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Quality of Clinical Practice Guidelines for the Diagnosis and Treatment of Erectile Dysfunction: A Systematic Review
ORIGINAL RESEARCH & REVIEWS
Quality of Clinical Practice Guidelines for the Diagnosis and Treatment of Erectile Dysfunction: A Systematic Review Carolina Sandoval-Salinas, MSc, José P. Saffon, GP, FECSM, and Héctor A. Corredor, MD
ABSTRACT
Introduction: Clinical practice guidelines (CPGs) guide the diagnosis and treatment of erectile dysfunction using different methodologies. Nonetheless, the quality of published CPGs is unknown. Aim: To evaluate the quality of CPGs for diagnosis and treatment of patients with erectile dysfunction. Methods: The Medline, Embase, and LILACS databases were searched using structured strategies. The evidence was complemented by searches on websites of scientific societies and guideline developers. The CPG quality was assessed using the Appraisal of Guidelines for Research & Evaluation (AGREE II) instrument. Main Outcome Measure: The outcome measure included the quality of CPGs in accordance with the AGREE II instrument score. Results: 17 guidelines met the selection criteria. 15 had recommendations for diagnosis, 16, had recommendations for treatment, and 1 included a follow-up. Most of the guidelines were developed in Europe (35.3%) and North America (29.4%), 2 were prepared by specialized groups (11.7%), and 1 was funded by public resources. The most common development method was the panel of experts (9 guides, 52.9%). 5 guidelines were of high quality as per the methodological rigor, as follows: Cancer Care Ontario 2016 (76.5%), European Urology Association 2018 (65.6%), American Urological Association 2018 (62.5%), American College of Physicians (62.5%), and Japanese Society for Sexual Medicine (60.4%). There was a significant relationship (P ¼ .043) between the methodological quality of the guidelines and the funding source. Clinical Implications: By knowing the quality of the clinical practice guidelines, users can make more objective decisions about their use, which has an impact on patient care. Strength & Limitations: High-quality CPGs frequently used in health-care practice were identified. Solely CPGs in Spanish, English, and Portuguese were included, which generates selection bias in the results. Conclusions: The number of CPGs for erectile dysfunction developed using international standards that meet the AGREE II quality criteria is low. Scientific societies have a strong interest in developing guidelines on this topic, whereas the participation of governmental organizations is limited. Sandoval-Salinas C, Saffon JP, Corredor HA. Quality of Clinical Practice Guidelines for the Diagnosis and Treatment of Erectile Dysfunction: A Systematic Review. J Sex Med 2020;XX:XXXeXXX. Copyright 2020, International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.
Key Words: Clinical Practice Guidelines; Evidence-Based Medicine; Erectile Dysfunction; Quality
INTRODUCTION Evidence-based medicine is defined as “the thorough, unequivocal, and judicious use of the best current evidence to make health-care decisions,”1 that is, the search for the best scientific evidence to apply in daily clinical practice. In this process, clinical practice guidelines (CPGs) developed for decision-making on Received September 6, 2019. Accepted December 23, 2019. Elexial Research Center, Clinical Research Group, Bogotá, Colombia Copyright ª 2020, International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved. https://doi.org/10.1016/j.jsxm.2019.12.023
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specific topics are usually controversial, which are useful to guide physicians, health-care professionals, patients, and decision-makers in specific circumstances and are defined as “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.”2 In recent decades, private and government institutions have developed CPGs using different methodologies. Nowadays, institutions such as the National Institute for Health and Care Excellence, the Scottish Intercollegiate Guidelines Network, and Guidelines International Network are international references with 1
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Table 1. Description of the domains in the AGREE II tool Domains Domain 1. scope and purpose Domain 2. stakeholder involvement
Domain 3. rigor of development
Domain 4. clarity of presentation Domain 5. applicability
Domain 6. editorial independence Overall assessment
Description
Items
It is concerned with the overall aim of the guideline, the specific health questions, and the target population. It focuses on the extent to which the guideline was developed by the appropriate stakeholders and represents the views of its intended users. This domain relates to the process used to gather and synthesize the evidence and the methods to formulate the recommendations and to update them. Domain 4 deals with the language, structure, and format of the guideline. It pertains to the likely barriers and facilitators to implementation, strategies to improve uptake, and resource implications of applying the guideline. It is concerned with the formulation of recommendations not being unduly biased with competing interests. This assessment includes the rating of the overall quality of the guideline and whether the guideline would be recommended for use in practice.
1e3 4e6
7e14
15e17 18e21
22e23 Not apply
AGREE II ¼ Appraisal of Guidelines for Research & Evaluation.
validated methods for developing CPGs with reliable results and recommendations.3 A high-quality CPG must be elaborated using systematic and transparent methodologies to obtain the best available evidence to generate unbiased recommendations that will guide health-care practiceeseeking patient well-being and users' confidence.4 The diagnosis and management of erectile dysfunction are of interest for patients and physicians because it affects a significant number of men worldwide, with a prevalence of up to 53% in men older than 40 years, and increases in older age groups.5 Moreover, erectile dysfunction is associated with other comorbidities, including diabetes and cardiovascular disease, whose prevalence is high in the general population, and decreases the quality of life of the affected individuals and their partners. Given the variability of clinical practice, guideline developers and scientific societies in urology, sexology, and other areas have developed CPGs for erectile dysfunction using different methodologies. The objective of this study is to evaluate the quality of these CPGs and determine the association between quality and other characteristics of these guidelines and developers.
MATERIALS AND METHODS Search Strategy A systematic literature review was carried out as per the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement,6 when this was applicable. CPGs for erectile dysfunction were initially identified from systematic searches of the Embase, Medline, and The Latin American and Caribbean Center on Health Sciences Information (LILACS) databases, using a structured strategy with descriptors and Embase subject headings terms, with no date limit (Supplementary Material
1). In addition, targeted searches were conducted on the websites of guideline developers, including Guidelines International Network, National Institute for Health and Care Excellence, Scottish Intercollegiate Guidelines Network, Agency for Healthcare Research and Quality, National Center for Health Technology Excellence, Ministry of Health of Colombia, and Ministry of Health of Chile. Targeted searches were also conducted on the websites of the following scientific societies: American Urological Association, European Association of Urology, Canadian Urological Association, Colombian Society of Urology, Mexican Society of Urology, Argentinian Society of Urology, Brazilian Society of Urology, Canadian Urological Association, Spanish Association of Urology, International Society for Sexual Medicine, World Association for Sexual Health, and European Society of Sexual Medicine. The search was conducted in July 2018 and updated in May 2019. The results of all searches were exported to Excel spreadsheets.
Selection Criteria The identified studies were screened after reading the title and abstract to assess compliance with the following inclusion criteria established previously in the protocol: (i) CPGs for the diagnosis, treatment, prevention, or monitoring of erectile dysfunction; (ii) publications in English, Spanish, or Portuguese; and (iii) documents in press or published. Publications of s without full text were excluded because it was not possible to evaluate the quality of the guideline. Previous versions of the same guideline were also excluded. The documents eligible for inclusion in the review were selected after reading the full text.
Quality Assessment The quality of the selected guides was evaluated by the 3 authors of the study independently and in a paired way J Sex Med 2020;-:1e10
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(C.S.-S.-J.P.S., C.S.-S.-H.A.C., or J.P.S.-H.A.C.), using the Appraisal of Guidelines for Research & Evaluation (AGREE II) Instrument.4,7,8 This instrument was developed and validated by a group of international guideline developers and researchers (AGREE Collaboration), and its purpose is to address the issue of variability in guideline quality, assessing the methodological rigor and transparency in which a guideline is developed.4 AGREE II contains 23 items organized in 6 domains to evaluate quality-related aspects of CPGs7,8: scope and purpose, stakeholder(s) involvement, clarity of presentation, rigor of development, applicability, and editorial independence (Table 1). The tool also included an assessment of the overall quality of each guideline and a question about whether the guideline should be used in clinical practice. All items are scored with a 7-point scale, where 1 is “strongly disagree” and 7 is “strongly agree.” The score was given based on the criteria established for each item in the tool user's manual: a score of 1 was given when there was no information that was relevant to the AGREE II item or if the concept was very poorly reported, and a score of 7 was given when the quality of reporting was exceptional and the full criteria and considerations described in the user's manual were met.
