Optimization of Diagnostic Laboratory Testing

Citation: Singh G, Plapp FV (2024) Optimization of Diagnostic Laboratory Testing, 21st Century Pathology, Volume 4 (1): 158

Abstract

Objectives

To assess the degree of overuse of laboratory testing, risks of over testing, causes of over testing and evaluation of approaches to optimize laboratory testing.

Methods

Personal observations based on more 90-year experience, and review of literature were used to determine the causes of over-testing and proposed methods for improving the optimization of testing. Opinions from personal experiences and issues about the future are expressed.

Results

Laboratory tests drive about 70% of clinical decisions, however, there is marked overuse of testing that adds an appreciable amount to the cost of healthcare, without improving the quality of healthcare. The cost of laboratory testing in the US exceeds the gross domestic product of more than 67% of countries. Despite having the highest cost of healthcare per capita, the US ranks at number 18 in terms of healthcare quality. Over-testing also poses safety risks to patients in the form of misdiagnoses, overtreatment, added cost to patients, society, and phlebotomy-induced anemia.

Conclusion

Laboratory testing costs can be curtailed without affecting the quality of healthcare. Issues of testing without specimen collection need to be addressed. National organizations are implored to include standards for optimal laboratory use in the accreditation of laboratories and hospitals.

Keywords:

Diagnostic laboratory testing; Appropriateness of laboratory testing; Efficiency of laboratory testing; Risk of excessive laboratory testing; Laboratory testing without specimen collection

Running Head: Optimization of Diagnostic Lab Testing

Introduction

Laboratory costs of health care in the US account for 0.47% of gross domestic product (GDP) [1]. However, this cost exceeds the total GDP of more than 67% of all other countries [2,3]. In the USA, healthcare costs account for about 18% of GDP and are the highest costs/capita of all countries, yet the US ranks at number 18 in terms of healthcare quality [4]. Thus, it could be argued that improvements in efficiency of healthcare, including diagnostic laboratory testing need not result in deterioration of the quality of healthcare. Various reports mention an overuse of laboratory tests of 20-60% [5-9]. It is generally recognized that laboratory test results drive about 70% of clinical decisions, however, excessive testing does not add value. Promotion of appropriate utilization of laboratory testing can increase the efficiency of healthcare.

Paradoxes in Laboratory Cost Controls

In-patient vs. out-patient testing

Cost of diagnostic testing, including laboratory tests, for hospitalized patients (in-patients) is included in the Diagnosis Related Groups (DRG) based reimbursements and the laboratory is a cost center for hospitals, as there is no separate reimbursement for laboratory testing [10]. Thus, the hospital administration is generally and appropriately concerned with reducing laboratory costs. On the other hand, testing done on non-hospitalized patients (out-patients) is reimbursed by Centers for Medicaid and Medicaid Services (CMS) and insurance companies, thereby removing incentives for controlling laboratory testing costs. It bears noting that before 1980s, the federal government reimbursed hospitals on a cost-plus basis. This changed markedly with the Tax Equity and Fiscal Responsibility Act of 1982 (TEFRA) passage. In a series of steps, the funding for hospitals was based on the admitting diagnosis, e.g., a patient admitted with community-acquired pneumonia garnered a fixed payment from CMS. In the earlier version, an additional payment was added if the patient developed a urinary tract infection during the hospital stay or developed decubiti. However, now CMS does not increase the amount of payment for hospital-acquired complication. So, under this diagnosis-based reimbursement model, referred to as DRG, the payment for a given diagnosis is fixed, irrespective of how many diagnostic tests, imaging studies or antibiotics are used. Similarly, payment to physicians for their services was systematized using the amount of training, experience, and resources needed for a given service, i.e., relative value-based units (RVUs). CMS periodically revises these payments, usually mandating reductions in payments.

The hospital administration generally implores the laboratory to increase its outreach to increase test volume and reduce the cost/test without focusing on appropriateness of testing. It warrants noting that reimbursement for testing, especially for tests sent to a reference laboratory, may not be fully reimbursed, and an appropriate use of laboratory tests remains relevant even when costs may be reimbursed. A notable exception to the reimbursement issue is when a test cost may not be covered fully by reimbursement, but performing the test is appropriate as the result may engender savings in other areas of the hospital. For example, when a test for fetal fibronectin was introduced, the cost of the kit exceeded the reimbursement for the test, however, laboratory implemented the test as it saved the institution far more than the cost of test by avoiding unwarranted hospital admission for women in threated labor for childbirth. (Personal observation)

Fragmented, redundant, and duplicative testing facilities

Almost all hospitals have full-service laboratories. Even hospitals situated a stone’s throw from each other have separate diagnostic facilities. It would be eminently suitable to consolidate testing not requiring a less than 4-hour turn-around time for all healthcare providers in a city, or a geographic area. However, this was not feasible even in the nationally integrated healthcare system of the Department of Veterans Affairs (VA). For example, a tertiary care VA in Western Pennsylvania offered elective testing, free of charge, to the four surrounding spoke hospitals, providing mostly ambulatory and nursing home care, however, the hospital directors resisted the change. (Personal observation)

Regional or national issues are usually beyond the scope of authority and control for a given medical director of a clinical laboratory so most of the remainder of this communication will focus on issues that can be addressed at individual medical centers regarding optimization of laboratory usage [11]. However, national agencies, e.g., The Joint Commission (TJC), College of American Pathologists (CAP), American Medical Association and other professional associations could prescribe appropriate laboratory usage by creating standards that become a factor in the accreditation of laboratories and hospitals. At the hospital level, administration could assign the cost and responsibility for appropriate testing to the ordering services. State departments of health could use their authority for improvements in quality of healthcare to expedite consolidation of laboratory services.

Causes of Overuse of Laboratory Testing

The causes of laboratory test overutilization are multifaceted, multifactorial, and usually entrenched through generations of poor practices aggravated by less than evidence-based recommendations by organizations with apparent conflicts of interest [12-15]. Well-promoted national initiatives like “Choosing Wisely” have not significantly decreased the improper use of laboratory testing [16,17]. Even though futility of overuse has been documented in the literature, the practice continues unabated [18-20]. One notable exception to this unsatisfactory situation in laboratory usage has been a marked reduction in volume of blood and blood products used through initiatives like, “Why give two when one will do.” [21,22]. Some of the likely causes of overuse are addressed below.

