A systematic review of outcome and outcome-measure reporting in randomised trials evaluating surgical interventions for anterior-compartment vaginal prolapse: a call to action to develop a core outcome set

Introduction We assessed outcome and outcome-measure reporting in randomised controlled trials evaluating surgical interventions for anterior-compartment vaginal prolapse and explored the relationships between outcome reporting quality with journal impact factor, year of publication, and methodological quality. Methods We searched the bibliographical databases from inception to October 2017. Two researchers independently selected studies and assessed study characteristics, methodological quality (Jadad criteria; range 1–5), and outcome reporting quality Management of Otitis Media with Effusion in Cleft Palate (MOMENT) criteria; range 1–6], and extracted relevant data. We used a multivariate linear regression to assess associations between outcome reporting quality and other variables. Results Eighty publications reporting data from 10,924 participants were included. Seventeen different surgical interventions were evaluated. One hundred different outcomes and 112 outcome measures were reported. Outcomes were inconsistently reported across trials; for example, 43 trials reported anatomical treatment success rates (12 outcome measures), 25 trials reported quality of life (15 outcome measures) and eight trials reported postoperative pain (seven outcome measures). Multivariate linear regression demonstrated a relationship between outcome reporting quality with methodological quality (β = 0.412; P = 0.018). No relationship was demonstrated between outcome reporting quality with impact factor (β = 0.078; P = 0.306), year of publication (β = 0.149; P = 0.295), study size (β = 0.008; P = 0.961) and commercial funding (β = −0.013; P = 0.918). Conclusions Anterior-compartment vaginal prolapse trials report many different outcomes and outcome measures and often neglect to report important safety outcomes. Developing, disseminating and implementing a core outcome set will help address these issues.


Introduction
The most common type of pelvic organ prolapse (PO) is anterior-compartment prolapse. Hendrix et al. demonstrated in a group of 16,616 postmenopausal women a prevalence of anterior-compartment prolapse of 34%, and this was much higher than the rates of apical-or posterior-compartment prolapse [1]. The aetiology of pelvic organ prolapse (POP) is complex and associated with various factors such as age, menopausal status and childbirth-related pelvic floor trauma [2,3]. Possible surgical interventions include biological-graft, mesh and native tissue repair [4,5]. The development of new surgical interventions is urgently required, and potential surgical interventions require robust evaluation. Selecting appropriate efficacy and safety outcomes is a crucial step in designing randomised trials. Outcomes collected and reported in randomised trials should be relevant to a broad range of stakeholders, including women with anterior-compartment prolapse, healthcare professionals and researchers. For example, resolution of bladder symptoms is an important outcome for all stakeholders; however, it is not commonly reported across trials. Even when outcomes have been consistently reported, secondary research methods, including pair-wise meta-analysis, may be limited by the use of different definitions and measurement instruments [6,7]. A core outcome set should help address these issues. The first stage in core outcome-set development is to evaluate outcome and outcome-measure reporting across published trials. Therefore, we systematically evaluated outcome and outcome-measure reporting in published randomised trials evaluating surgical interventions for anterior-compartment prolapse. In addition, we assessed the relationships between outcome reporting quality with other important variables, including year of publication, impact factor and methodological quality.

