Clinical Decision Making During the COVID-19 Pandemic
Authors: Joshua P. Metlay, Katrina A. Armstrong
Journal: Annals of Internal Medicine (2021)

Special Articles2 February 2021Clinical Decision Making During the COVID-19 PandemicFREEJoshua P. Metlay, MD, PhD and Katrina A. Armstrong, MD, MSCEJoshua P. Metlay, MD, PhDMassachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (J.P.M., K.A.A.).Search for more papers by this author and Katrina A. Armstrong, MD, MSCEMassachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (J.P.M., K.A.A.).Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M20-8179 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Among the many extraordinary aspects of the coronavirus disease 2019 (COVID-19) pandemic, the rapidity with which new scientific information has been shared and incorporated into clinical decision making is almost unprecedented. Undoubtedly, rapid incorporation of new scientific information into preventive and therapeutic strategies has been critical in minimizing the morbidity and mortality of this illness. At the same time, the rapid spread of new data has created the potential for premature implementation of new evidence to have widespread negative effects on decisions at the individual patient and health system levels. At the core of this dilemma is an understanding of how much certainty we require for new information to be adopted and change practice.Uncertainty in medicine is a fact of life. Annals has recently published a series of articles that provides a road map for translating imprecision in diagnostic and therapeutic information into clinical decisions (1). Here, we apply some of those principles to address the following 3 ongoing areas of uncertainty in COVID-19 management: the broad categories of diagnosis, treatment, and prevention. In each case, we briefly review the current state of knowledge, highlight the level of uncertainty, and then suggest a pathway forward for clinical decision making during the pandemic.DiagnosisYour patient presents with fever, anosmia, cough, and dyspnea to a local emergency department. The patient is 67 years old and has stable coronary artery disease. Oxygen saturation is normal on room air. A viral polymerase chain reaction (PCR) test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has negative results. Is the diagnosis of COVID-19 ruled out?The key to using diagnostic tests is the ability to integrate information about a patient's pretest probability and test characteristics into the selection of the appropriate test and interpretation of test results. Several tests are available for detecting SARS-CoV-2 infection. Viral PCR tests are the standard for diagnosing COVID-19 because they have the highest sensitivity, leading to a lower rate of false-negative results. Antigen tests have lower sensitivity but may be useful for rapid identification of infectivity in community settings (2). Antibody tests do not return positive results early in the disease course and are not helpful for acute diagnosis. Fortunately, the correct test was done for this patient, which is the first step in the diagnosis.To estimate pretest probability of COVID-19, you are able to access current national and state epidemiologic data online that indicate that 30% of all patients having COVID-19 testing receive positive results and that this percentage is even higher among symptomatic adults seen in emergency departments. Moreover, certain clinical and epidemiologic factors, including the presence of anosmia (3), increase the probability of infection further, resulting in a pretest estimate of at least 50% in this case. As Woloshin and colleagues (4) recently calculated using a sensitivity of 70% and specificity of 95% for the test characteristics and an online tool or 2-by-2 table, such a patient still has a 24% probability of having COVID-19 despite a negative test result.How then can we decide whether the patient truly has COVID-19? One strategy is to understand more about why the test result might be a false negative in this patient. Reviewing the published evidence, it is clear that results of a PCR test can be negative early in the disease course because the viral load is still below the limit of detection (5). Thus, repeating the test after 24 to 48 hours can be useful in improving sensitivity. Repeated testing can also rectify false negatives resulting from inadequate sampling of the nasopharynx. In addition, viral load in the nasopharynx may decrease as the immune response grows during the infection—an issue that cannot be addressed by repeated nasopharyngeal testing. In that setting, other tests can provide additional information about the probability that the patient has COVID-19. For example, patients with significant immune response are likely to have abnormal findings on chest imaging, so