A critical appraisal of the quality of critical care pharmacotherapy clinical practice guidelines and their strength of recommendations

Department of Pharmacy, Capital District Health Authority, College of Pharmacy, Dalhousie University, c/o Rm 2043 Victoria Building, 1276 South Park Street, Halifax, NS, B3H 2Y9, Canada.
Intensive Care Medicine (Impact Factor: 7.21). 03/2010; 36(10):1636-43. DOI: 10.1007/s00134-010-1786-8
Source: PubMed
ABSTRACT
Clinical practice guideline (CPG) quality assessment is important before applying their recommendations. Determining whether recommendation strength is consistent with supporting quality of evidence is also essential. We aimed to determine quality of critical care pharmacotherapy CPGs and to assess whether high quality evidence supports strong pharmacotherapy recommendations.
MEDLINE (1966-February 2008), EMBASE (1980-February 2008), National Guideline Clearinghouse (February 2008) and personal files were searched to identify CPGs. Four appraisers evaluated each guideline using the appraisal of guidelines, research and evaluation (AGREE) instrument. AGREE assesses 23 items in six domains that include scope/purpose, stakeholder involvement, rigor of development, clarity, applicability and editorial independence. Standardized domain scores (0-100%) were determined to decide whether to recommend a guideline for use. One appraiser extracted strong pharmacotherapy recommendations and supporting evidence quality.
Twenty-four CPGs were included. Standardized domain scores were clarity [69% (95% confidence interval (CI) 62-76%)], scope/purpose [62% (95% CI 55-68%)], rigor of development [51% (95% CI 42-60%)], editorial independence [39% (95% CI 26-52%)], stakeholder involvement [32% (95% CI 26-37%)] and applicability [19% (95% CI 12-26%)]. The proportion of guidelines that could be strongly recommended, recommended with alterations and not recommended was 25, 37.5 and 37.5%, respectively. High quality evidence supported 36% of strong pharmacotherapy recommendations.
Variation in AGREE domain scores explain why one-third of critical care pharmacotherapy CPGs cannot be recommended. Only one-third of strong pharmacotherapy recommendations were supported by high quality evidence. We recommend appraisal of guideline quality and the caliber of supporting evidence prior to applying recommendations.

Full-text

Available from: Peter J Zed
Sean K. Gorman
Michelle Ho Chung
Richard S. Slavik
Peter J. Zed
Kerry Wilbur
Vinay K. Dhingra
A critical appraisal of the quality of critical
care pharmacotherapy clinical practice
guidelines and their strength
of recommendations
Received: 27 November 2009
Accepted: 4 February 2010
Ó Copyright jointly held by Springer and
ESICM 2010
Electronic supplementary material
The online version of this article
(doi:10.1007/s00134-010-1786-8) contains
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to authorized users.
S. K. Gorman (
)
) P. J. Zed
Department of Pharmacy, Capital District
Health Authority, College of Pharmacy,
Dalhousie University, c/o Rm 2043 Victoria
Building, 1276 South Park Street, Halifax,
NS, B3H 2Y9, Canada
e-mail: sean.gorman@dal.ca
Tel.: ?1-902-4736576
Fax: ?1-902-4731606
M. H. Chung
Department of Pharmacy,
St. Paul’s Hospital, 1081 Burrard Street,
Vancouver, BC, V6Z 1Y6, Canada
R. S. Slavik
Pharmacy Department, Interior Health
Authority, Faculty of Pharmaceutical
Sciences, University of British Columbia,
200-1835 Gordon Drive, Kelowna,
BC, V1Y 3H5, Canada
P. J. Zed
Department of Emergency Medicine,
Dalhousie University, Halifax Infirmary,
Suite 355 (Room 345), 1796 Summer
Street, Halifax, NS, B3H 3A7, Canada
K. Wilbur
College of Pharmacy, Qatar University,
P.O. Box 2713, Doha, Qatar
V. K. Dhingra
Intensive Care Unit, Vancouver General
Hospital, 855 West 12th Avenue,
Vancouver, BC, V5Z 1M9, Canada
V. K. Dhingra
Faculty of Medicine, University of British
Columbia, Vancouver, BC,
V5Z 1M9, Canada
Abstract Objective: Clinical
practice guideline (CPG) quality
assessment is important before
applying their recommendations.
