Screening is the use of diagnostic tests in apparently healthy individuals with no clinical symptoms.1-2 Its purpose is to detect asymptomatic disease with the presumption that this can allow earlier, more effective intervention and will reduce suffering and delay or prevent death. Of course, screening is widespread in human medicine, though it is increasingly a subject of controversy and debate.3 Large-scale programs in human medicine to promote testing for specific diseases have been used widely, such as prostate-specific antigen (PSA) testing for prostate cancer and mammography for detection of asymptomatic breast cancer. These are examples of screening programs that are now being questioned and scaled back in light of better evidence concerning their risks and benefits.4-5 However, one could argue any diagnostic test employed in an individual with no clinical symptoms of illness is a screening test. In veterinary medicine, there are few large-scale, coordinated screening programs, but routine well-pet exams are a common screening practice. There are also calls for more extensive and intensive screening efforts, such as the recent guideline from the American Animal Hospital Association (AAHA) and diagnostic laboratory, IDEXX, promoting routine lab testing for nearly all pets.6 How does screening benefit patients? Most veterinarians understand the potential benefits of screening. Individual patients will benefit if a disease is identified that can be treated more effectively when asymptomatic rather than at a later stage. Some diseases that cannot be so effectively managed if not detected until there are clinical symptoms can be delayed or even cured when treated at an early stage. Identifying IRIS Stage 2 chronic kidney disease and instituting dietary therapy is an example of effective screening and intervention.7-8 This is what most of us assume all screening accomplishes when it’s done. True negative results might be considered beneficial as well, as they provide reassurance and, depending on the tests involved, potentially a baseline value that can be used for diagnostic purposes in the future, even though they don’t directly impact the patient’s morbidity or mortality. When is screening not beneficial to patients? Screening is of no benefit if it: fails to detect disease that is present (false negative results); detects disease that is not present (false positive results); detects disease that is indolent and would not ever cause clinical symptoms (overdiagnosis); or detects disease for which treatment is not effective or no more effective than it would be if it had not been identified until the symptomatic stage. When does screening harm patients? Screening is harmful when patients are given an incorrect diagnosis. False positive results create anxiety and discomfort and often incur risk and cost from additional testing or treatment for a disease that does not exist. False negative results provide reassurance when there actually is a disease present, which can delay truly beneficial diagnosis and treatment. Even correct diagnoses can cause harm.9-10 The distress associated with a diagnosis of cancer in an asymptomatic patient, for example, is not counterbalanced by any benefit if there is no effective treatment. The patient simply lives longer knowing they have an illness they cannot treat. And overdiagnosis, which is the correct identification of disease that is nonprogressive and does not lead to illness, exposes patients and owners to the risks and costs of the initial diagnosis and any further testing and treatment without any potential benefit from intervention. Patients may perceive a benefit from false positive results or from knowing about and treating indolent disease, but objectively this can only cause harm.11-13 How do we evaluate the risks and benefits of screening? It is rarely possible to know if screening has been beneficial or harmful for a particular individual because the outcome in the absence of testing cannot be known. Patients, pet owners, and clinicians nearly always feel as if testing is worthwhile even when no objective benefit can be demonstrated. True negative and false negative results are always reassuring, and if disease develops later, there is rarely any recognition these results may have delayed identification and treatment of it. Even if a false positive test is later shown to be false by further evaluation, many people experience such relief at the eventual result that they are grateful for the screening even though objectively, the cost and discomfort associated with it have no possible