Reducing unnecessary laboratory testing
- Jessica S. Tischendorf, MD, MS1,2
- The High Value Practice Academic Alliance Future Leaders Program3
- Brad Karon, MD, PhD4
- George Hoke, MD5
- Christopher Petrilli, MD6
- Jennifer M. Schmidt, MD7
- Pamela T. Johnson, MD8
- Nasia Safdar, MD, PhD1,2
- 1William S. Middleton Memorial VA Hospital, Madison, Wisconsin
- 2University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
- 3Contributing authors below
- 4Mayo Clinic College of Medicine, Rochester, Minnesota
- 5University of Virginia Medical Center, Charlottesville, Virginia
- 6Michigan Medicine, Ann Arbor, Michigan
- 7 Saint Louis University School of Medicine, Saint Louis, Missouri
- 8Johns Hopkins Medicine, Baltimore, Maryland
- Oluwasayo Adeyemo, MD, Saint Louis University, Saint Louis, Missouri
- Clarice Bunag, MD, University of California Riverside School of Medicine, Riverside, California
- Stephanie Carr, MD, MBA, VA Puget Sound Health Care System, Seattle, Washington
- Mike Kai-Wick Cheng, MD, University of Chicago, Chicago, Illinois
- Abimbola Chris-Olaiya, MD, MPH, Grand Strand Medical Center, Myrtle Beach, South Carolina
- Shirley Cohen-Mekelburg, MD, Weill Cornell Medicine, New York, New York
- Carl V. Crawford, MD, Weill Cornell Medicine, New York, New York
- Christopher Grondin, MD, Michigan Medicine, Ann Arbor, Michigan
- Arjun Gupta, MD, University of Texas Southwestern Medical Center, Dallas, Texas
- Kevin Hsu, MD, Cedars-Sinai Medical Center, Los Angeles, California
- Charity Huang, MD, University of California Riverside School of Medicine, Riverside, California
- Ashley Kosier, MD, Our Lady of the Lake Children’s Hospital, Baton Rouge, Louisiana
- Benjamin O. Lawson, MD, Honor Health Internal Medicine Residency Program, Scottsdale, Arizona
- Kasey Little, MD, University of Virginia Medical Center, Charlottesville, Virginia
- Joshua D. Newman, MD, Loyola University Medical Center, Maywood, Illinois
- Michelle Ogunwole, MD, UT Health San Antonio, San Antonio, Texas
- Ariella Pratzer, MD, New York University, New York, New York
- Rachna Rawal, MD, Saint Louis University, Saint Louis, Missouri
- Javad Savoj, MD, University of California Riverside School of Medicine, Riverside, California
- Christopher Steele, MD, MPH, MS, Johns Hopkins Medicine, Baltimore, Maryland
- Garth W. Strohbehn, MD, MPhil, Michigan Medicine, Ann Arbor, Michigan
- Jian Liang Tan, MD, Crozer-Chester Medical Center, Upland, Pennsylvania
- Branden Tarlow, MD, PhD, University of Texas Southwestern Medical Center, Dallas, Texas
- Foram Thakkar, MD, University of Texas Health Northeast/CHRISTUS Good Shepard Medical Center, Longview, Texas
- Jessica S. Tischendorf, MD, MS
- University of Wisconsin Hospital and Clinics
- UWMF Centennial Building
- 1685 Highland Avenue
- Madison, WI 53705
- email: firstname.lastname@example.org
Jessica Tischendorf’s work was supported with resources and the use of facilities at the William S. Middleton Memorial VA Hospital in Madison, Wisconsin in academic year 2017-2018.
There are no relevant conflicts of interest for any contributing author. All authors had a role in writing the manuscript.
This work has not been published previously.
Key Words: utilization, healthcare costs, practice patterns, quality of healthcare
Background: Medical costs are a leading financial concern for Americans, and medical providers must play an integral role in reducing cost of care by avoiding inappropriate laboratory testing. Residents and fellows can champion value-based quality improvement work to promote high quality patient care and reduce costs associated with unnecessary laboratory testing in their institutions. This narrative review of appropriate use of laboratory testing can direct trainee value-based quality improvement initiatives to reduce inappropriate testing in the inpatient, outpatient and emergency department setting.
Methods: In the 2017-2018 academic year, faculty mentors from the High Value Practice Academic Alliance compiled a list of laboratory tests to target for value-based quality improvement work. Under faculty mentorship, trainees contributed to this narrative review by reviewing relevant literature and providing recommendations for quality improvement targets for each of the proposed target laboratory tests.