Determining whether recommenda-
tion strength is consistent with
supporting quality of evidence is also
essential. We aimed to determine
quality of critical care pharmaco-
therapy CPGs and to assess whether
high quality evidence supports strong
pharmacotherapy recommendations.
Methods: MEDLINE (1966–Febru-
ary 2008), EMBASE (1980–February
2008), National Guideline Clearing-
house (February 2008) and personal
files were searched to identify CPGs.
Four appraisers evaluated each
guideline using the appraisal of
guidelines, research and evaluation
(AGREE) instrument. AGREE asses-
ses 23 items in six domains that
include scope/purpose, stakeholder
involvement, rigor of development,
clarity, applicability and editorial
independence. Standardized domain
scores (0–100%) were determined to
decide whether to recommend a
guideline for use. One appraiser
extracted strong pharmacotherapy
recommendations and supporting
evidence quality. Results: Twenty-
four CPGs were included. Standard-
ized domain scores were clarity [69%
(95% confidence interval (CI) 62–
76%)], scope/purpose [62% (95% CI
55–68%)], rigor of development
[51% (95% CI 42–60%)], editorial
independence [39% (95% CI 26–
52%)], stakeholder involvement [32%
(95% CI 26–37%)] and applicability
[19% (95% CI 12–26%)]. The
proportion of guidelines that could
be strongly recommended, recom-
mended with alterations and not
recommended was 25, 37.5 and
37.5%, respectively. High quality
evidence supported 36% of strong
pharmacotherapy recommendations.
Conclusion: Variation in AGREE
domain scores explain why one-third
of critical care pharmacotherapy
CPGs cannot be recommended. Only
one-third of strong pharmacotherapy
recommendations were supported by
high quality evidence. We recom-
mend appraisal of guideline quality
and the caliber of supporting evidence
prior to applying recommendations.
Keywords Clinical practice
guideline Critical appraisal
Quality of evidence Critical care
Pharmacotherapy
Intensive Care Med
DOI 10.1007/s00134-010-1786-8
REVIEW
Page 1
Introduction
Clinical practice guidelines are systematically developed
statements whose primary purpose is to assist clinical
decision-making by providing a rational basis of therapy
using the best available scientific evidence [1]. Akin to a
randomized controlled trial, a guideline should be criti-
cally appraised prior to endorsing its recommendations
because poor quality guidelines fail to reduce unnecessary
variations in care [2]. Quality assessment techniques have
traditionally focused on evaluating the methods used to
obtain, formulate and report recommendations rather than
to appraise the validity of individual recommendations by
linking recommendation strength to the quality of sup-
porting evidence [3]. A recent analysis of cardiovascular
disease guidelines revealed that almost half of their rec-
ommendations were supported by low quality evidence
[4]. Many guidelines provide pharmacotherapy recom-
mendations for the critically ill, yet their quality and the
caliber of scientific evidence supporting their strong rec-
ommendations are unknown. The aims of this study were
to determine the quality of guidelines that provide critical
care pharmacotherapy recommendations and to assess the
quality of evidence supporting their strong pharmaco-
therapy recommendations.
Methods
Clinical practice guideline selection
MEDLINE (1966–February 2008), EMBASE (1980–
February 2008) and National Guideline Clearinghouse
(February 2008) databases were searched using a prede-
termined critical care topic list. Review of critical care
medicine and related professional society websites and
hand-search of references of retrieved articles were also
performed. English-language guidelines were included if
they addressed critical care topics and were published
prior to 1 February 2008. Those that did not provide
pharmacotherapy recommendations, addressed pediatric
populations or were considered outdated (a revised ver-
sion was available from same guideline developer) were
excluded.
Clinical practice guideline quality assessment tool
The appraisal of guidelines, research and evaluation
(AGREE) instrument was used as the guideline assess-
ment tool [5]. This validated tool requires appraisal of 23
items that are organized into six domains: scope and
purpose, stakeholder involvement, rigor of development,
clarity and presentation, applicability and editorial inde-
pendence. Items were independently scored on a 4-point
Likert scale by four investigators [5]. Standardized
domain scores were calculated by summing the scores of
individual items in a domain and by standardizing the
total as a percentage (0–100%) of the maximum possible
score for that domain [5]. A guideline can be strongly
recommended if the majority of item scores are 3 or 4 and
the majority of standardized domain scores are 60% or
greater. A guideline can be recommended with alterations
if there are equal numbers of item scores 3 or 4 and 1 or 2,
and most standardized domain scores are between 30 and
60%. A guideline cannot be recommended if the majority
of item scores are 1 or 2, and most standardized domain
scores are 30% or less [5].
