By Sten Westgard, MS
I want to draw your attention to a recent article in the November/December 2008 issue of IVDT:
Upgradinig quality control in molecular diagnostics.
This article was written by a good friend of the website, Dr. Clark Rundell. He has previously written articles on this topic for us.
As you probably know, molecular diagnostics is in a period of explosive growth right now. The potential is great, but so are the risks. Some of these genetic tests will be taken only once in someone's life, so the need to get the the correct, accurate result is even more important than with "normal" testing. So the QC used in molecular diagnostics methods is extra robust, right?
Molecular diagnostics has a different development history than the "usual" methods. Dr. Rundell, helpfully, has made a table of all the differences:
Among other issues, It's been harder to develop uniform control materials. Methodologies have changed rapidly, making it more difficult to develop standard materials. Given the expense of the tests and materials, labs have been less willing to pay more for controls, etc., etc.
Dr. Rundell explains it better:
"Despite [growing] resources, the majority of molecular tests continue to lack quality controls useful for traditional QC practices. Historically, QC is developed only after new tests are implemented and somewhat standardized. Understandably, most IVD manufacturers prefer to sell test platforms that are high-ticket items. More so than in other laboratory disciplines, molecular test methods are continuously changing, making it difficult for controls manufacturers to develop products compatible with current and future test systems. Furthermore, the response to current commercial multiplex controls has been lukewarm. Laboratories using free patient samples, or no samples at all, for rare mutations are reluctant to pay for controls. The value of monitoring qualitative tests to prevent failure has not been demonstrated for molecular tests. The test results for all alleles are not monitored, and therefore the failure rates are unknown."
In other words, we are dealing with a lot of unknowns. We don't have regulatory specifications for quality requirements (CLIA does not give PT criteria for these tests). Which also means we don't know how well these tests should perform. So it's hard to determine the actual error rate of these tests.
We also have a lot of market forces that work against common control materials. Manufacturers have incentives to create unique testing products, ones that aren't comparable to competitor products. They also have incentives to avoid determining or releasing information on error rates.
Regulations are still catching up with molecular diagnostic testing. While the laboratory director has the same reponsibilities (basically, all the responsibility) for adequate quality of molecular diagnostics, the tools for assessment are primitive.
Quality control for molecular diagnostics is going to grow in importance in the coming years, and Dr. Rundell's article is a good assessment of the current state of the art. We hope QC in molecular diagnostics will catch up with the growth in the use of the testing, and before a crisis occurs that will trigger a CLIA-type response.