benefit. Subjective evaluation of screening, then, nearly always supports it, but this is a limited and unreliable measure of the value of such testing. Statistical evaluation of specific tests can be useful. The well-known parameters of sensitivity and specificity tell us something about the reliability of tests. However, the parameters of positive and negative predictive value (PPV and NPV, respectively) are arguably more important clinically. These are a function not only of the tests, but of the prevalence of the disease for which we are testing. If the majority of the population does not have the disease (as is usually the case with screening of asymptomatic individuals), the PPV will be quite low, and most positive results will be false positives. Since most patients diagnosed through screening don’t actually have the disease for which they are tested, the overall risks and costs of screening and follow-up testing or treatment may outweigh the benefits, even if some individual patients are helped.14 The most accurate way to determine whether more patients benefit or are harmed by screening is through epidemiologic data regarding specific diseases and the outcome of screening and treatment.1-3,10-11,15 Data on large populations has shown, for example, that most prostate cancer detected by PSA testing is nonprogressive. While some individuals do benefit from early detection, statistically, many more undergo psychological distress (including a rise in heart attacks and suicide) and physical harm (e.g. incontinence, impotence, and even death) due to testing and treatment. PSA screening is no longer recommended as widely as it once was because such evidence shows the practice does more harm than good.4,9-10 Similar evidence has led to reduced use of mammography and many other screening tests in humans.5, 9-10 Unfortunately, there is little data and awareness of this issue in veterinary medicine, and screening is widely viewed as an unqualified good. For example, the recent AAHA/IDEXX effort to encourage more laboratory testing of asymptomatic individuals never mentions overdiagnosis and suggests even normal results or abnormal findings of no clinical significance should be “celebrated” and treated as useful information.6 Screening is frequently promoted as a marker of high-quality, effective medicine.16-19 The financial benefits of screening—to veterinary practices and companies that provide testing services—are also often mentioned as a benefit,6 without any discussion about the issue of veterinary health-care costs and the potential impact of this on availability of care.20-21 There is little evidence that screening improves outcomes, such as quality of life or mortality in veterinary patients for most conditions. Research shows testing of asymptomatic individuals often finds abnormalities and that some of these lead to potentially beneficial intervention.6,9 However, few studies have looked at costs and risks of screening or gathered objective data on the balance between these and the potential benefits. The power of stories Anecdotes are the primary justification for screening in veterinary medicine. The AAHA/IDEXX protocol, for example, includes a section called “The Power of Stories,” which provides anecdotes of patients who benefitted from screening tests. Apart from not being an objective measure of the balance between risks and benefits, anecdotes can just as easily be used to challenge screening as to defend it. Here are two brief examples. Case example: 10-year-old whippet The patient presented for an annual examination and was offered a complete blood count (CBC) and chemistry panel. Thrombocytopenia was identified, as well as mild neutropenia, elevated amylase, and decreased antimicrobial susceptibility testing and creatine phosphokinase. Follow-up testing confirmed thrombocytopenia, and the patient was referred for further testing. Tick-borne disease panel, abdominal ultrasound, and thoracic radiographs were unremarkable. A subsequent CBC was unchanged, and pathology review concluded the findings were likely normal for the individual and breed. Despite the lack of any preceding or subsequent clinical illness, the owner experienced great distress at the possibility of serious illness in her pet, and the patient was exposed to the discomfort of numerous diagnostic procedures at a total cost of $924. Case example: Five-year-old Labrador retriever The patient presented with acute-onset lameness in the left hind leg and no other symptoms. Physical examination identified acute cranial cruciate ligament rupture. Pre-anesthetic chemistry panel