Data synthesis
Five investigators (two critical care pharmacy specialists,
one emergency medicine pharmacy specialist, one inter-
nal medicine pharmacy specialist and one pharmacy
practice resident) were involved in guideline quality
assessment [6]. Two investigators (SG, MHC) indepen-
dently appraised 24 guidelines and others evaluated 17
(PZ), 16 (RS) and 15 (KW) guidelines, respectively. Item
scores for each guideline were entered into a Microsoft
Excel 2003 (Microsoft Corporation, Redmond, WA)
database and were electronically transferred to one
investigator (SG) for aggregation into a master database.
One investigator (MHC) extracted pre-defined guideline
characteristics and the quality of evidence supporting
strong pharmacotherapy recommendations. Pharmaco-
therapy recommendations were characterized as ‘strong’
if the respective guideline authors defined them as such.
The quality of supporting evidence was standardized
according to a modified Center for Evidence-Based
Medicine (CEBM) level of evidence criteria [7] (supple-
mentary Appendix 1). The primary outcome was the
mean standardized score for each of the six AGREE
domains [5]. Secondary outcomes included the proportion
of guidelines that were strongly recommended, recom-
mended with alterations and not recommended according
to the AGREE criteria; and the proportion of strong
pharmacotherapy recommendations that were supported
by highest quality evidence.
Data validation
To determine whether errors may have occurred in item
scoring, one investigator (SG) examined all final item
scores across the four appraisals for potential item dis-
crepancies. Discrepancies were defined as inter-rater
score differences of three points on any domain item. All
appraisers were then asked to perform another AGREE
assessment on the discrepant item in question. Only one
investigator (SG) was aware of other appraisers’ scores on
Page 2
those items at the time of reassessment. After item reas-
sessments were independently performed, the scores were
considered to be final and analyses were performed using
these data. The mean intraclass correlation (ICC) two-
way random model was calculated for each domain to
assess appraiser agreement [8].
Results
Clinical practice guideline selection
and characteristics
The electronic search yielded 128 guidelines and a hand-
search of personal files yielded 25 guidelines, and after
accounting for duplicates and exclusion criteria, 24
guidelines were included (Fig. 1). Guideline topics
included brain injury and cerebrovascular trauma [911],
aneurysmal subarachnoid hemorrhage and spontaneous
intracerebral hemorrhage [12, 13], status epilepticus [14],
sedation, analgesia and neuromuscular blockade [15, 16],
ventilator-associated pneumonia (VAP) [17, 18], com-
munity-acquired pneumonia [19], ARDS [20], severe
acute respiratory syndrome (SARS) [21], nitric oxide
therapy [22], severe sepsis and septic shock [23, 24],
colloid use [25], cardiopulmonary resuscitation [26],
stress ulcer prophylaxis [27], intra-abdominal infections
[28, 29], pancreatitis [30] and catheter-related blood
stream infections [31, 32] (Appendix 1). All guidelines
were developed in association with a critical care-related
professional society, all were published in peer-reviewed
journals, two-thirds addressed the adult-only population
and were published after the Conference on Guideline
Standardization (COGS) in 2003 (Supplementary
Table 1). Half of the guidelines were first versions, and
less than one-fifth were considered consensus statements.
Data validation
There were 544 AGREE items scored, and after initial
assessment, 42 (7.6%) discrepancies were identified in 21
(88%) guidelines. After independent reassessment of
these items, 15 (2.7%) discrepancies remained in 7 (29%)
guidelines. The mean ICCs for scope and purpose,
stakeholder involvement, rigor of development, clarity,
applicability and editorial independence were 0.79, 0.86,
0.94, 0.84, 0.89 and 0.96, respectively.
AGREE domain scores and overall recommendations
Clarity and presentation domain scored highest [69%
(95% confidence interval (CI) 62–76%)] and applicability
domain scored lowest [19% (95% CI 12–26%)] (Fig. 2).