chest imaging can improve the sensitivity of a COVID-19 diagnostic strategy (6).For this patient, the clinician decided to order a chest radiograph, which showed bilateral infiltrates. A follow-up computed tomography scan showed bilateral ground-glass opacities, a pattern consistent with COVID-19. Given a sufficiently high probability of COVID-19 and additional risk factors for clinical deterioration (advanced age and cardiovascular disease), the patient was hospitalized. However, the posttest probability was not judged to be high enough to begin potential empirical treatments or consider enrollment in a clinical trial because the threshold is much higher for treatment decisions than for admission decisions. The next day, results of a repeated viral PCR test were positive, the patient started receiving remdesivir because of risk for disease progression, and the question of whether to start dexamethasone treatment was raised.The key principles of clinical decision making to consider include the following. First, diagnostic tests are neither perfectly sensitive nor perfectly specific. Interpretation of test results requires an understanding of pretest probability (7). Second, testing and treatment decisions involve thresholds that do not require certainty that a diagnosis has been ruled in or ruled out (7, 8).TreatmentThe patient is hospitalized and now has confirmed COVID-19. Oxygen saturation on room air remains normal. Should the patient be treated with corticosteroids?Clinical trials of therapeutic agents for COVID-19 have occurred at a remarkable pace. Given the significant role of inflammation and lung injury in causing morbidity and mortality, considerable attention has focused on immunomodulatory therapies. Corticosteroids have long been evaluated as potential adjunct therapies for patients with a range of inflammatory conditions due to pulmonary infections, with evidence for and against their use depending on the pathogens and conditions (9). The RECOVERY (Randomized Evaluation of Covid-19 Therapy) trial (10) was a multigroup pragmatic trial that published results in July 2020 showing a mortality benefit for dexamethasone among hospitalized patients with COVID-19. Of note, the demonstration of significant benefit was restricted to preplanned subgroups of patients who received mechanical ventilation or supplemental oxygen. Hospitalized patients without an oxygen requirement did not show a mortality benefit.It is sometimes tempting to dismiss subgroup effects, especially if subgroup size raises concern about power. Mortality is an obviously important end point to evaluate in COVID-19 trials, but death is uncommon among patients who are not initially hospitalized and do not require ventilatory support. However, therapies also carry risk, and as the absolute benefit of a therapy declines, the importance of adverse risks increases—as observed with clinical trials of corticosteroids for pneumonia (11).Uptake of approved therapies for secondary indications is often much swifter than uptake of new therapeutics because of familiarity with the agent. Corticosteroids are used throughout medical settings and are widely prescribed, raising concern that consideration of benefit could lead to rapid use, even in the absence of clear, demonstrated benefit. In this case, the patient was not prescribed a corticosteroid. Key principles of clinical decision making to emphasize include the following. First, quality of evidence is a critical element to assess when incorporating new data into clinical decision making, and randomized trials with masked assessment of outcomes provide the best nonbiased estimates of benefit (12). Second, subgroup effects are important to consider in deciding whether the results of a trial apply to your patient. Although the average treatment effect for the entire study population is often the best estimate of the effect for all participants, individuals will have heterogeneous responses that can sometimes be predicted on the basis of effect sizes in valid, prespecified subgroups (13, 14).PreventionYou are rounding on the patient at the hospital. Do you need to wear an N95 mask to provide better protection than a regular surgical mask from COVID-19?Although clear evidence shows that various infection control procedures, including hand hygiene and use of gowns and face masks, are highly effective at reducing nosocomial transmission of a range of pathogens, further details about these procedures are largely not driven by high-grade evidence. For example, a cluster randomized trial from before COVID-19 of N95 respiratory masks versus surgical masks worn during the care of patients with respiratory illnesses during successive respiratory illness seasons did not detect a significant difference in the frequency of laboratory-confirmed influenza among