revealed moderate elevation of alanine aminotransferase. Abdominal ultrasound identified mildly hypoechoic, indistinct nodular foci in the liver. Ultrasound-guided biopsy identified benign nodular hyperplasia. The patient died of hemorrhage following the biopsy. Bottom line “All screening programs do harm; some do good as well, and, of these, some do more good than harm at reasonable cost” (Gray et al, 2008).22 The challenge for veterinary medicine is to recognize the potential harms of screening and to actively collect evidence to identify the risks and benefits of certain tests in specific populations. The current approach of assuming the theoretical benefits of screening must apply and that harms are negligible is inconsistent with the evidence from human medicine and not a cost-effective, evidence-based approach for improving patients’ welfare. References 1 Wilson JMG. Jungner G. (1968) Principles and practice of screening for disease. World Health Organization Public Health Papers #34. Geneva, Switzerland. 2 Speechley M. Kunnilathu A. Aluckal E. et al. Screening in Public Health and Clinical Care: Similarities and Differences in Definitions, Types, and Aims – A Systematic Review. Journal of Clinical and Diagnostic Research. 2017;11(3):LE01-LE04. 3 Bulliard JL. Chiolero A. Screening and overdiagnosis: Public health implications. Public Health reviews. 2015:36(8). 4 Tabayoyong W, Abouassaly R. Prostate Cancer Screening and the Associated Controversy. Surg Clin North Am. 2015 Oct;95(5):1023-39. 5 Berry DA. Breast cancer screening: controversy of impact. Breast. 2013 Aug;22 Suppl 2:S73- 6 American Animal Hospital Association. Promoting preventative care protocols: Evidence, enactment, and economics. 2018. Accessed September 21, 2018. Available at bit.ly/2CDzb0g 7 International Renal Interest Society. IRIS staging of CKD. 2017. Accessed September 21, 2018. Available at bit.ly/2IQ3DVc 8 Ross SJ, Osborne CA, Kirk CA, et al. Clinical evaluation of dietary modification for treatment of spontaneous chronic kidney disease in cats. J Am Vet Med Assoc. 2006 Sep 15;229(6):949-57. 9 McKenzie, BA. Overdiagnosis. J Amer Vet Med Assoc. 2016;249(8):884-889. 10 Welch HG, Schwartz LM, Woloshin S. Overdiagnosed: making people sick in pursuit of health. Boston: Beacon Press, 2011. 11 Raffle AE. Gray JAM. Screening: Evidence and Practice. Oxford: Oxford University Press, 2007. 12 Boone D. Mallett S. Zhu S. et al. Patients’ & Healthcare Professionals’ Values Regarding True- & False-Positive Diagnosis when Colorectal Cancer Screening by CT Colonography: Discrete Choice Experiment. PLoS ONE 2017;8(12): e80767. 13 Brodersen J, Siersma VD. Long-Term Psychosocial Consequences of False-Positive Screening Mammography. Annals of Family Medicine. 2013;11(2):106-115. 14 Maxim LD, Niebo R, Utell MJ. Screening tests: a review with examples. Inhalation Toxicology. 2014;26(13):811-828. 15 Gates TJ. Screening for cancer: concepts and controversies. Am Fam Physician. 2014 Nov 1;90(9):625-31. 16 Lewis HB. Healthy pets benefit from blood work. Banfield Data Savant. Accessed September 21, 2018. Available at bit.ly/2pO0bSm 17 Irwin J. Do tests first: pre-surgical blood work may eliminate variety of surprises. DVM 360 Nov 1, 2003. 18 IDEXX Laboratories. Preanesthetic testing: don’t compromise—change happens fast. Accessed September 21, 2018. Available at bit.ly/2yArKmg 19 Ward E. Ask the expert: preanesthetic testing in private practice. NAVC Clinician’s Brief. January 2010. Accessed September 21, 2018. Available at bit.ly/2CcQK6v 20 LaVallee E, Mueller MK, McCobb E. A Systematic Review of the Literature Addressing Veterinary Care for Underserved Communities. J Appl Anim Welf Sci. 2017 Oct-Dec;20(4):381-394. 21 Stull JW. Shelby J. Bonnett B. et al. Broadening access to veterinary care: Barriers and next steps to providing a spectrum of effective healthcare to our patients. J Amer Vet Med Assoc. 2018. In press 22 Gray JAM, Patnick J, Blanks RG. Maximising benefit and minimising harm of screening. British Medical Journal. 2008;336(7642):480-483. Brennen McKenzie, MA, MSc, VMD, cVMA, discovered evidence-based veterinary medicine after attending the University of Pennsylvania School of Veterinary Medicine and working as a small animal general practice veterinarian. He has served as president of the Evidence-Based Veterinary Medicine Association and reaches out to the public through his SkeptVet blog, the Science-Based Medicine blog, and more. He is certified in medical acupuncture for veterinarians. Columnists’ opinions do not necessarily reflect those of Veterinary Practice News.
