Recently, two CPMP Points to Consider, one on adjustment for baseline covariates and the other on multiplicity issues in clinical trials, have included recommendations on the use of subgroup analysis for regulatory purposes. However, despite their regular use and regulatory attention, the validity and nature of subgroup analyses are still frequently questioned. This article provides guidance on when subgroup analyses can be done, when they should be done, and their interpretation. The validity of common regulatory claims based on subgroup analyses is then discussed.

The boundary entropy log(g) of a critical one-dimensional quantum system (or two-dimensional conformal field theory) is known to decrease under renormalization group (RG) flow of the boundary theory. We study instead the behavior of the boundary entropy as the bulk theory flows between two nearby critical points. We use conformal perturbation theory to calculate the change in g due to a slightly relevant bulk perturbation and find that it has no preferred sign. The boundary entropy log(g) can therefore increase during appropriate bulk flows. This is demonstrated explicitly in flows between minimal models. We discuss the applications of this result to D-branes in string theory and to impurity problems in condensed matter.

Human obesity shows clustering within families. The hypothesis for the presence of a major gene or genes acting in human obesity is supported by recent evidence from studies of obesity in adoptees and their biological parents and siblings. The heterogeneity of obesity may be demonstrated by the shape of fat distribution and the prolactin response to insulin hypoglycaemia. Fat distribution has been shown to have a genetic background whereas a primary disorder of hypothalamic function is suspected in obese women who show an impaired prolactin response to insulin-induced hypoglycaemia. We have investigated the possible association between fat distribution and hypothalamic function in 23 extremely obese, nondiabetic premenopausal women who have been characterized using their absolute body weight, body mass index (BMI), fat distribution (expressed as waist to hip ratio), fasting insulin, basal prolactin and prolactin response to hypoglycaemia. Fasting insulin values showed a significant correlation (P less than 0.05, R = 0.604) with increasing waist to hip ratio (upper body segment obesity), whereas the graded prolactin response to hypoglycaemia of the obese women showed a negative association with increasing upper body segment obesity (P less than 0.05; R = -0.446). No relationship was observed between fasting insulin and the prolactin response to hypoglycaemia. We suggest that this previously unrecognized association of an impaired prolactin response to hypoglycaemia and upper body segment fatness may be useful for the investigation of the genetics of obesity.

By combining clinical data from independent Phase II trials, the logistic model developed could predict the probability of fotemustine hematologic and hepatic toxicity.