Results: High Value Practice Academic Alliance faculty mentors identified 25 laboratory tests to target for value-based quality improvement work. These tests range the inpatient, outpatient and emergency settings and span several medical specialties.
Discussion: Trainees are poised to lead impactful value-based quality improvement initiatives. The present review provides trainees interested in this work with an actionable list of laboratory tests to target for optimization.
The United States healthcare system is fraught with inefficiencies, with reports of $750 billion worth of waste contributing to poor quality, disparities, and patient harm1. Healthcare costs are a leading concern for families2 and many adults forgo recommended care or avoid seeking care when ill due to cost3. To deliver higher value healthcare, many institutions are implementing quality improvement initiatives to reduce unnecessary tests, treatments and procedures. In academic medical centers, nearly two-thirds of laboratory testing in the inpatient setting does not affect patient management4. In addition to unnecessary costs and patient discomfort, inappropriate laboratory testing contributes to anemia, misguided management and unnecessary downstream testing.
As the front line providers in academic medical centers, trainees are especially poised to lead initiatives to reduce costs by reducing unnecessary laboratory testing across disciplines and care settings. The purpose of this narrative review is to provide trainees with an actionable list of laboratory studies to target for optimization as part of quality improvement efforts in the inpatient, outpatient and emergency department settings.
This narrative review is a collaborative effort among the faculty leaders and trainees engaged in the High Value Practice Academic Alliance in the 2017-2018 academic year. The High Value Practice Academic Alliance is an organization of faculty from 90 United States academic institutions with a mission to improve the quality and safety of patient care while reducing costs5.
Participants collaborate on quality improvement, education and research in value-based care. Faculty leaders direct a trainee mentorship program, the Future Leaders Program6.
To engage trainees in value-based scholarship in the 2017-2018 academic year, faculty compiled a list of laboratory tests to target for quality improvement. The list was generated through an emailed faculty survey conducted by a senior author (P.J.). Alongside a faculty mentor, trainees authored a synopsis for one or more of the targeted laboratory tests. Trainees reviewed relevant primary literature and existing guideline statements to inform a brief synopsis on overuse and appropriate indications for each laboratory test. Content experts reviewed synopses where necessary and three authors (J.T., P.J., and N.S.) compiled the review.
High Value Practice Academic Alliance faculty leaders identified 25 laboratory tests as targets for optimization (Table 1). These tests crossed medical specialties and spanned the care continuum.
Basic and Comprehensive Metabolic Panel
The basic and comprehensive metabolic panels are frequently ordered for hospitalized patients without clear indication4. Repeated ordering of chemistries in the setting of clinical stability is recommended against7. In patients without clinical suspicion for hepatobiliary disease, carefully consider whether the additional data a comprehensive metabolic panel provides is necessary given the added cost.
Amylase in Pancreatitis
Combined with clinical features or characteristic imaging, elevated serum amylase or lipase can establish a diagnosis of acute pancreatitis. Amylase is less specific than lipase and can be falsely normal, particularly in alcohol- and hypertriglyceridemia-induced pancreatitis8, limiting its utility. Testing both serum lipase and amylase in pancreatitis is discouraged because of increased cost without clinical benefit9.
CK-MB was widely used before introduction of Troponin T and I, the current gold standard cardiac biomarker given high sensitivity and specificity for myocardial necrosis10. Previously, CK-MB was advocated to help diagnose reinfarction and used by some for diagnosis of peri-procedural infarction though troponin has subsumed that role. Routine use of CK-MB is not recommended9,11–13.
Complete Blood Count (CBC)
Ordering repetitive CBCs (with and without differential) in hospitalized patients in the setting of clinical and laboratory stability is not recommended7. Studies show reduction of routine use saves costs without negatively impacting quality of care14,15.
Type and screen (TS)
There is currently no standard for determining the safe duration or validity of TS results in patients not pregnant or recently transfused16. For these patients, reordering a TS is likely unnecessary if ordered within the past three months. If a patient has received a transfusion, their history is unknown, or they have been pregnant in the past three months, the TS is valid only for three days17.
Perioperative TS is often ordered inappropriately for minimally invasive or low-intermediate risk surgery. For operations with minimal anticipated blood loss, TS is likely unnecessary18. Implementation of a validated model to guide TS ordering for non-anemic pre-surgical patients could reduce unnecessary TS orders by up to 35%, without causing significant harm19,20.
Peripheral blood smear
Manual review of peripheral blood smears by hematopathologists prompted by abnormalities detected on automated equipment is costly due to provider fees, volume and technician time21,22. The evolution of automated analyzers and middleware systems have reduced the volume of manual reviews23 and efforts to improve accuracy of these systems to cut costs associated with manual reviews should be pursued24. International consensus criteria for manual peripheral blood smear review have been attempted, however, there is great variability in the accuracy of these machines and each hospital should set their own standards for when hematopathologist review is required25,26.