health care workers (15). Yet, an early assumption of the COVID-19 pandemic was that N95 masks provided significantly more protection than surgical masks, with the understanding that absolute risk for transmission likely varied significantly by other factors, including proximity to the patient, whether the patient was also wearing a mask, and whether the patient was having an invasive and/or aerosol-generating procedure. The issue was further complicated by the national shortage of N95 masks, with the immediate consequence that use of N95 masks during all patient interactions would not be sustainable.In this setting, infection control leaders and hospital administrators needed to make policy decisions to balance the availability of N95 masks with the available evidence regarding effectiveness—a situation in which a different perspective of the decision maker (hospital administrator vs. individual health care worker) would likely lead to a different set of decisions. Indeed, guidance from the Centers for Disease Control and Prevention during this time explicitly noted that N95 mask use could be limited in non–aerosol-generating settings if N95 supply was limited. The mixing of supply issues with clinical decisions, a form of rationing, feels uncomfortable to many.A systematic review and meta-analysis reported that N95 masks were statistically more likely than surgical masks to reduce risk for COVID-19 among health care workers (16), further highlighting this tension. In fact, the level of evidence supporting that conclusion was weak. No studies directly compared the effectiveness of the 2 types of masks, and only 1 study of N95 masks was of patients with COVID-19. This study compared outcomes across units in a single hospital; the high degree of protection attributed to N95 masks was largely the result of an outbreak on a non-N95 unit attributed to a single patient. Yet, such data continue to fuel concerns that health care worker risk is unacceptably high in the absence of N95 masks for all patient care activities in the era of COVID-19.As a result of these concerns, your hospital requires N95 mask wearing as part of any direct care activities for patients with confirmed or suspected COVID-19. This decision reflects an additional core principle of clinical decision making: Different perspectives can render different decisions even in the face of the same clinical evidence (17). Hospital administrators may need to preserve N95 masks for the highest-risk procedures, recognizing that a small but real absolute risk may exist for other workers who use alternative personal protective equipment in lower-risk settings. Recognizing the effect of perspective on clinical decisions can help lead to better acceptance of these decisions at all levels and ongoing plans to reassess decisions over time.The unprecedented health challenges created by the rapid emergence and spread of SARS-CoV-2 have resulted in information being released through faster-tracked channels without time for deliberative review and consensus building; thus, end users of this information need to have a framework for evaluating the quality of the information and the relevance of the results to everyday clinical decision making. Our goal in this brief article was not to conduct systematic reviews of some of these issues, but rather to illustrate how one could use available strategies to evaluate new information as it emerges and incorporate evidence into clinical decisions at the individual and hospital levels. We recognize that the information that will inform these decisions will evolve over time, potentially rendering the conclusions we have illustrated in this article no longer correct—this highlights the dynamic nature of clinical decision making. We can only make decisions based on the information in front of us, recognizing that these decisions may often come due at a time when the information is incomplete.References1. Taichman DB, Williams SV, Laine C. Clinical decision making: nurturing our core skills. Ann Intern Med. 2020;172:627. doi:10.7326/M20-1423 LinkGoogle Scholar2. Manabe YC, Sharfstein JS, Armstrong K. The need for more and better testing for COVID-19. JAMA. 2020. [PMID: 33185688] doi:10.1001/jama.2020.21694 CrossrefMedlineGoogle Scholar3. Sacks CA, Dougan M, McCoy TH, et al. The association between symptoms and COVID-19 test results among healthcare workers. Ann Surg. 2020;272:e329-e332. [PMID: 32941277] doi:10.1097/SLA.0000000000004483 CrossrefMedlineGoogle Scholar4. Woloshin S, Patel N, Kesselheim AS. False negative tests for SARS-CoV-2 infection — challenges and implications. N Engl J Med. 2020;383:e38. [PMID: 32502334] doi:10.1056/NEJMp2015897 CrossrefMedlineGoogle Scholar5. Kucirka LM, Lauer SA, Laeyendecker O, et al. Variation in false-negative rate of reverse transcriptase polymerase