Recognizing “diagnostic futility” ‐ stopping earlier to protect patients
Authors: Ohad Oren, Robert A. Kyle, David P. Steensma
Journal: American Journal of Hematology (2020)

Mr. H, an 86-year-old man residing in an assisted living facility, was admitted to the hospital with status epilepticus. Over the course of 2 weeks, he was intubated and extubated three times, never regaining his pre-hospitalization mental status. At best, when extubated and after discontinuation of sedatives, he was able to say his name and answer simple yes or no questions. A comprehensive evaluation to elucidate the cause of his mental status alteration revealed the presence of a neuronal autoantibody that is sometimes associated with malignancy. Mr. H's clinical team, prompted by his family, sought to determine whether an undiagnosed cancer might have resulted in his encephalopathy. The patient underwent whole-body computed tomography (CT) and positron emission tomography-CT (PET-CT) scans, endoscopy, and several tissue biopsies to clarify indeterminate radiographic findings noted on the PET-CT scans. However, even before his hospitalization, Mr. H suffered from multiple serious chronic illnesses including heart failure and oxygen-dependent chronic obstructive pulmonary disease, and he likely would not have been a candidate for therapeutic medical or surgical interventions to treat a cancer even if one had been discovered. Yet Mr. H went through numerous costly tests, some invasive, to try to establish a diagnosis for which he would not have been able to undergo treatment. Was Mr. H's evaluation medically appropriate? In one sense, an evidence-based clinical indication existed for his CT and PET-CT scans, in view of his unexplained and persistent encephalopathy and concern for a paraneoplastic process. And while Mr. H himself was unable to consent to procedures, his family insisted on “getting to the root of the problem”. However, reflex testing for a neoplasm did not consider that the patient would not have been a candidate for disease-specific interventions regardless of findings. How can we encourage a culture of conscientious and practical use of medical resources that goes beyond satisfying a need to make a diagnosis? In 1992, the Institute of Medicine introduced appropriateness criteria to ensure that “the expected health benefit [of an intervention] exceeds the expected negative consequences by a sufficient margin”.1 Clinical guidelines and care pathways were formulated to standardize the care of patients, with a goal of improving clinical outcomes. The following year, the American College of Radiology (ACR) proposed imaging appropriateness criteria, with the objective of presenting a consensus about the superior imaging study in a given clinical setting. The ACR imaging appropriateness criteria have been updated multiple times and are now available for many clinical scenarios including chronic dyspnea, acute hip pain, and jaundice.2 These guidelines are sensitive to cost and radiation exposure, have been well received, and likely have led to reduction in unnecessary imaging and expenses. Clinical appropriateness, however, is not a binary state, but a spectrum that ranges from entirely appropriate to futile. At one extreme are clearly indicated interventions with high benefit-to-risk profile. At the other are futile actions with little potential to improve patient health and substantial cost or risk. At the heart of the appropriateness assessment is determination of a patient's likelihood of a clinical gain and the prospect of deleterious events that may result from clinical action or inaction. Medical futility has been defined as an intervention that is “clearly futile in achieving its physiological objective and so offer(s) no physiological benefit to the patient”.3 In other words, futile care describes a situation in which a proposed action is not capable of improving a patient's medical condition. A search of Pubmed for “medical futility” or “futile care” reveals hundreds of entries describing potentially futile interventions, procedures, or therapies. Yet, futility that occurs in the diagnostic cascade - i.e., ordering and performing of tests with marginal likelihood of resulting in patient betterment - is less commonly considered, except in the context of population screening (eg, at what age or life expectancy is screening colonoscopy or mammography no longer indicated). Wise evaluation and avoidance of futility with respect to diagnosis means performing tests that are likely to be actionable in the individual patient. That is with abnormal findings triggering further evaluation and, if needed, an intervention with the overarching goal of improving health. “Diagnostic futility” could be viewed as any test, study or evaluation component where results are exceedingly unlikely to lead to clinical interventions or to additional investigation with the potential to improve patient wellbeing. Central to diagnostic decision-making is not just whether a positive or negative test result in the context of a specific pre-test probability is likely to be false, but also whether expected or unexpected findings would likely be followed by further analysis or medical or surgical actions to ameliorate the underlying pathologic process. If the likelihood of ultimate clinical benefit is minimal no matter what is detected, the diagnostic evaluation should be considered futile. Identifying diagnostically futile scenarios is important, as any form of clinical testing sacrifices time, convenience and costs for both patient and society. As