Guidance vs. guidelines: the role of evidence-based medicine in the COVID-19 pandemic

Under normal circumstances, every day as a clinician is challenging. Each morning we face the possibility that we will see something we have never before encountered. Each night we reflect on our new knowledge: “What did I learn today that will make me a better doctor?” “How can I keep my patients safer?” We are forever in training. New challenges make the practice of medicine simultaneously stressful and stimulating. We are comfortable with uncertainty and we have learned how to provide the highest quality care with evidence-based practice.

However, we have never seen anything like COVID-19. The pandemic has shuttered our elective surgical practices, closed our clinics, and turned us into battlefield doctors; our enemy is a lipid enveloped, encapsulated RNA virus. In just a matter of months, this enemy has brought the world to its knees. One of the most frustrating aspects of this battle is that we have no uniformly accepted treatments or therapeutic protocols. Without standard treatment, how are we to fight an enemy that we do not fully understand? How can we ensure the highest quality care when we lack confidence in our treatment options? How can we provide safe care when new hidden threats to patient safety have rapidly appeared as we have been forced to change nearly everything we do in clinical medicine?

Clinical judgment is the process by which we attempt to make consistently good decisions in the face of uncertainty. Trained in the era of evidence-based medicine, we read the literature, critically examine the data, and base decisions on science. We distill this process into practice management guidelines, developed with rigor to offer clinicians actionable recommendations. We create and use guidelines because we want to provide the highest quality care and offer the best opportunity for meaningful outcomes. Guidelines reduce inappropriate practice variation, speed translation of research into practice, improve safety and quality, reduce disparities, and cut costs. ¹ Ideally, we would have guidelines to treat COVID-19 patients. Unfortunately, this pandemic poses innumerable challenges to the medical community with little scientific evidence to manage our uncertainty.^2,3 Patients are ill and decisions must be made.

When we practice medicine without the foundation of scientific evidence, we expect heterogeneity of treatment paradigms and wide variation in clinical practice. What stretches before us is an array of management options which may or may not be available to all clinicians. Should we intubate early in the disease or attempt non-invasive ventilation? Pressure control or volume control? Supine or prone? Should we place a tracheostomy? If so, how and when? Should we anticoagulate? What medications should we administer? With COVID-19 information rapidly populating social media and news outlets, it may be tempting to scour the internet for answers. However, anecdotal experiences or “promising” reports that circulate in the media cannot be a substitute for rigorous science.

Science takes time. It does not have to take a long time, however, especially when answers are needed quickly. We need guidance, even though we may not have time for the routine guideline creation process. The Cochrane network is working to establish methods for ‘rapid review’ which accelerates the traditional systematic review process to produce evidence in a resource-efficient manner. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) framework, adopted by hundreds of governments, professional societies and organizations worldwide, is the leader in guideline methodology. GRADE provides a systematic approach to clarify clinical questions, prioritize outcomes with attention to patient preferences, summarize the evidence, and make recommendations. ⁴ Ideally, guidelines are based upon a systematic review (with meta-analyses) of the literature usually comprised of randomized clinical trials and observational studies. GRADE can be applied to evidence assembled from narrative reviews, indirect evidence, or other sources. A structured assessment is required but does not have to be time-consuming as long as underlying judgments about the certainty of the evidence are transparent and based on GRADE domains. It is entirely possible—and sometimes necessary—to develop evidence-based guidelines with urgency. Now, in the midst of the COVID-19 pandemic, is one of those times. Rapidity, in and of itself, does not necessarily compromise the quality of a systematic review. ⁵

GRADE has been used in prior emergency responses when evidence assessments were needed urgently. ⁶ For example, the Flint water contamination crisis in Michigan required a response in a matter of hours. Fortunately, lead is a known chemical with a large literature base and existing risk assessments. In 2006, the World Health Organization responded to the avian influenza virus with recommendations based on mostly indirect evidence. While the certainty in the evidence was lowered because of indirectness and imprecision, evidence-based recommendations were available in just three months. New guidelines for management of patients with COVID-19 using GRADE have been published by the Infectious Diseases Society of America (IDSA). ⁷ While they were co-authored by infectious disease content experts and GRADE methodology authorities, they are not very helpful to the bedside clinician. They report on seven PICO questions, six of which suggest that novel therapies be offered in the context of clinical trials. One concrete conditional recommendation was “against the use of corticosteroids” based on very low certainty of evidence. ⁷ However, more recent randomized clinical trials, evaluated with a prospective meta-analysis by the World Health Organization Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group, have found administration of systemic corticosteroids associated with lower all-cause mortality when compared with usual care. ⁸ This provides a prime example of rapidly changing recommendations from two prestigious organizations and reemphasizes the need to stay current in these times of rapidly changing evidence.

The scope of the current COVID-19 pandemic is without precedent in our lifetimes and in the memory of modern medicine. As we treat COVID-19 patients and make decisions, we do so without the usual wisdom of guidelines. The scientific evidence will come in time. Until we have guidelines we can trust, we will have to rely on other types of guidance. Decisions should be made based on critical appraisal of the available scientific evidence. However, when evidence is not available, we may have no choice but to practice “eminence-based medicine” rather than truly evidence-based medicine, as a last resort. ⁹

The wisdom we gain will do good as we pass it on to the generations we train. For now, we must lay hands on the patients who need us. We must be discerning with what we read and avoid the cognitive biases introduced by anecdote, sensationalism, and fear. ¹⁰ We must enroll our patients in clinical research, trials, and cohort studies whenever possible. We need to collect data and contribute to the collective effort to build a foundation of knowledge and scientific evidence. We must stay up to date on the most recent findings and attempt to rapidly modify hospital protocols and pathways to standardize care for COVID patients, even in these uncertain times. We will change our practice with experience, and, eventually with data. We will take care of our patients, take care of ourselves, and take care of each other. ¹¹ In the face of uncertainty, we must practice how we were trained.