Identification
The AGREE II allows evaluating each domain separately to obtain standardized total scores that indicate the percentage of the highest possible score in each domain using the following formula4,7,8:
Obtained score Minimum possible score 100 Maximum possible score Minimum possible score
Where maximum possible score is 7 (strongly agree) total items total appraisers and minimum possible score is 1 (strongly disagree) total items total appraisers For this study, the quality of each CPG was determined by the methodological rigor as per the suggestions of the methodological guideline for the elaboration of CPGs in Colombia.9 Therefore, it was established that high-quality CPGs presented a score higher than 60% in the methodological development domain of the AGREE II instrument. The medical researchers (J.P.S., H.A.C.) were previously trained in the use of the AGREE II tool by an expert in research methodology and development of clinical practice guidelines (C.S.-S.) who led the methodological part of the study.
Data Extraction and Analysis Data on the publication and guideline developer were transferred to an Excel spreadsheet. The characteristics of the CPGs were analyzed descriptively. Absolute and relative frequencies were estimated for categorical variables. Measures of central tendency and dispersion were estimated for quantitative
Records iden fied through database searching (n = 594)
Addi onal records iden fied through other sources (n = 4)
Included
Eligibility
Screening
Records a er duplicates removed (n =551)
Records screened (n =551)
Full-text ar cles assessed for eligibility (n =59)
Records excluded (n =492)
Full-text ar cles excluded, with reasons (n =42) Not CPGs=11 Language=14 Abstract=8 Earlier version=9
CPGs included (n = 17)
Figure 1. PRISMA flow diagram. PRISMA ¼ Preferred Reporting Items for Systematic Reviews and Meta-Analyses. J Sex Med 2020;-:1e10
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Table 2. Characteristics of the clinical practice guidelines for erectile dysfunction published in English or Spanish Guideline name Guidelines for the assessment of the vasculogenig erectile dysfunction10 Interventions to address sexual problems in people with cancer11
2015 CUA Practice guidelines for erectile dysfunction12 UK management guidelines for erectile dysfunction13
Developer
Continent
Italian society for vascular investigation
Europe
Cancer Care Ontario
North America
Methodology Not reported
Year Funding 2012
Not reported
Expert panel 2016 Own resources literature review
2015
Not reported
2000 Pharmaceutical company 2018 Own resources 2015
Not reported
2010 Own resources
Scope
Diagnosis
National
Treatment men with cancer
National
Diagnosis and treatment Diagnosis, treatment and follow up Diagnosis and treatment Diagnosis and treatment Diagnosis and treatment
National National
National National National
Information sources Not reported
Level of evidence Reported
Not Medline, Embase, reported CINAHL, PsycINFO, and Cochrane Database Not reported Not reported Reported Cochrane Library, Excerpta Medica, Medline, Embase PubMed, Embase, Reported Cochrane Fabumed Reported (Metabuscador) Medline, Cochrane, Reported base de Francia, sociedades
2018 Own resources
Diagnosis and treatment
National
Embase, Medline, Central
Reported
2018 Own resources
Diagnosis and treatment
International
Reported
2010 Pharmaceutical company
Diagnosis and treatment
International
2008 Own resources
Diagnosis and treatment
National
Medline, Embase, Cochrane library databases PubMed, organizational websites PubMed
Reported
2018
Diagnosis and treatment
International
Not reported
Reported
Not reported
Reported
(continued)
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Canadian Urological North Expert panel Association America literature review Europe Expert Erectile Dysfunction consensus— Alliance Steering literature review Group Erectile dysfunction: AUA American Urological North Expert panel guideline14 Association America literature review South Adaptation Guidelines for erectile dysfunction. Colombian Urological Society America Colombian Urological Society15 Guidelines for general practitioners Multidisciplinary Europe Expert for first-line management of working group consensus— erectile dysfunction (updated literature review 2010)16 British society for sexual medicine British society for Europe Expert guidelines on the management of sexual medicine consensus— erectile dysfunction in men e literature review 201717 Guidelines on male sexual European asociation of Europe Expert dysfunction: erectile dysfunction urology consensus— and premature ejaculation18 literature review Erectile dysfunction and coronary Sexual Advice International Expert artery disease prediction: EvidenceAssociation consensus— based guidance and consensus19 literature review JSSM guidelines for erectile Japanese Society for Asia Expert dysfunction20 Sexual Medicine consensus— literature review Survivorship: Sexual Dysfunction National North Expert (Male), Version 1.2013: Clinical Comprehensive Cancer America consensus— Practice Guidelines in Oncology21 Network literature review
Subject
Guideline name
Developer
Continent
Methodology
Hormonal testing and American College of North Expert panel pharmacologic treatment of erectile Physicians America literature review dysfunction: A clinical practice guideline from the American College of Physicians22 Sexual Rehabilitation After International Expert International Treatment for Prostate Cancer: consensus— Consultation for Recommendations From the Fourth literature review Sexual Medicine International Consultation for Sexual Medicine (ICSM 2015)23,24 Spanish consensus on sexual health Spanish scientific Europe Expert in men and women over 5025 onsensus societies related to sexual health Disfunção erétil: tratamento com Sociedade Brasileira de South Not reported drogas inibidoras da fosfodiesterase Urologia America tipo 526 Clinical practice guidelines on Malaysia urological Asia Not reported erectile dysfunction27 association
Year Funding
Subject
Scope
Information sources
Level of evidence
2009 Own resources
Hormonal evaluation and treatment
National
Medline, Embase, Central, PsycINFO, Amed, Scopus
Reported
2017 Own resources
Diagnosis and treatment
International
Google and PubMed
Reported
2014 Own resources
Diagnosis and treatment
National
Not reported
Reported
2006 Not reported Pharmacotherapy
National
PubMed
Reported
2000 Not reported
National
Not reported
Not reported
Diagnosis and treatment
AUA ¼ American Urology Association; CUA ¼ Canadian Urology Association; JSSM ¼ Japanese Society for Sexual Medicine; UK ¼ United Kingdom.
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Table 2. Continued
5
6
Table 3. Standardized score by domain and global quality evaluated with AGREE II Guideline name
D2. Stakeholder involvement %
D3. Rigor of development
D4. Clarity of presentation
D5. D6. Editorial Applicability independence
Overall quality
100.0
66.7
85.4
94.4
60.4
87.5
6.5
86.1
58.3
78.1
97.2
37.5
100
6
97.2 100.0
69.4 58.3
76.0 62.5
86.1 86.1
20.8 20.8
91.7 100.0
6 6
86.1 63.9
47.2 44.4
60.4 50.0
77.8 66.7
25.0 43.8
54.2 58.3
4.5 4.5
88.9
66.7
47.9
83.3
16.7
75.0
5
38.9
47.2
41.7
61.1
12.5
70.8
4
63.9
30.6
34.4
61.1
8.3
70.8
4
83.3
27.8
31.3
61.1
0.0
83.3
3
94.4
33.3
31.3
94.4
0.0
91.7
5
61.1
11.1
27.1
38.9
0.0
50.0
2
58.3
38.9
26.0
75.0
20.8
79.2
4.5
44.4
19.4
11.5
58.3
12.5
45.8
2.5
63.9
33.3
7.3
52.8
12.5
79.2
3
27.8
8.3
6.3
55.6
2.1
0.0
2.5
0.0
11.1
4.2
44.4
12.5
0.0
2
AGREE II ¼ Appraisal of Guidelines for Research & Evaluation; AUA ¼ American Urology Association; CUA ¼ Canadian Urology Association; JSSM ¼ Japanese Society for Sexual Medicine; UK ¼ United Kingdom. Bold values in domain 3 indicate guidelines that exceeded the cutoff point of 60%.
