The plethora of complex and ever-changing clinical guidelines for disease diagnosis and treatment presents a significant challenge for physicians trying to keep up-to-date while maintaining a busy practice. The specialized expertise of lab professionals can help ensure patients get the right immunodiagnostic tests for early diagnosis, leading to earlier treatment. Using their expertise in immunodiagnostics, empowered lab professionals can contribute to better patient care, reduced complications, and better patient outcomes.
The physician’s challenge
For every major disease, there are hundreds, if not thousands, of publications that are of value to clinicians. To aid physicians’ efforts to assimilate the large amount of information for each disease, including detection, monitoring, and treatment options, clinical guidelines have been developed. As our body of knowledge continues to advance rapidly, these guidelines are updated every few years, often by committees of specialists in particular fields.
While specialists who focus on one disease state maintain up-to-date knowledge largely through the primary literature, generalist clinicians such as internal medicine physicians and family practice physicians cannot, as a practical matter, maintain the same level of knowledge on all of the diseases that they may encounter.
Less common diseases
Some of the most common diseases, such as diabetes, hypertension, and asthma, are frequently seen by the primary care or internal medicine physician. Thus, those doctors usually are aware of the clinical guidelines. For less common diseases, it is more difficult for generalists to maintain a current knowledge. In fact, deep knowledge of treatment guidelines for less common diseases is probably not necessary for primary care physicians because the patient is referred to specialists for treatment. However, the presentation of symptoms of these diseases often occurs in the primary care context, and the appropriate diagnostic tests should be run in order to refer to the appropriate specialist.
It is in this arena, where patients present with symptoms that may be due to less common diseases, that the laboratory professional can play an essential role helping primary care physicians with guideline-recommended tests in order to provide the patient with the best quality of care. Let’s use the example of multiple myeloma, a blood cancer that often presents with vague symptoms, to highlight how lab professionals can assist in ensuring guideline compliance for immunodiagnostic testing.
Case study: multiple myeloma
Multiple myeloma is a cancer of plasma cells which affects approximately 30,000 new patients in the United States every year, and 12,000 deaths are expected in 2017. In the general population, 118,000 are living with multiple myeloma in the U.S. The overall incidence is seven new cases per 100,000, but the incidence is elevated in people 50 years and older.1
According to a valuable study by Kariyawasan and colleagues,2 more than 50 percent of multiple myeloma patients present to the primary care physician. Nonspecific and vague symptoms such as back pain, bone pain, or fatigue are often the first presenting symptoms. Such vague symptoms may be due to any of a number of causes. After clinicians rule out some of the more common causes of these symptoms, testing for multiple myeloma as the underlying cause may be appropriate. If diagnosis is delayed (i.e., more than six months from first presentation), secondary complications such as renal dysfunction, anemia, and bone involvement are increased. Of patients who present to primary care physicians, more than 50 percent remain undiagnosed six months after first presentation. In contrast, patients who present to hematologists or nephrologists generally are diagnosed within the first six months. These observations highlight, first, the importance of the primary care physicians as the first line of presentation, and, second, their potential need for assistance in the diagnosis of patients with multiple myeloma.
The immunodiagnostic tests recommended by the International Myeloma Working Group (IMWG) for the initial symptomatic screening of patients for suspected monoclonal gammopathy such as multiple myeloma include serum protein electrophoresis (SPEP), serum immunofixation, and serum free light chains (free kappa and free lambda with ratio).3 These three tests, or even a simplified scheme of only SPEP and free light chains, are sufficient to detect more than 99 percent of multiple myeloma cases.4
While this recommendation is relatively simple and straightforward, there is a legacy of tests that have been ordered by physicians including these three plus urine protein electrophoresis (uPEP) and urine immunofixation (uIFE). Of these five tests, SPEP is one of the least sensitive, and yet solo orders of SPEP only represent 20 percent of all initial myeloma screens.5 In two independent studies examining the initial myeloma screening tests ordered by physicians, it was found that only two percent to six percent of initial myeloma screens ordered the guideline-recommended tests.5,6 Of these initial suspected myeloma orders, nearly 30 percent came from internal medicine physicians.6 It is this poor guideline compliance rate that offers an opportunity for knowledgeable and empowered lab professionals to intervene and directly improve the quality of patient care.
