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CLIA Final Rule

"Equivalent" QC Option 4: Back to the future

Back to the Future: CLIA EQC Option 4

A recent meeting held by the Institute formerly known as NCCLS (now CLSI) proclaimed EQC as the "QC for the Future", then promptly proposed a new option that would replace thecurrent options. Even more interesting, the new option comes out of CLIA's past...

March 2005

A workshop on “QC for the Future” took place on March 18, 2005, in Baltimore, MD. This workshop was sponsored by CLSI, the Clinical Laboratory Standards Institute (the Institute formerly known as NCCLS). The workshop was also promoted under the name of “Equivalent QC,” suggesting that EQC was the QC for the future.

I found the two themes to be somewhat contradictory because EQC is so seriously flawed. (See Testing Equivalent Quality – A Better Way.) However, the outcome of the workshop is a proposal for an alternative QC procedure that will be developed as EQC “option 4.” It was interesting to see that a new CLSI committee had already been approved prior to the workshop, thus the outcome was predetermined. Fortunately, this outcome has the potential to have a positive impact on QC and the quality of laboratory testing.

Filling the QC Hole

Dr. Joe Boone from CDC was forthright in explaining that CLIA left a big hole in the laboratory world of QC when the Final Rule eliminated the requirement for FDA clearance of manufacturer’s QC instructions. Remember that the original CLIA rules were published on February 28, 1992, and contained a phase-in period of two years for the QC requirements. During this phase-in period, it was expected that FDA would develop a “QC clearance process” to approve a manufacturer’s QC instructions, which would allow laboratories to simply follow those instructions and fully satisfy the CLIA QC requirements. This phase-in period was to end September 1, 1994, but was extended to May 12, 1997, then till October 14, 1998, then till December 29, 2000, and then until publication of the CLIA Final Rule on January 24, 2003. (See CLIA QC Clearance Postponed Again & Again & Again & Again.)

When the Final Rule appeared, the provision for QC clearance had been deleted from the regulations. (See Final CLIA Rule: Part I. Key Changes.) This left a “hole” in the regulations, which was to be filled by the CMS options for “equivalent QC procedures” (EQC). These EQC options have met with considerable doubt from laboratories and even from industry. At the Baltimore meeting, CMS came close to admitting that the EQC options were a bust, hence the need for a new option #4 to accommodate new technology where traditional statistical QC may not be applicable.

Option #4: Same as Before

The proposal for EQC option #4 was presented by Luann Ochs (from Roche Diagnostics) on behalf of AdvaMed, an industry trade group that represents diagnostic manufacturers. In May 2004, AdvaMed met with representatives from CMS, FDA, and CDC to discuss EQC and propose another EQC option. As presented at the Baltimore workshop, here is the proposal for “option #4”:

Manufacturers may validate an alternative quality control procedure.

If FDA agrees that the validation shows that the alternative is equivalent to traditional QC, then

Labs may use the alternative QC instead of the CLIA-mandated QC.

This sounds much like the original CLIA rule that called for FDA to review a manufacturer’s QC instructions as part of the 510K approval process. There is a significant difference, however. CLIA originally called for QC clearance for all new measurement procedures, whereas the proposed EQC option #4 will apply only to those manufacturers who claim an alternative QC procedure as part of their product labeling.

A risk assessment approach to QC

The development of manufacturer’s guidelines for validating QC will be undertaken by a new CLSI committee, which will be chaired by Greg Cooper from Bio-Rad and includes the following members: George Brotea from Ortho Clinical; Fred Lasky from Genzyme; Dai J. Li from FDA; Gregory Makowski from University of Connecticut; Curtis Parvin from Washington University; George Plummer from Dade Behring; Jeffrey Vaks from Beckman Coulter; and Rhonda Whalen from CDC.

The approach is to be based on a risk assessment analysis whereby individual risk factors are identified, controls are put in place to mitigate the risk, and a study is performed to document that the risk is adequately controlled. As part of the workshop program, Dr. Don Powers discussed approaches to risk management for manufacturers and the clinical laboratories. Dr. Powers is the chair of the group that developed ISO 15198 “Clinical laboratory medicine – In vitro diagnostic medical devices – Validation of manufacturer’s recommendations for user quality control.” This ISO document proposes the use of Failure Mode Effect and Critically Analysis (FMECA) and/or Fault Tree Analysis (FTA). This is a “high-level document”, meaning it provides no practical guidelines, just identifies principles and approaches. (See ISO Says So: Recommendations for validation of user QC.) Therefore, there is a need for another committee to develop a document that provides practical guidelines.

Back to the future

So, here we are in March 2005 getting ready to finally implement a QC clearance process, as originally called for in the 1992 CLIA rules. The expected timetable for development and approval of the new CLSI document is 2 years. Assuming no problems or delays, that will make it 2007 before the CLIA rules finally get implemented in the way they were intended.

Some may call this progress and it certainly happens in mysterious ways! I recall a two-day conference organized by FDA in the early 90s to discuss the original QC clearance provision and to discuss guidelines for implementation. And I also recall that the Health Industry Manufacturers Association (HIMA) mounted a vigorous opposition to the proposed QC clearance regulations. HIMA later became AdvaMed, which is now sponsoring EQC option #4. Yes, what goes around comes around and sometimes it almost makes one dizzy. While I applaud the manufacturers present support for QC clearance, this issue could have been resolved many years ago if they had supported it back then!

QC in the future may mean more QC

Since the 1992 regulations, the quality of laboratory testing processes has suffered due to the CLIA minimums becoming laboratory maximums. Getting laboratories to run even two levels of control per day has become difficult and QC deficiencies are still commonly found during laboratory inspections. In the face of these difficulties, it is hard to understand the rationale for the proposed CMS options for EQC that would reduce daily QC to weekly or even monthly QC. Data from proficiency testing surveys indicates that the average quality of laboratory tests is only 3 to 4 sigma, which also means that laboratories generally should be doing more QC than 2 per day. See recent discussions on this website about the quality of laboratory tests, specifically cholesterol, calcium, glucose, and glycohemoglobin.

It was heartening to see that some manufacturers also recognize that QC in the future must be better than the minimums under CLIA. Some recognize that a totally automated QC process is needed to guarantee that the quality of laboratory tests will satisfy medical requirements. Development and implementation of Option #4 will hopefully provide manufacturers with a path and process to improve laboratory QC.

See the Entire CLIA Final Rule Series:

  • Part I: Key Changes
  • Part II: Perplexity about Personnel and Complexity, by Sharon S. Ehrmeyer, Ph.D.
  • Part III: Conflict between Quality vs. Compliance in QC.
  • Part IV: New Regulations for Method Validation, by Sharon S. Ehrmeyer, Ph.D.
  • Part V: Method Validation Process and Procedures
  • Part VI: Statistical Sense, Sensitivity, and Significance
  • Part VII: "Equivalent" QC Procedures
  • Part VIII: The Interpretive Guidelines
  • Part IX: Appropriate QC Procedures
  • Part X: Lies, Damn Lies, and "Equivalent" QC
  • Find out even more in the CLIA Final Rules for Quality Systems manual
  • Attend the CLIA Final Rules Workshop on June 14
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