Normal/reference values

Normal values/reference ranges are usually set at the central 95% of test results in a healthy population. This results in a false positive rate of 5% in otherwise healthy people. If 20 analytes are tested on a healthy person, one of those results will likely fall outside the normal range [23,24]. “Abnormal” results prompt additional testing with the risk of additional false positives and anemia from blood loos due to phlebotomy [25,26]. Expert opinion is needed to standardize population-based results, as has been done for blood lipids, BMI and blood pressure, to provide clinically meaningful baselines. One major hinderance to developing uniform reference ranges is the lack of harmonization of laboratory tests. It strains credulity that only three analytes, Cholesterol, Creatinine, and Hemoglobin A1c have undergone international standardization, i.e., harmonization. The coagulation calculated value of INR comes close to harmonization. With different laboratories using different methods for testing, references ranges would have to be developed for each method, not a feasible undertaking. For some analytes, e., g., electrolytes, it may be easier to establish uniform reference ranges, however, that would be impossible for troponin. Despite being a critical test there is a 40-fold variation in results from different methods measuring Troponin I.

Fear of malpractice

The threat of malpractice is an oft-cited reason for over-testing as there is no penalty for over-testing but not testing may result in malpractice lawsuits due to perceived missed or delayed diagnoses. A comparison of providers engaged in over-testing vs. judicious testing did not reveal meaningful differences in outcomes [18,19,27,28].

Poor training environment

There is generally no accounting for excessive testing by trainees, but students and house staff are commonly taken to task for not getting laboratory tests [29]. Such a poor training environment also leads to more frequent and repetitive testing [30,31].

Patient portal

Release of results to patients, often before the provider has reviewed the data, is likely to lead to additional testing due to perception of abnormal test results, by patients, even when the variation from normal is not clinically meaningful. On the website, HealthTap, about 21% of the questions by users are about interpreting laboratory test results. (Personal observation)

Patient satisfaction surveys

While it is appropriate to seek client input, this has led to distortions in care. A provider with appropriately conservative use of laboratory testing and use of pharmaceuticals is likely to receive lower scores than a provider who caters to the whims of the patient, without necessarily providing optimum care [32].

Vendor access to providers and bypassing the lab

Sales personnel from companies that offer new tests often approach providers directly without involving the laboratory. This often results in providers ordering tests of doubtful usefulness that may not meet the criterion of medical necessity. Examples of overzealous marketing leading to overuse include assays for placental alpha microglobulin-1 for rupture of membranes, serum free light chain quantification, and Esoguard for esophageal lesions, without evidence of improved outcomes [33-35].

Treatment protocols of questionable quality and utility:

Many treatments become the community standards of care without undergoing rigorous testing for improvement in outcomes, e.g., endoscopic debridement of knee for osteoarthritis, and transfusion of fresh frozen plasma before endoscopic or diagnostic interventional radiology procedures for patients with questionably abnormal INR, without evidence of benefit of the unneeded treatment [36,37]. The number of endoscopic procedures at a given facility is proportional to the number of providers with privileges for such procedures, rather than a demonstrated benefit of the procedures [38-40]. Such procedures are usually associated with biopsies that often provide little benefit. A recent example of a treatment protocol of doubtful usefulness is autologous stem cell transplantation in the treatment of multiple myeloma. The treatment not only does not improve overall survival, but it also does not improve quality of life [41,42]. All these treatments of dubious value add to the cost of laboratory testing and the overall cost of healthcare without improvement in the quality of healthcare.

Misplaced incentives for providers:

Relative value units (RVU) based compensation is partly responsible for laboratory overuse and misuse. As alluded to earlier, physician service payments are based on nationally developed standards for the relative value of a given service. Procedure-based services generally command higher payments and thus promote procedure-based care. Endoscopy is reimbursed at a higher value than interpreting an imaging study. Another example of wasteful use due to this incentive is hematologists using bone marrow examination when urine examination would be better for settling the diagnosis and monitoring of multiple myeloma. As mentioned above and addressed here, the RVU incentive is likely responsible for the vast overuse of endoscopies and endoscopic biopsies [38-40]. This applies to hospital-based physicians as well, for example doing more special stains increases RVU for the histopathologic interpretation service. Performing more immunofixation procedures adds revenue to the hospital and raises the RVUs generated for the physician. Many institutions base part of the compensation of a hospital-based physician on RVUs generated by the provider thus promoting excessive and inappropriate use of services. Medical centers should consider value-based compensation rather than favoring volume of service and procedures.

Lab tests of questionable usefulness

Overuse of laboratory tests of limited usefulness may be driven by reference laboratories with financial incentives for promoting such use. Two examples of such tests are serum free light chain assays and MASS-FIX MALDI for diagnosis of monoclonal gammopathy and ostensible detection of minimal residual disease without demonstrated superiority over gel-based assays or any improvement in outcomes [43,44]. Additional tests of limited usefulness that have been recommended for removal from the lab test menu include RBC folate, CK-MB, AST, free PSA, procalcitonin, and ova and parasite examination of stool. Several analytes are also suitable for minimum testing intervals such as Vitamin D, Vitamin B12, A1c, tumor markers, D-dimer, and gamma glutamyl transferase [45-56].

Lack of incentive for pathologists to enforce medical necessity criteria

CMS ostensibly does not pay for medical tests that do not meet the requirement of medical necessity and, in theory, a laboratory medical director can refuse to honor such test requests [43]. A similar issue applies to repetitive testing [18,45,47]. Such actions are perceived by the providers as infringing on their prerogative of ordering diagnostic testing and creating an adversarial relationship with the laboratory medical director.

Optimization at Each Individual Health Center: Recommended Interventions

The medical director of a given laboratory can try to promote measures to optimize laboratory utilization. A partial list of the various measures that have been employed at different centers is given in Table 1. All of these techniques are effective, depending on the commitment and persistence of the person implementing them [47]. Almost all the measures for optimization of laboratory utilization require support from the medical and administrative leadership of the hospital, which may not be an easy task for an introverted pathologist [57]. It is recommended that pathologists and laboratory scientists establish their bona fide with the hospital authorities by first focusing on non-controversial changes, e.g. reducing the frequency of panel testing, to demonstrate savings to the institution and gradually add changes to promote optimum use of laboratory. Suggesting new, scientifically valid tests in lieu of traditional ones would be useful in establishing the expertise of the laboratory. Similarly promoting measures that would improve the CMS ranking of the hospital would be welcomed. The techniques used with some success by the authors are presented first, followed by other suggestions.

