Standards of laboratory practice: guidelines for the maintaining of a modern therapeutic drug monitoring service

Department of Pathology, New York University Medical Center, Bellevue Hospital, First Avenue & 27^th Street, New York, NY 10016. Fax 212-263-8284; e-mail kaplan{at}is2.nyu.edu.

	Introduction

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On Saturday, June 19, 1997 the National Academy of Clinical Biochemistry held a meeting to publicly review a draft document containing recommendations on the provision of basic therapeutic drug monitoring (TDM) services. This was the third in a continuing series of meetings on Standards of Laboratory Practice (SOLP), which was established to provide practice guidelines for laboratory scientists in a focused area of laboratory medicine. The manuscripts and summaries of two earlier SOLPs, on Thyroid Disease (1) and on Support of the Newborn (2), were published in this Journal, and the monographs are available from the NACB.

By facilitating discussion between clinical laboratory analysts and physicians during the SOLP process, we hope to learn the most efficient way to provide laboratory services. The need for these recommendations in the area of TDM has been established by studies indicating that as many as 70–80% of TDM results are useless because of such problems as improper sampling and lack of an appropriate clinical indication.

The TDM SOLP meeting, attended by approximately 75 laboratory scientists, included discussions of seven classes of drugs: cardiac, antiepileptic, antibiotic, antidepressant, pulmonary, immunosuppressive, and analgesic. Discussion focused on the number of drugs in these classes and addressed issues such as the problems of sample types and timing, assay performance, and need for monitoring in various types of clinical situations. Drug interactions were of concern because this will be an increasing problem in an aging population for which polydrug therapy is common. Another discussion point was theophylline, long a widely used antiasthmatic drug. It is now not considered to be a safe drug and is being used less frequently. Many participants reported that the number of requests for TDM of this drug has dropped.

Participants agreed on the need for laboratory directors to work closely with physicians and clinical pharmacists to develop guidelines for establishing and handling critical drug concentrations.

There was a degree of controversy regarding the most appropriate phlebotomy tube for TDM samples. Although there was concern about scientific documentation, there seemed to be agreement that phlebotomy tubes with silicon "barrier" gels should be avoided.

There was discussion on the degree of analytical precision required and also on the amount and type of cross-reactivity that can be tolerated. In addition, there was a fair amount of discussion of when analyses need to be available Stat and how rapid routine and Stat analyses must be for various patient populations.

One of the most contentious discussions was on the need for free drug measurements. From the discussion came the acknowledgment that, although free drugs concentrations should be the most accurate reflection of drug available at the cellular level, there is insufficient documentation that free drug measurements make any significant difference in treatment for cardiac drugs. In addition, there is a sparsity of good data to establish useful therapeutic ranges for free drug measurements. From the discussion came the recommendation that additional research needs to be performed on the clinical efficacy of free drug measurements.

As laboratory scientists and physicians grapple with new clinical effectiveness regulations, the guidelines in this SOLP, particularly those addressing appropriate clinical indications, should serve as an excellent foundation for that effort. Recommendations for all these areas were reviewed and discussed by meeting participants.

	References

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1. 1995 National Academy of Clinical Biochemistry Standards of Laboratory Practice Symposium on Thyroid Testing. Clin Chem 1996;42:119–92..
2. 1996 National Academy of Clinical Biochemistry Standards of Laboratory Practice Guidelines for the Evaluation and Management of the Newborn Infant. Clin Chem 1997;43:202–48..