chain reaction-based SARS-CoV-2 tests by time since exposure. Ann Intern Med. 2020;173:262-267. doi:10.7326/M20-1495 LinkGoogle Scholar6. Salameh JP, Leeflang MM, Hooft L, et al; Cochrane COVID-19 Diagnostic Test Accuracy Group. Thoracic imaging tests for the diagnosis of COVID-19. Cochrane Database Syst Rev. 2020;9:CD013639. [PMID: 32997361] doi:10.1002/14651858.CD013639.pub2 MedlineGoogle Scholar7. Armstrong KA, Metlay JP. Annals clinical decision making: using a diagnostic test. Ann Intern Med. 2020;172:604-609. doi:10.7326/M19-1940 LinkGoogle Scholar8. Pauker SG, Kassirer JP. The threshold approach to clinical decision making. N Engl J Med. 1980;302:1109-17. [PMID: 7366635] CrossrefMedlineGoogle Scholar9. Jantz MA, Sahn SA. Corticosteroids in acute respiratory failure. Am J Respir Crit Care Med. 1999;160:1079-100. [PMID: 10508792] CrossrefMedlineGoogle Scholar10. Horby P, Lim WS, Emberson JR, et al; RECOVERY Collaborative Group. Dexamethasone in hospitalized patients with Covid-19 — preliminary report. N Engl J Med. 2020. [PMID: 32678530] doi:10.1056/NEJMoa2021436 Google Scholar11. Metlay JP, Waterer GW, Long AC, et al. Diagnosis and treatment of adults with community-acquired pneumonia. An official clinical practice guideline of the American Thoracic Society and Infectious Diseases Society of America. Am J Respir Crit Care Med. 2019;200:e45-e67. [PMID: 31573350] doi:10.1164/rccm.201908-1581ST CrossrefMedlineGoogle Scholar12. Metlay JP, Armstrong KA. Annals clinical decision making: weighing evidence to inform clinical decisions. Ann Intern Med. 2020;172:599-603. doi:10.7326/M19-1941 LinkGoogle Scholar13. Armstrong KA, Metlay JP. Annals clinical decision making: translating population evidence to individual patients. Ann Intern Med. 2020;172:610-616. doi:10.7326/M19-3496 LinkGoogle Scholar14. Oxman AD, Guyatt GH. A consumer's guide to subgroup analyses. Ann Intern Med. 1992;116:78-84 LinkGoogle Scholar15. Radonovich LJ Jr, Simberkoff MS, Bessesen MT, et al; ResPECT investigators. N95 respirators vs medical masks for preventing influenza among health care personnel: a randomized clinical trial. JAMA. 2019;322:824-833. [PMID: 31479137] doi:10.1001/jama.2019.11645 CrossrefMedlineGoogle Scholar16. Chu DK, Akl EA, Duda S, et al; COVID-19 Systematic Urgent Review Group Effort (SURGE) study authors. Physical distancing, face masks, and eye protection to prevent person-to-person transmission of SARS-CoV-2 and COVID-19: a systematic review and meta-analysis. Lancet. 2020;395:1973-1987. [PMID: 32497510] doi:10.1016/S0140-6736(20)31142-9 CrossrefMedlineGoogle Scholar17. Metlay JP, Armstrong KA. Annals clinical decision making: incorporating perspective into clinical decisions. Ann Intern Med. 2020;172:743-746. doi:10.7326/M19-3469 LinkGoogle Scholar Comments0 CommentsSign In to Submit A Comment Pankaj MathurUniversity of Arkansas Medical Sciences, Medical Center, Little Rock, Arkansas27 February 2021 Effective masking is still the best way to slow the spread of COVID 19 The authors (1) have presented their case in a lucid and interesting way. It is a challenge to simplify clinical decision making during the COVID-19 pandemic because almost every day we are getting new insight into the disease process and ways to prevent transmission of COVID 19. Much has already been said about the masks and it is still surprising that there is still an ongoing debate about what is the best way to protect the general public and Health care workers (HCWs) who may get repeated exposure to the virus. A recent CDC study by Brooks et al (2) explored the role of proper mask fitting to improve the efficacy of masking and reducing transmission. They found that the efficacy of cloth mask is 51.4% in blocking particles from stimulated cough and medical procedure mask alone blocked 56.1% of the particles. The combination of the cloth mask covering the medical procedure mask (double mask) blocked 85.4% of the cough particles and the efficacy of knotted and tucked medical procedure mask is 77.0%. The data in this report emphasize the common knowledge that mask wearing technique and good fit mask is key to reduce transmission. Interestingly, same argument can be made for choosing N95 over surgical masks. It is widely known that N95 offers the best protection against airborne/ aerosolized transmission because of variety of reasons including the filtration efficiency of over 95% for particles above 3 micron in diameter and facial seal. Therefore, FIT testing is done in all the medical facilities for N95. Each individual gets his own N95 mask size and fit. On the other hand, surgical masks, are not effective at blocking particles smaller than 100 microns. Besides other factors affecting the efficacy of masks are as room air flow/ ventilation, type of fabric of the mask and mask wearing technique of the person (3). A randomized trial of surgical masks vs N95 respirators was not powered to conclude that the surgical mask and the N95 respirator are equivalent (4). Here the practical consideration of efficacy vs availability also comes. What is the best vs what is practical and available has been always a case with medical decision making in the field. In my personal opinion if available, for all HCWs N95 might be better to use routinely whereas for general public properly fitted surgical masks or double masking as per the CDC recommendations should be used. Unambiguous guidelines go long way in ensuring slowing of the transmission COVID 19 till we get vaccination for the general public. Even CDC updated its guidelines on how to improve masking for more protection we need to follow the suit (5). References https://www.acpjournals.org/doi/10.7326/M20-8179 2. https://www.cdc.gov/mmwr/volumes/70/wr/mm7007e1.htm Tcharkhtchi A, Abbasnezhad N, Zarbini Seydani M, Zirak N, Farzaneh S, Shirinbayan M. An overview of filtration efficiency through the masks: Mechanisms of the aerosols penetration. Bioact Mater. 2020 Aug 11;6(1):106-122. Clynes N. Surgical Masks vs N95 Respirators for Preventing Influenza. JAMA. 2010;303(10):937–939. doi:10.1001/jama.2010.194 https://www.cdc.gov/coronavirus/2019-ncov/your-health/effective-masks.html Joshua Metlay, Katrina ArmstrongMassachusetts General Hospital3 March 2021 Comment on Mathur We appreciate the comment submitted by Dr. Mathur in response to our article on Clinical Decision Making during the COVID-19 Pandemic. Dr. Mathur challenges our statement that the evidence favoring N95 masks over surgical masks for reduction of COVID-19 transmission is relatively weak. First, it is easy to agree that in setting of any shortage, it is more important to have N95 availability for healthcare workers, who have a much higher burden of exposure, compared to the general public. Second, the foundation of clinical decision making is to emphasize patient and population level clinical outcomes over more upstream surrogate endpoints. All the biological data about N95 mask efficacy for reducing particle transmission can be true but the translation to patient or population health benefits may still be relatively small. Finally, the assessment of prevention options must also be informed by the adaptions that occur when these masks are used in practice. Optimal N95 functioning with fit testing may not be realized in real world settings and may further reduce the observed difference in protection between these options. Author, Article, and Disclosure InformationAuthors: Joshua P. Metlay, MD, PhD; Katrina A. Armstrong, MD, MSCEAffiliations: Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (J.P.M., K.A.A.).Disclosures: Authors have reported no disclosures of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M20-8179.Corresponding Author: Joshua P. Metlay, MD, PhD, Division of General Internal Medicine, Department of Medicine, Massachusetts General Hospital, 100 Cambridge Street, 16th Floor, Boston, MA 02114; e-mail, jmetlay@mgh.harvard.edu.Current Author Addresses: Dr. Metlay: Division of General Internal Medicine, Department of Medicine, Massachusetts General Hospital, 100 Cambridge Street, 16th Floor, Boston, MA 02114.Dr. Armstrong: Department of Medicine, Massachusetts General Hospital, Gray-Bigelow 7, 55 Fruit Street, Boston, MA 02114.Author Contributions: Conception and design: J.P. Metlay, K.A. Armstrong.Analysis and interpretation of the data: J.P. Metlay, K.A. Armstrong.Drafting of the article: J.P. Metlay, K.A. Armstrong.Critical revision of the article for important intellectual content: J.P. Metlay, K.A. Armstrong.Final approval of the article: J.P. Metlay, K.A. Armstrong.Administrative, technical, or logistic support: J.P. Metlay.Collection and assembly of data: J.P. Metlay, K.A. Armstrong.This article was published at Annals.org on 2 February 2021. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byLa geriatría puede salvar la medicinaThe IDentif.AI-x pandemic readiness platform: Rapid prioritization of optimized COVID-19 combination therapy regimensReal-World Use of Molnupiravir in the Treatment of Outpatients with SARS-CoV-2 Infection—A Patient Profile Based on the Experience of a Tertiary Infectious Disease CenterModified EDAS Method for MAGDM Based on MSM Operators with 2-Tuple Linguistic T -Spherical Fuzzy SetsHospital or Home?Laboratory medicine in the COVID-19 era: six lessons for the future May 2021Volume 174, Issue 5Page: 691-693KeywordsClinical trialsCOVID-19Decision makingHealth care providersHospital medicineMortalityOxygenPneumoniaPulmonary diseasesThorax ePublished: 2 February 2021 Issue Published: May 2021 Copyright & PermissionsCopyright © 2021 by American College of Physicians. 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