Testing panels

Testing panels, including CMS approved panels, promote wasteful over testing. For example, including AST in liver panels adds little value [58,59]. Well-meaning panels created by individual laboratories also promote excessive, non-productive testing, e.g., anemia panels, and hypercoagulation panels [60,61]. Further duplication is added when providers add tests for individual analytes included in the panels. Panels tend to be repeated rather than testing only for those analytes specific to a patient’s needs. Curtailment of panels, including CMS approved panels, can be implemented by limiting the frequency of panel orders. At this institution, Comprehensive Metabolic Panel (CMP), Basic Metabolic Panel (BMP) and Complete Blood Cell Count (CBC) with differential cell count are limited to once a day for in-patients, except in critically ill patients [62]. Data has been presented for removing AST, uric acid and calcium from chemistry panels [58-64]. The limited usefulness of eclampsia panel testing has been recommended for curtailment [65]. Hypercoagulation profile is not suitable for use in hospitalized patients and is not available for ordering for in-patients [66,67]. Panels for auto-antibody testing are screened and testing narrowed to the medically necessary analytes [68,69]. Use of clinical decision support software may be beneficial in controlling overuse and costs [62].

Tests with limited utility

Several tests have limited usefulness and can/should be removed from the laboratory test menu, e.g., RBC folate, 1, 25 hydroxy vitamin D, total T4, insulin levels, CK-MB, thrombophilia testing, cancer screening tests, and procalcitonin [51-56,58-70]. If one of these tests is needed by a particular specialist, it could be ordered as a miscellaneous test. Pre-operative and post-operative testing without known risk factors are also suitable for curtailment because most such testing does not add value [71-73].

Algorithmic testing and diagnostic management teams

Stepwise testing is a more prudent use of laboratory resources and can be promoted by clinical laboratories. Examples of clinical situations suitable for algorithmic testing include the work-up of anemia, celiac disease, autoimmune disorders, monoclonal gammopathy, bleeding diathesis, and hypercoagulation [7,74-76]. Development of Diagnostic Management Teams, as promoted by Laposata, should be considered by institutions with appropriate expertise and resources [77]. Diagnostic management Team (DMT) consists of a multidisciplinary group that operates in a manner similar to that of a tumor board. The DMTs have emphasis on diagnosis and monitoring of hard to diagnose issues and are dependent on a high level of expertise by a laboratory physician. The DMT produces an expert-driven, patient-specific narrative not only for cases in which one is requested, but for all cases in multiple areas of laboratory medicine and anatomic pathology. This value-added activity considers clinical information and laboratory data, meets on a regular schedule, includes their diagnostic conclusions in the medical record, and provides information not known to non-expert physicians. The success of such teams depends on the contribution of a person with outstanding expertise recognized by providers outside the laboratory. Diagnosis and monitoring of coagulation disorders are a common condition where DMTs have reduced errors.

Change from culture to molecular testing in microbiology

Most laboratories have embraced the shift from culture to molecular testing for microbiologic testing. The change has improved sensitivity and reduced turn-around time for results [78]. Such testing is suitable for consolidation within a town or geographic area.

Shifting the cost of diagnostic tests to the ordering service

Under the current system of fee for service, providers have little incentive for curtailing laboratory tests. For in-patient testing a hospital could assign budgets for laboratory tests to each service. A more practical method, as a first step, may be billing the ordering service for reference laboratory testing costs. This was a short-lived experiment, seen by one of the authors, at one institution. Department of Medicine that generated the bulk of test requests requiring use of reference laboratories objected to this model and given the usual status of Chief of Medicine in the hierarchy, the hospital discontinued the practice with resulting increase in reference laboratory use that was then the responsibility of the laboratory. (Personal experience)

Cost controls of questionable ethical practice

Laboratory tests done during the three days prior and 14 days following discharge are considered part of the in-patient stay and are not reimbursed. Laboratories may engage in unethical behavior by postponing testing for follow-up care, e.g., genetic testing for tumors, to more than 14 days after discharge [79].

Provider education

Educating the providers about appropriate utilization of laboratory tests is essential, time consuming and requires on-going effort, which provides little return to the pathologist or laboratory scientist. A new category of laboratory professional, namely, Doctor in Clinical Laboratory Sciences (DCLS) could be deployed to round with providers and advise about laboratory tests in the same vein as Pharm Ds do for stewardship of pharmaceuticals, especially antibiotics [80].

Anatomic pathology optimization of diagnosis through consolidation at centers of excellence

While not exactly appropriateness of use, digital pathology is eminently suited for facilitating consultation with experts in each area [81]. If it could be paired with centralized tissue processing facilities and slide imaging at large centers in a given geographic area, it has the potential to shorten the time to diagnosis and ease of consultation. Remote experts could be engaged to review representative samples as a quality assurance/improvement measure.

Conclusion

Controlling laboratory testing overuse and diagnostic stewardship have gained national attention and this may be an opportune time for a concerted effort by individual laboratory directors and national laboratory medicine, and healthcare organizations to bring about change [82]. Radical changes based on market economy should be considered, e.g., assigning budgets to clinical services for laboratory and imaging testing based on the DRG reimbursement model.

Table 1: Partial list of various measures that have been tried to reduce lab costs [47].