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Interventions to address sexual problems in people with cancer11 Guidelines on male sexual dysfunction: erectile dysfunction and premature ejaculation18 Erectile dysfunction: AUA guideline14 Hormonal testing and pharmacologic treatment of erectile dysfunction: A clinical practice guideline from the American College of Physicians22 JSSM guidelines for erectile dysfunction20 Guidelines for general practitioners for first-line management of erectile dysfunction (updated 2010)16 Survivorship: Sexual Dysfunction (Male), Version 1.2013: Clinical Practice Guidelines in Oncology21 Guidelines for erectile dysfunction. Colombian Urological Society15 UK management guidelines for erectile dysfunction13 Spanish consensus on sexual health in men and women over 5025 Sexual Rehabilitation After Treatment for Prostate Cancer: Recommendations From the Fourth International Consultation for Sexual Medicine (ICSM 2015)23,24 Disfunção erétil: tratamento com drogas inibidoras da fosfodiesterase tipo 526 British society for sexual medicine guidelines on the management of erectile dysfunction in mene201717 2015 CUA Practice guidelines for erectile dysfunction12 Erectile dysfunction and coronary artery disease prediction: Evidence-based guidance and consensus19 Guidelines for the assessment of the vasculogenig erectile dysfunction10 Clinical practice guidelines on erectile dysfunction27
D1. Scope and purpose %
Quality of Clinical Practice Guidelines for the Diagnosis and Treatment of ED
Table 4. Association between the quality of the clinical practice guidelines and their characteristics Standardized score Variable Development Government agencies Scientific societies Other Per capita income of the country High income Upper-middle income Systematic review Yes No Specialized database 1 database 2 databases 3 or more databases Not reported Evidence level Reported Not reported Funding Pharmaceutical company Own resources Not reported Scope International National Publication year Before 2010 After 2010
P-value (Fisher exact test)
<60%
60%
0 9 3
1 4 0
.168
7 3
4 0
.505
6 6
4 1
.338
2 3 2 5
1 0 4 0
.072
10 2
4 1
.870
2
0
.043
4 6
5 0
3 8
1 4
.755
5 7
2 3
.686
16 included recommendations for treatment, and 1 included a follow-up. 2 CPGs (11.8%) focused on managing erectile dysfunction in men with cancer11,21 and 1 in men with coronary heart disease.19 15 guidelines10,12e20,22e27 (88.2%) were developed by scientific societies of physicians or specialists, whereas the remaining 2 guidelines11,21 were prepared by specialized developers. The continents with the highest number of CPGs on erectile dysfunction were Europe and North America (6 and 5, respectively). The funding sources of 9 guidelines (52.9%) were scientific societies or own resources,11,14,16e18,20,22e25 and funding was not revealed in 6 documents (35.2%).10,12,15,21,26,27 With regard to the methodology of development and formulation of recommendations, the most used method was the panel of experts with the evaluation of scientific evidence (9 guidelines, 52.9%), whereas the methodology was not described in 3 reports.10,26,27 In 14 guidelines,10,13e26 the authors reported the level of evidence for the proposed recommendations (Table 2).
Evaluation of the Quality of CPGs
variables, and median and interquartile ranges were reported because data distribution was non-normal. The association between the quality score and year of publication (before and after 2010), type of developer, funding, methodology, scope, and per capita income of the country of origin was analyzed using Fisher's exact test at a level of significance of 0.05.
RESULTS Characteristics of CPGs A total of 551 documents were identified in the systematic search; of these, 48 were CPGs, and 17 met the selection criteria and were included in the review (Figure 1).10e27 The general characteristics of the CPGs are presented in Table 2. The selected documents were published between 2000 and 2018. 15 guidelines presented recommendations for diagnosis, J Sex Med 2020;-:1e10
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In the evaluation of the quality of CPGs using the AGREE II instrument, the overall score varied between 2.0 and 6.5 (median: 4.5). The CPGs prepared by Cancer Care Ontario,11 European Association of Urology,18 American Urological Association,14 and American College of Physicians22 obtained the highest scores. 6 guidelines were recommended for use by the evaluators,11,14,16,18,21,22 6 were recommended with modifications,13,15,17,19,20,23,24 and 5 were not recommended.10,12,25e27 In the overall analysis by domain, editorial independence had the highest standardized score (median: 70.8%; range: 0e100%), followed by clarity of presentation, scope and purpose, stakeholder involvement and rigor of development domains (medians: 66.7%, 63.9%, 38.8%, 34.4%, respectively), whereas applicability obtained the lowest score (median: 12.5%; range: 0e60%). For the domain scope and purpose, which evaluated the general purpose of the guideline, specific health aspects, and the target population (items 1e3), 12 guidelines11,13,14,16,18e23,25,26 had standardized scores higher than 60%, with a range between 61.1% and 100%. The CPGs developed by Cancer Care Ontario,11 American College of Physicians,22 American Urological Association,14 and International Consultation for Sexual Medicine23,24 obtained the highest scores (100%, 100%, 97.2%, and 94.4%, respectively) (Table 3). For the stakeholder involvement domain, which assesses the degree to which the guideline was prepared by those involved or interested in the topic and reflect the points of view of users (items 4e6), American Urological Association,14 Cancer Care Ontario,11 and the National Comprehensive Cancer Network22 guidelines obtained standardized scores higher than 60% (69.4%, 66.7%, and 66.7%, respectively) (Table 3).
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12 guidelines11,13e18,20e25 obtained standardized scores higher than 60% in the clarity of presentation domain (range: 61.1e97.2%), which analyzes the language, structure, and format of the guideline (items 15e17). The CPGs prepared by the European Association of Urology,18 Cancer Care Ontario,11 and the International Consultation for Sexual Medicine23,24 presented the highest scores (97.2%, 94.4%, and 94.4%, respectively) (Table 3).
internally and externally valid, and are feasible for practice.”4 The results of this study indicate that 29.4% of the currently published CPGs for erectile dysfunction in Spanish or English meet standards of methodological quality proposed internationally being the guides developed by government agencies in Canada11 and recent versions of the guides of the most recognized scientific urological societies14,18 those that obtained the highest scores in the evaluation of domain 3 with the AGREE II tool.
In the applicability domain, which evaluates possible barriers and facilitating factors for its implementation, the strategies to improve the use of the CPG and the effects of the application of the guideline on the available resources (items 18e21), only Cancer Care Ontario11 had a score higher than 60% (60.4%) (Table 3).
Our analysis indicates that the guideline developed by the Cancer Care Ontario institute, which is specific for cancer patients, has the highest score in methodological rigor (85.4%). This can be explained by the experience of this institution in the development of practice guidelines based on evidence under the highest established international methodological standards.
In the editorial independence domain, which analyzes whether the formulation of the recommendations is not biased by conflicts of interest (items 22e23), 11 guidelines11,13e15,17e19,21e25 presented scores higher than 60%, with a range between 70.8% and 100%. The guidelines of the European Association of Urology,18 American College of Physicians,22 American Urology Association,14 and International Consultation for Sexual Medicine presented the highest scores23,24 (100%, 100%, 91.7%, and 91.7%, respectively) (Table 3).
Despite the low percentage of high-quality guidelines, the progress of different groups such as the European association of urology, the American Urological Association, and the Japanese Society for Sexual Medicine in improving the methodological rigor is highlighted, adopting more structured processes that have achieved better and more accepted results by health professionals. This process makes recommendations more reliable and produces documents that meet global standards and can, therefore, serve as references and be adapted or adopted by other countries.
