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.

Joint servoing for robust manipulator force control

An experimental and theoretical comparison is made of force control performance with different types of innerloop joint servoing techniques. The problem of disturbance rejection and sensitivity to plant dynamics variations (robustness) is addressed. Position, velocity, strain gauge derived joint torque, and current servos are designed and implemented on a specially instrumented industrial robot, and the end-effector force feedback performances achieved are compared. Joint strain derived torque servoing is found to provide the best overall robust force control performance. Experimental results of the robust hard-on-hard contact achieved with the novel force controller implementation based on joint torque sensing are provided. Conclusions are drawn on the force control performance achievable on a geared robot given the joint servoing technique.