Stop recurrent orders	e.g., daily CBC in nonbleeding patient [83].
Stop extra work	e.g., (a) manual diff on routine CBCs, (b) Urine culture on negative dipsticks [84], (c) IFE on normal SPEPs and specimens with known monoclonal Ig [7].
Pathologist approval for expensive tests	e.g., genetic testing [85]
Limit the frequency of testing	e.g., viral load assays, Hep B surface antigen testing, Hb A1c [86,87].
Pathologist approval for frequently mis-ordered tests	e.g., hypercoagulable state work-up [88].
Substitute tests for low yield methods	e.g., Giardia and Cryptosporidium antigen testing for stool ova and parasites [89,90].
Limit panels	e.g., anemia work up; hypercoagulation panel; must order individual tests [91].
Shift blood drawing to requesting party/site
Offer/facilitate add-on tests and reflex tests [92].
Pop-up information for, or stopping, frequently mis-ordered tests	e.g., Protein C, Protein S and Anti-thrombin III, frequent repeats [93,94].
Reveal cost of tests with test menu
Provide data on laboratory costs incurred by each provider, peer group comparison, and best practice data [95].
Report inappropriate test utilization to credentialing and privileging committee, similar to inappropriate blood utilization [96].
Bring high volume reference lab tests in-house [97].
Discontinue outdated/obsolete tests	e.g. LE prep, bleeding time, stool O&P, RBC folate, Urine hemosiderin cells [70,98].
Issue vouchers for Lab tests or establish quota for lab tests/house staff [47].
Limit ordering privileges to specialists	e.g., IGRA TB testing and HIV genotyping to Infectious Disease and Pulmonary Medicine [99].
Promote use of diagnostic algorithms with reflex testing	e.g., work up of Celiac disease, protein electrophoresis [7,100].
Educate users about tests of limited usefulness	e.g., stool culture in children with non-bloody diarrhea [101].
Reduce the volume of blood collected [102].
Shift testing from hospitalized patients to out-patient status [103].
Cancel duplicate orders	e.g., Magnesium and CMP [104].
Present objective data specific to your setting	e.g., overuse of SPEP with IFE, Serum free light chains [7,44].
Limit tests of dubious value	e.g., tumor markers for screening, CMP and CBC for annual physicals, PSA in an 85-year-old, ANA for joint pain, influenza screen during off-season [105].
Reduce false positive blood cultures [106].
Reduce/eliminate stat tests [107].
Consolidate services within a geographic area [108].
Join buying consortia	e.g. Novation [109].
Shift costs	e.g., Activated prothrombin complex in-lieu of FFP [110].
Do not repeat critical value [111].
Remove analyte of dubious utility from panels	e.g., AST and calcium in panels [58].
Charge the lab cost to the ordering service [112].

