OPINION. A Troponin Assay Conversion: What Success Looks Like WHAT MAKES TROPONIN ASSAYS DIFFERENT FROM ONE ANOTHER? ...

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1 A Troponin Assay Conversion: What Success Looks Like Brad P. Mayeux 1 * Cardiac troponin (ctn) 2 assays have been available to the medical community for over 20 years for the aid in diagnosis, risk stratification/ prognosis, and guiding management of patients with signs and symptoms of myocardial injury and necrosis. However, we still struggle with how to synthesize the amount of information that these highly specialized assays deliver during a patient chest pain crisis. The amount of information is small a single number but the complexities are large. Transitioning assays is only one of many challenges that the majority of laboratories, and their clinician customers, face. However, successfully transitioning from one troponin assay to another is a different matter. In many instances, a laboratory makes a decision based on a number of other aspects, such as integrated platform analyzers, or middleware, and not just a ctn assay. Nonetheless, ctn can be a very polarizing assay and appears to make its way to the forefront of any instrument transition for many institutions. WHAT MAKES TROPONIN ASSAYS DIFFERENT FROM ONE ANOTHER? It is essential for stakeholders, laboratorians, and clinicians alike to understand the nuances of the different ctn assays on the market, to make decisions of which assay to use, and to have a strategy for implementation. However, if this job is done well, which includes the proper education, the average clinical practitioner will learn how to understand the performance characteristics of the ctn assays they use and how it may affect patients and their clinical practice. On the other hand, advancements in ctn assay technology have created a conundrum for clinicians and laboratorians, who must determine which assay is the best fit for optimal patient care (1). The walls that separate the laboratory from the clinical units are not only physical. Reality in the ctn world has brought to light the disparities of opinions that exist between laboratory medicine and the clinical realm. Many emergency department (ED) physicians and cardiologists, not to mention hospitalists, do not have a full understanding that many different ctn assays are available, or that concentrations obtained from the different assays do not necessarily correlate with one another. The notion of a troponin is a troponin is a troponin is quite widespread in the clinical community and difficult to dispel without proper education. Moreover, with the availability of highly sensitive ctn assays available throughout the rest of the world, and their imminent clearance by the Food and Drug Administration, more indepth knowledge and understanding will be imperative. Questions surrounding earlier and 1 Roche Diagnostics, Boston, MA. *Address correspondence to the author at: Roche Diagnostics, 9115 Hague Rd., Indianapolis, IN brad.mayeux@roche.com. DOI: /jalm American Association for Clinical Chemistry 2 Nonstandard abbreviations: ctn, cardiac troponin; ED, emergency department; MI, myocardial infarction. March : JALM 1 Copyright 2017 by American Association for Clinical Chemistry.

2 A Troponin Assay Conversion Fig. 1. Processes that have proven to be successful. Key aspects of each stage are highlighted that should be considered for clinicians and laboratorians alike during any troponin transition. more sensitive detection, possible sex-specific thresholds, cardiac injury, and types of myocardial infarction (MI) are still to be answered (2). Thought leaders throughout the US agree on one fundamental aspect; education will be critical to the success of any high-sensitivity ctn implementation. The approach that manufacturers have taken to design and develop ctn assays have many differences and are for many different reasons. The first principle is that different isoforms of ctn (ctn I and ctnt) are measured by different manufacturers' assays. Additionally, sensitivity and specificity, positive and negative predictive value, as well as accuracy and precision vary among ctn assays, creating very different tests, which physicians and other prescribing clinicians have little or no knowledge about. To overcome this knowledge gap during a ctn assay transition, implementation of a sound educational plan is essential for the laboratory to be successful in providing their clinical customers the tools they need to provide the best patient care possible. PILLARS OF SUCCESS The successful implementation of a new ctn assay occurs in several distinct stages, which can be divided into 3 main categories: pre-implementation, implementation, and post-implementation (Figure 1). Each stage has distinct attributes that contribute equally to the success of the troponin assay transition. Careful thought must be given to each stage to ensure the best outcome. In the pre-implementation stage, once selection of ctn assay has been determined, the laboratory management and staff must begin to design the education and implementation plan. Laboratory administration, pathologists, laboratory directors or managers, and chemistry supervisors alike must understand the nuances of the ctn assay selected, as well as how it 2 JALM :05 March 2017

