiar diagnostic measure for the overall diagnostic accuracy. Nevertheless, since it may not differentiate the diverse shapes of the ROC curves with different diagnostic significance, the partial area under the ROC (PAUROC) curve, another summary measure emerges for such diagnostic processes that require the false-positive rate to be in the clinically interested range. Traditionally, to estimate the PAUROC, the golden standard (GS) test on the true disease status is required. Nevertheless, the GS test may sometimes be infeasible. Besides, in a lot of research fields such as the epidemiology field, the true disease status of the patients may not be known or available. Under the normality assumption on diagnostic test results, based on the expectation-maximization algorithm in combination with the bootstrap method, we propose the heuristic method to construct a non-inferiority test for the difference in the paired PAUROCs without the GS test. Through the simulation study, although the proposed method might provide a liberal test, as a whole, the empirical size of the proposed method sufficiently controls the size at the significance level, and the empirical power of the proposed method in the absence of the GS is as good as that of the non-inferiority in the presence of the GS. The proposed method is illustrated with the published data.     

Prioritizing Environmental Health Risks in the UAE

This article presents the results of a comparative environmental risk‐ranking exercise that was conducted in the United Arab Emirates (UAE) to inform a strategic planning process led by the Environment Agency‐Abu Dhabi (EAD). It represents the first national‐level application of a deliberative method for comparative risk ranking first published in this journal. The deliberative method involves a five‐stage process that includes quantitative risk assessment by experts and deliberations by groups of stakeholders. The project reported in this article considered 14 categories of environmental risks to health identified through discussions with EAD staff: ambient and indoor air pollution; drinking water contamination; coastal water pollution; soil and groundwater contamination; contamination of fruits, vegetables, and seafood; ambient noise; stratospheric ozone depletion; electromagnetic fields from power lines; health impacts from climate change; and exposure to hazardous substances in industrial, construction, and agricultural work environments. Results from workshops involving 73 stakeholders who met in five separate groups to rank these risks individually and collaboratively indicated strong consensus that outdoor and indoor air pollution are the highest priorities in the UAE. Each of the five groups rated these as being among the highest risks. All groups rated soil and groundwater contamination as being among the lowest risks. In surveys administered after the ranking exercises, participants indicated that the results of the process represented their concerns and approved of using the ranking results to inform policy decisions. The results ultimately shaped a strategic plan that is now being implemented.     

MODIFIED STEPPING-STONE METHOD AS A TEACHING AID FOR CAPACITATED TRANSPORTATION PROBLEMS

This paper extends the standard stepping-stone method to the case of capacitated transportation problems. The purpose is to offer an alternative to network-oriented or simplex-based methods (such as the out-of-kilter and upper-bounding techniques) often used in handling the capacitated transportation problem but generally beyond the scope of introductory decision sciences courses. The proposed procedure is based on the simple stepping-stone method and requires only a few modifications in the cost/assignment matrix and some alterations in the pivoting rules. As such, it is much easier to understand and apply than the above-mentioned solution algorithms. It therefore can serve as an effective tool for teaching capacitated transportation problems. Two numerical examples illustrate applications of the proposed method, procedures for sensitivity analysis, and comparisons with linear programming.     

A new bivariate beta distribution

A new bivariate beta distribution capable of providing better fits than all its competitors is introduced. Various representations are derived for its product moments, marginal densities, marginal moments, conditional densities and conditional moments. The method of maximum likelihood is used to derive the associated estimation procedure. Applications to six bivariate data sets are illustrated.