References

1. Economic Impact of Clinical Labs - American Clinical Laboratory Association (acla.com). https://www.acla.com/economic-impact-of-clinical-labs/
2. Healthcare expenditures as a percent of GDP – USA Facts. https://usafacts.org/data/topics/people-society/health/healthcare-expenditures/healthcare-expenditures-as-of-gdp/
3. List of countries by GDP (nominal) – Wikipedia. https://en.wikipedia.org/wiki/List_of_countries_by_GDP_(nominal)
4. Best Healthcare in the World 2023 (worldpopulationreview.com). https://worldpopulationreview.com/country-rankings/best-healthcare-in-the-world
5. Müskens JLJM, Kool RB, van Dulmen SA, Westert GP. Overuse of diagnostic testing in healthcare: a systematic review. BMJ Qual Saf. 2022;31(1):54-63. https://doi.org/10.1136/bmjqs-2020-012576
6. Kurt-Mangold ME, Grieme CV, Krasowski MD, Rosenthal NS. Clinical utility of ordered pathology blood smear reviews-an overused resource? Clin Lab. 2018;64(1):99-104. https://doi.org/10.7754/Clin.Lab.2017.170703
7. Heaton C, Vyas SG, Singh G. Audit of use and overuse of serum protein immunofixation electrophoresis and serum free light chain assay in tertiary healthcare. A case for algorithmic testing to optimize laboratory utilization. Amer J Clin Pathol. 2016;145(4):531-537. https://doi.org/10.1093/ajcp/aqw026
8. Wahed A, Rodriguez JJ, Nguyen A, Dasgupta A, Segal G. overutilization of test for hemoglobinopathy evaluation: Experience from a tertiary care academic medical center. Ann Clin Lab Sci. 2019;49(3):400-402.
9. Cadamuro J, Gaksch M, Wiedemann H, Lippi G, von Meyer A, Pertersmann A, et al. Are laboratory tests always needed? Frequency and causes of laboratory overuse in a hospital setting. Clin Biochem. 2018;54(April):85-89. https://doi.org/10.1016/j.clinbiochem.2018.01.024
10. Design and development of the Diagnosis Related Group (DRG) (cms.gov). https://www.cms.gov/icd10m/version37-fullcode-cms/fullcode_cms/Design_and_development_of_the_Diagnosis_Related_Group_(DRGs).pdf
11. Zhi M, Ding EL, Theisen-Toupal J, Whelan J, Arnaout R. The landscape of inappropriate laboratory testing: a 15-year meta-analysis. PloS one. 2013 Nov 15;8(11):e78962. https://doi.org/10.1371/journal.pone.0078962
12. Vrijsen BEL, Naaktgeboren CA, van Solinge WW, Kaasjager HAH, ten Berg MJ. Inappropriate laboratory testing in internal medicine inpatients: Prevalence, causes and interventions. Ann Med Surg. 2020;51(Feb 7):48-55. https://doi.org/10.1016/j.amsu.2020.02.002.
13. Kotecha N, Shapiro JM, Cardasis J, Narayanswami G. Reducing unnecessary laboratory testing in the medical ICU. Amer J Med. 2017;130(6): 648-651. https://doi.org/10.1016/j.amjmed.2017.02.014
14. Rudin RS, Thakore N, Mulligan KL, Ganguli I. Addressing the drivers of medical test overuse and cascades: user-centered design to improve patient–doctor communication. Jt Comm Qual Patient saf. 2022;48(4):233-240. https://doi.org/10.1016/j.jcjq.2022.01.005
15. Cadamuro J, Ibarz M, Cornes M, Nybo M, Haschke-Becher E, von-Meyer A, et al. Managing inappropriate utilization of laboratory resources. Diagnosis. 2019:6(1):5-13. https://doi.org/10.1515/dx-2018-0029
16. Kroft SH, Bertholf RL. ASCP Continues to Choose Wisely. Am J Clin Pathol. 2019;152(5):542-543. https://doi.org/10.1093/ajcp/aqz174
17. Ahrari A, Barrett SS, Basharat P, Rohekar S, Pope JE. Appropriateness of laboratory tests in the diagnosis of inflammatory rheumatic diseases among patients newly referred to rheumatologists. Joint Bone Spine. 2020;87(6):588-595. https://doi.org/10.1016/j.jbspin.2020.05.007
18. Stephens JR, Hall M, Markham JL, Tchou MJ, Cotter JM, Shah S, et. al. Outcomes associated with high- versus low-frequency laboratory testing among hospitalized children. Hosp Pediatr. 2021;11(6):563-570. https://doi.org/10.1542/hpeds.2020-005561
19. Hall SF, Webber C, Groome PA, Booth CM, Nguyen P, DeWit Y. Do doctors who order more routine medical tests diagnose more cancers? A population?based study from Ontario Canada. Cancer Med 2019;8(2):850-859. https://doi.org/10.1002/cam4.1925
20. Baird S. The choosing wisely initiative and laboratory test stewardship. Diagnosis (Berl). 2019;6(1):15-23. https://doi.org/10.1515/dx-2018-0045
21. Berger MD, Gerber B, Arn K, Senn O, Schanz U, Stussi G. Significant reduction of red blood cell transfusion requirements by changing from a double-unit to a single-unit transfusion policy in patients receiving intensive chemotherapy or stem cell transplantation. Haematologica. 2012;97(1):116-122. https://doi.org/10.3324/haematol.2011.047035
22. Why give two when one will do. https://choosingwiselycanada.org/wp-content/uploads/2017/07/CWC_Transfusion_Toolkit_v1.2_2017-07-12.pdf (Accessed on April 27, 2023)
23. Houben PHH, Winkens RAG, van der Weijden T, Vossen RCRM, Naus AJM, Grol RPTM. Reasons for ordering laboratory tests and relationship with frequency of abnormal results. Scand J Prim Health Care. 2010; 28(1):18-23. https://doi.org/10.3109/02813430903281758
24. Alshekhabobakr HM, AlSaqatri S, Rizk NM. Laboratory test utilization practices in hamad medical corporation; Role of laboratory supervisors and clinicians in improper test utilization; A descriptive pilot study. J Multidiscip Healthc. 2022;15(March 3):413-429. https://doi.org/10.2147/JMDH.S320545
25. Lam JH, Pickles K, Stanaway FF, Bell KJL. Why clinicians overtest: development of a thematic framework. BMC Health Serv Res 2020;20: 1011. https://doi.org/10.1186/s12913-020-05844-9
26. Thavendiranathan P, Bagai A, Ebidia A, Detsky AS, Choudhry NK. Do blood tests cause anemia in hospitalized patients? The effect of diagnostic phlebotomy on hemoglobin and hematocrit levels. J Gen Intern Med. 2005;20(6):520-524. https://doi.org/10.1111/j.1525-1497.2005.0094.x
27. Albarqouni L, Arab-Zozani M, Abukmail E, Greenwood H, Pathirana T, Clark J, et al. Overdiagnosis and overuse of diagnostic and screening tests in low-income and middle-income countries: a scoping review. BMJ Glob Health. 2022 Oct 1;7(10):e008696. https://doi.org/10.1136/bmjgh-2022-008696
