J. PKPD Online First

• Stanski, Rowland, and Sheiner, "Getting the Dose Right: Report From the Tenth European Federation of Pharmaceutical Sciences (EUFEPS) Conference on Optimizing Drug Development"
• Zingmark, ..., and Karlsson, "Modelling a Spontaneously Reported Side Effect by Use of a Markov Mixed-Effects Model"
• Murphy & Dunne, "Mixed Effects versus Fixed Effects Modelling of Binary Data with Inter-subject Variability"
  • Yano I らの論文を受けて．

Our conclusion is that the Laplace approximation may be unreliable in certain circumstances.   The data analyst would be well advised to use adaptive Gaussian quadrature rather than the Laplace method to approximate the likelihood if the numbre of observations per subject is small.

• • そりゃあ，そう結論しないと気がおさまらないさ．
• Pillai, Mentré, and Steimer, "Non-Linear Mixed Effects Modeling – From Methodology and Software Development to Driving Implementation in Drug Development Science"
• Miller, et al, "How Modeling and Simulation Have Enhanced Decision Making in New Drug Development"
  • Gabapentin の経験．

the (PK/PD) analyses were further tested and reviewed by the FDA, who reached similar conclusions:-   The PK/PD results confirmed evidence of efficacy across the three studied doses, so that additional trials would not be needed for approval of the product.

• Zhang & Sheiner, "Analyzing Multi-Response Data Using Forcing Functions"
• Beal, "Conditioning on Certain Random Events Associated with Statistical Variability in PK/PD"

  This paper is based on a lecture given as a memorial to my friend and colleague Lewis B. Sheiner (see acknowledgements)

• • See ACKNOWLEDGEMENTS.