In the rigor of development domain, which assesses the quality of the methods used to gather and synthesize the evidence, and the methods used to formulate and update the recommendations (items 7e14), 5 guidelines were considered high quality in accordance with the definition established in the methodology (standardized score higher than 60%), with scores between 60.4% and 85.4%: Cancer Care Ontario,11 European Association of Urology,18 American Urological Association,14 American College of Physicians,22 and Japanese Society for Sexual Medicine20 (Table 3). The median domain score was 34.4% (range: 4.2e85.4%).
It is worth highlighting the limited participation of government agencies in developing CPGs for erectile dysfunction, suggesting that in many health systems, sexual impotence is not a high-priority problem. Furthermore, health resources are limited and consequently are spent on treating diseases whose prevalence, morbidity and mortality, and costs are higher.
There was a statistically significant relationship between the methodological quality of the guidelines and the source of funding (P ¼ .043). Nonetheless, there was no significant association between quality and the other variables (P > .05) (Table 4).
DISCUSSION CPGs are not only a reference for health professionals but also a source of information for patients and government legislators in many countries and are developed to provide valid recommendations for decision-makers,4 without being considered mandatory for all patients, because as Isidori et al28 suggest in their study, in real life, the characteristics and needs of the patients are not always standard, so the recommendations of the guidelines should be adjusted to their conditions. The AGREE II collaboration defines the quality of CPGs as “the confidence that the potential biases of guideline development have been addressed adequately and that the recommendations are both
The low participation of patients in developing CPGs was also evident, which is a critical aspect for their implementation.29 This participation involves 2 aspects: (i) formulation of outcomes that are relevant for the affected individuals and their partners, who can define the applicability of the recommendations; moreover, these outcomes are not acknowledged by developers, including quality of life, self-esteem, and perception of the partner, among others; (ii) points of view and preferences related to the use of technologies, medications, procedures, or therapies,4 or other aspects of interest, including self-care, which should be included in CPGs and which are not considered by clinical staff.30 Another relevant finding of this study is that only 2 guidelines11,16 included aspects related to the applicability of CPGs, considered as “likely barriers and facilitators to implementation, strategies to improve uptake, and resource implications of applying the guideline.”4 This limitation may be associated with the type of developer because scientific societies and private groups do not use public resources from health systems, and their interest is more focused on clinical practice than on guideline implementation. However, the use of these CPGs can be affected not only by the quality but also by the tools provided by developers for implementing the guideline. Therefore, the development and analysis of strategies for adopting CPGs should be
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included by developers of government or private guidelines in their documents to promote their use and apply the recommendations because they are adjusted to the reality and context of clinical practice in each country. Most of the recommendations presented in different guidelines were based on expert opinions. With the exception of clinical trials for pharmacological treatments, the evidence supporting other recommendations comes from studies with a low level of evidence or expert opinion, which demonstrates the lack of higher quality research in other topics related to erectile dysfunction. Moreover, the recommendations made in different guidelines were similar, suggesting that regardless of the place of origin, experts agree on the practice and concept of disease management, with the exception of the use of shockwave therapy, which is not recommended by the American Society of Urology, but it is recommended14 by the European Society of Urology.18 Developers should propose and execute processes to update documents because there is scientific evidence that can support the use of new technologies or that increases the level and strength of the recommendations proposed previously. The results indicated that guidelines published before 2009 were not updated. In a few cases, societies such as the European Urology Society made efforts to update their documents periodically and implement more robust and standardized methods in their updating process, including patient participation.18 This study has several limitations. First, there is a possibility of selection bias because only documents in English, Spanish, or Portuguese were included in the review. Second, the quality of the recommendations was not evaluated because the study focused on the overall evaluation of the documents and assessment of the methodological rigor. Notwithstanding, one of the strengths of the study was the use of the AGREE II instrument to assess the quality of CPGs because, although there are other tools for this purpose, AGREE II is a generic instrument validated in an international collaboration between 13 countries and can be applied to guidelines with different scopes or areas, is easily accessible and applicable, and is widely used by CPG developers worldwide.7,8
CONCLUSIONS
9
Conflict of Interest: The authors declare no conflict of interest that may affect the results and conclusions of this study. Funding: The authors are researchers of Elexial Research Center.
STATEMENT OF AUTHORSHIP Category 1 (a) Conception and Design Carolina Sandoval-Salinas (b) Acquisition of Data Carolina Sandoval-Salinas; José P. Saffon; Héctor A. Corredor (c) Analysis and Interpretation of Data Carolina Sandoval-Salinas Category 2 (a) Drafting the Article Carolina Sandoval-Salinas; José P. Saffon; Héctor A. Corredor (b) Revising It for Intellectual Content Carolina Sandoval-Salinas; José P. Saffon; Héctor A. Corredor Category 3 (a) Final Approval of the Completed Article Carolina Sandoval-Salinas; José P. Saffon; Héctor A. Corredor
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The number of CPGs on erectile dysfunction developed with high methodological standards is low, which compromises the reliability of the recommendations. Most available CPGs were developed by scientific societies and private groups. Physicians, health-care staff, and other users should acknowledge the quality standards of these guidelines, allowing these groups to choose those with the most reliable recommendations.
8. Brouwers MC, Kho ME, Browman GP, et al. Development of the AGREE II, part 2: Assessment of validity of items and tools to support application. CMAJ 2010;182:E472-E478.
Corresponding Author: Carolina Sandoval-Salinas, MSc, Carrera 10 No. 97 A - 13 Torre A Oficina 308, Bogotá, Colombia. Tel: þ57 320 8899777; E-mail: carolina_ss81@ yahoo.es
9. Ministerio de Salud y Protección Social. Guía metodológica para la elaboración de guías de práctica clínica con evaluación económica en el Sistema General de Seguridad Social en Salud Colombiano. Bogotá, Colombia: Ministerio de Salud y Protección Social; 2014.
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7. Brouwers MC, Kho ME, Burgers JS, et al. Development of the AGREE II, part 1: Performance, usefulness and areas for improvement. Can Med Assoc J 2010;182:1045-1052.
10 10. Antignani P, Benedetti-Valentini FL, Aluigi TA, et al. Guidelines for the assessment of the vasculogenig erectile dysfunction. Int Angiol 2012;(Supplement):36-39. 11. Barbera L, Zwaal C, Elterman D, et al. Interventions to address sexual problems in people with cancer. Curr Oncol 2017; 24:192-200. 12. Bella AJ, Lee JC, Carrier S. 2015 CUA Practice guidelines for erectile dysfunction. Can Urol Assoc J 2015;9:23-29. 13. Ralph D, McNicholas T. Erectile Dysfunction. UK management guidelines for erectile dysfunction. BMJ 2000;321:499-503. 14. Burnett AL, Nehra A, Breau RH, et al. Erectile dysfunction: AUA guideline. Am Urol Assoc Educ Res 2018:1-90. 15. Ceballos P, Álvarez JD, Miguel J, et al. Guías de disfunción eréctil. Sociedad Colombiana de Urología. Rev Colomb Urol 2015;24:185.e1-185.e22. 16. Cuzin B, Cour F, Bousquet P, et al. Guidelines for general practitioners for first-line management of erectile dysfunction (updated 2010). Sexologies 2011;20:23-35. 17. Hackett G, Kirby M, Wylie K, et al. British Society for Sexual Medicine guidelines on the management of erectile dysfunction in men - 2017. J Sex Med 2018:1-28. 18. Hatzimouratidis K, Giuliano F, Moncada I, et al. EAU guidelines on erectile dysfunction, premature ejaculation, penile curvature and priapism. Arnhem, The Netherlands: EAU Guidelines Office; 2018. p. 7-26. 19. Jackson G, Boon N, Eardley I, et al. Erectile dysfunction and coronary artery disease prediction: Evidence-based guidance and consensus. Int J Clin Pr 2010;64:848-857. 20. Kimoto Y, Nagao K, Sasaki H, et al. JSSM Guidelines for erectile dysfunction. Int J Urol 2008;15:564-576.
