To Test or Not to Test?

To form a diagnosis, practitioners used to rely almost solely on patient history and physical examination. Although the method remains essential, advances in the field of hematology have redefined clinical practice with sophisticated imaging and laboratory testing for diagnosis, risk stratification, response assessment, and follow-up.

“Hematology is a unique field in that testing in all forms, whether laboratory, radiology, or other specialized types of testing, is really integral to our practice,” said Lisa K. Hicks, MD, of St. Michael’s Hospital in Toronto, Canada. “However, whenever we think about testing, we want to make sure that the right patients are getting the right tests at the right time.”

As Dr. Hicks intimates, there is a growing concern about over-testing in the field. The downsides of running unnecessary tests include pain, stress, and financial burden for the patient.

In an effort to curb the use of unnecessary med­i­cal tests in medicine, the ABIM Foundation launched its Choosing Wisely® initiative in 2012. The campaign called upon national organizations representing medical specialists to “identify tests or procedures commonly used in their field whose necessity should be questioned and discussed.”¹

Soon after, the American Society of Hematology (ASH) partnered with the ABIM Foundation to develop a list that highlighted potentially unnecessary, sometimes harmful practices relevant to blood disorders.

“This list was designed to help clinicians evaluate whether the benefits of any given intervention outweigh the harms,” said Dr. Hicks, who is former chair of the ASH Choosing Wisely Task Force. “The spirit of the Choosing Wisely campaign is for us to always be asking ourselves if that is the case instead of ordering tests reflexively.”

ASH Clinical News spoke with Dr. Hicks and other experts about the dangers of over-testing, the types of tests that may be overused in hematology, and how Choosing Wisely can provide guidance.

Superfluous Scans

There are many types of tests that are overused, but scanning has been identified by numerous specialties as a point of focus. In fact, a search for the word “scan” among the Choosing Wisely recommendations yields 40 results.

Specific to scanning and hematologic malignancies, ASH has two recommendations on its Choosing Wisely list:

• Clinicians should limit surveillance CT scans in asymptomatic patients following curative-intent treatment for aggressive lymphoma.
• Clinicians should not perform baseline or routine surveillance CT scans in patients with asymptomatic, early-stage chronic lymphocytic leukemia (CLL).²

Among the evidence against surveillance CT scans in lymphoma is a 2012 study that evaluated whether relapses in follicular lymphoma (FL)  or diffuse large B-cell lymphoma detected by different methods influenced patient outcomes. Among relapses, 22.1% were detected using routine surveillance with CT. The rest were detected by patient-reported symptoms (60.2%), physical examination (13.3%), or abnormal laboratory data (4.4%). Of those patients who went on to be treated, there was no difference in overall survival by detection method.³

Active Surveillance

In his practice, Brian T. Hill, MD, PhD, director of the Lymphoid Malignancies Program at Cleveland Clinic’s Taussig Cancer Center in Ohio, sees many patients with CLL and other lymphomas seeking second opinions. Often these patients have been managed in a general oncology office for quite some time and are in active surveillance.

“Most indolent lymphomas and CLL are diagnosed incidentally from an asymptomatic elevation in lymphocyte count in the peripheral blood or an incidentally noted lymphadenopathy,” Dr. Hill explained. “The standard recommendation for CLL and other indolent lymphoid malignancies is not to initiate treatment at the time of diagnosis in the absence of symptoms or other objective criteria.”

Dr. Hill added that it is reasonable in many circumstances to get a full staging study in a patient diagnosed with indolent lymphoma, but this is not indicated in patients with CLL. Specifically, a PET scan might be useful in an indolent lymphoma like FL but should not be used as a surveillance tool.

“In cases of suspicion of Richter transformation to aggressive lymphoma, imaging may be necessary,” Dr. Hill said. “In CLL, if there is suspicion of rapid pro­gression of non-palpable disease – which can sometimes occur in small lymphocytic lymphoma – imaging may be reasonable if there are symptoms of pain not resolving or other obstructive-type symptoms.”