Materials and methods
This systematic review is part of a wider project of the International Collaboration for Harmonising Outcomes, Research and Standards in Urogynaecology and Women's Health (CHORUS) (i-chorus.org) and was registered with the Core Outcome Measures in Effectiveness Trials (COMET) initiative database, registration number 981, and with the International Prospective Register of Systematic Reviews (PROSPERO), registration identification CRD42017062456. We searched bibliographical databases comprising the Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE and MEDLINE from inception to September 2017. The search strategy used several MeSH terms, including bladder prolapse, cystocele and POP. Randomised trials evaluating surgical interventions for anterior-compartment prolapse were eligible. We included trials evaluating the surgical management of anterior prolapse as a unicompartmental prolapse procedure, as well as trials in which anterior repair was undertaken in addition to other surgical interventions. Non-randomised studies, observational studies and case reports were excluded.
Two researchers (CD and AE) independently screened the titles and abstracts of electronically retrieved articles. The articles potentially eligible for inclusion were retrieved in full text to assess eligibility, and reference lists were independently reviewed. Any discrepancies between the researchers were resolved by review of a third senior researcher (SKD). Two researchers (CD and AE) independently extracted the study characteristics, including year of publication, journal topicality (subspecialist, general obstetrics and gynaecology or general medicine), journal's impact factor and commercial funding (yes/no). The journal's impact factor was determined using InCites Journal Citation Reports (Clarivate Analytics, Thomson Reuters, New York, NY, USA). Funding status was identified by reviewing the article text and included the   original study, c secondary analysis donation of equipment or other resources. Two researchers (CD and AE) independently assessed the methodological quality of included randomised trials using the modified Jadad criteria (score range 1-5) [8]. Studies were assessed as high quality when they achieved a score >4. Outcome reporting quality was assessed using the Management of Otitis Media with Effusion in Cleft Palate (MOMENT) criteria (score range 1-5) [9]. Studies were assessed as high quality when they achieved a score >4. The non-parametric Spearman's rank correlation coefficient (Spearman's rho) was used to explore univariate associations between outcome reporting quality and impact factor during the year of publication, year of publication and methodological quality. Multivariate linear regression analysis using the Enter model was also undertaken to assess the combined association of quality of outcome reporting and journal type, impact factor during the year of publication, year of publication and methodological quality (independent variables) with outcome reporting (dependent variable). All tests were two-tailed. Statistical significance was set at 0.05, and analyses were conducted using the SPSS statistical software (IBM Corp. Released 2013. IBM SPSS Statistics for Windows, Version 22.0. Armonk, NY, USA).
This study was reported with reference to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement [6].

Summary of main findings
This study demonstrated considerable variation in outcome and outcome-measure reporting across published trials evaluating surgical interventions for anterior-compartment prolapse. Commonly reported outcomes included normalised anatomy, QoL and pain. Patient-reported outcomes were infrequently reported, and a minority of trials reported on patient satisfaction. Mesh-related complications, including erosion, shrinkage and morbidity, were rarely reported. Forty-five different questionnaires were used as measurement instruments; most were validated. Only a few trials considered cost effectiveness.

Strengths and limitations
Strengths of our systematic review include originality, a rigorous search strategy and methodological robustness. To our     x knowledge, this systematic review is the first to evaluate outcomes and outcome measures in anterior-compartment prolapse trials. Study screening and selection and data extraction and assessment were conducted independently by two researchers to avoid bias. Our findings were based on outcome reporting in published randomised trials. The exclusion of observational studies may have potentially missed outcomes related to harm [89,90] and selecting only trials reported in English may have introduced selection bias. The variation of interventions for correcting anterior prolapse may have caused variation in outcome and outcome-measure reporting.

Interpretation
Randomised trials require a substantial investment of resources. Variation in outcomes and outcome measures limits the ability of trials to be combined with meta-analyses, which contributes to inevitable research waste, as identified in various areas of women's health, including childbirth trauma, endometriosis and pre-eclampsia [91][92][93][94]. This systematic review is the first step in the development of a minimum data set, which will be known as a core outcome set. It will be developed with reference to methods described by the COMET initiative, Core Outcomes in Women's and Newborn Health (CROWN) initiative and other coreoutcome-set development studies, including those on endometriosis, pre-eclampsia, termination of pregnancy, Twin-Twin Transfusion Syndrome and neonatal medicine [95][96][97][98][99]. CHORUS is aiming to work towards a standardisation of outcomes and outcome measures and subsequently establish a minimum of standards in research and clinical practice. Chorus working groups are currently evaluating reported outcomes in all areas of urogyneacology and have been registered with the COMET (registration number 981, http://www. comet-initiative.org/studies/details/981) and CROWN initiatives. Each working group has carefully considered the scope of its work [100], and CHORUS will replicate the   success of other international initiatives that have standardised outcome selection, collection and reporting across preterm birth research [101].
In the absence of a core outcome, we recommend QoL (incorporating sexual function), postoperative complications, patient and physician satisfaction and postoperative prolapse, bladder and bowel symptoms be collected across all anterior prolapse trials.

Conclusion
Anterior-compartment prolapse trials report many different outcomes and outcome measures and often neglect to report important safety outcomes. Developing, disseminating and implementing a core outcome set will help address these issues.

Compliance with ethical standards
Conflicts of interest The authors report that they have no conflicts of interest.
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