physicians, we feel compelled to understand the pathophysiological process that mediates a patient's symptoms and organ impairment, and patients and families often are also eager to define the cause of symptoms. Yet, in some cases, diagnostic cascade and definitive pathological confirmation are not in the best interest of the patient. Although the mere knowledge of a diagnosis is often a source of significant relief for a patient or caregiver and has some therapeutic power in itself, and sparing unnecessary suffering and inconvenience is also an important goal. When one can confidently predict that a test's findings would not alter future medical care because of a patient's extreme frailty, severe comorbidities, or poor performance status, the presence of diagnostic futility must be considered and empathetically discussed with the patient and their family. In patients who are very sick and who are poor candidates for additional testing, the nature of the medical conversation should shift from an indication-based assessment to a utility/futility-based determination. Instead of embracing the next diagnostic step or the most sensitive assay, clinicians need to pause and contemplate whether the study is medically reasonable. To assist with what may be a challenging question, a diagnostic utility/futility score could be formulated. For instance, an imaging diagnostic metric could grade the likelihood that new information obtained from a chest or abdominal CT scan would result in evaluation and interventions with real potential to improve a patient's outcome (Table 1). To calibrate for the frequency of (expected or unexpected) abnormal findings, one can use data from studies that report the incidence of CT findings in a large number of patients as a gross surrogate for the chance of detecting incidental radiographic abnormalities. Likely more evaluation, but not with invasive tests For example, one such study showed that incidental liver lesions are seen in 18/700 abdominal images and adrenal lesions in 46/700.4 The various findings have different likelihoods of catapulting further evaluation, depending on the individual patient's acute health, chronic health profile, goals of care, and the overall status. If liver lesions suspected for metastases were to be visualized, for instance, there is a certain likelihood of further steps being taken, which might be different with an adrenal lesion, colonic abnormality of pulmonary vascular pathology, and different for each patient. A grade ranging from 0 to 10 could describe the physician-perceived assessment of the likely next step in the specific patient (eg, definitely more tests, more tests but not invasive procedures, likely more evaluation but only if clinical status improves, no further evaluation, etc.) for each of the possible findings. The summation of the individual scores, each multiplied by the relative frequency of each finding, could provide a utility/futility score. A threshold score would have to be defined as futile (ie, <7), which could be different in different health care systems, ethnic populations and cultures. Creating such a personalized metric to quantify the yield of downstream testing could be useful for medical teams challenged with caring for a complicated patient such as Mr. H. An evidence-based assessment of diagnostic futility could also be valuable information for a patient or family struggling to comprehend a broad array of available evaluation tests and treatment options. A standardized utility/futility score could also become part of a goals-of-care conversation. Here patients and caregivers contemplate not only their wishes about cardio-pulmonary resuscitation and endotracheal intubation, but also their threshold for stopping the sequence of diagnostic testing, if the odds of a favorable outcome are extremely low. In many cases, such as for a young and otherwise healthy patient where there is the possibility of a remediable serious pathology contributing to symptoms, the decision to embark on diagnostic testing is intuitive and would not require calculating a utility score. However, in some settings, such as a frail patient deteriorating despite conventional therapy with no diagnosis found, or an elderly patient with numerous comorbidities who is at high risk for serious medical complications with invasive diagnostic interventions, a diagnostic futility score could help patients and clinicians think through the next steps of medical evaluation and contemplate the practical value of each test. William Osler taught that treating the patient with the disease is more important than treating the disease. Keeping that Oslerian maxim in mind may prevent us from reflexively moving to the next branch of the diagnostic algorithm. Just because a particular study is likely to provide diagnostic confirmation does not mean that it is the action most congruent with a patient's well-being or values. Aggressively focusing on the capturing of a diagnosis without paying attention to the whole patient could, in certain circumstances, worsen outcomes. How to identify cases most likely to benefit from a diagnostic momentum-interruption is difficult. Until machine learning technologies point us in the right direction, a simple “pause and think” intervention is likely to be the wisest strategy. Dr. Oren and Dr. Kyle have no relationships to disclose. Dr. Steensma has the following disclosures: Research funding to institution - Celgene, Aprea, H3 Biosciences. Data safety monitoring committee - Onconova, Takeda. Consulting - Celgene, Summer Road. Travel support - Janssen.