PREDICT-1 (CNA106030): the first powered, prospective trial of pharmacogenetic screening to reduce drug adverse events

Pharmacogenetics (PGx) – the study of DNA variation in the human genome and the way this impacts the efficacy and safety of medicines – is becoming an increasingly important research tool as physicians, patients, regulatory authorities and payers look for innovative ways to improve the risk:benefit ratio of medicines. While scientific knowledge about PGx is rapidly increasing, implementation of PGx findings to patient care has yet to be fully achieved. One area where significant progress has been made is in the identification of PGx markers associated with variable response to antiretroviral medicines. For example, the major histocompatibility complex HLA‐B*5701 allele has been associated with hypersensitivity to abacavir (ABC) by several independent researchers. While PGx associations have been identified largely through retrospective examination, the clinical utility of these PGx markers in patient care has not been prospectively determined in a randomized study. This paper outlines the design of a study to evaluate the utility of prospective screening for HLA‐B*5701 to reduce the incidence of ABC hypersensitivity in an ABC‐naïve population of HIV‐infected subjects. This represents the first fully powered, randomized, blinded, prospective study to determine the clinical utility of PGx screening to reduce drug‐associated adverse events in any patient population. This type of trial design may have utility for other important medicines which have treatment‐limiting side effects. Copyright © 2007 John Wiley & Sons, Ltd.     

Variance estimation when donor imputation is used to fill in missing values

Donor imputation is frequently used in surveys. However, very few variance estimation methods that take into account donor imputation have been developed in the literature. This is particularly true for surveys with high sampling fractions using nearest donor imputation, often called nearest‐neighbour imputation. In this paper, the authors develop a variance estimator for donor imputation based on the assumption that the imputed estimator of a domain total is approximately unbiased under an imputation model; that is, a model for the variable requiring imputation. Their variance estimator is valid, irrespective of the magnitude of the sampling fractions and the complexity of the donor imputation method, provided that the imputation model mean and variance are accurately estimated. They evaluate its performance in a simulation study and show that nonparametric estimation of the model mean and variance via smoothing splines brings robustness with respect to imputation model misspecifications. They also apply their variance estimator to real survey data when nearest‐neighbour imputation has been used to fill in the missing values. The Canadian Journal of Statistics 37: 400–416; 2009 © 2009 Statistical Society of Canada     

Sex role perceptions and the abortion decision

This paper is concerned with the relationship between two aspects of self‐concept—perception of gender role and perceived competence—and the decision to have an abortion as a solution to a problem pregnancy. It was hypothesized that (1) there will be a positive relationship between the choice of abortion and perceived competence, and (2) there will be a negative relationship between the choice of abortion and the degree to which female role is perceived traditionally. The data came from a broader study conducted throughout Michigan during 1974–75. The study group consisted of 921 women who chose to have an abortion. A comparison group included 360 women with problem pregnancies who chose to keep their child. Data were obtained through an anonymous questionnaire which included the two relevant indices. The abortion group was found to be significantly higher in perceived competence than those who chose to keep the child, and the black abortion group was significantly less traditional than the black group which chose to keep the child. These relationships remained significant when age was controlled. Race did not affect subjects' degree of perceived competence, but blacks were more traditional than whites regardless of decision.     

How Tautological Are Interspecies Correlations of Carcinogenic Potencies?

Crouch and Wilson demonstrated a strong correlation between carcinogenic potencies in rats and mice, supporting the extrapolation from mouse to man. Bernstein et al. , however, show that the observed correlation is mainly a statistical artifact of bioassay design. Crouch et al. have a comeback. This paper will review the arguments and present some new data. The correlation is largely (but not totally) tautological, confirming results in Bernstein et al.     

Perceptions of nonreciprocal touch in romantic relationships

College students attributed meaning on a questionnaire to 31 types of nonreciprocal touch occurring in opposite-sex romantic relationships. Subject sex and origin of touch (self vs. partner) had minor effects on attributed meanings. Subjects most often perceived these touches as expressing warmth/love, and rarely as expressing dominance/control.The authors are grateful to Richard Heslin and Jeffrey Fisher for their assistance in designing the study, and to C. Van Nelson for assistance in data analysis.