Sandoval-Salinas et al dysfunction : A clinical practice guideline from the American College of Physicians. Ann Intern Med 2009;151:639-650. 23. Salonia A, Adaikan G, Buvat J, et al. Sexual rehabilitation after treatment for prostate cancer — Part 1 : Recommendations from the Fourth International Consultation for Sexual Medicine (ICSM 2015). J Sex Med 2017;14:285-296. 24. Salonia A, Adaikan G, Buvat J, et al. Sexual rehabilitation after treatment for prostate cancer — Part 2 : Recommendations from the Fourth International Consultation for Sexual Medicine (ICSM 2015). J Sex Med 2017;14:297-315. 25. Sanchez-Borrego R, Molero F, Castaño R, et al. Spanish consensus on sexual health in men and women over 50. Maturitas 2014;78:138-145. 26. Sociedade Brasileira de Urologia. Disfunção Erétil : Tratamento Com Drogas Inibidoras Da Fosfodiesterase Tipo 5. Brazil: Associação Médica Brasileira e Conselho Federal de Medicina; 2006. p. 1-29. 27. Malaysia Urological Association and MEDACT. Clinical practice guidelines on erectile dysfunction. p. 1-60. www.acadmed.org. my/view_file.cfm?fileid¼211. Accessed August 10, 2018. 28. Isidori AM, Giammusso B, Corona G, et al. Diagnostic and therapeutic workup of erectile dysfunction: Results from a Delphi consensus of andrology experts. Sex Med 2019; 7:292-302. 29. Armstrong MJ, Mullins CD, Gronseth GS, et al. Impact of patient involvement on clinical practice guideline development: a parallel group study. Implement Sci 2018;13:1-13. 30. Leach MJ, Segal L. Patient attributes warranting consideration in clinical practice guidelines, health workforce planning and policy. BMC Health Serv Res 2011;11:221.
21. Denlinger CS, Carlson RW, Are M, et al. Survivorship: Sexual dysfunction (Male), version 1.2013: Clinical practice guidelines in oncology. J Natl Compr Cancer Netw 2015;12:356-363.
SUPPLEMENTARY DATA
22. Qaseem A, Snow V, Denberg TD, et al. Clinical guidelines hormonal testing and pharmacologic treatment of erectile
Supplementary data related to this article can be found at https://doi.org/10.1016/j.jsxm.2019.12.023.
J Sex Med 2020;-:1e10
Quality of Clinical Practice Guidelines for the Diagnosis and Treatment of Erectile Dysfunction: A Systematic Review Carolina Sandoval-Salinas, MSc, José P. Saffon, GP, FECSM, and Héctor A. Corredor, MD
ABSTRACT
Introduction: Clinical practice guidelines (CPGs) guide the diagnosis and treatment of erectile dysfunction using different methodologies. Nonetheless, the quality of published CPGs is unknown. Aim: To evaluate the quality of CPGs for diagnosis and treatment of patients with erectile dysfunction. Methods: The Medline, Embase, and LILACS databases were searched using structured strategies. The evidence was complemented by searches on websites of scientific societies and guideline developers. The CPG quality was assessed using the Appraisal of Guidelines for Research & Evaluation (AGREE II) instrument. Main Outcome Measure: The outcome measure included the quality of CPGs in accordance with the AGREE II instrument score. Results: 17 guidelines met the selection criteria. 15 had recommendations for diagnosis, 16, had recommendations for treatment, and 1 included a follow-up. Most of the guidelines were developed in Europe (35.3%) and North America (29.4%), 2 were prepared by specialized groups (11.7%), and 1 was funded by public resources. The most common development method was the panel of experts (9 guides, 52.9%). 5 guidelines were of high quality as per the methodological rigor, as follows: Cancer Care Ontario 2016 (76.5%), European Urology Association 2018 (65.6%), American Urological Association 2018 (62.5%), American College of Physicians (62.5%), and Japanese Society for Sexual Medicine (60.4%). There was a significant relationship (P ¼ .043) between the methodological quality of the guidelines and the funding source. Clinical Implications: By knowing the quality of the clinical practice guidelines, users can make more objective decisions about their use, which has an impact on patient care. Strength & Limitations: High-quality CPGs frequently used in health-care practice were identified. Solely CPGs in Spanish, English, and Portuguese were included, which generates selection bias in the results. Conclusions: The number of CPGs for erectile dysfunction developed using international standards that meet the AGREE II quality criteria is low. Scientific societies have a strong interest in developing guidelines on this topic, whereas the participation of governmental organizations is limited. Sandoval-Salinas C, Saffon JP, Corredor HA. Quality of Clinical Practice Guidelines for the Diagnosis and Treatment of Erectile Dysfunction: A Systematic Review. J Sex Med 2020;XX:XXXeXXX. Copyright 2020, International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.
Key Words: Clinical Practice Guidelines; Evidence-Based Medicine; Erectile Dysfunction; Quality
INTRODUCTION Evidence-based medicine is defined as “the thorough, unequivocal, and judicious use of the best current evidence to make health-care decisions,”1 that is, the search for the best scientific evidence to apply in daily clinical practice. In this process, clinical practice guidelines (CPGs) developed for decision-making on Received September 6, 2019. Accepted December 23, 2019. Elexial Research Center, Clinical Research Group, Bogotá, Colombia Copyright ª 2020, International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved. https://doi.org/10.1016/j.jsxm.2019.12.023
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specific topics are usually controversial, which are useful to guide physicians, health-care professionals, patients, and decision-makers in specific circumstances and are defined as “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.”2 In recent decades, private and government institutions have developed CPGs using different methodologies. Nowadays, institutions such as the National Institute for Health and Care Excellence, the Scottish Intercollegiate Guidelines Network, and Guidelines International Network are international references with 1
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Table 1. Description of the domains in the AGREE II tool Domains Domain 1. scope and purpose Domain 2. stakeholder involvement
Domain 3. rigor of development
Domain 4. clarity of presentation Domain 5. applicability
Domain 6. editorial independence Overall assessment
Description
Items
It is concerned with the overall aim of the guideline, the specific health questions, and the target population. It focuses on the extent to which the guideline was developed by the appropriate stakeholders and represents the views of its intended users. This domain relates to the process used to gather and synthesize the evidence and the methods to formulate the recommendations and to update them. Domain 4 deals with the language, structure, and format of the guideline. It pertains to the likely barriers and facilitators to implementation, strategies to improve uptake, and resource implications of applying the guideline. It is concerned with the formulation of recommendations not being unduly biased with competing interests. This assessment includes the rating of the overall quality of the guideline and whether the guideline would be recommended for use in practice.
1e3 4e6
7e14
15e17 18e21
22e23 Not apply
AGREE II ¼ Appraisal of Guidelines for Research & Evaluation.
validated methods for developing CPGs with reliable results and recommendations.3 A high-quality CPG must be elaborated using systematic and transparent methodologies to obtain the best available evidence to generate unbiased recommendations that will guide health-care practiceeseeking patient well-being and users' confidence.4 The diagnosis and management of erectile dysfunction are of interest for patients and physicians because it affects a significant number of men worldwide, with a prevalence of up to 53% in men older than 40 years, and increases in older age groups.5 Moreover, erectile dysfunction is associated with other comorbidities, including diabetes and cardiovascular disease, whose prevalence is high in the general population, and decreases the quality of life of the affected individuals and their partners. Given the variability of clinical practice, guideline developers and scientific societies in urology, sexology, and other areas have developed CPGs for erectile dysfunction using different methodologies. The objective of this study is to evaluate the quality of these CPGs and determine the association between quality and other characteristics of these guidelines and developers.
