Comparison of clinical practice guidelines methods to reach diagnostic test recommendations regarding diagnostic laparoscopy for endometriosis: A scoping review

Endometriosis affects 10% of reproductive-age women worldwide and is characterized by chronic pain and infertility [ 1 – 3 ]. However, diagnosing endometriosis remains challenging, involving a delay of 6 to 11.7 years [ 4 – 7 ]. While laparoscopy is considered the reference standard based on its results in diagnostic accuracy outcomes, it is important to consider the certainty of these results, the operator-dependent accuracy [ 8 ] and to keep in mind that the effects on clinically important outcomes for patients should also be known [ 9 ]. Additionally, laparoscopy is an invasive, expensive procedure, difficult to access in certain contexts, which is not devoid of complications, and there may be other alternatives to the use of laparoscopy as a diagnostic test that are non-invasive, such as empirical medical treatment [ 10 , 11 ]. Clinical practice guidelines (CPGs) can address these types of uncertain scenarios by issuing recommendations based on systematic searches and appropriate methodological procedures to resolve questions about the use of diagnostic tests. In this regard, the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology proposes methodological guidelines for addressing this type of clinical questions, emphasizing decision-making on the clinical impact of diagnostic test such as laparoscopy on clinically important outcomes for patients, and considering a transparent multicriteria framework for issuing recommendations [ 12 – 16 ]. Prioritizing or not the decision-making process based on the clinical impact of the use of diagnostic tests, as well as employing different methods for issuing recommendations and properly adhering to them, can lead to contradictory recommendations among CPGs. In consequence, this study aims to evaluate the quality of CPGs for endometriosis that address the use of diagnostic laparoscopy, analyzing recommendations and methods to reach recommendations for this type of clinical question.

We identified 4353 records from systematic search. After removed duplicates, 2479 records were screened by title and abstract, resulting in 54 records to evaluate full text for eligibility. We excluded 50 records after full text analysis and finally 4 CPGs were included. In addition, no other guideline was added from the citation searching of the included CPGs. Fig 1 presents the flow diagram of CPG selection in detail and the list of excluded articles and reasons for exclusion is available in S3 Table . The included CPG were: “Guía de práctica clínica para el diagnóstico y tratamiento de la endometriosis sintomática en mujeres en edad reproductiva” developed by IETSI (IETSI-2022) [ 23 ], “Endometriosis” developed by European Society of Human Reproduction and Embryology (ESHRE-2022) [ 11 ], “Manejo de la paciente con endometriosis en la edad fértil” developed by Sociedad Española de Fertilidad (SEF-2018) [ 24 ], and Endometriosis: diagnosis and management” developed by NICE (NICE-2017) [ 25 ]. The CPG were developed in Peru [ 23 ], Spain [ 24 ], United Kingdom [ 25 ], and in a collaboration between European countries [ 11 ]. The perspective was not reported in three of four (3/4) guidelines [ 11 , 24 , 25 ], and one guideline used a population perspective [ 23 ]. The main scope for guideless was diagnosis and treatment. Two of four (2/4) guidelines were published in 2022 [ 11 , 23 ]. All CPG used GRADE as the method to assess the certainty of the evidence and three of four (3/4) CPG used GRADE as the system to classify the strength of recommendations. Definitions for the certainty of the evidence, strength of recommendations and the terminology used to phrase the strength of the recommendations varied among the guidelines. In addition, two guidelines were funded by public funds [ 23 , 25 ], and the remaining ones did not report the source of funding [ 11 , 24 ]. Table 1 presents the characteristics and definitions used by CPG in detail. * The GRADE methodology used the term “weak” previously, but currently, the term “conditional” is used. Abbreviations: UK: United Kingdom; GRADE: Grading of Recommendations Assessment, Development and Evaluation; NICE: National Institute for Health and Care Excellence. Only one guideline (NICE-2017) [ 25 ] had an adequate quality in all domains of AGREE-II and all the CPG had an adequate methodological quality. In this sense, the CPG with the highest score was IETSI-2022 (91.0%) [ 23 ], while the one with the lowest score was SEF-2018 (66.7%) [ 24 ]. Table 2 . Presents the quality appraisal of guidelines in detail. Abbreviations: AGREE-II: Appraisal of guidelines research and evaluation—II; IETSI-2022: “Guía de práctica clínica para el diagnóstico y tratamiento de la