How should I go about introducing a new clinical flow cytometry test? 

You’re unlikely to find the answer to this question by searching the literature or posting a query online, and will probably resort to asking someone who might have done this before.  When asked this question my answer usually starts with “Well, um…” and in the pause that follows I’m desperately trying to think of something authoritative to say and worrying that my approach might not be ideal.  What do you think?  To stimulate discussion, I have written an article outlining the things I consider when introducing a new flow cytometry tube.  My thoughts do not reflect the opinion of the Society, but have certainly been influenced by information I’ve learned from other members.

There are some regulations that apply to this question.  CLIA outlines the responsibilities of laboratories performing clinical testing and considers two basic categories of assay: those cleared by the FDA and those not.  For FDA cleared assays the laboratory must verify the performance of the assay, as established by the manufacturer.  For most clinical flow cytometry laboratories this only refers to CD4 enumeration kits.  Confirming the performance of a quantitative test, such as this, is relatively straightforward, conforms to various guidelines for laboratory testing from the Clinical and Laboratory Standards Institute (CSLI), and is often done with assistance from the manufacturer.  For non-FDA cleared testing the laboratory has more responsibility, but fewer guidelines.  These are considered laboratory developed tests (LDT).  The FDA recommends that clinical laboratories use ASR reagents for these tests, for which the manufacturer must comply with current GMP practice but cannot issue claims about clinical utility or performance characteristics.  Therefore, it’s up to the laboratory to establish accuracy, precision, sensitivity, specificity, reportable range, reference range, calibration, and control procedures.  So you’re on your own.  Fortunately, a group of experts from ICCS and ICSH have been meeting to develop guidelines.  In this issue of the eNewsletter, Teri Oldaker and Bruce Davis report on the ICSH/ICCS LDT Validation Consensus Meeting held in Maine earlier this year.  In addition, there is a plenary session dedicated to this topic at the ICCS annual meeting in Portland in October 2011.

If you are prompted to ask the question in relation to switching to a flow cytometry system that can detect more colors, I would recommend viewing the presentation by Brent Wood on designing and implementing a high-level multicolor flow cytometry assay.  This is one of the new web presentations collected by the ICCS Education Committee and posted in the members section of the ICCS website.  Read the article by Paul Wallace for more details about this educational resource.  In addition, I would recommend that you consult other laboratories that have made a similar switch.  The article by Anand Lagoo in this issue of the eNewsletter summarizes the results of a questionnaire distributed to some users who have implemented a higher color flow cytometry system.  You’ll see that although each of the participants took a different approach, they shared similar struggles.  It’s clear that introducing a new flow cytometry test requires a good understanding of the entire procedure including the performance characteristics of the reagents and instrumentation.  These skills are also essential for maintaining optimal test performance after implementation, and troubleshooting problems.  Can you identify the unexpected findings in the eNewsletter CSI challenge presented by Jeannine Holden and figure out what went wrong? 

I hope you find this issue thought provoking and invite you to share your experiences with the ICCS eNewsletter readership.  How do you go about introducing a new flow cytometry test?  Do you have an interesting story about troubleshooting a problem in your flow cytometry laboratory?  Send me an e-mail or meet me at the ICCS meeting in Portland.

 



Fiona Craig (Editor)
your editor
craigfe@upmc.edu