MATERIALS AND METHODS Search Strategy A systematic literature review was carried out as per the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement,6 when this was applicable. CPGs for erectile dysfunction were initially identified from systematic searches of the Embase, Medline, and The Latin American and Caribbean Center on Health Sciences Information (LILACS) databases, using a structured strategy with descriptors and Embase subject headings terms, with no date limit (Supplementary Material
1). In addition, targeted searches were conducted on the websites of guideline developers, including Guidelines International Network, National Institute for Health and Care Excellence, Scottish Intercollegiate Guidelines Network, Agency for Healthcare Research and Quality, National Center for Health Technology Excellence, Ministry of Health of Colombia, and Ministry of Health of Chile. Targeted searches were also conducted on the websites of the following scientific societies: American Urological Association, European Association of Urology, Canadian Urological Association, Colombian Society of Urology, Mexican Society of Urology, Argentinian Society of Urology, Brazilian Society of Urology, Canadian Urological Association, Spanish Association of Urology, International Society for Sexual Medicine, World Association for Sexual Health, and European Society of Sexual Medicine. The search was conducted in July 2018 and updated in May 2019. The results of all searches were exported to Excel spreadsheets.
Selection Criteria The identified studies were screened after reading the title and abstract to assess compliance with the following inclusion criteria established previously in the protocol: (i) CPGs for the diagnosis, treatment, prevention, or monitoring of erectile dysfunction; (ii) publications in English, Spanish, or Portuguese; and (iii) documents in press or published. Publications of s without full text were excluded because it was not possible to evaluate the quality of the guideline. Previous versions of the same guideline were also excluded. The documents eligible for inclusion in the review were selected after reading the full text.
Quality Assessment The quality of the selected guides was evaluated by the 3 authors of the study independently and in a paired way J Sex Med 2020;-:1e10
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Quality of Clinical Practice Guidelines for the Diagnosis and Treatment of ED
(C.S.-S.-J.P.S., C.S.-S.-H.A.C., or J.P.S.-H.A.C.), using the Appraisal of Guidelines for Research & Evaluation (AGREE II) Instrument.4,7,8 This instrument was developed and validated by a group of international guideline developers and researchers (AGREE Collaboration), and its purpose is to address the issue of variability in guideline quality, assessing the methodological rigor and transparency in which a guideline is developed.4 AGREE II contains 23 items organized in 6 domains to evaluate quality-related aspects of CPGs7,8: scope and purpose, stakeholder(s) involvement, clarity of presentation, rigor of development, applicability, and editorial independence (Table 1). The tool also included an assessment of the overall quality of each guideline and a question about whether the guideline should be used in clinical practice. All items are scored with a 7-point scale, where 1 is “strongly disagree” and 7 is “strongly agree.” The score was given based on the criteria established for each item in the tool user's manual: a score of 1 was given when there was no information that was relevant to the AGREE II item or if the concept was very poorly reported, and a score of 7 was given when the quality of reporting was exceptional and the full criteria and considerations described in the user's manual were met.
Identification
The AGREE II allows evaluating each domain separately to obtain standardized total scores that indicate the percentage of the highest possible score in each domain using the following formula4,7,8:
Obtained score Minimum possible score 100 Maximum possible score Minimum possible score
Where maximum possible score is 7 (strongly agree) total items total appraisers and minimum possible score is 1 (strongly disagree) total items total appraisers For this study, the quality of each CPG was determined by the methodological rigor as per the suggestions of the methodological guideline for the elaboration of CPGs in Colombia.9 Therefore, it was established that high-quality CPGs presented a score higher than 60% in the methodological development domain of the AGREE II instrument. The medical researchers (J.P.S., H.A.C.) were previously trained in the use of the AGREE II tool by an expert in research methodology and development of clinical practice guidelines (C.S.-S.) who led the methodological part of the study.
Data Extraction and Analysis Data on the publication and guideline developer were transferred to an Excel spreadsheet. The characteristics of the CPGs were analyzed descriptively. Absolute and relative frequencies were estimated for categorical variables. Measures of central tendency and dispersion were estimated for quantitative
Records iden fied through database searching (n = 594)
Addi onal records iden fied through other sources (n = 4)
Included
Eligibility
Screening
Records a er duplicates removed (n =551)
Records screened (n =551)
Full-text ar cles assessed for eligibility (n =59)
Records excluded (n =492)
Full-text ar cles excluded, with reasons (n =42) Not CPGs=11 Language=14 Abstract=8 Earlier version=9
CPGs included (n = 17)
Figure 1. PRISMA flow diagram. PRISMA ¼ Preferred Reporting Items for Systematic Reviews and Meta-Analyses. J Sex Med 2020;-:1e10
4
Table 2. Characteristics of the clinical practice guidelines for erectile dysfunction published in English or Spanish Guideline name Guidelines for the assessment of the vasculogenig erectile dysfunction10 Interventions to address sexual problems in people with cancer11
2015 CUA Practice guidelines for erectile dysfunction12 UK management guidelines for erectile dysfunction13
Developer
Continent
Italian society for vascular investigation
Europe
Cancer Care Ontario
North America
Methodology Not reported
Year Funding 2012
Not reported
Expert panel 2016 Own resources literature review
2015
Not reported
2000 Pharmaceutical company 2018 Own resources 2015
Not reported
2010 Own resources
Scope
Diagnosis
National
Treatment men with cancer
National
Diagnosis and treatment Diagnosis, treatment and follow up Diagnosis and treatment Diagnosis and treatment Diagnosis and treatment
National National
National National National
Information sources Not reported
Level of evidence Reported
Not Medline, Embase, reported CINAHL, PsycINFO, and Cochrane Database Not reported Not reported Reported Cochrane Library, Excerpta Medica, Medline, Embase PubMed, Embase, Reported Cochrane Fabumed Reported (Metabuscador) Medline, Cochrane, Reported base de Francia, sociedades
2018 Own resources
Diagnosis and treatment
National
Embase, Medline, Central
Reported
2018 Own resources
Diagnosis and treatment
International
Reported
2010 Pharmaceutical company
Diagnosis and treatment
International
2008 Own resources
Diagnosis and treatment
National
Medline, Embase, Cochrane library databases PubMed, organizational websites PubMed
Reported
2018
Diagnosis and treatment
International
Not reported
Reported
Not reported
Reported
(continued)
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Canadian Urological North Expert panel Association America literature review Europe Expert Erectile Dysfunction consensus— Alliance Steering literature review Group Erectile dysfunction: AUA American Urological North Expert panel guideline14 Association America literature review South Adaptation Guidelines for erectile dysfunction. Colombian Urological Society America Colombian Urological Society15 Guidelines for general practitioners Multidisciplinary Europe Expert for first-line management of working group consensus— erectile dysfunction (updated literature review 2010)16 British society for sexual medicine British society for Europe Expert guidelines on the management of sexual medicine consensus— erectile dysfunction in men e literature review 201717 Guidelines on male sexual European asociation of Europe Expert dysfunction: erectile dysfunction urology consensus— and premature ejaculation18 literature review Erectile dysfunction and coronary Sexual Advice International Expert artery disease prediction: EvidenceAssociation consensus— based guidance and consensus19 literature review JSSM guidelines for erectile Japanese Society for Asia Expert dysfunction20 Sexual Medicine consensus— literature review Survivorship: Sexual Dysfunction National North Expert (Male), Version 1.2013: Clinical Comprehensive Cancer America consensus— Practice Guidelines in Oncology21 Network literature review
Subject
Guideline name
Developer
Continent
Methodology
Hormonal testing and American College of North Expert panel pharmacologic treatment of erectile Physicians America literature review dysfunction: A clinical practice guideline from the American College of Physicians22 Sexual Rehabilitation After International Expert International Treatment for Prostate Cancer: consensus— Consultation for Recommendations From the Fourth literature review Sexual Medicine International Consultation for Sexual Medicine (ICSM 2015)23,24 Spanish consensus on sexual health Spanish scientific Europe Expert in men and women over 5025 onsensus societies related to sexual health Disfunção erétil: tratamento com Sociedade Brasileira de South Not reported drogas inibidoras da fosfodiesterase Urologia America tipo 526 Clinical practice guidelines on Malaysia urological Asia Not reported erectile dysfunction27 association
Year Funding
Subject
Scope
Information sources
Level of evidence
2009 Own resources
Hormonal evaluation and treatment
National
Medline, Embase, Central, PsycINFO, Amed, Scopus
Reported
2017 Own resources
Diagnosis and treatment
International
Google and PubMed
Reported
2014 Own resources
Diagnosis and treatment
National
Not reported
Reported
2006 Not reported Pharmacotherapy
National
PubMed
Reported
2000 Not reported
National
Not reported
Not reported
Diagnosis and treatment
AUA ¼ American Urology Association; CUA ¼ Canadian Urology Association; JSSM ¼ Japanese Society for Sexual Medicine; UK ¼ United Kingdom.