endometriosis sintomática en mujeres en edad reproductiva” developed by IETSI in 2022; ESHRE-2022: “Endometriosis” developed by European Society of Human Reproduction and Embryology in 2022; SEF-2018: “Manejo de la paciente con endometriosis en la edad fértil” developed by Sociedad Española de Fertilidad in 2018; and NICE-2017: “Endometriosis: diagnosis and management” developed by NICE in 2017. Note: With AGREE-II, global score for each domain ranging from 0 to 100%, where higher score indicates better quality. We considered that a GPC had an adequate quality when all six domains had a score ≥ 60%, and an adequate methodological quality when the third domain (rigor of development) had a score ≥ 60%. Two guidelines state recommendations against the use of laparoscopy to diagnose endometriosis (IETSI-2022 and SEF-2018) [ 23 , 24 ], one guideline state a recommendation for either the use of diagnostic laparoscopy or medical empirical treatment (ESHRE-2022) [ 11 ], and one guideline state a recommendation in favor the use of laparoscopy to diagnose endometriosis (NICE-2017) [ 25 ]. The strength of recommendations was conditional in three guidelines (IETSI-2022, SEF-2018, and NICE-2017) [ 23 – 25 ] and not reported in one guideline (ESHRE-2022) [ 11 ]. Finally, the certainty of the evidence for the recommendations was not reported in two guidelines, state as very low in one guideline (IETSI-2022) [ 23 ], and state as high in one guideline (SEF-2018) [ 24 ]. Table 3 details characteristics and methodological steps for each guideline. * The certainty of evidence for the recommendation was reported in this table as mentioned in the clinical practice guideline (⊕⊕⊕⊕ = high certainty). Abbreviations: IETSI-2022: “Guía de práctica clínica para el diagnóstico y tratamiento de la endometriosis sintomática en mujeres en edad reproductiva” developed by IETSI in 2022; ESHRE-2022: “Endometriosis” developed by European Society of Human Reproduction and Embryology in 2022; SEF-2018: “Manejo de la paciente con endometriosis en la edad fértil” developed by Sociedad Española de Fertilidad in 2018; and NICE-2017: “Endometriosis: diagnosis and management” developed by NICE in 2017; CPG: Clinical practice guideline; SR: Systematic review; RCT: Randomized clinical trial, AMSTAR-II: A MeaSurement Tool to Assess systematic Reviews—II; RoB: Risk of bias tool; QUADAS-2: A Revised tool for the Quality Assessment of Diagnostic Accuracy Studies; Sof: Summary of findings; EtD: Evidence to decision; GRADE: Grading of Recommendations Assessment, Development and Evaluation. Two guides did not fully report information for all components of the PICO framework (SEF-2018 and NICE-2017) [ 24 , 25 ]. The population of interest were reproductive-age women with suspected endometriosis for all guidelines. However, only one guideline specified details regarding the use of previous diagnostic tests and the type of endometriosis (IETSI-2022) [ 23 ]. Diagnostic laparoscopy was the intervention of interest in all guidelines but only one guideline specified the role of the test (IETSI-2022) [ 23 ]. Empirical medical treatment was the comparator in two guidelines (IETSI-2022 and ESHRE-2022) [ 11 , 23 ]. Clinical benefits and complications or consequences of correct/incorrect classification were outcomes of interest in two guidelines (IETSI-2022 and ESHRE-2022) [ 11 , 23 ], diagnostic test accuracy were outcomes of interest in two guidelines (IETSI-2022 and NICE-2017) [ 23 , 25 ], and one guideline did not specify prioritized outcomes. Regarding importance of outcomes, two guidelines did not report the importance of outcomes. The clinical patient important outcomes were at least important in one guideline (IETSI-2022) [ 23 ] and diagnostic test accuracy outcomes were critical in the remaining one (NICE-2017) [ 25 ]. All guidelines searched at least two databases and the date of search varied between 2016 to 2022. Three guidelines applied language restrictions, while this information was not reported by one guideline (SEF-2018) [ 24 ]. All CPG searched systematic reviews; three guidelines proposed searching for RCT; and one guideline prioritized searching for diagnostic accuracy observational studies (NICE-2017) [ 25 ]. All guidelines planned to use an instrument for risk of bias or study quality assessment, but only two guidelines specified QUADAS-2 (IETSI-2022 and NICE-2017) [ 23 , 25 ]. Regarding the certainty of evidence assessment, all guidelines mentioned using the GRADE methodology. Only one guideline used SoF tables to report summaries of evidence and report the pre-test probability for the target condition (IETSI-2022) [ 23 ]. In general, guidelines mentioned a lack of studies on the clinical impact of using diagnostic laparoscopy. Sensitivity and specificity values were reported by three guidelines and showed slight variations (IETSI-2022, SEF-2018, and