UpToDate is updated daily following a continual comprehensive review of peer-reviewed journals, clinical databases and other resources (see the Evidence section for a detailed list). Topics in UpToDate are revised whenever important new information is published, not according to any specific time schedule. Updates are integrated carefully, with specific statements as to how the new findings should be applied clinically, and after extensive peer review.
Important and practice-changing updates, in addition to appearing in a traditional UpToDate topic, are highlighted in our What's New section and in a topic called "Practice Changing UpDates." Practice Changing UpDates focus on changes that may have significant and broad impact on practice, and therefore do not represent all updates that affect practice.
The deputy editor for a specialty, as well as the editor-in-chief and/or section editors assigned to a topic, review all UpToDate content, including new topics, updates and recommendations. In addition, each UpToDate specialty has assembled a group of peer reviewers, often in conjunction with a sponsoring specialty society, who are responsible for reviewing selected topics in each specialty. Finally, any comments from users of UpToDate are formally addressed, with changes and/or additions incorporated as necessary.
UpToDate's policies and procedures are continuously reviewed in consultation with our Evidence-Based Medicine Advisory Group led by Dr. Gordon Guyatt from McMaster University.
All topics in UpToDate are written by the listed authors in conjunction with a deputy editor. Authors are identified as experts by the editors-in-chief, our editorial staff and the participating societies. All material is originally prepared by the contributing author(s) whose name(s) and affiliation(s) appear in the upper left corner of each topic. This material is reviewed extensively by our physician editors and peer reviewers for accuracy and completeness of the literature search, and for consistency with all aspects of the editorial policy. Physician editors suggest changes to ensure that topics summarize the relevant evidence and that recommendations are consistent with the evidence, with our understanding of patients' values and preferences, and with our editorial policy. Some of the content may be taken from other topics in UpToDate. In such cases, the text is hyperlinked to the topic from which it originated.
Occasionally authors of a particular topic are replaced. A new author is required to thoroughly review the topic and make necessary revisions, but is not required to completely rewrite the topic. The revised topic undergoes the same peer review process as new topics in UpToDate. When an author is replaced, the previous author is acknowledged at the bottom of the topic for at least one year.
UpToDate Pathways and Lab Interpretation topics
UpToDate Pathways and Lab Interpretation topics (require a subscription to UpToDate Advanced) are prepared by the listed Authors in conjunction with UpToDate Deputy Editors, based exclusively on content synthesized from UpToDate topics that have been developed in accord with the above policies. The UpToDate Pathways and Lab Interpretation topics are electronically linked to the underlying UpToDate topics within our editorial system, so that a revision or update to a relevant section in an UpToDate topic will generate a simultaneous review and revision of the related UpToDate Pathway and/or Lab Interpretation topic(s). The UpToDate Pathways and Lab Interpretation topics themselves therefore directly reflect the updating policies for the underlying topics, and the underlying evidence is explicitly available in the linked topics. Any comments from users of UpToDate are formally addressed, with changes and/or additions incorporated as necessary.
UpToDate follows a hierarchy of evidence consistent with most evidence-based resources. At the top of the hierarchy are meta-analyses of randomized trials of high methodological quality, followed by randomized trials with methodological limitations, observational studies and unsystematic clinical observations. Inferences are stronger when the evidence is summarized in systematic reviews of the literature that present all relevant data.
Each topic has an author who is an expert in the area discussed, and at least two separate physician reviewers. This group works together to perform a comprehensive review of the literature and carefully select studies for presentation based on the quality of the study, the hierarchy of evidence discussed above, and clinical relevance. When current, high-quality systematic reviews are available, UpToDate topics and recommendations rely heavily on these reviews. When such reviews are unavailable, UpToDate summarizes the key studies bearing on the clinical issues at hand. Systematic reviews and the design of primary studies (eg, randomized trials, observational studies) are often identified explicitly in the text, with the relevant data provided. However, in cases where either the type of study or the data are not stated explicitly, users can click on the reference and bring up the Medline abstract to obtain this information. Evidence is derived from a number of resources, including but not limited to:
- Hand-searching of over 450 peer-reviewed journals
- Electronic searching of databases including Medline, The Cochrane Library, Clinical Evidence, and the Agency for Healthcare Research and Quality
- Guidelines that adhere to principles of evidence evaluation described above
- Published information regarding clinical trials such as reports from the US Food and Drug Administration and the European Medicines Agency, as well as other sources of information produced by governmental and nongovernmental agencies such as the Centers for Disease Control and Prevention and the World Health Organization
- Proceedings of major national and international scientific meetings
- The clinical experience and observations of our authors, editors and peer reviewers
UpToDate's process of arriving at recommendations involves constructing a structured clinical question. That structure includes carefully defining the patient population of interest, the alternative management strategies, and the outcomes of importance to patients (PICO format: Population, Intervention, Comparators, Outcomes).
Values and Preferences
A fundamental principle of evidence-based medicine, as described by Dr. Gordon Guyatt from McMaster University, is that "Evidence alone is never sufficient to make a clinical decision. Decision makers must always trade the benefits and risks, inconvenience, and costs associated with alternative management strategies, and in doing so consider the patient's values"1. Expertise is thus required to move from evidence to recommendations.