Quality of Clinical Practice Guidelines for the Diagnosis and Treatment of ED
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Table 2. Continued
5
6
Table 3. Standardized score by domain and global quality evaluated with AGREE II Guideline name
D2. Stakeholder involvement %
D3. Rigor of development
D4. Clarity of presentation
D5. D6. Editorial Applicability independence
Overall quality
100.0
66.7
85.4
94.4
60.4
87.5
6.5
86.1
58.3
78.1
97.2
37.5
100
6
97.2 100.0
69.4 58.3
76.0 62.5
86.1 86.1
20.8 20.8
91.7 100.0
6 6
86.1 63.9
47.2 44.4
60.4 50.0
77.8 66.7
25.0 43.8
54.2 58.3
4.5 4.5
88.9
66.7
47.9
83.3
16.7
75.0
5
38.9
47.2
41.7
61.1
12.5
70.8
4
63.9
30.6
34.4
61.1
8.3
70.8
4
83.3
27.8
31.3
61.1
0.0
83.3
3
94.4
33.3
31.3
94.4
0.0
91.7
5
61.1
11.1
27.1
38.9
0.0
50.0
2
58.3
38.9
26.0
75.0
20.8
79.2
4.5
44.4
19.4
11.5
58.3
12.5
45.8
2.5
63.9
33.3
7.3
52.8
12.5
79.2
3
27.8
8.3
6.3
55.6
2.1
0.0
2.5
0.0
11.1
4.2
44.4
12.5
0.0
2
AGREE II ¼ Appraisal of Guidelines for Research & Evaluation; AUA ¼ American Urology Association; CUA ¼ Canadian Urology Association; JSSM ¼ Japanese Society for Sexual Medicine; UK ¼ United Kingdom. Bold values in domain 3 indicate guidelines that exceeded the cutoff point of 60%.
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Interventions to address sexual problems in people with cancer11 Guidelines on male sexual dysfunction: erectile dysfunction and premature ejaculation18 Erectile dysfunction: AUA guideline14 Hormonal testing and pharmacologic treatment of erectile dysfunction: A clinical practice guideline from the American College of Physicians22 JSSM guidelines for erectile dysfunction20 Guidelines for general practitioners for first-line management of erectile dysfunction (updated 2010)16 Survivorship: Sexual Dysfunction (Male), Version 1.2013: Clinical Practice Guidelines in Oncology21 Guidelines for erectile dysfunction. Colombian Urological Society15 UK management guidelines for erectile dysfunction13 Spanish consensus on sexual health in men and women over 5025 Sexual Rehabilitation After Treatment for Prostate Cancer: Recommendations From the Fourth International Consultation for Sexual Medicine (ICSM 2015)23,24 Disfunção erétil: tratamento com drogas inibidoras da fosfodiesterase tipo 526 British society for sexual medicine guidelines on the management of erectile dysfunction in mene201717 2015 CUA Practice guidelines for erectile dysfunction12 Erectile dysfunction and coronary artery disease prediction: Evidence-based guidance and consensus19 Guidelines for the assessment of the vasculogenig erectile dysfunction10 Clinical practice guidelines on erectile dysfunction27
D1. Scope and purpose %
Quality of Clinical Practice Guidelines for the Diagnosis and Treatment of ED
Table 4. Association between the quality of the clinical practice guidelines and their characteristics Standardized score Variable Development Government agencies Scientific societies Other Per capita income of the country High income Upper-middle income Systematic review Yes No Specialized database 1 database 2 databases 3 or more databases Not reported Evidence level Reported Not reported Funding Pharmaceutical company Own resources Not reported Scope International National Publication year Before 2010 After 2010
P-value (Fisher exact test)
<60%
60%
0 9 3
1 4 0
.168
7 3
4 0
.505
6 6
4 1
.338
2 3 2 5
1 0 4 0
.072
10 2
4 1
.870
2
0
.043
4 6
5 0
3 8
1 4
.755
5 7
2 3
.686
16 included recommendations for treatment, and 1 included a follow-up. 2 CPGs (11.8%) focused on managing erectile dysfunction in men with cancer11,21 and 1 in men with coronary heart disease.19 15 guidelines10,12e20,22e27 (88.2%) were developed by scientific societies of physicians or specialists, whereas the remaining 2 guidelines11,21 were prepared by specialized developers. The continents with the highest number of CPGs on erectile dysfunction were Europe and North America (6 and 5, respectively). The funding sources of 9 guidelines (52.9%) were scientific societies or own resources,11,14,16e18,20,22e25 and funding was not revealed in 6 documents (35.2%).10,12,15,21,26,27 With regard to the methodology of development and formulation of recommendations, the most used method was the panel of experts with the evaluation of scientific evidence (9 guidelines, 52.9%), whereas the methodology was not described in 3 reports.10,26,27 In 14 guidelines,10,13e26 the authors reported the level of evidence for the proposed recommendations (Table 2).
Evaluation of the Quality of CPGs
variables, and median and interquartile ranges were reported because data distribution was non-normal. The association between the quality score and year of publication (before and after 2010), type of developer, funding, methodology, scope, and per capita income of the country of origin was analyzed using Fisher's exact test at a level of significance of 0.05.
RESULTS Characteristics of CPGs A total of 551 documents were identified in the systematic search; of these, 48 were CPGs, and 17 met the selection criteria and were included in the review (Figure 1).10e27 The general characteristics of the CPGs are presented in Table 2. The selected documents were published between 2000 and 2018. 15 guidelines presented recommendations for diagnosis, J Sex Med 2020;-:1e10
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In the evaluation of the quality of CPGs using the AGREE II instrument, the overall score varied between 2.0 and 6.5 (median: 4.5). The CPGs prepared by Cancer Care Ontario,11 European Association of Urology,18 American Urological Association,14 and American College of Physicians22 obtained the highest scores. 6 guidelines were recommended for use by the evaluators,11,14,16,18,21,22 6 were recommended with modifications,13,15,17,19,20,23,24 and 5 were not recommended.10,12,25e27 In the overall analysis by domain, editorial independence had the highest standardized score (median: 70.8%; range: 0e100%), followed by clarity of presentation, scope and purpose, stakeholder involvement and rigor of development domains (medians: 66.7%, 63.9%, 38.8%, 34.4%, respectively), whereas applicability obtained the lowest score (median: 12.5%; range: 0e60%). For the domain scope and purpose, which evaluated the general purpose of the guideline, specific health aspects, and the target population (items 1e3), 12 guidelines11,13,14,16,18e23,25,26 had standardized scores higher than 60%, with a range between 61.1% and 100%. The CPGs developed by Cancer Care Ontario,11 American College of Physicians,22 American Urological Association,14 and International Consultation for Sexual Medicine23,24 obtained the highest scores (100%, 100%, 97.2%, and 94.4%, respectively) (Table 3). For the stakeholder involvement domain, which assesses the degree to which the guideline was prepared by those involved or interested in the topic and reflect the points of view of users (items 4e6), American Urological Association,14 Cancer Care Ontario,11 and the National Comprehensive Cancer Network22 guidelines obtained standardized scores higher than 60% (69.4%, 66.7%, and 66.7%, respectively) (Table 3).
