For decades, many laboratories have performed chemistry testing on non-standard body fluids (NSBF). NSBFs include everything beyond a blood or urine sample, including but not limited to: CSF, pleural, synovial, peritoneal, dialysate, drain, etc (1). However, the majority of tests that labs offer are generally FDA approved and validated for clinical testing on serum, plasma, and urine only. Less frequently CSF has undergone such scrutiny. Accrediting institutes like the CAP have ascertained that serum is not interchangeable with plasma, and as such, NSBFs are definitely considered an alternative matrix. Today’s practice, with CAP’s guidance, is to treat NSBFs as FDA-modified, which requires extensive validation at the level of a lab developed test, much to many laboratory’s dismay (2). This means each laboratory is responsible for determining precision, accuracy, reportable range, reference interval, analytical sensitivity, and analytical specificity. The specifics of the validation are largely at the discretion of the laboratory director. Some common concerns include:
- How should accuracy be validated in a NSBF matrix?
- How should we handle odd requests including ones with limited utility?
- Do we need to validate the use of hyaluronidase for viscous samples?
- Reference intervals??!! Impossible.
The approach that I would recommend is to first evaluate the tests your lab performs and current test volumes. Next, I would extensively research the literature to establish the existing clinical utility. This exercise will help guide which tests and fluid types to focus your energies on in the validation. Limited details of NSBF analytical validation are available elsewhere (3) and are beyond the scope of this blog. It is crucial to establish accuracy of testing in the NSBF matrix, which is accomplished by dilution and spiking recovery experiments and/or comparing with a reference lab. It is quite important to understand the analytical specificity (effects of sample pretreatment, hemolysis, etc) because in many cases it is different from serum and plasma and warrants thorough investigation. Ultimately, you will need to provide interpretive information, which was hopefully obtained earlier in your literature search.
Now is probably a good time to discontinue those tests with limited or no clinical utility. Deanna Franke, PhD, DABCC, Pathology Consultants of South Broward, LLP (Hollywood, FL) recently shared in her AACC Expert Access (Oct. 20, 2011) that she discontinued all NSBF electrolyte testing at her institution due to limited clinical utility. She experienced very little pushback. At Mayo Clinic, we require laboratory director approval for NSBF testing requests of limited or questionable utility. Occasionally, we approve these requests, but the clinician must provide a convincing case. We then verify the accuracy by performing dilution or spiked recovery experiments on that specimen and report the results with a disclaimer about using clinical judgment in the interpretation. You can consult a CAP checklist or the CLSI guidelines for suggestions (3,4).
The pay off for all this extra work and attention is improvement in the quality of patient care. Ultimately, your lab will only offer clinically useful tests, using methods analytically validated for NSBFs, and with interpretive information to guide proper management.
- Wians, FH. To test or not to test? Opening Pandora’s Box. Lab Medicine. 2004; 35:707.
- Ritchie, JC. NACBlog Is it Time to Remove the Stigma of LDT from Body Fluid Chemistry Assays? July 26, 2011
- Clinical and Laboratory Standards Institute: Analysis of Body Fluids in Clinical Chemistry; Approved Guideline. Clinical and Laboratory Standards Institute, Wayne, PA, 2007, CLSI document C49-A (ISBN 1-56238-638-7)
- Chemistry and Toxicology CAP checklist. 2011