TDM: standardisation and quality control

In the UK, where all TDM is currently performed at Liverpool University, validated assays are already established and results from studies there correlate closely with groups from the Netherlands, who are similarly experienced.

However, as new laboratories develop assays to offer this service, it is vital that a quality control programme is supported and maintained between sites. To this end, the International Inter-laboratory Quality Control (QC) Programme for TDM has been established by David Burger at the University Medical Centre, Nijmegen, the Netherlands.

Evaluations are based on analysing drug-free plasma spiked with weighed concentrations (low, medium and high) for each approved PI. The results from this study showed a 20% variation between assays used at different sites (sites remained anonymous in the results), which is actually very close to the 12-15% inter-assay susceptibility accepted for similar assays.

The variations detected between sites were believed to come from differences in weighing of the drug used when calibrating each test and hope to be resolved by increased standardisation of the HPLC-UV or LC-MS systems that are used. Based on these encouraging results, a second round of QC is already underway, and it will be important that new sites providing TDM support are enrolled in this scheme.

This QC programme will involve monitoring samples from each site on a quarterly basis, and the frequency and continuous nature of this approach is itself expected to lead to a further refining of this technology. [1] These results, are also a significant improvement on the fivefold difference found between US labs, in an Agouron study, that was presented last May at the AIDS Treatment Project (ATP) Symposium on TDM.