Phase I studies: what to measure?
Drug law require the assessment of quality, safety and efficacy of new compounds. In this context, phase I studies are performed in order to investigate their tolerability, pharmacodynamic effects and pharmacokinetics. For the assessment of safety aspects, standard clinical (eg blood pressure, heart rate, body temperature, ECG), laboratory data (eg checklist recommended by local clinical chemistry societies) and subjective rating scales (eg open or structured questionnaires) are the main parameters. Additional investigations may be included according to the results obtained in pharmacological and toxicological studies. The selection of appropriate measuring times is crucial. The maximum pharmacological effects in many cases are seen at the time of peak serum concentration, whereas in other cases they may be a delay (eg effect on coagulation factors, toxic granulocytopenia). For the assessment of the pharmacodynamic effects of a new drug, standardized procedures should be used which predict its therapeutic effect in patients. The main purposes of pharmacodynamic studies in healthy volunteers are: proof of efficacy and mechanism of action in man, dose finding, search for possible adverse events, for additional therapeutically relevant mechanisms or pharmacodynamic interactions. For all these studies, it is crucial to select the appropriate variables, the appropriate validated and non-invasive method and the appropriate time points.
Rosenkranz
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Clinical Research/Clinical Pharmacology, Hoechst AG Frankfurt, Germany.
D004341:Drug Evaluation; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D010599:Pharmacokinetics; D010601:Pharmacology, Clinical