28. Failure to order tests cause of medical malpractice (seattlemalpracticelawyers.com). https://www.seattlemalpracticelawyers.com/blog/2016/07/failure-to-order-tests/
29. Faisal A, Andres K, Rind JAK, Das A, Alter D, Subramanian J, et al. Reducing the number of unnecessary routine laboratory tests through education of internal medicine residents. Postgrad Med J. 2018;94(1118):716-719. https://doi.org/10.1136/postgradmedj-2018-135784
30. Lippi G, Brambilla M, Bonelli P, Aloe R, Balestrino A, Nardelli A, et al. Effectiveness of a computerized alert system based on re-testing intervals for limiting the inappropriateness of laboratory test requests. Clin Biochem. 2015;48(16-17):1174-1176. https://doi.org/10.1016/j.clinbiochem.2015.06.006
31. Brownlee S, Chalkidou K, Doust J Eshaug AG, Glasziou P, Health I, et al. Evidence for overuse of medical services around the world. Lancet. 2017;390(10090):156-168. https://doi.org/10.1016/S0140-6736(16)32585-5
32. Cohen JB, Myckatyn TM, Brandt K, The importance of patient satisfaction: A blessing, a curse, or simply irrelevant? Plast Reconstr Surg. 2017;139(1):257-261. https://doi.org/10.1097/PRS.0000000000002848
33. https://prevention.cancer.gov/news-and-events/blog/new-technology-gives-patients-access-5-minute-office-based-test-identify-risk-esophageal-cancer
34. Galletta MA, Bittar RE, Rodrigues AS, Francisco RP, Zugaib M. Comparative analysis of Insulin-like growth factor binding protein-1, placental alpha-microglobulin-1, phenol and pH for the diagnosis of preterm premature rupture of membranes between 20 and 36 weeks. J Obstet Gynaecol Res. 2019;45(8):1448-1457. https://doi.org/10.1111/jog.13991
35. Singh G. Free monoclonal immunoglobulin light chains in serum and urine. 21st Cent Pathol. 2023;3(2):143-154.
36. Moseley JB, O'Malley K, Petersen NJ, Menke TJ, Brody BA, Kuykendall DH, et al. A controlled trial of arthroscopic surgery for osteoarthritis of the knee. N Engl J Med. 2002;347(2):81-88. https://doi.org/10.1056/NEJMoa013259
37. Bull-Henry K. Endoscopy in the coagulopathic patient. Curr Opin Gastroenterol. 2019;3595):401-407. https://doi.org/10.1097/MOG.0000000000000559
38. Fraiman J, Brownlee S, Stoto MA, Lin KW, Huffstetler AN. An estimate of the US rate of overuse of screening colonoscopy: A systematic review. J Gen Intern Med. 2022;37(7):1754-1762. https://doi.org/10.1007/s11606-021-07263-w
39. de Jong JJ, Lantinga MA, Drenth JP. Prevention of overuse: A view on upper gastrointestinal endoscopy World J Gastroenterol. 2019;25(2):178-189. https://doi.org/10.3748/wjg.v25.i2.178
40. Korenstein D, Husain S, Gennarelli RL, White C, Masciale JN, Roman BR. Impact of clinical specialty on attitudes regarding overuse of inpatient laboratory testing. J Hosp Med. 2018:13(12):844-847. https://doi.org/10.12788/jhm.2978
41. Attal M, Lauwers-Cances V, Hulin C, Leleu X, Caillot D, Escoffre M, et al. Lenalidomide, bortezomib, and dexamethasone with transplantation for myeloma. N Engl J Med. 2017;376(14):1311-1320. https://doi.org/10.1056/NEJMoa1611750
42. Richardson PG, Jacobus SJ, Weller EA, Hassoun H, Lonial S, Raje NS, et al. Triplet therapy, transplantation, and maintenance until progression in myeloma. N Engl J Med. 2022;387(2):132-147. https://doi.org/10.1056/NEJMoa2204925
43. Wilhite D, Arfa A, Cotter T, Savage NM, Bollag RJ, Singh G. Multiple myeloma: Detection of free monoclonal light chains by modified immunofixation electrophoresis with antisera against free light chains. Pract Lab Med. 2021; Oct 12 27: e00256. https://doi.org/10.1016/j.plabm.2021.e00256
44. Singh G. Serum and urine protein electrophoresis and serum-free light chain assays in the diagnosis and monitoring of monoclonal gammopathies. J Appl Lab Med. 2020;5(6):1358-1371. https://doi.org/10.1093/jalm/jfaa153
45. Abboud H, Probasco J, Irani SR, Ances B, Benavides DR, Bradshaw M, et al. Autoimmune encephalitis: proposed recommendations for symptomatic and long-term management. J Neurol Neurosurg Psychiatry. 2021;92(8):897-907. https://doi.org/10.1136/jnnp-2020-325302 Online ahead of print.
46. Yaari EB, Rosenbloom E, Paitan Y, Zifman E. Yield of emergency department stool culture tests among children with acute gastroenteritis in israel. Clin Pediatr (Phila) 2022; https://doi.org/10.1177/00099228221140772 Online ahead of print.
47. May TA, Clancy M, Critchfield J, Ebeling F, Enriquez A, Gallagher C, et al. Reducing unnecessary inpatient laboratory testing in a teaching hospital. Am J Clin Pathol. 2006;126(2):200-206. https://doi.org/10.1309/WP59-YM73-L6CE-GX2F
48. Golanski J, Pluta J, Baraniak J, Watala C. Limited usefulness of the PFA-100 for the monitoring of ADP receptor antagonists--in vitro experience. Clin Chem Lab Med. 2004;42(1):25-29. https://doi.org/10.1515/CCLM.2004.006
49. Jelski W, Mroczko B. Biochemical markers of colorectal cancer - present and future. Cancer Manag Res. 2020 June 22;12:4789-4797. https://doi.org/10.2147/CMAR.S253369
50. Andersen S, Karmisholt J, Bruun NH, Riis J, Noahsen P, Westergaard L, et al. Interpretation of TSH and T4 for diagnosing minor alterations in thyroid function: a comparative analysis of two separate longitudinal cohorts. Thyroid Res. 2022;15:19. https://doi.org/10.1186/s13044-022-00137-1
51. Wahed A, RodriguezJJ, Nguyen A, Dasgupta A, Segal G. Overutilization of test for hemoglobinopathy evaluation: experience from a tertiary care academic medical center. Ann Clin Lab Sci. 2019;49(3):400-402.
52. Galli C, Basso D, Plebani M. CA 19-9: handle with care. Clin Chem Lab Med. 2013;51(7):1369-1383. https://doi.org/10.1515/cclm-2012-0744
53. Panteghini M, Dolci A, Birindelli S, Szoke D, Aloisio E, Caruso S. Pursuing appropriateness of laboratory tests: a 15-year experience in an academic medical institution. Clin Chem Lab Med. 2022;60(11):1706-1718. https://doi.org/10.1515/cclm-2022-0683
54. https://www.cms.gov/Outreach-and-Education/Medicare-Learning-Network-MLN/MLNProducts/Downloads/ProviderComplianceLabServices-Fact-Sheet-ICN909221.pdf
55. Eaton KP, Levy K, Soong C, Pahwa A, Petrilli C, Ziemba JB, et al. Evidence-based guidelines to eliminate repetitive laboratory testing. JAMA Intern Med. 2017;177(12):1833-1839. https://doi.org/10.1001/jamainternmed.2017.5152
