A single-instrument approach to TDM toxicology.

A single-instrument approach to TDM and toxicology

Prospective payment has spurred demand for rapid analytical throughput in the laboratory while putting a cap on labor and operating costs. These pressures are particularly strong in the therapeutic drug monitoring and toxicology areas.

Most laboratories performing such procedures have seen an increase in Stat requests--part of the effort to reduce hospital stays--as well as a rise in reagent prices. In addition, personnel reductions have left labs short of highly trained clinical toxicology technologists.

Our 500-bed hospital laboratory was responding inadequately to an increased therapeutic drug monitoring demand with a five-year-old labor-intensive centrifugal analyzer. The instrument required daily calibration and duplicate testing for TDM, the latter because results demonstrated intra-run imprecision. Not surprisingly, operating costs were relatively high, and turnaround time was slow. These problems prompted us last year to institute a search for a more cost-effective instrument.

Ideally, the new instrument would also handle immunoassays for substances of abuse because of our rapidly expanding toxicology volume. It had increased after we took over testing for a local drug rehabilitation center. To perform that work, we used a manual spectrophotometer and a semiautomated diluter.

Our search narrowed the field to three instruments, each with specific technological advantages of its own: 1) a dedicated fluorescence polarization immunoassay (FPIA) batch analyzer, 2) a random access multitest analyzer, and 3) a wet chemistry/TDM/toxicology batch analyzer. We made a thorough review of the literature on these instruments and witnessed on-site manufacturer demonstrations.

Instrument price was one of many considerations, but the final decision rested in large measure on cost per reportable patient result, which depends on such factors as reagent cost, reagent volume, calibration cost and frequency, and labor as measured by CAP workload units. We also sought flexibility in the technologies and reagents used by the instrument, and in the variety of tests it could perform.

Based on these criteria, we selected the chemistry/TDM/toxicology batch analyzer. It was cost-effective, reliable, and precise, and it did not require intensive operator maintenance. It also had the flexibility to perform either enzyme or fluorescent TDM immunoassays, enzyme immunoassays for toxicology confirmation, and specific enzyme assays for other chemical analytes.

The main apparent disadvantage of the instrument was its lack of random access capability. We decided to acquire a second model of the same analyzer and use it primarily for Stat work.

The instruments we rejected had varying drawbacks--an ability to perform only TDM and not toxicology procedures, reliance on a single TDM methodology, an unacceptably high cost per reportable patient result, and/or a lack of operator convenience.

The instrument we chose has been configured to perform 11 TDM procedures (Figure I). We also use it to perform 11 automated enzyme immunoassays for substances of abuse in serum or urine. In addition, it is used as a backup for five enzymatic procedures performed on a dry-slide chemistry analyzer.

Thirty chemistry tests are built into the analyzer by the manufacturer, and five more are user-programmable. The programming feature provided our laboratory with cost-effective automation of an enzymatic procedure for ethanol. We no longer have to do batches of ethanol testing on a costly discrete pack analyzer or on a highly labor-intensive gas chromatograph during the day shift.

Similarly, we added a barbiturate screen by enzyme immunoassay. This replaced a more expensive and labor-intensive thin-layer chromatographic method.

Figure II shows a cost analysis of theophylline testing on the new instrument. The analysis was conducted via a microcomputer program we developed. Similar workups for the same test on other instruments enable us to compare costs.

As Figure II shows, the instrument is calibrated once a month, in contrast to a daily frequency on our old centrifugal analyzer. Moreover, the yield of tests per kit has increased because we use less reagent per test and no longer have to perform duplicate testing. The first-year savings due to these factors totaled $20,000.

The instrument can run the same test on up to 60 specimens. Batch capability of that magnitude drives the cost per reportable patient result down to a very competitive level. Exact expenses vary by size of batch, but when dealing with prospective off-site clients, we are confident of quoting an attractive price that is above breakeven. Once the number of tests is known, our microcomputer program rapidly works out the cost.

Such cost analyses led us to introduce an enzyme immunoassay for cannabinoids and to reinstate in-house TDM, once volume had increased, for procainamide and its major metabolite.

The instrument manufacturer also provided us with microcomputer software for pharmacokinetic calculations. This will be used by the hospital's clinical pharmacology section to identify inappropriate dosage regimens, which reduces the need for TDM.

We can now perform TDM or toxicology tests on large batches --more than 20 specimens--in less than 30 minutes. Thanks to the high degree of automation, a single technologist on most days can manage the entire workload for both TDM and toxicology, including thin-layer chromatography as a screen for substances of abuse.

To make the right instrument choice, laboratorians must be fully aware of what is available, understand the immediate and future needs of their institution, and have the ability to determine test costs and other aspects of instrument performance. Resulting reductions in operating costs, increased productivity, and improved service demonstrate to hospital administration that laboratory personnel can bridge the gap between technical and financial management.

Table: Figure I The TDM-toxicology test menu

Table: Figure II Theophylline test cost calculations