This principle has led some evidence-based resources to avoid making specific recommendations for patient care, since the recommendation needs to account for all of the factors cited. UpToDate has taken a different approach. It is the policy of UpToDate to make specific recommendations for patient care whenever possible.
Recommendations in UpToDate are based on a synthesis of evidence, including that obtained from clinical trials as well as clinical experience; whenever possible, the evidentiary basis for recommendations is stated explicitly. When there is no published systematic evidence available (eg, prednisone dosing regimen in pulmonary sarcoidosis), recommendations are based on the unsystematic clinical observations of our experts and reviewers, and on pathophysiologic rationale.
UpToDate recommendations identify situations in which different decisions might be appropriate for patients with different values and preferences. Furthermore, UpToDate recognizes that recommendations will not apply to every patient, and counts on clinicians to evaluate the recommendations in light of the individual circumstances of their patient. Nevertheless, UpToDate feels that providing recommendations based on a sophisticated understanding of the clinical issues, the best evidence, and a consideration of patient values and preferences allows clinicians to make informed decisions with and for their patients.
As discussed in the following section, UpToDate commonly uses the terminology "We recommend..." or "We suggest..." when describing recommended courses of action, since recommendations generally reflect a consensus of the author(s) and editors of a topic. When there are disagreements, this same wording is used; however, the recommendations are those of the author(s), and the disagreement among experts is discussed within the text. If other topics in UpToDate make alternative recommendations, those topics and recommendations are hyperlinked.
UpToDate began grading recommendations for treatment and screening in 2006. This is a continuing process, with thousands of graded recommendations in the program, although not all recommendations have yet been graded. Graded recommendations appear in the Summary and Recommendations sections at the end of topics.
UpToDate uses the GRADE system.2 Grades have two components, a number (1 or 2) reflecting the strength of the recommendation and a letter (A, B, or C) reflecting the quality of the evidence supporting that recommendation.
A Grade 1 recommendation is a strong recommendation to do (or not do) something, where the benefits clearly outweigh the risks (or vice versa) for most if not all patients. A Grade 2 recommendation is a weaker recommendation, where the risks and benefits are more closely balanced or are more uncertain. The majority of recommendations will be grade 2 recommendations. UpToDate uses a wording that reflects the strength of the recommendation: Strong (Grade 1) recommendations are "recommended" and weak (Grade 2) recommendations are "suggested."
Grade A evidence refers to high-quality evidence that comes from consistent results from well-performed randomized controlled trials, or overwhelming evidence of some other sort (such as well-executed observational studies with very strong effects). Grade B evidence refers to moderate-quality evidence from randomized trials that suffer from serious flaws in conduct, inconsistency, indirectness, imprecise estimates, reporting bias, or some combination of these limitations, or from other study designs with special strength. Grade C evidence refers to low-quality evidence from observational evidence, or from controlled trials with several very serious limitations.
Additional detailed information about the GRADE system, including an online grading tutorial, is available for those interested in learning more about how we apply evidence grades and for those who wish to use the system.
Grading recommendations involves subjective judgments about evidence, benefits and harms. Users of UpToDate are welcome to communicate concerns about grades to the editorial staff.
Moving from Evidence to Recommendations
The following table presents the criteria that UpToDate authors and editors consider when weighing the advantages and disadvantages of treatments, both in order to decide on a recommendation and to grade the strength of that recommendation.
|Issue (and what should be considered)||Recommended process|
|Quality of evidence||Strong recommendations usually require at least moderate-quality evidence for all the critical outcomes. The lower the quality of evidence, the less likely there should be a strong recommendation.|
|Relative importance of the outcomes
(benefits, harms, burdens)
|Authors and editors consider the relative values and preferences that patients and other stakeholders place on outcomes and the variability in values and preferences across patients. If values and preferences vary widely, a strong recommendation becomes less likely.|
|Baseline risks of adverse outcomes
(typically most relevant for benefits)
|The higher the baseline risk of an adverse outcome, the greater the magnitude of benefit a treatment will offer, and the more likely there should be a strong recommendation. If the baseline risk is very different for two subpopulations, then UpToDate may make separate recommendations for these different groups.|
|Magnitude of effect (benefits - eg,
reduction in RR; harms - eg, increase in RR; burden)
|Larger relative risk reductions with treatment make a strong recommendation for treatment more likely, while larger increases in the relative risk of harms make a strong recommendation for treatment less likely.|
|Absolute magnitude of the effect (benefits,
|The larger the absolute benefits with treatment, the greater the likelihood of a strong recommendation in favor of treatment. The larger the absolute increase in harms, the less likely there should be a strong recommendation in favor of treatment.|
|Precision of the estimates of the effects
(benefits, harms and burdens)
|The greater the precision, the more likely there should be a strong recommendation.|
|Cost||The higher the incremental cost, the less the likelihood of a strong recommendation in favor of a treatment.|
- Guyatt GH, Rennie D, Meade MO, Cook DJ. Users' Guides to the Medical Literature: A Manual for Evidence-based Clinical Practice, 2nd ed, McGraw-Hill, New York 2008.
- Guyatt GH, Oxman AD, Vist GE, et al, for the GRADE Working Group. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ 2008; 336:924.
This policy last reviewed on January 22, 2018.