Laboratorians providing guidance
How, then, can laboratory professionals help to get the “best” tests orders in this situation? First clinical laboratory directors can make themselves aware of the guidelines as they pertain to diagnostics and immunodiagnostics. Imagine a scenario where an internal medicine, primary care, or family physician orders just an SPEP in querying multiple myeloma. An educated and proactive lab director may know that SPEP is only 80 percent to 88 percent sensitive, and that the guidelines recommend ordering SPEP, a free light chain test, and serum immunofixation.4
How should a lab director proceed, balancing patient needs, healthcare costs—and it must be said, physician feelings? One option is to simply run the requested test and report the result. A second option is to run the test, report the result, and add a comment explaining the guidelines with reference for the physician. A third option is for the lab director to add the additional tests on his or her own initiative.
The first approach does not address the underlying problem that the physician did not order all of the appropriate tests needed. The third approach would probably be considered by most physicians to be too aggressive. The second option strikes a balance that provides the physician with pertinent and timely knowledge for the case at hand while still leaving to him or her the control and clinical judgement.
Realizing that their expertise can help both physicians and patients, larger reference laboratories are beginning to make use of such comments. For example, the following comment has been listed as a limitation for SPEP:
“In the evaluation of multiple myeloma (MM), 12% of patients will not be detected by SPEP. The addition of serum free light chains (sFLC) and IFE increases detection of MM to >99% and is consistent with the International Myeloma Working Group recommended guidelines. (In Related Information, see profile 120256 Immunofixation (IFE), Serum, Protein Electrophoresis (PE), Serum, and Quantitative Free κ and λ Light Chains (FLC) Plus Ratio, Serum.)”
Adding this comment to the lab results may bring it to the physician’s attention, allowing him or her to act on it readily, and ultimately lead to quicker referral and reduced secondary complications such as advanced renal disease.
This example reminds us of how clinicians, laboratory directors, and laboratory staff can work together to share their expertise for the benefit of patients. Lab directors and staff are knowledgeable experts who play an integral part in our healthcare system, and it is important for them to feel confident and empowered in interacting with clinical colleagues to help shape the ordering of the most appropriate immunodiagnostic tests.
REFERENCES
- US SEER database (seer.cancer.gov). Seer Cancer Statistics Review: Myeloma 2017.
- Kariyawasan CC, Hughes DA, Jayatillake MM, Mehta AB. Multiple myeloma: causes and consequences of delay in diagnosis. QJM. 2007;100(10):635-640.
- Dispenzieri A, Kyle R, Merlini G, et al. International Myeloma Working Group guidelines for serum-free light chain analysis in multiple myeloma and related disorders.
Leukemia. 2009;23(2):215-224. - Katzmann JA, Kyle RA, Benson J, et al. Screening panels for detection of monoclonal gammopathies. Clin Chem. 2009;55(8):1517-1522.
- Murray, D. (Mayo Clinic) 2015. Oral Presentation at American Association of Clinical Chemistry Annual Meeting. Data courtesy of CAP Diagnostic Immunology Resource.
- Bennett ST. Slow adoption of the recommended test combination for multiple myeloma screening. Hematology Reports. 2015;7 (s1) (7th International Symposium on Clinical Applications of Free Light Chains and Heavy/light Chain analysis.
Naveen Bangia, PhD, serves as Director, Scientific Affairs, for Binding Site, manufacturer and distributor of specialized immunodiagnostic assays and instrumentation, including the Freelite assays, used in diagnosing and monitoring monoclonal gammopathies, and the Optilite chemistry analyzer, used in special protein testing.