NICE-2017) [ 23 – 25 ] ranging from 0.94 to 0.98 for sensitivity and 0.79 for specificity. However, only one guideline explicitly addressed the clinical consequences of correct/incorrect classification with diagnostic laparoscopy and express it in number of cases per 100 individuals (IETSI-2022) [ 23 ]. In addition, two guidelines report the incidence of complications of the procedure, ranging from 2.3% to 6.8% (IETSI-2022 and ESHRE-2022) [ 11 , 23 ]. The certainty of the evidence was appropriately expressed using the GRADE terminology in only one guideline and stated as low to very low certainty of the evidence (IETSI-2022) [ 23 ]. The remaining guidelines highlighted study limitations based on the risk of bias, using terms like "methodological limitations" or "high risk of bias", or based on the indirectness of the evidence, but did not detail the assessment of the remaining criteria proposed by GRADE. Only one guideline used the EtD table to report the discussion regarding evidence to decision criteria and explicitly report the judgement for each criterion as proposed by GRADE (IETSI-2022) [ 23 ]. Regarding benefits, two guidelines, IETSI-2022 and ESHRE-2022, focused on potential clinical effects [ 11 , 23 ], one on laparoscopy’s diagnostic accuracy (NICE-2017) [ 25 ], and the last, SEF-2018 [ 24 ], did not discuss benefits. IETSI-2022 considered benefits trivial, emphasizing empirical therapy’s comparable advantages for high pre-test probability cases. ESHRE-2022 highlighted a lack of evidence for laparoscopy’s superiority over empirical treatment. Regarding harms, two guidelines discussed the consequences of incorrect classification or potential complications of laparoscopy concerning harms (IETSI-2022 and ESHRE-2022) [ 11 , 23 ], while others did not address this criterion. IETSI-2022 found harms to be trivial due to infrequent and not severe consequences, and ESHRE-2022 [ 11 ] highlighted the need to consider potential risks without explicitly judging this criterion. Regarding the overall certainty of the evidence and the balance between benefits and harms, only one guideline reported the judgment for this criterion using the terminology proposed by GRADE (IETSI-2022) [ 23 ]. For IETSI-2022 [ 23 ] guideline, the overall certainty of the evidence was very low, and the balance possibly does not favor either the use of diagnostic laparoscopy or the empirical medical treatment in based of previous judgements for benefits, harms, and the certainty of the evidence. Similarly, ESHRE-2022 [ 11 ] guideline mention that there is no evidence of superiority of either approach and psychological benefits of a confirmed diagnosis should be weight against the value and risk of diagnostic laparoscopy. In contrast, SEF-2018 [ 24 ] guideline mention that the evidence on diagnostic accuracy of laparoscopy for endometriosis had limitations and there are empirically effective and safe treatments for symptom management. Finally, NICE-2017 [ 25 ] did not report discussions for this criterion. Regarding resource use or cost-effectiveness, only one guideline reports the judgement for this criterion using the terminology proposed by GRADE (IETSI-2022) [ 23 ]. The IETSI-2022 [ 23 ] guideline, assess the costs associated with the use of diagnostic laparoscopy and concluded moderate costs. The ESHRE-2022 [ 11 ] guidelines classified the diagnostic laparoscopy as “expensive” and NICE-2017 [ 25 ] guidelines conducted an economic model, considering the limitations of assuming that diagnostic laparoscopy is the “gold standard”, and concluded that is a cost-effective form of diagnosis. Nevertheless, mention that when taken as one of many possible diagnosis/treatment strategies, surgical diagnosis is not preferred to empirical diagnosis and not expensive treatment. In addition, SEF-2018 [ 24 ] guideline did not report discussion for this criterion. Regarding the remaining criteria, patient values and preferences were discussed by three guidelines (IETSI-2022, ESHRE-2022, and NICE-2017) [ 11 , 23 , 25 ], the impact on health equity was discussed by one guideline (probably reduced) (IETSI-2022) [ 23 ], the acceptability of laparoscopy was discussed by two guidelines (varies) (IETSI-2022 and ESHRE-2022) [ 23 , 25 ], and feasibility was discussed by one guideline (likely feasible in specialized centers but may not be available in other regions in the short term) (IETSI-2022) [ 23 ].

This scoping review highlights the variability in recommendations for diagnostic laparoscopy in endometriosis among different CPGs. Despite similar evidence on diagnostic accuracy, discrepancies stem from differing prioritizations of clinical impact assessment and methodological approaches. There’s a need for standardized and transparent guideline development processes, especially addressing the clinical utility of diagnostic tests.