In 2014, at least $300 million was spent on inpatient thrombophilia testing, which typically includes evaluating for Factor V Leiden, prothrombin gene mutation, and deficiencies of antithrombin, protein C, and protein S27. Identification of a heritable thrombophilia does not predict or reduce the risk of recurrent venous thromboembolism (VTE)28. Additionally, thrombophilia testing is difficult to interpret in acute VTE and while on anticoagulation29. Thrombophilia testing is recommended only in select patients with a first episode of unprovoked VTE in whom there is a plan to stop anticoagulation30,31 and is not recommended for adults with a provoked VTE32. If indefinite anticoagulation is planned, testing is of limited utility27.
Heparin-induced Thrombocytopenia (HIT) Testing
HIT is an immune-mediated reaction to heparin that can lead to thromboembolism. Inappropriate testing for HIT in low risk patients is performed frequently in US hospitals; up to 60% of tests were not appropriate in one retrospective study33. The 4 T’s score is a well-validated tool to classify patients as low, intermediate, and high risk for HIT. Intermediate and high-risk groups warrant further laboratory testing34,35.
Folic acid levels are often measured in anemia36 and in the workup of dementia, delirium, and peripheral neuropathy37,38 despite the dramatic decline in folate deficiency in the US since mandatory fortification of processed grains was instituted. Multiple studies have documented the overuse of folic acid testing38–40. Empiric supplementation for suspected folate deficiency is more cost effective than a test-and-treat strategy. If testing is required, serum folic acid is recommended over RBC folate9.
Nearly 60% of total serum T3 and free T3 (FT3) levels orders are inappropriate41. For a host of biochemical reasons, measuring T3 is of limited utility and indicated only in select diagnostic circumstances including along with TSH and FT4 for diagnosing hyperthyroidism in pregnancy, diagnosing TSH-secreting pituitary adenoma, and follow-up after initiation of anti-thyroid drugs or radioactive iodine ablation42,43. T3 should not be ordered as initial testing for suspected thyroid disease or to monitor levothyroxine dosing44. Employing algorithms that reflex thyroid hormone testing only when the TSH is abnormal present an additional opportunity for cost savings45.
Vitamin D Screening
There is insufficient evidence to recommend screening asymptomatic adults for vitamin D deficiency because no consensus exists regarding a level at which replacement provides clinical benefit46. Among those at high risk for deficiency, namely those with osteoporosis, chronic kidney disease, malabsorption, obesity and some infections, screening with 25-hydroxyvitamin D is recommended9. There are few indications for measuring 1,25-dihydroxyvitamin D and testing in the absence of hypercalcemia or renal insufficiency is not recommended44.
Fecal lactoferrin is a highly sensitive biomarker of active neutrophils and is useful to distinguish intestinal inflammation from non-inflammatory bowel disease, such as irritable bowel syndrome, though is not specific for exact cause of intestinal inflammation47–49. In patients with inflammatory bowel disease, fecal lactoferrin can assess disease activity and degree of mucosal healing non-invasively and can predict relapse and response to therapy48. Fecal calprotectin is used similarly and may offer better test characteristics50. As they often provide the same clinical information, routine testing of both fecal lactoferrin and calprotectin is not indicated.
Fecal Occult Blood Testing (FOBT)
FOBT is a validated outpatient colorectal cancer screening tool but is often misused in the acute setting to evaluate gastrointestinal bleeding (GIB)51. They are of two types: guaiac-based tests measuring heme (gFOBT), and immunochemical tests (FIT) measuring globin. FOBT cannot identify bleeding acuity and can be positive with clinically insignificant esophagitis, epistaxis, or certain foods. FIT testing is more specific for GIB, but is less sensitive for upper GIB since globin becomes denatured in the upper tract51. When used inappropriately in the acute setting, the indirect costs of delay in care, unnecessary testing and prolonged hospitalization are high51. Instead of FOBT, GIB should be evaluated with history, physical exam including digital rectal exam, hemoglobin, BUN, and iron store measurement52,53.
Helicobacter pylori Serology
Helicobacter pylori infection is common, particularly in the developing world, and can lead to peptic ulcer disease, GIB, and gastric malignancy. Available diagnostics include serology, endoscopy, breath tests, and fecal antigen tests. Serology is the least effective owing to poor test characteristics and inability to determine chronicity of infection54 and is not recommended for diagnosis of H. pylori infection9. Fecal antigen testing is the preferred testing strategy54.