In neither case are these subtle changes, he added.

Michael W. Drazer, MD, PhD, assistant professor of medicine at the University of Chicago, agreed that overuse of scans in CLL is a classic example of over-testing.

“I have a lot of older, clinically stable patients who have been untreated for CLL, and I can’t think of a single one that I have scanned in the absence of clinical changes,” Dr. Drazer said.

Among referred patients, however, he commonly sees clinically stable patients who have had serial CT or PET scans.

“Benign” Examples

Over-testing is not limited to the realm of malignant hematology. For Colleen Morton, MBBCh, associate professor of medicine at Vanderbilt University in Nashville, Tennessee, the immediate example that comes to mind is routine blood draws in hospitalized patients.

“It is a fairly common scenario when patients have been hospitalized for a long time that they get daily blood draws, causing them to become anemic,” said Dr. Morton, who is vice chair of the ASH Committee on Practice.

In fact, in its Choosing Wisely recommendations, the Society of Hospital Medicine recommends against performing complete blood counts and chemistry testing in the setting of clinical and lab stability.⁴

Dr. Morton said that her hospital and others have started initiatives to cut back on daily testing unless it is deemed necessary for patient management or safety.

Dr. Drazer often sees over-testing in other areas of his practice, including the use of unnecessary imaging to screen for pulmonary embolism (PE).

“I may be called to see a patient for whom a PE is very low on the differential, and the treating physician reflexively wants to perform imaging,” Dr. Drazer said. “You see this situation commonly in the emergency department.”

In its Choosing Wisely list, the American College of Radiology (ACR) recommends not to image for suspected PE without moderate or high pretest probability of PE. According to the ACR, deep vein thrombosis (DVT) and PE are “rare in the absence of elevated blood D-dimer levels and certain specific risk factors” and imaging “has limited value” in patients who are very unlikely to have DVT or PE based on serum or clinical criteria.⁵

Instead, before even turning to a D-dimer test, Dr. Drazer recommended that clinicians take a detailed history, perform a physical exam, and use the Wells’ criteria to calculate risk of DVT.⁶

D-Dimer Dos and Don’ts

One of the American College of Physicians’ (ACP’s) original Choosing Wisely recommendations was to obtain a high-sensitivity D-dimer measurement as an initial diagnostic test in patients with low pretest probability of venous thromboembolism (VTE),⁷ but D-dimer tests can also be overused, according to Dr. Morton.

“There are a very limited number of times that you actually need to run a D-dimer test, the most beneficial of which is when a patient presents to the emergency room with a suspected blood clot,” she said.

Dr. Morton added that she has seen some physicians order a D-dimer test after a patient has had a DVT or a PE to determine whether it is safe to take the patient off an anticoagulant.

“There are some limited data on using D-dimer after treatment to determine the risk of recurrence, but it is rarely used correctly,” Dr. Morton said. “There are other times D-dimer is ordered for unclear reasons.”

A retrospective chart review of inappropriate use of D-dimer orders in a Canadian tertiary care center showed that of 237 patients with a D-dimer ordered during a three-month period, only three had an initial pretest probability score recorded. The researchers retrospectively calculated Wells’ DVT or PE scores and found that only 69% of patients had at least one risk factor for development of VTE.⁸

“The problem is that D-dimer tests are often abnormal in people as they get older, during pregnancy, or after an injury, recent surgery, or infection,” Dr. Morton said. “[For cases in which] these tests should not have been performed, often the clinician doesn’t know what to do with the results, and the patient is left in a panic because they are told they have an elevated D-dimer.”

Consequently, the patient may be referred to a hematologist for additional evaluation and testing.

What’s the Harm?

Additional evaluation and testing are among the many potential drawbacks of over-testing. Further­more, incidental findings may lead to more tests and perhaps even biopsies. All of this creates more anxiety, worry, and discomfort for patients.

