Applying decision analysis in therapeutic drug monitoring: using decision trees to interpret serum theophylline...

In the second of a three-part series, decision analysis is applied to therapeutic drug monitoring decisions that affect individual patients, using theophylline concentration and toxicity data to illustrate general concepts. Likelihood ratios and conditional probability curves were developed. The curves were used to determine the probability of toxicity based on the clinician's assessment of patient status and a measured serum theophylline concentration. A decision tree to "rule in" or "rule out" toxicity was constructed. Selection of a serum concentration cutoff level for classifying patients as toxic or nontoxic depends on the probabilities of the possible outcomes of the decision process and the clinician's assessment of the value of each possible outcome; therefore, no single concentration value is best for classifying patients. A decision tree was also constructed for evaluating therapeutic options when the clinician is confronted with adverse effects that may be drug related. In three prototype cases, the expected utility for discontinuing theophylline, continuing the drug at the same dosage, or lowering the dosage was determined and used to evaluate the relative worth of each therapeutic option. A more comprehensive interpretation of the serum theophylline concentration is provided by decision-analysis techniques than by observation of pharmacologic effect alone, because other factors such as merit, risk, and consequences of alternative decisions are considered.