A Standardized BCR-ABL Monitoring Test: Assessment of Potential Adoption Impacts In Healthcare In the United States

• Published in: Blood 2010-11, Vol.116 (21), p.4754-4754
• Main Authors: Trosman, Julia R, Weldon, Christine B, Tsongalis, Gregory J, Phillips, Kathryn A
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V116.21.4754.4754

Abstract 4754 BCR-ABL transcript monitoring is a guideline recommended component of Chronic Myeloid Leukemia (CML) management. BCR-ABL monitoring in the U.S. is mainly done using laboratory developed tests (LDTs). Studies found accuracy and reliability problems with LDTs which may lead to undesirable health and economic impacts (Gabert et al, Leukemia, 2003, Zhang et al, J Mol Diagn 2007, Muller et al, Leukemia 2008). There are ongoing efforts to standardize BCR-ABL LDTs in the U.S. and globally (Hughes et al, Blood 2006, Branford et al Blood 2006). A standardized BCR-ABL monitoring test (SBAT) may be an effective method to propagate standardization and improve quality of BCR-ABL testing. A standardized BCR-ABL monitoring test is one which minimizes operator error, and is stringently reviewed and shown to be validated under health authorities' quality systems regulations (principally Food and Drug Administration's Quality Systems Regulations and European Union's In-Vitro Diagnostics Directive), ensuring the safety and effectiveness of the test, as well as its reliable performance across multiple operators and labs through a thorough examination of its initial design, manufacturing, and associated processes. Our study qualitatively assessed potential benefits and drawbacks of adopting a SBAT, compared to current LDTs. We conducted peer-reviewed and grey literature review to answer questions: (1) How may the shortcomings of current BCR-ABL LDTs be impacting patient care, outcomes and quality of life? (2) How may adoption of a SBAT address the LDT shortcomings and propagate standardization? (3) What are potential health, economic and care process benefits and drawbacks of SBAT adoption for healthcare stakeholders? We identified BCR-ABL LDT shortcomings: (a) methodologic shortcomings resulting in suboptimal test accuracy; (b) process shortcomings (e.g. operator error; batch to batch variation in materials) leading to suboptimal reproducibility and (c) variability in methods across labs leading to incomparability of results. Three key results are: (1) Inaccurate over-quantitation of BCR-ABL results may lead to unnecessary further testing (e.g. mutation testing; bone marrow cytogenetic testing) and misinformed therapy decisions, e.g. drug dose escalation. False under-quantitation may lead to missed indications of relapse, resistance to therapy, or problems with therapy compliance. Due to result incomparability, patients often cannot change providers without losi