ELECTRONIC SEARCH
n = 128
DUPLICATE CPGs
n = 20
REASONS FOR EXCLUSION (n = 133)
NO DRUG-THERAPY RECOMMENDATION 99
PEDIATRIC FOCUS 5
OUT-DATED VERSION 4
NON-ENGLISH
1
TOTAL EXCLUDED 109
HANDSEARCH
n = 25
INCLUDED
n = 24
Fig. 1 Trial flow diagram
Page 3
Based on AGREE criteria for the appropriate develop-
ment of CPGs, 25% of the guidelines are strongly
recommended, 37.5% are recommended with alterations,
and 37.5% are not recommended (Appendix 1).
Quality of evidence supporting strong
pharmacotherapy recommendations
Two hundred forty-eight strong pharmacotherapy rec-
ommendations were extracted from 24 guidelines, and 89
(36%) of these recommendations were supported by the
highest quality evidence.
Discussion
Only one quarter of the assessed critical care guidelines
are of the highest quality and can be strongly recom-
mended for use in practice. Examples of guidelines that
can be strongly recommended address management of
severe traumatic brain injury, prevention of VAP and
stress ulcer prophylaxis [10, 17, 27]. Despite using a more
liberal definition of high-quality guidelines to include
guidelines that could be recommended with alterations
as per AGREE, only two-thirds of all critical care
pharmacotherapy guidelines assessed could be considered
high quality. Examples of guidelines that cannot be rec-
ommended address penetrating brain injury, SARS and
hemodynamic support of sepsis [9, 21, 24].
Wide variability existed in scores across the six
AGREE domains. Overall low guideline quality may be
accounted for by low scores within applicability, stake-
holder involvement and editorial independence domains.
Applicability consists of three items pertaining to the
likely organizational, behavioral and cost implications of
applying the guideline [5]. Most guidelines failed to dis-
cuss implications of applying the guideline, nor did they
discuss key review criteria that could be used for moni-
toring or audit purposes. Stakeholder involvement
consists of four items that focus on the extent to which the
guideline represents the views of its intended users [5].
The two items addressing solicitation of patients’ views
and target-user piloting of the guidelines usually scored
low. Editorial independence consists of two items that are
concerned with the independence of the recommendations
and acknowledgement of possible conflict of interest from
the guideline development group [5]. Explicit statements
that the views/values or interests of the funding body have
not influenced the final recommendations and conflict of
interest declarations were often absent. Despite these
shortcomings, it is encouraging to note that rigor of
development, which is the most highly weighted AGREE
62
32
51
69
19
39
0
10
20
30
40
50
60
70
80
Standardized Domain Score (%)
Scope/Purpose
Rigor of
Development
Clarity
Involvement
Stakeholder
Applicability
Editorial
Independence
Fig. 2 Mean (95% confidence
intervals) standardized AGREE
domain scores
Page 4
domain consisting of seven items, was one of the highest
scoring domains.
This is not the first published analysis of the quality of
critical care guidelines; however, our analysis is unique as
it examined both guideline quality and the quality of
evidence supporting strong pharmacotherapy recommen-
dations [33]. Quality of evidence should reflect the extent
to which confidence in an estimate of the effect is ade-
quate to support recommendations, and study design is a
crucial factor in determining this [34]. It is disconcerting,
however, that only one-third of all ‘strong’ critical care
pharmacotherapy recommendations were supported by
the highest quality evidence. Processes of evidence
assessments that rely on consensus in making recom-
mendations introduce an opaque dimension to how the
recommendations are made and compromise objectivity
[35].
Many suggestions can be made for using the results of
this analysis. Organizations that produce guidelines
should adhere to the methods suggested by the AGREE
Collaboration because they encourage a systematic
approach to addressing the most important traits of a
guideline. It is also recommended that there be a trans-
parent link between quality of evidence and the strength
of recommendations included in their guideline docu-
ments. One suggested approach is to utilize the Grading
of Recommendations Assessment, Development and
Evaluation (GRADE) Working Group approach [36]. Our
final recommendation is that guidelines are not necessary
for every disease, but are required for diseases having
significant practice variability and for which a valid evi-
dence base can guide recommendations [37].
