Interpretation of results
In the 30 years or so that TDM has been practised in routine clinical laboratories, it has been demonstrated repeatedly that making drug concentration measurements available to clinicians does not in itself result in improved clinical care. Improved outcome depends on the application of the result to a specific clinical situation with appropriate expertise. This is facilitated by a multidisciplinary approach in which pharma cists, laboratory staff and clinicians work together to share expertise and promote best use of the service. If the laboratory is to provide an effective service, clinicians must be prepared to provide basic data, such as the reason for a particular request, the dose regime, the time of the last dose and the presence of any drugs that may cause pharmacological or analytical interference.
In particular, it is important to understand that the widely quoted (and just as often misused) ‘therapeutic ranges’ for drugs represent a guide to the approximate concentrations that produce a therapeutic response in the majority of patients, rather than a set of inflexible limits between which patients must be forced. ‘Target ranges’ has been suggested as a better term, which at least carries the connotation that the ranges are something to aim at rather than implying that all concentrations within the range are therapeutic (and all outside are not). Many patients need plasma drug concentrations above (sometimes substantially above) the upper limit of the therapeutic range for effective therapy, and such concentrations must not provoke a knee-jerk dosage reduction. Specialist clinicians usually appreciate this fact, but nonspecialists frequently do not and the laboratory or pharmacist has an important educational role here. Conversely, plasma drug concentrations below the lower limit of the therapeutic range may produce perfectly satisfactory responses in some patients, for whom arbitrary dose increases to move concentrations into the ‘therapeutic range’ will merely increase the like lihood of toxicity without added benefit. ‘Interpretation’ of plasma drug concentrations by comparing them with an arbitrary range and designating them as ‘subtherapeutic’ or ‘toxic’ does far more harm than good. Optimum drug concentrations for a particular patient are highly individual, and depend on many pharmacodynamic factors, as well as on the severity of the underlying disease process. This does not undermine the relevance of TDM, but it does require a degree of interpretative expertise and an understanding of the reason behind a particular request and how the result obtained relates to the clinical question. Whether this expertise resides with the clinician, the pharmacist or the laboratory scientist is less important than the fact that it exists somewhere and can be accessed when needed, although in the nature of the service, laboratory staff are likely to be best placed to monitor interpretation across a range of clinical situations. The cardinal principle, oft repeated but still forgotten, is to treat the patient, not the drug level.
