The trial: how procedure shapes substance

The rules and the principles of the common law are formed from the cases decided in courts of common law. The unique nature of the evolution of the common law has long been the subject of study. Less frequently studied has been the impact of procedure upon the development of substantive law. This paper examines how the procedures applicable to the trial of a case can affect the substance of the resulting decision. The focus of the examination is the decision in Bell v Lever Bros [1932] AC 161. While the case has long been regarded as a leading, albeit confusing, contract law case it is also greatly concerned with the conduct of litigation. This paper argues that the substantive decision was largely determined by the civil procedure available. Different rules of civil procedure, it is suggested, would have resulted in a better decision in the English law of contract.

Fitting models for the joint action of two drugs using SAS(R)

Combinations of drugs are increasingly being used for a wide variety of diseases and conditions. A pre-clinical study may allow the investigation of the response at a large number of dose combinations. In determining the response to a drug combination, interest may lie in seeking evidence of synergism, in which the joint action is greater than the actions of the individual drugs, or of antagonism, in which it is less. Two well-known response surface models representing no interaction are Loewe additivity and Bliss independence, and Loewe or Bliss synergism or antagonism is defined relative to these. We illustrate an approach to fitting these models for the case in which the marginal single drug dose-response relationships are represented by four-parameter logistic curves with common upper and lower limits, and where the response variable is normally distributed with a common variance about the dose-response curve. When the dose-response curves are not parallel, the relative potency of the two drugs varies according to the magnitude of the desired effect and the models for Loewe additivity and synergism/antagonism cannot be explicitly expressed. We present an iterative approach to fitting these models without the assumption of parallel dose-response curves. A goodness-of-fit test based on residuals is also described. Implementation using the SAS NLIN procedure is illustrated using data from a pre-clinical study. Copyright © 2007 John Wiley & Sons, Ltd.