A potential limitation to this study is that the sample
of guidelines assessed may not represent the larger pool
of critical care pharmacotherapy guidelines. Selection
bias may have resulted in omission of high quality
guidelines from this analysis due to an incomplete
search strategy. We aimed to minimize the potential for
introducing this bias by performing a systematic search
of multiple electronic databases using predefined criteria
encompassing a heterogeneous mix of critical care
pharmacotherapy topics. Secondly, while one-fifth of the
guidelines we assessed were considered consensus
statements, these are intended to be applied to practice
in a similar fashion as a guideline and should be held to
the same rigorous quality standards. Another potential
limitation pertains to the instrument employed to assess
guideline quality. The AGREE instrument evaluates the
methods used to synthesize and report the guideline
rather than evaluate the quality of its contents [38]. We
attempted to minimize this limitation by systematically
evaluating the quality of scientific evidence to support
strong pharmacotherapy recommendations. However, we
did not incorporate the degree of concordance between
evidence quality and strength of recommendation into
each guideline’s quality assessment. It is possible that a
guideline that would not be recommended for use based
on the AGREE instrument because of poor methodology
or reporting could provide pharmacotherapy recom-
mendations based on high quality evidence. The
significant disconnect observed across the guidelines in
terms of evidence quality backing pharmacotherapy
recommendations makes this unlikely. There also is
potential for lack of reliability among appraisers when
using the AGREE instrument. We aimed to mitigate this
by insuring that each appraiser first understood the
AGREE instrument by using the training manual and by
employing the maximum recommended number of
appraisers [8]. The ICCs for each AGREE domain were
similar to or higher than reported in the AGREE vali-
dation study, which reflects a high degree of agreement
among the four appraisers [8]. Because of the large
quantity of items that were scored across the four
appraisals, there was potential for data entry or scoring
errors, which could have led to inaccurate results. After
identifying potential erroneous scores and independently
re-scoring these items, fewer than 3% of items appeared
discordant, which could be explained by normal varia-
tion in scoring across four appraisers. Finally, it is
unlikely that the entire contents of high quality guide-
lines can be adopted into practice without first being
adapted, and tools exist to facilitate this [39, 40].
In conclusion, only two-thirds of critical care phar-
macotherapy-related clinical practice guidelines can be
recommended for use, and most strong pharmacotherapy
recommendations are backed by low quality scientific
evidence. Guideline developers should endorse the
AGREE Collaboration recommendations when con-
structing future critical care guidelines and should employ
the GRADE approach when formulating pharmacother-
apy recommendations. Critical care clinicians should
critically appraise guidelines and scrutinize the scientific
evidence supporting recommendations prior to applying
them to practice.
Acknowledgments We would like to thank Jerrold Perrott, Doctor
of Pharmacy Student at the University of British Columbia, for his
assistance in reviewing this manuscript.
Page 5
Appendix 1
See Table 1.
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Guideline title AGREE recommendation
Guidelines for the management of penetrating brain injury [9] Not recommended
Guidelines for the management of severe traumatic brain injury [10] Strongly recommended
Blunt cerebrovascular injury practice management guidelines [11] Not recommended
Guidelines for the management of aneurysmal subarachnoid hemorrhage [12] Not recommended
Guidelines for the management of spontaneous intracerebral hemorrhage [13] Recommended with
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Guideline on the management of status epilepticus [14] Recommended with
alterations
Clinical practice guidelines for sustained use of sedatives and analgesics in the critically ill adult [15] Recommended with
alterations
Clinical practice guidelines for sustained neuromuscular blockade in the adult critically ill patient [16] Recommended with
alterations
Evidence-based clinical practice guideline for the prevention of ventilator-associated pneumonia [17] Strongly recommended
Guidelines for the management of adults with hospital-acquired, ventilator-associated and health care-
associated pneumonia [18]
Recommended with
alterations
Consensus guidelines on the management of community-acquired pneumonia in adults [19] Strongly recommended
The American-European consensus conference on ARDS, part 2 [20] Not recommended
Hospital management of adults with severe acute respiratory syndrome (SARS) if SARS re-emerges [21] Not recommended
Inhaled nitric oxide therapy in adults: European expert recommendations [22] Not recommended
Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock
[23]
Strongly recommended
Practice parameters for hemodynamic support of sepsis in adult patients [24] Not recommended
Evidence-based colloid use in the critically ill [25] Recommended with
alterations
Guidelines for cardiopulmonary resuscitation and emergency cardiovascular care [26] Strongly recommended
Guidelines for stress ulcer prophylaxis [27] Strongly recommended