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12 guidelines11,13e18,20e25 obtained standardized scores higher than 60% in the clarity of presentation domain (range: 61.1e97.2%), which analyzes the language, structure, and format of the guideline (items 15e17). The CPGs prepared by the European Association of Urology,18 Cancer Care Ontario,11 and the International Consultation for Sexual Medicine23,24 presented the highest scores (97.2%, 94.4%, and 94.4%, respectively) (Table 3).
internally and externally valid, and are feasible for practice.”4 The results of this study indicate that 29.4% of the currently published CPGs for erectile dysfunction in Spanish or English meet standards of methodological quality proposed internationally being the guides developed by government agencies in Canada11 and recent versions of the guides of the most recognized scientific urological societies14,18 those that obtained the highest scores in the evaluation of domain 3 with the AGREE II tool.
In the applicability domain, which evaluates possible barriers and facilitating factors for its implementation, the strategies to improve the use of the CPG and the effects of the application of the guideline on the available resources (items 18e21), only Cancer Care Ontario11 had a score higher than 60% (60.4%) (Table 3).
Our analysis indicates that the guideline developed by the Cancer Care Ontario institute, which is specific for cancer patients, has the highest score in methodological rigor (85.4%). This can be explained by the experience of this institution in the development of practice guidelines based on evidence under the highest established international methodological standards.
In the editorial independence domain, which analyzes whether the formulation of the recommendations is not biased by conflicts of interest (items 22e23), 11 guidelines11,13e15,17e19,21e25 presented scores higher than 60%, with a range between 70.8% and 100%. The guidelines of the European Association of Urology,18 American College of Physicians,22 American Urology Association,14 and International Consultation for Sexual Medicine presented the highest scores23,24 (100%, 100%, 91.7%, and 91.7%, respectively) (Table 3).
Despite the low percentage of high-quality guidelines, the progress of different groups such as the European association of urology, the American Urological Association, and the Japanese Society for Sexual Medicine in improving the methodological rigor is highlighted, adopting more structured processes that have achieved better and more accepted results by health professionals. This process makes recommendations more reliable and produces documents that meet global standards and can, therefore, serve as references and be adapted or adopted by other countries.
In the rigor of development domain, which assesses the quality of the methods used to gather and synthesize the evidence, and the methods used to formulate and update the recommendations (items 7e14), 5 guidelines were considered high quality in accordance with the definition established in the methodology (standardized score higher than 60%), with scores between 60.4% and 85.4%: Cancer Care Ontario,11 European Association of Urology,18 American Urological Association,14 American College of Physicians,22 and Japanese Society for Sexual Medicine20 (Table 3). The median domain score was 34.4% (range: 4.2e85.4%).
It is worth highlighting the limited participation of government agencies in developing CPGs for erectile dysfunction, suggesting that in many health systems, sexual impotence is not a high-priority problem. Furthermore, health resources are limited and consequently are spent on treating diseases whose prevalence, morbidity and mortality, and costs are higher.
There was a statistically significant relationship between the methodological quality of the guidelines and the source of funding (P ¼ .043). Nonetheless, there was no significant association between quality and the other variables (P > .05) (Table 4).
DISCUSSION CPGs are not only a reference for health professionals but also a source of information for patients and government legislators in many countries and are developed to provide valid recommendations for decision-makers,4 without being considered mandatory for all patients, because as Isidori et al28 suggest in their study, in real life, the characteristics and needs of the patients are not always standard, so the recommendations of the guidelines should be adjusted to their conditions. The AGREE II collaboration defines the quality of CPGs as “the confidence that the potential biases of guideline development have been addressed adequately and that the recommendations are both
The low participation of patients in developing CPGs was also evident, which is a critical aspect for their implementation.29 This participation involves 2 aspects: (i) formulation of outcomes that are relevant for the affected individuals and their partners, who can define the applicability of the recommendations; moreover, these outcomes are not acknowledged by developers, including quality of life, self-esteem, and perception of the partner, among others; (ii) points of view and preferences related to the use of technologies, medications, procedures, or therapies,4 or other aspects of interest, including self-care, which should be included in CPGs and which are not considered by clinical staff.30 Another relevant finding of this study is that only 2 guidelines11,16 included aspects related to the applicability of CPGs, considered as “likely barriers and facilitators to implementation, strategies to improve uptake, and resource implications of applying the guideline.”4 This limitation may be associated with the type of developer because scientific societies and private groups do not use public resources from health systems, and their interest is more focused on clinical practice than on guideline implementation. However, the use of these CPGs can be affected not only by the quality but also by the tools provided by developers for implementing the guideline. Therefore, the development and analysis of strategies for adopting CPGs should be
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Quality of Clinical Practice Guidelines for the Diagnosis and Treatment of ED
included by developers of government or private guidelines in their documents to promote their use and apply the recommendations because they are adjusted to the reality and context of clinical practice in each country. Most of the recommendations presented in different guidelines were based on expert opinions. With the exception of clinical trials for pharmacological treatments, the evidence supporting other recommendations comes from studies with a low level of evidence or expert opinion, which demonstrates the lack of higher quality research in other topics related to erectile dysfunction. Moreover, the recommendations made in different guidelines were similar, suggesting that regardless of the place of origin, experts agree on the practice and concept of disease management, with the exception of the use of shockwave therapy, which is not recommended by the American Society of Urology, but it is recommended14 by the European Society of Urology.18 Developers should propose and execute processes to update documents because there is scientific evidence that can support the use of new technologies or that increases the level and strength of the recommendations proposed previously. The results indicated that guidelines published before 2009 were not updated. In a few cases, societies such as the European Urology Society made efforts to update their documents periodically and implement more robust and standardized methods in their updating process, including patient participation.18 This study has several limitations. First, there is a possibility of selection bias because only documents in English, Spanish, or Portuguese were included in the review. Second, the quality of the recommendations was not evaluated because the study focused on the overall evaluation of the documents and assessment of the methodological rigor. Notwithstanding, one of the strengths of the study was the use of the AGREE II instrument to assess the quality of CPGs because, although there are other tools for this purpose, AGREE II is a generic instrument validated in an international collaboration between 13 countries and can be applied to guidelines with different scopes or areas, is easily accessible and applicable, and is widely used by CPG developers worldwide.7,8
CONCLUSIONS
9
Conflict of Interest: The authors declare no conflict of interest that may affect the results and conclusions of this study. Funding: The authors are researchers of Elexial Research Center.
STATEMENT OF AUTHORSHIP Category 1 (a) Conception and Design Carolina Sandoval-Salinas (b) Acquisition of Data Carolina Sandoval-Salinas; José P. Saffon; Héctor A. Corredor (c) Analysis and Interpretation of Data Carolina Sandoval-Salinas Category 2 (a) Drafting the Article Carolina Sandoval-Salinas; José P. Saffon; Héctor A. Corredor (b) Revising It for Intellectual Content Carolina Sandoval-Salinas; José P. Saffon; Héctor A. Corredor Category 3 (a) Final Approval of the Completed Article Carolina Sandoval-Salinas; José P. Saffon; Héctor A. Corredor
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The number of CPGs on erectile dysfunction developed with high methodological standards is low, which compromises the reliability of the recommendations. Most available CPGs were developed by scientific societies and private groups. Physicians, health-care staff, and other users should acknowledge the quality standards of these guidelines, allowing these groups to choose those with the most reliable recommendations.
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Corresponding Author: Carolina Sandoval-Salinas, MSc, Carrera 10 No. 97 A - 13 Torre A Oficina 308, Bogotá, Colombia. Tel: þ57 320 8899777; E-mail: carolina_ss81@ yahoo.es
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SUPPLEMENTARY DATA
22. Qaseem A, Snow V, Denberg TD, et al. Clinical guidelines hormonal testing and pharmacologic treatment of erectile
Supplementary data related to this article can be found at https://doi.org/10.1016/j.jsxm.2019.12.023.
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