Probability of success for phase III after exploratory biomarker analysis in phase II

The probability of success or average power describes the potential of a future trial by weighting the power with a probability distribution of the treatment effect. The treatment effect estimate from a previous trial can be used to define such a distribution. During the development of targeted therapies, it is common practice to look for predictive biomarkers. The consequence is that the trial population for phase III is often selected on the basis of the most extreme result from phase II biomarker subgroup analyses. In such a case, there is a tendency to overestimate the treatment effect. We investigate whether the overestimation of the treatment effect estimate from phase II is transformed into a positive bias for the probability of success for phase III. We simulate a phase II/III development program for targeted therapies. This simulation allows to investigate selection probabilities and allows to compare the estimated with the true probability of success. We consider the estimated probability of success with and without subgroup selection. Depending on the true treatment effects, there is a negative bias without selection because of the weighting by the phase II distribution. In comparison, selection increases the estimated probability of success. Thus, selection does not lead to a bias in probability of success if underestimation due to the phase II distribution and overestimation due to selection cancel each other out. We recommend to perform similar simulations in practice to get the necessary information about the risk and chances associated with such subgroup selection designs.     

A new look at an old problem: Finding temporal patterns in homicide series—the Canadian case

It is believed by criminologists that the incidence of crimes committed against persons is highest in the summer. Knowledge about the annual patterns and other temporal behavior of such crimes can help authorities in prevention. The objective of this study is to reveal the temporal behavior of murders in Canada and assess if they are affected by trend-cyclical and/or seasonal influences. The series analyzed comprise the period 1961 to 1980 and are classified according to suspects and victims. Only the quarterly series display a significant seasonal pattern, with the peak occurring in the third quarter. We have also analyzed the relationship between the trend cycle of the murder series and two other variables, namely unemployment rate and rate of growth of the 15-to-44 age group.     

Basic Issues on the Seasonal Adjustment of the Canadian Consumer Price Index

This study is mainly concerned with basic issues that arise in connection with the seasonal: adjustment of the Canadian Consumer Price Index when used as a current indicator of inflation. It analyzes the seasonal characteristics of the series and evaluates whether a direct or an indirect adjustment is preferred from the viewpoint of the degree of smoothness of the monthly rate of change. The use of ARIMA extrapolations versus no ARIMA extrapolations and the application of concurrent versus year-ahead seasonal factors are also discussed. The selection of the optimal procedure is made according to the degree of smoothness and size of the revisions of the seasonally adjusted monthly rate of change.     

User-centred responses to child sexual abuse: the way forward?

Two parallel surveys were carried out based in the north-east of England and Cumbria: one ascertaining statutory social work services provided for child and adult survivors of sexual abuse, the other drawing upon the perceptions of adult survivors of child sexual abuse about existing and desirable forms of provision for adults and children. The surveys indicate the need for greater genuine partnership between service users and statutory agencies in the field of child sexual abuse, similar to that which is being pioneered in the field of adult care and disability. A community-orientated response to sexual abuse, centred on service-users, is required if one of the largest social problems facing us today is to be effectively challenged.