Hepatitis A Virus (HAV) Serology
Routine infant vaccination has reduced HAV incidence in the US. Vaccination of high risk adults is also recommended55 and some advocate pre-vaccination screening in high-prevalence groups as a cost-effective approach to HAV prevention, assuming the cost of a single test is not greater than the vaccine series56. Testing for HAV in acute hepatitis among otherwise healthy, previously vaccinated patients is unlikely to aid diagnosis because immunity persists for 15-25 years following vaccination57. In patients without known immunity, anti-HAV IgM antibody could be considered in the evaluation of severe acute liver injury58.
Hepatitis B Virus (HBV) Serology
Screening for HBV is cost effective given the burdens associated with reactivation of chronic infection, cirrhosis and hepatocellular carcinoma59. Screening high-risk individuals, including vulnerable healthcare personnel, with hepatitis B surface antigen, surface antibody and core antibody is recommended59. Hepatitis B serologic testing is complex, and inappropriate testing is frequently performed. One study found a substantial number of laboratory orders for anti-HBe antibody and HBeAg, which have no role in the routine screening for HBV immunity or infection60.
Hepatitis C Virus (HCV) Viral Load and Genotype
HCV viral load can diagnose acute infection, establish chronic infection in antibody-positive patients, and monitor response to treatment. A viral load is not an appropriate screening test for chronic HCV. For patients with chronic HCV, viral load testing is indicated at diagnosis and to monitor response to treatment, however, is not recommended at other times. In patients with sustained virologic response after treatment, a viral load is only necessary for a new exposure or unexplained hepatic dysfunction. Genotype testing is only indicated if treatment with a non-pan-genotypic regimen is planned61.
Gastrointestinal Pathogen Nucleic Acid Amplification Test (NAAT) Panels
Most cases of acute infectious diarrhea are self-limited and routine diagnostics are discouraged unless Clostridioides (Clostridium) difficile infection (CDI) is suspected62. Gastrointestinal-specific NAAT panels rapidly identify pathogens including viruses, bacteria and parasites with sensitivity and specificity of >90% and >97%, respectively, though can pose high cost to patients and institutions. These panels do not distinguish between colonization and infection, so clinically irrelevant pathogens can be detected62,63. Without concern for CDI, testing should be reserved for patients with a history of recent travel, those at risk for severe disease, and those with greater than seven days of symptoms64. Understanding the consequences of testing is important, as treating a generally self-limited process comes at additional cost and side effects62.
C. difficile is the leading cause of nosocomial infectious diarrhea among adults and is rising in children. CDI testing is recommended for unexplained, new-onset diarrhea of three or more unformed stools in 24 hours. In settings without established criteria for patient stool submission, an initial stool toxin test as part of a multistep diagnostic algorithm is preferred over NAAT alone owing to the high rate of false positives for NAAT, though both are acceptable. Testing asymptomatic patients and tests of cure are not recommended. Due to high rate of colonization, infants under 12 months should not be tested. Among children 1 to 2 years of age, testing can be considered after excluding other causes of diarrhea. After age 2, testing should be performed as it would be for adults65.
Rapid Antigen Testing and Culture for Group A Streptococcal Pharyngitis
Viruses cause the majority of outpatient cases of pharyngitis. Group A Streptococcus (GAS) accounts for 10%-30% of pharyngitis in children and 5-15% in adults66. GAS pharyngitis is treated to prevent acute rheumatic fever (ARF). GAS testing is not indicated for children <3 years old without risk factors, such as sibling contact, due to the extremely rare occurrence of ARF in this age group. Due to risk of ARF in children, back-up throat culture when RAT is negative is indicated. Among adults, routine use of back-up culture is not recommended due to lower incidence of GAS and lower risk of ARF66. It is not necessary to submit a positive swab for confirmatory culture at any age given high specificity of RAT. Follow-up post treatment throat cultures are not routinely recommended66.
Legionella pneumophila Urinary Antigen Testing (UAT)
Legionella pneumophila causes fewer than 2% of non-epidemic community acquired pneumonia cases annually67. Legionella pneumonia is clinically differentiated through its extrapulmonary manifestations, including relative bradycardia, headache, confusion, diarrhea, transaminitis, and hyponatremia68. While the sensitivity and specificity of Legionella UAT, which detects 80% of serogroup 1, is improving, the low pretest probability of Legionella pneumonia limits its utility69. Legionella UAT should be limited to severe pneumonia, immunocompromise, characteristic extrapulmonary manifestations, critical illness, failure of outpatient antibiotic therapy, active alcohol abuse, travel within the past two weeks or presence of a pleural effusion70.
