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."
Peer Review
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.
Policy Review
UpToDate's policies and procedures are continuously reviewed in
consultation with our Evidence-Based Medicine Advisory Group. Members of
this group include Dr. Gordon Guyatt and Dr. Roman Jaeschke from
McMaster University, Dr. Holger Schünemann from the Italian National
Cancer Institute in Rome/McMaster University, and Dr. Yngve Falck-Ytter
from Case Western Reserve University.
Authors
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.
Evidence
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
(e.g., 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 460 peer-reviewed journals
Electronic searching of databases including Medline, The Cochrane Database, Clinical Evidence and ACP Journal Club
Guidelines that adhere to principles of evidence evaluation described above
Published information regarding clinical trials such as reports from the Food and Drug Administration, as well as other sources of information produced by federal agencies such as the Centers for Disease Control and Prevention and the National Institutes of Health
Proceedings of major national meetings
The clinical experience and observations of our authors, editors and peer reviewers
Recommendations
Structured Questions
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 (e.g., 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.
Grading Process
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 - e.g., reduction in RR; harms - e.g., 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, harms, burden)
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.
