Prospective Investigations of Concentration--Clinical Response for Immunosuppressive Drugs Provide the Scientific Basis for Therapeutic Drug Monitoring (Tdm Conference) (Clinical Report‪)‬

Traditionally, the clinical response of patients to most new drugs has been evaluated by comparison of a group receiving a single dosage in parallel with either a placebo group or one or more additional dosage groups. Patients are randomized to one of the dosage groups for the duration of the study. Such studies, usually referred to as randomized dose-controlled clinical trials, often lead to large variability in response within comparison groups, because of extensive interpatient variability of both pharmacokinetics (PK) (4) and pharmacodynamics (PD), i.e., clinical response, effectiveness, and undesirable effects. Thus, understanding the factors that account for patients' clinical response variability is hampered by the lack of control of drug concentration when both PK and PD variabilities are considerable [1-3]. A recommended approach to controlling PK variability among patients during clinical drug trials is performance of prospective concentration-controlled studies. Such investigations can provide the basis for implementation of effective therapeutic drug monitoring (TDM) early after introduction of new medications into clinical practice. This will lead to early utilization of the new drug in the safest and most efficacious manner