We performed a scoping review following the methodology detailed by the Joanna Briggs Institute [ 17 ], following the guidelines of the Preferred Reporting Items for Systematic and Meta-Analysis extension for Scoping Reviews (PRISMA-ScR) [ 18 ] ( S1 Table ) , and registered the study protocol in the repository Figshare [ 19 ]. We included only evidence-based clinical practice guidelines (CPG), defined as a document that formulates recommendations based on systematic reviews of the literature, that provide recommendations regarding the use of laparoscopy for the diagnosis of pelvic endometriosis in reproductive age women with endometriosis, published or fully/partially updated during 2017 to 2023, and were available in English or Spanish language. We excluded guidelines whose recommendations are adopted or adopted, and those whose methodology and recommendations cannot be obtained in full text. In addition, we excluded systematic reviews, observational studies, clinical trials, conference abstracts, letters to the editor, and case reports. We searched in databases (Trip Database, MEDLINE/PubMed, Web of Science, SCOPUS, and EMBASE), web pages of guideline development organizations (Scottish Intercollegiate Guidelines Network [SIGN], National Institute for Health and Care Excellence [NICE], Australian Clinical Practice Guidelines, New Zealand Guidelines Group, Centro Nacional de Excelencia Tecnológica en Salud [CENETEC], Guías Salud, Instituto de Evaluación de Tecnologías en Salud e Investigación [IETSI], and the American College of Physicians Clinical Practice Guidelines), and web pages of guideline compilers (Canadian Medical Association Infobase, Base Internacional de Guías GRADE, Guidelines International Network, National Guideline Clearinghouse, EGuideline, and Best Practice Guideline); from January 1st, 2017, to July 23th, 2023. Complete search strategy for each database in S2 Table . We imported the articles from databases into Rayyan software, where duplicates were manually removed. Then, the obtained results were merge with articles sourced from guideline development organization web pages and guideline compilers, followed by a second manual removal of duplicates. Subsequently, four researchers (JNL, FZC, MAC, CQV) independently screened titles and abstracts to identify potentially relevant articles for inclusion. These potential articles were found and full text reviewed independently by the same researchers to verify compliance with the inclusion criteria. The disagreements were resolved with a fifth researcher (SGL). Four researchers (JNL,FZC,MAC,CQV) independently extract the following information from each included guideline: CPGs characteristics (organization, year, country, perspective, scope, method used to assess the certainty of the evidence and its definition, system to classify the strength of recommendations and its definition, and funding), characteristics regarding the recommendations on the use of laparoscopy for the diagnosis of endometriosis, and the methods used to assess diagnostic test clinical questions. In addition, we performed the quality appraisal of each CPG. We used the Appraisal of Guidelines Research and Evaluation II (AGREE-II) instrument [ 20 ], which includes 23 items distributed in six domains (scope and purpose, involvement of stakeholders, rigor of development, clarity, and presentation, applicability, and editorial independence) to assess the quality of CPGs. Three researchers (forming groups distributed between JNL, FZC, MAC, CQV) independently rated each item on a seven-point scale from strongly disagree (score 1) to strongly agree (score 7). When a difference of two or more points was found in one of the items between researchers, a fifth researcher (SGL) solved the disagreement and reach a consensus. Then we followed the AGREE-II guidelines to calculate the global score for each domain ranging from 0 to 100%, where higher score indicates better quality. The guideline of the instrument does not provide a minimum domain score to classify the quality of the guidelines. In consequence, we used a cut-off point based on previous studies that evaluated the quality of GPCs in gynecology and obstetrics topics [ 21 , 22 ]. We considered that a CPG had an adequate quality when all six domains had a score ≥ 60%, and an adequate methodological quality when the third domain (rigor of development) had a score ≥ 60%. We extracted recommendations regarding the use of laparoscopy for the diagnosis of endometriosis from each CPG and described the following characteristics: recommendation (as state in the CPG), direction, strength, and certainty of the evidence. In addition, we described the methods used to reach the recommendations. To our best knowledge, there is no specific validated tool for reporting and appraising methods to assess diagnostic test questions in CPGs. We utilized the GRADE guidelines as a reference standard methodology for formulating recommendations on this type of questions. GRADE was chosen due to its explicit steps guiding guideline developers in assessing the certainty of evidence for test accuracy, transitioning from test accuracy to patient-important outcomes, and making recommendations about diagnostic tests using multicriteria frameworks [ 12 – 16 ]. In based on that, we analyzed and described the following methodological characteristics: procedures to generate clinical question and decide on the importance of outcomes (clinical question, PICO framework, role of the diagnostic test, assessment of patient important outcomes or consequences of correct/incorrect classification), perform the systematic review of the evidence and determine the certainty of the evidence (databases and date of search, restrictions, type of study to be search, tool to assess risk of bias or quality of studies, method or criteria to determine certainty of evidence), prepare and report summaries of evidence tables (type of evidence table used, pre-test probability, principal results), and to discuss evidence to decision criteria (EtD table use, benefits, harms, certainty of the evidence, values and preferences, balance between benefits and harms, resource use or cost-effectiveness, equity, acceptability, feasibility). The synthesis of the results was descriptive. We used tables to present our findings.

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