“Something like imaging is not discriminatory,” said George M. Abraham, MD, president of the ACP and chief of medicine at Saint Vincent Hospital in Worcester, Massachusetts. “Scans often show a small shadow or incidental findings that might sometimes lead to another additional workup that all turns out to be nothing.”

In addition to concern about incidental findings, there is also the risk of unnecessary radiation exposure, which can raise concern about developing malignancies.

According to the American Cancer Society, the average American is exposed to about 3 millisieverts (mSv) of radiation over the course of a year. A chest X-ray exposes a person to about 0.1 mSv, or 10 days’ worth of radiation. A CT scan of the abdomen and pelvis exposes a person to about 10 mSv and a PET/CT exposes a person to about 25 mSv, or the equivalent of about 8 years’ worth of typical background radiation.⁹

A 2009 study from researchers at Brigham and Women’s Hospital looked at cumulative CT radiation exposure and risk for cancer among more than 31,000 patients who underwent diagnostic CT in 2007. For the whole group there was only a 0.7% increased risk above the life risk for cancer in the U.S. However, for patients who had multiple CT scans, the increase in risk was higher, ranging from 2.7% to 12%.¹⁰ In the case of patients with CLL, the disease already puts them at increased risk of developing secondary malignancies.¹¹

Dollars and Sense

The associated financial toxicity of unnecessary scans also cannot be underestimated. The need to schedule follow-up appointments may result in indirect financial challenges for patients, such as lost wages. In some cases, an imaging scan might not be covered by insurance. And even when patients have private insurance, they may be responsible for hundreds or thousands of dollars out-of-pocket to meet their annual deductible.

Although exact numbers are difficult to quantify, it is estimated that between 30% and 50% of adults in the U.S. with private health insurance have high-deductible plans, with deductibles of $1,000 or more per year.^12-14

“The average American could not financially handle a surprise bill of $1,000 for a scan, and the type of testing we are talking about is of that magnitude,” Dr. Drazer said.

Patients screened unnecessarily for PE might get a bill from the hospital emergency department, the treating physician, and a radiology group – “three bills for one visit and some of them could be completely avoidable,” he added.

There are additional financial effects on the health care system itself, including administrative work to obtain preauthorization, and unnecessary testing ties up money that could be spent elsewhere.

“Any system can only afford to do so much, and at some point, there is a lost opportunity cost,” Dr. Hicks said. “If we are spending money on one thing, then we don’t have money to spend in another area.”

This is more obvious in a public payer system like the one in Canada, she noted, but is also relevant in a private payer system and certainly when dealing with Medicare.

Ordering the Test

There are multiple reasons clinicians may choose to order tests that are not necessary. A narrative literature review published in late 2020 by Australian researchers¹⁵ developed a thematic framework to raise awareness of over-testing and defined factors that led to test ordering:

• intrapersonal: fear of malpractice and litigation, clinician knowledge and understanding, intolerance of uncertainty and risk aversion, cognitive biases and experiences, and sense of medical obligation
• interpersonal: pressure from patients and doctor-patient relationship, pressure from colleagues, and medical culture
• environment/context: guidelines, protocols and policies, financial incentives, and ownership of tests; time constraints, physical vulnerability and language barriers, availability and ease of access to tests; pre-emptive testing to facilitate subsequent care, contemporary medical practice, and new technology

In terms of the fear of a missed diagnosis or potential litigation, Dr. Abraham said, “This may be more of an issue in the U.S. than in other parts of the world because of how readily available imaging is here. Other countries have longer wait times for availability of high-end imaging studies, which likely leads to less overuse.”

In active surveillance situations, clinicians are sometimes seeking reassurance.

“We all want reassurance, but at the end of the day we have to focus on the clinical benefit, or lack thereof, of our diagnostic approaches,” Dr. Drazer said, adding that it is important to rely on physical examination and lab testing, as well as prioritize the subjective concerns of the patient.

