Abstract and Introduction
Objectives: There is considerable variation in ordering practices for the initial laboratory evaluation of monoclonal gammopathies (MGs) despite clear society guidelines to include serum free light chain (sFLC) testing. We assessed the ability of a clinical decision support (CDS) alert to improve guideline compliance and analyzed its clinical impact.
Methods: We designed and deployed a targeted CDS alert to educate and prompt providers to order an sFLC assay when ordering serum protein electrophoresis (SPEP) testing.
Results: The alert was highly effective at increasing the co-ordering of SPEP and sFLC testing. Preimplementation, 62.8% of all SPEP evaluations included sFLC testing, while nearly 90% of evaluations included an sFLC assay postimplementation. In patients with no prior sFLC testing, analysis of sFLC orders prompted by the alert led to the determination that 28.9% (800/2,769) of these patients had an abnormal κ/λ ratio. In 452 of these patients, the sFLC assay provided the only laboratory evidence of a monoclonal protein. Moreover, within this population, there were numerous instances of new diagnoses of multiple myeloma and other MGs.
Conclusions: The CDS alert increased compliance with society guidelines and improved the diagnostic evaluation of patients with suspected MGs.
Monoclonal gammopathies (MGs) are a diverse set of conditions defined by the production of immunoglobulin proteins that arise from a clonal population of plasma cells. MGs encompass a spectrum of premalignant and malignant diseases. The clinical significance of monoclonal immunoglobulin proteins (M proteins) ranges from disease defining in entities such as multiple myeloma (MM) to an isolated laboratory finding conferring an increased risk of progression to malignancy in monoclonal gammopathy of uncertain significance (MGUS).
In the initial clinical evaluation of suspected MGs, M protein detection plays a central role in establishing the diagnosis. Numerous methods are now available in the clinical laboratory for quantitation and characterization of M proteins in both serum and urine. Prior to the advent of the serum free light chain assay (sFLC) in 2001, the gold standard for M protein detection was serum and urine protein electrophoresis (SPEP and UPEP) followed by immunofixation (IFE). The sFLC assay has since improved the diagnosis of MGs. The ratio of κ to λ free light chains (rFLCs) in sFLC assesses clonality, provides independent prognostic utility in a subset of diseases, and enhances diagnostic sensitivity. In addition, the sFLC assay has a lower limit of detection relative to the combination of SPEP with serum IFE (sIFE) for M proteins that lack an immunoglobulin heavy chain component such as those that give rise to AL (amyloid light chain) amyloidosis, light chain MGUS (LC-MGUS) and light chain MM (LC-MM), and nonsecretory MM.[8–12] In 2009, the International Myeloma Working Group (IMWG) recommended ordering an SPEP, sFLC, and sIFE for the initial screening of all MGs, except AL amyloidosis, which also requires urine IFE.
Despite subsequent studies further highlighting the favorable performance characteristics of the sFLC assay as a screening test for M proteins[13–15] and additional society recommendations, sFLC utilization in this setting varied substantially. In 2016, an international survey of over 700 clinical laboratories demonstrated a wide spectrum of ordering practices. Strikingly, sFLCs were included in the most common screening orders for the initial evaluation of MGs in only 19.7% of centers surveyed. Significant deviation from existing guidelines suggests that many MG diagnoses could be delayed, misclassified, or missed altogether due to the use of less sensitive diagnostic testing. In MM, there can be extensive early morbidity and mortality, underscoring the importance of early diagnosis.[18,19] The time interval from clinical presentation to diagnosis of MM can be long, and the use of less sensitive diagnostic testing may play a role.[20–22] To address this ongoing issue, an expert panel assembled by the College of American Pathologists (CAP) in 2021 issued evidence-based guidelines for the laboratory detection and characterization of M proteins, including for the initial evaluation of MGs. The first and strongest recommendation was to perform both SPEP and sFLC testing for all patients with suspected MGs.
It is well established that there may be significant delays between the publication of guidelines and adoption into clinical practice. Clinical decision support (CDS) tools are one of many potential solutions to address this multifactorial problem. Their deployment has also been shown to prevent patient harm, improve outcomes, increase cost savings, and enhance laboratory efficiencies.[25–27] CDS solutions can target all aspects of the laboratory testing process from test ordering to results reporting. Interruptive alerts are a particularly effective strategy for guiding provider ordering practices.[29,30] For example, it has been suggested that many sIFE orders are redundant or unnecessary.[31,32] We recently reported an interruptive CDS alert that decreased upfront sIFE orders by promoting sIFE ordering as a reflex test dependent on abnormal SPEP findings, yielding significant operational and cost savings with no apparent loss in sensitivity.
Herein, we implemented an interruptive CDS alert to align ordering practices for the initial evaluation of MGs with the IMWG and the 2021 CAP guidelines. Specifically, the alert prompts ordering providers to consider adding sFLC testing when an order for an SPEP is placed and an sFLC assay has not been ordered or recently resulted. We evaluated the effects of this intervention by assessing changes to sFLC ordering practices, provider alert burden, and the clinical impact of sFLC testing prompted by the alert.
Am J Clin Pathol. 2023;159(2):192-204. © 2023 American Society for Clinical Pathology