Guidelines for the selection of anti-infective agents for complicated intra-abdominal infections [28] Recommended with
alterations
Guidelines on antimicrobial therapy for intra-abdominal infections [29] Recommended with
alterations
Management of critically ill patients with severe acute pancreatitis [30] Not recommended
Guidelines for the prevention of intravascular catheter-related infections [31] Recommended with
alterations
Guidelines for the management of intravascular catheter-related infections [32] Not recommended
Page 6
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    • "In this study, we found that the quality of EB guideline in TCM for RA management was higher than that of CB–EB and CB guideline, as well as the recommendations from the EB were more recommended by the CPGs than those from the CB–EB and CB guidelines. Like CPG development in biomedicine, EB guideline development in TCM should be the right direction21222324, and more and more clinical evidence would give much help in the future CPG development in TCM. EB guideline is the mainstream and trend of guideline development, because guidelines based on a consensus of expert opinion or on unsystematic literature survey have been criticized as not reflecting current medical knowledge and being liable to bias [25,26], and EB guidelines have better quality than CB and CB–EB guidelines [14]. "
    [Show abstract] [Hide abstract] ABSTRACT: Introduction An increasing number of clinical practice guidelines (CPGs) in traditional Chinese medicine (TCM) for rheumatoid arthritis (RA) were issued, and all were developed in China. However it is not clear about their quality. This study is aimed to systematically review the quality and consistency of recommendations on the TCM CPGs for RA management with AGREE II instrument. Methods TCM CPGs identified from five electronic databases and hand searches through related handbooks published between January 1990 and December 2012. The CPG were categorized into Evidence Based (EB) guideline, Consensus Based with no explicit consideration of Evidence Based (CB-EB) guideline and Consensus Based (CB) guideline according to the method reported previously. Four reviewers independently appraised the CPGs based on the Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument, and compared the recommendation on TCM pattern (Zheng) classification and treatment. Results Five TCM CPGs were satisfied the inclusion criteria. The quality score of EB guideline was higher than CB-EB and CB guidelines. Five TCM patterns in the CPGs were recommended in the EB CPG. The herbal preparations including Tripterygium wilfordii recommended in the EB CPG were mostly recommended for RA treatment. The recommendations on non-drug management in the CPGs were fairly consistent, and the recommendations are different based on the different TCM patterns accordingly. Conclusions EB CPG for RA treatment in TCM show higher quality with measurement of AGREE II instrument, and it suggested that TCM CPG could be better developed with clinical evidence.
    Full-text · Article · Apr 2014 · European Journal of Integrative Medicine
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    • "Over the past few years, AGREE has become a benchmark in both the evaluation of existing guidelines567 and the development of new ones [8,9]. Application of AGREE has shown that the quality of clinical and preventive guidelines is generally poor [10,11], and that some aspects of their quality, such as their applicability and the involvement of stakeholders, are particularly unsatisfactory111213. The instrument has been applied to guidelines produced in virtually every field of clinical practice , focusing on therapies, treatments, and procedures, and was also recently applied to genetic guidelines on colorectal cancer [11]. "
    [Show abstract] [Hide abstract] ABSTRACT: Background We examined the methodological quality of guidelines on syndromes conferring genetic susceptibility to breast cancer. Methods PubMed, EMBASE, and Google were searched for guidelines published up to October 2010. All guidelines in English were included. The Appraisal of Guidelines, Research and Evaluation (AGREE) instrument was used to assess the quality of the guidelines, and their reported evidence base was evaluated. Results Thirteen guidelines were deemed eligible: seven had been developed by independent associations, and the other six had national/state endorsements. Four guidelines performed satisfactorily, achieving a score of greater than 50% in all six AGREE domains. Mean ± SD standardized scores for the six AGREE domains were: 90 ± 9% for 'scope and purpose', 51 ± 18% for 'stakeholder involvement', 55 ± 27% for 'rigour of development', 80 ± 11% for 'clarity and presentation', 37 ± 32% for 'applicability', and 47 ± 38% for 'editorial independence'. Ten of the thirteen guidelines were found to be based on research evidence. Conclusions Given the ethical implications and the high costs of genetic testing for hereditary breast cancer, guidelines on this topic should provide clear and evidence-based recommendations. Our analysis shows that there is scope for improving many aspects of the methodological quality of current guidelines. The AGREE instrument is a useful tool, and could be used profitably by guidelines developers to improve the quality of recommendations.
    Full-text · Article · Nov 2012 · BMC Medicine
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    Preview · Article · Oct 2010 · Intensive Care Medicine
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