Another cause of over-testing may be related to availability bias, Dr. Drazer said. If a clinician has experienced a puzzling case in which a suspected diagnosis turned out to be something else, the experience can affect decision-making in the future. He remembered a patient with immune thrombocytopenia (ITP) who had been under his care for many years. Before being referred to him, the patient had undergone an unnecessary bone marrow biopsy. Years later, the patient developed a malignancy that had metastasized to the bone.

“The patient asked if there had been evidence of the metastasis on the bone marrow biopsy years ago, and I was able to confidently tell him ‘no,’” Dr. Drazer said. “The next time I saw a similar patient with likely ITP I could have easily ordered a bone marrow biopsy just to make sure there was nothing else there. It only takes one patient to change your pattern of practice.”

Ultimately, it all comes down to physician experience and preference. There are myriad factors that go into treatment decisions, including the knowledge of the pros and cons of testing.

“Medicine is nuanced, but I am confident that clinicians can handle the complexity of parsing out when a test is truly needed versus when it unnecessary or potentially harmful,” Dr. Hicks said. “The trick is to make sure we don’t adopt reflexive testing practices.”

References

1. Choosing Wisely. Our Mission. Accessed February 4, 2022. https://www.choosingwisely.org/our-mission.
2. American Society of Hematology. Choosing Wisely. Accessed February 3, 2022. https://www.hematology.org/education/clinicians/guidelines-and-quality-care/choosing-wisely.
3. Lin T-L, Kuo M-C, Shih L-Y, et al. Value of surveillance computed tomography in the follow-up of diffuse large B-cell and follicular lymphomas. Ann Hematol. 2012;91(11):1741-1745.
4. Society of Hospital Medicine. Choosing Wisely. Reviewed 2016. Accessed February 4, 2022. https://www.choosingwisely.org/societies/society-of-hospital-medicine-adult.
5. American College of Radiology. Choosing Wisely. Updated 2021. Accessed February 4, 2022. https://www.choosingwisely.org/societies/american-college-of-radiology.
6. MD+Calc. Wells’ criteria for DVT. Accessed February 3, 2022. https://www.mdcalc.com/wells-criteria-dvt.
7. American College of Physicians. Choosing Wisely. Released April 4, 2012. Accessed February 3, 2022. https://www.choosingwisely.org/clinician-lists/american-college-physicians-high-senstive-d-dimer-measurement-for-vte.
8. Oliver M, Karkhanek M, Karathra J, Goubran M, Wu CM. A review of inappropriate D-dimer ordering at a Canadian tertiary care centre. Blood. 2019;134(supplement_1):5778.
9. American Cancer Society. Understanding radiation risk from imaging tests. Revised August 3, 2018. Accessed February 4, 2022. https://www.cancer.org/treatment/understanding-your-diagnosis/tests/understanding-radiation-risk-from-imaging-tests.html.
10. Sodickson A, Baeyens PF, Andriole KP, et al. Recurrent CT, cumulative radiation exposure, and associated radiation-induced cancer risks from CT of adults. Radiology. 2009;251(1):175-184.
11. Eichhorst B, Dreyling M, Robak T, Montserrat E, Hallek M. Chronic lymphocytic leukemia: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Hematologic Malignancies. 2011;22(supplement 6):V150-V154.
12. Collins SR, Gunja MZ, Aboulafia GN. U.S. Health Insurance Coverage in 2020: A Looming Crisis in Affordability. August 19, 2020. The Commonwealth Fund, Washington, DC.
13. Cattanach J. High-deductible health plans continue to grow in popularity, but are they right for you? Value Penguin. Updated January 24, 2022. Accessed February 3, 2022. https://www.valuepenguin.com/high-deductible-health-plan-study.
14. U.S. Bureau of Labor Statistics. Employee benefits survey: High deductible health plans and health savings accounts. Modified September 3, 2020. Accessed February 3, 2022. https://www.bls.gov/ncs/ebs/factsheet/high-deductible-health-plans-and-health-savings-accounts.htm.
15. Lam JH, Pickles K, Stanaway FF, Bell KJL. Why clinicians overtest: development of a thematic framework. BMC Health Services Research. 2020;20:1011.