56. Konger RL, Ndekwe P, Jones G, Schmidt RP, Trey M, Baty EJ, et al, Reduction in unnecessary clinical laboratory testing through utilization management at a US government veterans affairs hospital. Amer J Clin Pathol. 2016;145:355-364.
57. Jafrani S, Zehra N, Zehra M, et al. Assessment of personality type and medical specialty choice among medical students from Karachi; using Myers-Briggs type indicator (MBTI) tool. J Pak Med Assoc. 2017;67(4):520-526.
58. Singh G. Appraisal of analytes in the laboratory panels for liver function tests: Do we need Aspartate Aminotransferase and Direct Bilirubin in the panels? J Clin Exp Pathol. 2014;4:4-10. https://doi.org/10.4172/2161-0681.1000184
59. Ekblom K, Petersson A. Reducing AST orders by reviewing test panels. Clin Biochem. 2023 Feb;112:71-72. https://doi.org/10.1016/j.clinbiochem.2022.11.010
60. Katzman BM, Bryant SC, Karon BD. Is it time to remove total calcium from the basic and comprehensive metabolic panels? assessing the effects of american medical association-approved chemical test panels on laboratory utilization. Clin Chem. 2020;66(11):1444-1449. https://doi.org/10.1093/clinchem/hvaa203
61. Janssens PM, Staring W, Winkelman K, Krist G. Active intervention in hospital test request panels pays. Clin Chem Lab Med. 2015;53(5):731-742. https://doi.org/10.1515/cclm-2014-0575
62. Hughes AEO, Jackups R. Clinical decision support for laboratory testing. Clin Chem. 2022 4;68(3):402-412. https://doi.org/10.1093/clinchem/hvab201
63. Kandalam V, Lau CK, Guo M, Ma I, Naugler C. Inappropriate repeat testing of complete blood count (CBC) and electrolyte panels in inpatients from Alberta, Canada. Clin Biochem. 2020 Mar;77:32-35. https://doi.org/10.1016/j.clinbiochem.2019.12.011
64. Salinas M, Lopez-Garrigos M, Flores E, Leiva-Salinas C. Serum uric acid laboratory test request patterns in primary care: How panels may contribute to overutilization and treatment of asymptomatic patients. Lab Med. 2017;49(1):55-58. https://doi.org/10.1093/labmed/lmx075
65. Thompson X, Sullivan MB, Mathura P, Wong A, Crawford J, Sia W. Implementation of a clinical decision laboratory ordering algorithm for preeclampsia: A quality improvement initiative. J Obstet Gynaecol Can. 2020;42(10):1223-1229. https://doi.org/10.1016/j.jogc.2020.03.016
66. Rudolf JW, Dighe AS. Decision support tools within the electronic health record. Clin Lab Med. 2019;39(2):197-213. https://doi.org/10.1016/j.cll.2019.01.001
67. Favaloro E. The futility of thrombophilia testing. Clin Chem Lab Med. 2014;52(4):499-503. https://doi.org/10.1515/cclm-2013-0560
68. George N, Fotedar N, Abboud H. Confounders in the Interpretation of Paraneoplastic and Neuronal Autoantibody Panels. Clin Lab Med 2020;40(3):305-316. https://doi.org/10.1016/j.cll.2020.05.004
69. Cabezudo-Garcia P, Mena-Vazquez N, Ciano-Petersen NL, Garcia-Martin G, Estivill-Torrus G, Serrano-Castro. Prevalence of neural autoantibodies in epilepsy of unknown etiology: Systematic review and meta-analysis. PJ Brain Sci. 2021;11(3):392-404. https://doi.org/10.3390/brainsci11030392
70. Singh G, Hamdan H, Singh V. Clinical utility of serum folate measurement in tertiary care patients: Argument for revising reference range for serum folate from 3.0 ng/mL to 13.0 ng/mL. Pract Lab Med. 2015 Mar;1:35-41. https://doi.org/10.1016/j.plabm.2015.03.005
71. Garg V, Bryom I, Angew N, Starks, Phillips S, Malek IA. Routine postoperative blood tests in all patients undergoing Total Hip Arthroplasty as part of an enhanced recovery pathway: Are they necessary? J Clin Orthop Trauma. 2021 Jan;16:114–118. https://doi.org/10.1016/j.jcot.2021.01.003
72. Bookman JS, Romanelli F, Hutzler L, Bosco JA, Lajam C. The utility and cost effectiveness of immediate postoperative laboratory studies in hip and knee arthroplasty. Bull Hosp Jt Dis. (2013) 2019 Mar;77:132-135.
73. Martin SK, Cifu AS. Routine Preoperative Laboratory Tests for Elective Surgery. JAMA 2017;318(6):567-568. https://doi.org/10.1001/jama.2017.7508
74. Alshekhabobakr HM, AlSaqatri S, Rizk NM. Laboratory test utilization practices in hamad medical corporation; role of laboratory supervisors and clinicians in improper test utilization; a descriptive pilot study. J Multidiscip Healthc. 2022 Mar;15:415-429. https://doi.org/10.2147/JMDH.S320545
75. Sharp CN, Fletcher A, Muluhngwi P, Snyder J, Linder MW, Jortani AS. A shared diagnostic stewardship approach toward improving autoimmune encephalopathy send-out testing utilization. J Appl Lab Med. 2021;6(2):387-396. https://doi.org/10.1093/jalm/jfaa123
76. Van Cott EM. Laboratory test interpretations and algorithms in utilization management. Clinica Chimica Acta. 2014 Jan;427:188-192. https://doi.org/10.1016/j.cca.2013.09.025
77. Verna R, Velazquez AB, Laposata M. Reducing diagnostic errors worldwide through diagnostic management teams. Ann Lab Med. 2019;39(2):121-124. https://doi.org/10.3343/alm.2019.39.2.121
78. Rudkjobing VB, Thomsen TR, Xu Y, Melton-Kreft R, Ahmed A, Eickhardt S, et al. Comparing culture and molecular methods for the identification of microorganisms involved in necrotizing soft tissue infections. BMC Infect Dis. 2016;16(1): 652. https://doi.org/10.1186/s12879-016-1976-2
79. https://www.cms.gov/Medicare/Medicare-Fee-for-Service-Payment/ClinicalLabFeeSched/Clinical-Lab-DOS-Policy
80. Vaughn VM, Hersh AL, Spivak ES. Antibiotic overuse and stewardship at hospital discharge: The reducing overuse of antibiotics at discharge home framework. Clin Infect Dis. 2022;74(9):1696-1702. https://doi.org/10.1093/cid/ciab842
81. Nahal A, Batac CMO, Slaw RJ, Bauer TW. Setting up an ePathology service at Cleveland clinic Abu Dhabi: joint collaboration with Cleveland clinic, United States. Arch Pathol Lab Med. 2018;142(10):1216-1222. https://doi.org/10.5858/arpa.2017-0216-RA
82. Morgan DJ, Malani PN, Diekema DJ. Diagnostic stewardship to prevent diagnostic error. JAMA. 2023 329(15):1255-1256. https://doi.org/10.1001/jama.2023.1678