3 A Troponin Assay Conversion OPINION compares to the incumbent ctn measurements. Close collaboration with the manufacturer does indeed assist with understanding the assay so that transferring knowledge to clinicians across the institution can be facilitated. A cross-specialty, multidisciplinary team should be formed to involve all necessary parties who will use and/or interpret the assay. The backbone of this ctn transition team should, at a minimum, include the laboratory, ED, cardiology, internal medicine, and hospitalist clinicians. Other members who should be assembled to form a robust transition team include nursing, risk management, and quality assurance. One of the most crucial tasks for this team is to determine decision thresholds that the clinical staff will use for given patient populations. Discussion of non-st-elevation MI guidelines (3), as they relate to the universally recommended use of the 99th percentile of a reference control population for the ctn assay, should be conducted when determining appropriate decision thresholds. This, in many instances, requires explanation to the clinical staff as to what the 99th percentile actually is regarding ctn troponin testing. The use of a sensitive contemporary ctn assay at a decision threshold of the 99th percentile will improve diagnostic performance, and these assays can potentially have a substantial impact in improving early diagnosis and outcomes of acute MI patients (4). This should most certainly involve a clinical discussion between cardiology and the ED clinicians, as sensitivity and specificity are used differently within these 2 clinical areas. Successful ctn transitions include one, if not several, meetings among the laboratory and these 2 clinical areas to determine the most suitable decision thresholds for the patient population for which the institution provides care. Evidence-based laboratory guidance and input are essential during this process, since clinicians rely heavily on this knowledge, sometimes without question, and clinician groups do not always understand the analytical variables that influence laboratory results and potential issues that may arise during implementation (5). Therefore, laboratory medicine expertise and guidance helps to reduce the confusion and increase the understanding of the new troponin assay and its performance. Cardiac troponin assay correlation studies are not typical and should be designed and carried out carefully. Comparison of the current and new ctn assay should be executed carefully, eliminating any potential variables. For example, analyzing one ctn sample batch after a freeze-thaw cycle and not the other, or using the 99th percentile for one assay and not the other, may greatly affect the outcome of the study. Analytical comparison of ctn assays may be very complex. However, a clinical correlation is the most prudent method to compare the incumbent ctn and the new assays, to show how they compare clinically. Review of these data should be discussed in an open forum, and a qualified labortorian should be involved before implementation occurs. The implementation phase of any ctn may provoke anxiety for any laboratory, whether large or small. However, the thoughtfully laid plans mentioned earlier will help to ensure success during this stage of the transition. Preparation begins with more involvement and interaction among the multidisciplinary team. It is imperative to have laboratory representation at ED, cardiology, and hospitalist/internal medicine departmental meetings to help educate all physicians, nurse practitioners, physician assistants, and any other prescriber who interprets ctn results in their clinical decision-making. Most specialty groups within medical institutions have regular staff meetings, and this is frequently the best venue for reaching as many clinicians as possible. An intended short 10- to 15-minute time slot at the beginning of a departmental meeting agenda will frequently expand to minutes when discussing the value of the assay and clinical implications, including the potential March : JALM 3

4 A Troponin Assay Conversion impact on patient outcomes. This discourse will prove to be invaluable to the entire transition process. Another effective tool that should be used is to disseminate an informative implementation or transition letter, which is a simple way to distribute the vital assay information to all clinical staff. Recommended contents should include sections that speak to decision thresholds, analytical performance, reference to published literature, and other pertinent evidence deemed necessary by the multidisciplinary team. Opinions may differ on timing, but many believe that an initial announcement approximately 1 or 2 weeks before transition, with a follow-up letter the day before transition, would be highly advisable. FLIPPING THE SWITCH In all likelihood, ctn will not be the only assay that will be transitioning during an implementation. Additionally, one very important consideration is to continue serial measurements of the incumbent ctn assay on patients who presented to the ED during the transition. Keeping the current ctn available and online for hours to finish any patient serial measurements should be heavily weighted, since ctn assays do not correlate numerically and could have an adverse impact on the decisions clinicians will make. All newly presenting patients after the transition will then be followed serially with the newly implemented ctn assay. Laboratory vigilance during the first days of the transition is essential to help guide clinicians who were not able to benefit fully from the education before the transition, as well as answer any questions that may arise. The post-implementation stage is the final important part of any ctn transition process. During this period, an ongoing process of verifying the accuracy of assay performance should be continued, as is done for most clinical assays. To keep track of the effect of the transition on clinical care, key outcomes such as laboratory turnaround time and the prevalence of elevated ctn results in hospital admissions for suspected acute coronary syndrome should be monitored. Follow-up with clinicians at the aforementioned periodic departmental meetings is imperative to ensuring the success of any ctn transition. Reeducating on proper use of ctn assay will more than likely be necessary and will strengthen the probability of a successful transition. CONCLUSION Transition to a new ctn assay can be a daunting task for any laboratory and institution to undertake. However, with careful selection of the ctn assay appropriate for the patient population served, proper planning, and comprehensive collaboration and education of the clinical staff, the transition can occur without disruption of the medical value that the laboratory brings to their clinicians and the patients to whom they provide care. Moreover, this collaboration will likely have the effect of strengthening the relationship between the laboratory and the clinicians to whom they provide a valuable service and form a true partnership between 2 important entities within the institution. 4 JALM :05 March 2017

5 A Troponin Assay Conversion OPINION Author Contributions: All authors confirmed they have contributed to the intellectual content of this paper and have met the following 4 requirements: (a) significant contributions to the conception and design, acquisition of data, or analysis and interpretation of data; (b) drafting or revising the article for intellectual content; (c) final approval of the published article; and (d) agreement to be accountable for all aspects of the article thus ensuring that questions related to the accuracy or integrity of any part of the article are appropriately investigated and resolved. Authors Disclosures or Potential Conflicts of Interest: No authors declared any potential conflicts of interest. Role of Sponsor: No sponsor was declared. REFERENCES 1. Apple FS. A new season for cardiac troponin assays: it's time to keep a scorecard. Clin Chem 2009;55: Korley FK, Jaffe AS. High-sensitivity troponin: where are we now and where do we go from here? Biomark Med 2014;8: Amsterdam EA, Wenger NK, Brindis RG, Casey DE, Ganiats TG, Holmes DR, et al AHA/ACC guidelines for management of patients with non-stelevation acute coronary syndromes. J Am Coll Cardiol 2014;64: Korley FK, Jaffe AS. High sensitive cardiac troponin assays: how to implement them successfully. ejifcc 2016;27: Reichlin T, Hochholzer W, Bassetti S, Steuer S, Stelzig C, Hartwiger S, et al. Early diagnosis of myocardial infarction with sensitive cardiac troponin assays. N Engl J Med 2009;361: March : JALM 5