1 Practical Experience and Issues in Designing and Performing Population Pharmacokinetic/Pharmacodynamic Studies

L Aarons(1) , LP Balant(2) , F Mentre(3) , PL Morselli(4) , M Rowland(1) , J-L Steimer(5) , S Vozeh(6)

1. Department of Pharmacy, University of Manchester, UK,

2. Clinical Research Unit, Department of Psychiatry, University of Geneva, Switzerland,

3. Methodologie Informatique et Statistique en Medicine, INSERM, Paris, France,

4. Buc, France and Department of Clinical Pharmacology, Hospital ''Trias i Pujol'' Badalona, Universidad Autonoma Barcelona, Spain,

5. Drug Safety, Sandoz Pharma AG, Basel, Switzerland,

6. Office Intercantonal de Controle des Medicaments, Berne, Switzerland

The main conclusions from the meeting were: 1) a population PK/PD study should not compromise the main objectives of the clinical trial; 2) it is particularly important to communicate the purpose of the population PK/PD analysis to the investigators and to convince them of the importance of accurate timing; 3) some prior knowledge of the PK and PD models and covariate relationships is necessary for the analysis of sparse phase III data; 4) computer simulation and optimal design measures may be useful in defining sampling times; 5) population methods must be specified as completely as possible in the protocol.

An expert meeting to discuss issues relating to experimental design in population pharmacokinetic/pharmacodynamic (PK/PD) studies was held in Brussels in March 1995, under the auspices of the European Co-operation in Science and Technology (COST), Medicine (B1) programme. The meeting was the second meeting organized by the COST-B1 working party on population approaches, the previous one being concerned with population PK/PD software[1]. The purpose of the second meeting was to discuss current experience in the design and performance of population PK/PD studies. We were especially interested in information ideas which would not normally be published. A questionnaire was devised and circulated to the experts prior to the meeting and the meeting evolved from responses to that questionnaire. Because the topic of design with all its ramifications is so diverse it was not possible to produce a consensus document, as was done with the PK/PD software. The main reason for the lack of consensus in some areas was due to lack of experience rather than divergent opinions of the experts. Nevertheless, we report here a summary of the meeting together with general recommendations. Discussion focused on the following topics: current practice, logistical issues, ensuring the accuracy of data, covariate assessment, communication and protocol design.

1. Aarons L, Balant LP, Mentre F, Morselli PL, Rowland M, Steimer J-L, Vozeh S, (1994) Population approaches in drug development. Report on an expert meeting to discuss population pharmacokinetic/pharmacodynamic software. Eur J Clin Pharmacol, 46:389-391