December 2013 Clinical Laboratory News: Volume 39, Number 12
Why Harmonization Matters
The Latest From AACC’s Thought Leadership Series
By Bill Malone
Not many physicians, and even fewer patients, know that patients’ lab results often depend not only on their health, but also where the tests were performed. In fact, however, discrepancies among methods and labs can affect everything from treatment decisions to the quality of clinical practice guidelines. AACC’s International Consortium for Harmonization of Clinical Laboratory Results has been working with a variety of stakeholders to make progress on this global problem.
In a free AACC webcast, supported by a grant from Siemens Healthcare Diagnostics, Greg Miller, PhD, explains the current status of harmonization for clinical lab tests, as well as how leaders in laboratory medicine plan to tackle the formidable challenges of making different kinds of lab tests for the same analyte agree. Miller, past president of AACC, is professor of pathology at Virginia Commonwealth University in Richmond, and serves the university’s medical center as director of clinical chemistry and of pathology information systems.
To begin with, many people confuse the terms harmonization and standardization. “Harmonization and standardization are sometimes used interchangeably, but it’s important to distinguish between these two terms,” Miller said. “Harmonization means achieving comparable results among different measurement procedures, whereas standardization means achieving comparable results by having calibration traceable to a reference measurement procedure.”
While there are some 60 lab tests for which a gold standard reference measurement procedure exists, this is just the “tip of the iceberg,” according to Miller. “Most of the work in the field has been in the standardization area, but the interest in harmonization has been growing rapidly in the last few years and has become a major initiative for AACC together with international stakeholders.”
The goal of harmonization is not purely academic. “When lab measurement procedures give different results for the same specimen, patients may get the wrong treatment, because decision criteria are not appropriate for the procedure in use,” Miller emphasized. “In addition, many clinical guidelines used a fixed laboratory value for treatment decisions. In order to do this effectively, the results need to be harmonized.”
Likewise, clinical studies may also use a central lab with a single method, and guidelines from the study cannot be implemented until all other methods are harmonized to the central lab. On the other hand, if clinical studies use different methods, the data cannot be aggregated to develop guidelines without harmonized results.
In many cases, the solution to this problem involves pulling different methods into agreement by tracing them back to a secondary reference material—a calibrator that serves as a standard to which different tests may be compared. From this, a thornier dilemma emerges: even when such a calibrator exists, it may not solve the problem. Many secondary reference materials are not commutable with native clinical samples for routine clinical lab procedures, so while different assays may produce the same results compared to the calibrator, this uniformity does not hold true when it comes to actual patients samples, defeating the purpose of harmonization.
In the webcast, Miller outlines a new plan to deal with these scenarios. AACC is developing an infrastructure to coordinate harmonization activities worldwide, including prioritizing measurands to be harmonized, coordinating work by different organizations, developing technical processes to achieve harmonization, and tracking the success of harmonization. The initiative offers a transparent locus of communication among national and international organizations, and helps focus technical work on those measurands for which no reference measurement procedure exists.
The entire program, including an in-depth explanation of harmonization, traceability, and the technical challenges involved, is available for free on the AACC website.