C-Reactive Protein (CRP) and Erythrocyte Sedimentation Rate (ESR)
CRP is an acute phase reactant that responds quickly to inflammation. The ESR is a surrogate marker of the acute phase reaction but is affected by plasma albumin concentration, size, shape and number of red blood cells, and non-acute phase reaction proteins71. ESR can be negative in minor inflammation, takes longer to become elevated during an inflammatory process, and takes longer to clear once inflammation resolves9. CRP is a better marker of the acute phase reaction in nearly all inflammatory processes, with some exceptions such as low-grade musculoskeletal infections and some autoimmune diseases. CRP is preferred over ESR to detect acute phase inflammation9.
Antinuclear Antibody (ANA) and Sub-Serologies
ANA testing is used to evaluate suspected autoimmune disease, however, is falsely positive in up to 15% of healthy adults72. With few exceptions, if ANA is negative, ANA sub-serologies are also negative. Despite this, one U.S. medical center found 6.6% of ANA tests had at least one sub-serology tested simultaneously73. The financial implications of indiscriminate ANA testing are significant74. Testing ANA sub-serologies with a negative ANA and low pretest probability of immune-mediated disease is not recommended72.
Paraneoplastic encephalitis typically manifests acutely or subacutely, can precede cancer diagnosis by weeks to months, is often associated with cerebrospinal fluid pleocytosis, elevated protein, oligoclonal bands and elevated immunoglobulins75,76. Serum and cerebrospinal fluid panels are available to measure several antibodies associated with paraneoplastic encephalitis syndromes but inappropriate ordering results in a high number of false positives and unnecessary costs related to follow-up care75. Positive antibody tests in the absence of clinical features of paraneoplastic encephalitis is of limited utility and the absence of these antibodies does not preclude the diagnosis in the appropriate clinical situation75,76.
Tacrolimus is used in nearly all solid organ transplants77. Inpatient tacrolimus drug monitoring (TDM) is standard of care but variable pharmacokinetics, absorption, and medication interactions limit the utility and reliability of inpatient monitoring77. Further, the timing of inpatient TDM is unreliable, resulting in an estimated $22 million dollars in waste each year78. The impact of inpatient TDM needs to be clarified and inpatient-specific guidelines developed.
In this review, we identify 25 target laboratory tests for ordering optimization that span medical specialties and the care continuum. By improving appropriate use of laboratory tests across the clinical spectrum, medical providers can reduce waste and improve healthcare value. While our review is limited by the informal methodology, we have compiled an actionable summary to inform value-based quality improvement work in academic medical centers across the nation.
Implementing value-based quality improvement and education to reduce the unnecessary ordering of laboratory tests among housestaff has been successful79–81 and is a focus of nationwide campaigns including Choosing Wisely®82 and specialty-specific initiatives, such as the American College of Physicians and Alliance for Academic Internal Medicine High Value Care Curriculum83.
Engaging housestaff in the leading these initiatives is beneficial to patient care, institutions and to trainee career development. The involvement of residents in the planning, implementation and evaluation process of value-based quality improvement work has been successful in optimizing care while providing the trainee with valuable experience leading this work84,85. Aligning trainee value-based quality improvement projects with institutional priorities supports high quality patient care and the educational mission of academic medical centers85,86. Further, trainee involvement in value-based initiatives fulfills the Accreditation Council for Graduate Medical Education’s requirement for quality improvement work87.
Medical providers must improve ordering appropriateness as part of the national imperative to reduce waste and increase healthcare value. Engaging trainees in this work facilitates successful implementation and serves to ingrain principles of high value care into their practice. Our review is a resource for trainees interested in championing this vital work in their own institutions by providing actionable targets for quality improvement projects.
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- CBC: Complete blood count
- TS: Type and screen
- VTE: Venous thromboembolism
- HIT: Heparin-induced thrombocytopenia
- TSH: Thyroid stimulating hormone
- T3: Triiodothyronine
- FT3: Free T3
- GIB: gastrointestinal bleed
- FOBT: fecal occult blood test
- BUN: Blood urea nitrogen
- HAV: Hepatitis A virus
- HBV: Hepatitis B virus
- HCV: Hepatitis C virus
- CDI: Clostridioides (Clostridium) difficile infection
- NAAT: nucleic acid amplification test
- GAS: Group A Streptococcus
- ARF: Acute rheumatic fever
- RAT: rapid antigen test
- UAT: Urinary antigen test
- CRP: C-reactive protein
- ESR: Erythrocyte sedimentation rate
- ANA: Antinuclear antibody
- TDM: tacrolimus drug monitoring