83. Shen JZ, Hill BC, Polhill SR, Evans P, Galloway DP, Johnson RB, et al. Optimization of laboratory ordering practices for complete blood count with differential. Am J Clin Pathol. 2019;151(3):306-315. https://doi.org/10.1093/ajcp/aqy146
84. Marques AG, Doi AM, Pasternak J, Damascena MDS, França CN, Martino MDV. Performance of the dipstick screening test as a predictor of negative urine culture. Einstein (Sao Paulo). 2017;15(1):34-39. https://doi.org/10.1590/S1679-45082017AO3936
85. Kotzer KE, Riley JD, Conta JH, Anderson CM, Schahl KA, Goodenberger ML. Genetic testing utilization and the role of the laboratory genetic counselor. Clin Chim Acta. 2014 Jan 1;427:193-195. https://doi.org/10.1016/j.cca.2013.09.033
86. Lyon AW, Higgins T, Wesenberg JC, Tran DV, Cembrowski GS. Variation in the frequency of hemoglobin A1c (HbA1c) testing: population studies used to assess compliance with clinical practice guidelines and use of HbA1c to screen for diabetes. J Diabetes Sci Technol. 2009;3(3):411-417. https://doi.org/10.1177/193229680900300302
87. https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-arv/plasma-hiv-1-rna-cd4-monitoring#:~:text=the%20new%20regimen.,Repeat%20viral%20load%20measurement%20should%20be%20performed%20at%204%2D%20to,frequently%20if%20indicated%20(AIII)
88. Nakashima MO, Rogers HJ. Hypercoagulable states: an algorithmic approach to laboratory testing and update on monitoring of direct oral anticoagulants. Blood Res. 2014;49:85-94. https://doi.org/10.5045/br.2014.49.2.85
89. Nooshadokht M, Kalantari-Khandani B, Sharifi I, Kamyabi H, Liyanage NPM, Lagenaur LA, et al. Stool antigen immunodetection for diagnosis of Giardia duodenalis infection in human subjects with HIV and cancer. J Microbiol Methods. 2017 Oct;141:35-41. https://doi.org/10.1016/j.mimet.2017.07.004
90. Mergen K, Espina N, Teal A, Madison-Antenucci S. Detecting cryptosporidium in stool samples submitted to a reference laboratory. Am J Trop Med Hyg. 2020;103(1):421-427. https://doi.org/10.4269/ajtmh.19-0792
91. Vohra R, Hussain A, Dudyala AK, Pahareeya J, Khan W. Multi-class classification algorithms for the diagnosis of anemia in an outpatient clinical setting. PLoS One. 2022;17:e0269685. https://doi.org/10.1371/journal.pone.0269685
92. Simpson WG, Twomey PJ. Reflective testing. J Clin Pathol. 2004;57(3):239-240. https://doi.org/10.1136/jcp.2003.011668
93. Lapic I, Rogic D, Fucek M, Galovic R. Effectiveness of minimum retesting intervals in managing repetitive laboratory testing: experience from a Croatian university hospital. Biochem Med (Zagreb). 2019;29(3):030705. https://doi.org/10.11613/BM.2019.030705
94. Marlar RA, Gausman JN. Laboratory testing issues for protein C, protein S, and antithrombin. Int J Lab Hematol. 2014;36(3):289-295. https://doi.org/10.1111/ijlh.12219
95. Tamburrano A, Vallone D, Carrozza C, Urbani A, Sanguinetti M, Nicolotti N, et al. Evaluation and cost estimation of laboratory test overuse in 43 commonly ordered parameters through a Computerized Clinical Decision Support System (CCDSS) in a large university hospital. PLoS One. 2020;15(8):e0237159. https://doi.org/10.1371/journal.pone.0237159
96. Stehling L, Luban NL, Anderson KC, Sayers MH, Long A, Attar S. et al. Guidelines for blood utilization review. Transfusion. 1994;34(5):438-448. https://doi.org/10.1046/j.1537-2995.1994.34594249058.x
97. Pelosi R. The cost and benefits of in-house lab testing. Med Econ J. 2018;95: https://www.medicaleconomics.com/view/costs-and-benefits-house-lab-testing
98. Wu AHB, Lewandroski K. Antiquated tests within the clinical pathology laboratory. Amer J Managed Care. 2010;16(9): e220-e227.
99. Rudolf JW, Dighe AS, Coley CM, Kamis IK, Wertheim BM, Wright DE, et al. Analysis of daily laboratory orders at a large urban academic center: A multifaceted approach to changing test ordering patterns. Am J Clin Pathol. 2017;148(2):128-135. https://doi.org/10.1093/ajcp/aqx054
100. Rozenberg O, Lerner A, Pacht A, Grinberg M, Reginashvili D, Henig C, et al. A new algorithm for the diagnosis of celiac disease. Cell Mol Immunol. 2011;8(2):146-149. https://doi.org/10.1038/cmi.2010.63
101. Eliason BC, Lewan RB. Gastroenteritis in children: Principles of diagnosis and treatment. Am Fam Physician. 1998;58(8):1769-1776.
102. Whitehead NS, Williams LO, Meleth S, Kennedy SM, Ubaka-Blackmoore N, Geaghan SM, et al. Interventions to prevent iatrogenic anemia: a Laboratory Medicine Best Practices systematic review. Crit Care. 2019;23(1):278. https://doi.org/10.1186/s13054-019-2511-9
103. https://www.captodayonline.com/puzzling-positive-shift-final-14-day-rule/
104. Harb R, Hajdasz D, Landry ML, Sussman S. Improving laboratory test utilisation at the multihospital Yale New Haven Health System. BMJ Open Qual. 2019 Sep 18;8(3):e000689. https://doi.org/10.1136/bmjoq-2019-000689
105. Charkhchi P, Cybulski C, Gronwald J, Wong FO, Narod SA, Akbari MR. CA125 and ovarian cancer: A comprehensive review. Cancers (Basel). 2020;12:3730. https://doi.org/10.3390/cancers12123730
106. Hall KK, Lyman JA. Updated review of blood culture contamination. Clin Microbiol Rev. 2006;19(4):788-802.
107. Singh G, Savage NM, Gunsolus B, Foss KA. Requiem for the STAT test: Automation and point of care testing. Lab Med. 2020 Mar 10;51(2):e27-e31. https://doi.org/10.1093/labmed/lmz080
108. Cook J. Laboratory integration and consolidation in a regional health system. Lab Med 2017;48(3):e43-e52. https://doi.org/10.1093/labmed/lmw069
109. Nollet J, Beaulieu M. Should an organisation join a purchasing group? Supply Chain Manag Int J. 2005 Feb 1;10(1):11-7. https://doi.org/10.1108/13598540510578333
110. Awad NI, Cocchio C. Activated prothrombin complex concentrates for the reversal of anticoagulant-associated coagulopathy. Pharm Therap. 2013;38(11):696-701.
111. Saffar H, Abdollahi A, Hosseini AS, Torabi Farsani M, Hajinasrollah G, Mohaghegh P. Necessity of routine repeat testing of critical values in various working shifts. Iran J Pathol. 2020;15(3):161-166. https://doi.org/10.30699/ijp.2020.99403.1980
112. Danzon PM, Manning WG Jr, Marquis MS. Factors affecting laboratory test use and prices. Health Care Financ Rev. 1984;5(4):23-32.