The Long and Winding Road to Clinical Guidelines on the Diagnosis and Management of Gout

The new clinical practice guidelines (CPGs) on the diagnosis and management of gout from the American College of Physicians (ACP) Clinical Guidelines Committee (1, 2) have some distinct differences from the 2012 American College of Rheumatology (ACR) guidelines (3). Consequently, the ACP recommendations likely will ignite controversy. How can guideline committees from 2 highly respected professional organizations come up with different recommendations? Let's start by considering the definition of guidelines. In 1990, the Institute of Medicine released Clinical Practice Guidelines: Directions for a New Program, in which it defined CPGs as systematically developed statements to assist practitioner and patient decisions about appropriate health care for specific clinical circumstances (4). The 2011 Institute of Medicine report Clinical Practice Guidelines We Can Trust updated this definition as follows: Clinical practice guidelines are statements that include recommendations intended to optimize patient care that are informed by a systematic review of evidence and an assessment of the benefits and harms of alternative care options (5). Further, their 2011 report Finding What Works in Health Care: Standards for Systematic Reviews explicitly established definitions and standards for systematic reviews as rigorous protocol-driven literature reviews that summarize evidence and help clarify what is known and not known about the potential benefits and harms of treatments (6). The institute clearly distinguished systematic evidence reviews from other types of literature reviews as significant projects following explicit protocols and taking substantial resources. In 2013, in consideration of these updated definitions of CPGs and systematic reviews, the Agency for Healthcare Research and Quality National Guideline Clearinghouse specified criteria to consider before accepting a document for inclusion (www.guideline.gov/help-and-about/summaries/inclusion-criteria). To enter the clearinghouse, a guideline must contain systematically developed recommendations; have been produced under the auspices of a relevant professional organization; have included a process that includes a verifiable systematic review of existing evidence published in peer-reviewed journals; and have been developed, reviewed, or revised within the past 5 years. The charge of the ACP Clinical Guidelines Committee is to oversee the development of guidelines based on the best available evidence to help clinicians deliver the best health care possible. When I became a member of the committee in 2013, I quickly learned a great deal about the definitions of CPGs and systematic reviews and the standards the committee aims to follow. Many professional organizations, including the ACR in writing their gout recommendations, still develop guidelines that are actually consensus expert panel opinions that do not clearly meet the current 2013 Institute of Medicine and National Guideline Clearinghouse definitions and standards. Although consensus panel opinions clearly have a role, we must be careful about inappropriately labeling them as guidelines. If no specific evidence exists to answer a clinical question within a topic, the ACP Clinical Guidelines Committee refrains from making a clinical recommendation. Of course, the difficult questions are, What evidence? How good does it have to be? Who makes that determination? The ACP applies clear standards when assessing the quality of available evidence and the grading of a recommendation (strong, weak, or insufficient evidence) based on the available evidence. Creating a CPG for managing a condition is challenging when no high-quality evidence is available to compare treatment options. Many medical practices have evolved over time on the basis of what we know about the condition's physiology, clinical experience, and observational studies, without definitive evaluation in randomized, controlled trials. In some cases, only when an appropriately designed randomized trial is performed do we learn that an experience-based practice is erroneous. The ACP Clinical Guidelines Committee spends much time and effort dissecting the evidence in systematic reviews to decide how to grade it, and the ACP guideline development process does not consider retrospective observational studies strong enough by themselves to support a strong recommendation. Yet, even in the absence of evidence, clinicians must make decisions. If gaps exist in the evidence or a patient has comorbid conditions, contraindications, or complicating factors, clinical guidelines are imperfect vehicles for defining the path of care. Clinicians must always do what is appropriate and best for the patient at that time. Even if a guideline recommendation is based on high-quality evidence, following the path it specifies might not be right for a particular patient. When we deviate from a CPG recommendation, we should engage the patient in this decision and document in our clinical records why care deviated from the guidelines. Guidelines are not meant to be absolute directives; thus, it becomes problematic when third-party payers or regulatory agencies treat them as such (7). The 2012 ACR Guidelines for Management of Gout (3) were created before the 2013 National Guideline Clearinghouse criteria were established. The systematic review was conducted internally and not published in a peer-reviewed journal. The Methods section acknowledges use of a consensus methodology to reach a consensus among experts, with an understanding that published literature may not be adequate to provide sufficient evidence for day-to-day clinical decision-making. Further, the discussion section states that the majority of evidence reviewed, upon which recommendations were based, was level C, with less than 20% level A evidence. Level C evidence was defined in the Methods section as consensus opinion of experts, case studies, or standard of care, and level A as supported by multiple randomized clinical trials or meta-analyses. The ACP based the new gout guidelines on 2 systematic evidence reviews sponsored by Agency for Healthcare Research and Quality and conducted by the RAND Corporation's Southern California Evidence-based Practice Center (8, 9). As the committee evaluated the evidence analyzed in these systematic reviews, it became clear that some aspects of gout management that have evolved in recent years and were included in the 2012 ACR guidelines, particularly the strategy of treating to target to lower serum uric acid below 357 mol/L (6.0 mg/dL), were based on retrospective studies or studies that used surrogate outcomes (uric acid levels) rather than clinical ones (frequency of gout episodes). A recent commentary in a rheumatology journal acknowledges that the ACR's treat-to-target recommendation is based on indirect evidence and no randomized trials (10). With the limitations of this evidence, the ACP committee thought it inappropriate to make the treat-to-target recommendation that the ACR made. The ACP Clinical Guidelines Committee finds it difficult when it cannot endorse a widely disseminated recommendation from a fellow professional society because of a lack of adequate supporting evidence. Yet, it believes that evidence must direct guideline recommendations. Specifying clinical options when evidence is lacking is the role of expert consensus panels or best-practice statements, but these documents must not masquerade as the type of evidence-based guidelines defined by the Institute of Medicine. As we try to provide our patients with the best possible care, we must be clear about when the best clinical decision is defined by high-quality evidence and when it is suggested by consensus.