Significant risk of bias and limitations in outcome selections in trials evaluating conservative treatments for the management of Pelvic Organ Prolapse (POP) have been highlighted and preclude comparability of outcomes, synthesis of primary studies and high quality evidence. A Cochrane review on conservative treatments for the management of POP identified significant risk of bias and limitations in outcome selections in trials evaluating conservative treatments for the management of POP.[1] 

Given the impact on women’s quality of life, the economic burden of disease, and high incidence of pelvic organ prolapse (POP), the quality of published evidence is hindered by this factor. The variation in outcomes leads to resource waste, impeding high quality research and hindering generating high quality results when performing meta-analyses. These variations are only part of a series of methodological limitations in RCTs on POP interventions.

As conservative treatment of POP is a first-choice treatment, the measure of outcome is pivotal for the further management. A combination of subjective and objective outcomes might serve as basis for further treatment algorithms. The aim of this systematic review was to identify the selected and reported outcomes and outcome measures in trials on conservative treatments for POP and to create relevant inventories as well as classifying them into domains and themes, as well as to suggest an interim measure until a Core Outcome Set (COS) is developed. We also aimed to evaluate the methodological quality of these trials, their outcome reporting quality and other publication characteristics including year of publication, type of journal and impact factor of the journal and their associations among published RCTs.

A standardised methodological approach was used in line with previous experience and expertise developed within CHORUS, An International Collaboration for Harmonising Outcomes, Research, and Standards in Urogynaecology and Women’s Health, [2] as well as recommended by the COMET Handbook in relation to systematic reviews for the development of a Core Outcome Set.[3]

A systematic review of RCTs was undertaken, searching the Cochrane Central Register of Controlled Trials (CENTRAL), Pubmed, Medline, and Embase from database inception to November 2019 using the Medical Subject Headings (MeSH) terms ‘pelvic’, ‘organ’, ‘vaginal’, ‘uterine’, ‘uterovaginal’, ‘prolapse’, ‘cystocele’, ‘rectocele’, ‘pelvic organ prolapse’, ‘vaginal prolapse’, ‘uterine prolapse’, ‘uterovaginal prolapse’. RCTs evaluating the effectiveness of conservative interventions for the management of POP were considered for inclusion. 

Outcomes and outcome measures were identified from the RCTs and an inventory was created. Outcomes were grouped into domains and themes based on the taxonomy model recommended by the COMET Handbook.[3](Figure 1) Outcome measures were categorised into Clinician reported, Patient reported and Procedure related (Table 1). Methodological quality was assessed using the five-point JADAD criteria. Outcome reporting quality was analysed using the six-point Management of Otitis Media with Effusion in Cleft Palate (MOMENT) scoring system referenced in the COMET handbook.[3] Publication characteristics were evaluated and statistically analysed.

Our literature search revealed 973 studies of which 423 were RCTs related to pelvic organ prolapse and 40 evaluated conservative treatments. Follow up articles of previous randomised control trials, and articles researching conservative measures employed postnatally and perioperatively were excluded from analysis. Of the 40 papers, 7 were duplicate search findings and 7 articles were excluded as full texts were not found by 3 independent researchers. This resulted in 25 papers used in this analysis. 

There were a total of 3179 female research participants. Six out of 25 trials (24%) included more than 250 research participants, whereas 15 of 25 studies (60%) enrolled fewer than 100 women in their studies. In 20 out of 25 studies (80%) the follow-up was less than or equal to 6 months and in the remaining 5 studies (20%) it was 12 months (2 studies) or 24 months (3 studies). The trials included reported on 31 outcomes and used 50 outcome measures. 

Reporting rates of the outcomes investigated ranged between 4% and 56%. The most frequently reported outcome domain was patient reported symptoms, followed by stage of POP, quality of life and sexual function.(Figure 1) The most frequently used validated questionnaires were Pelvic Floor Distress Inventory 20 (PFDI-20), Pelvic Floor Impact Questionnaire/Health related quality of life (PFIQ-7/HRQOL), and Pelvic Organ Prolapse Impact Questionnaire (POPIQ-7). (Table 1)

The quality of outcome reporting scored a median value of 5 (MOMENT score, with a maximum value of 6, interquartile range 3–5) and the methodological quality also scored 5 (JADAD score, with a maximum value of 5, interquartile range 3–5). Six out of 25 (24%) trials did not clearly state the primary outcome; and only one of the trials used a method designed to enhance quality of outcome measures. Univariate analysis demonstrated no significant correlations of methodological and outcome reporting parameters.

We applied a previously standardised methodology and measures to prevent bias in data selection, collection, and analysis. This study included RCTs only, which are considered high-quality studies and are commonly included in meta-analyses that examine the effect of various interventions on selected and reported outcomes. This systematic review also carries some limitations, however. We did not include non- randomised studies, and restricted our inclusion criteria to studies in English language only. However, including other languages at this stage and translating terms from other languages may result in terminology misinterpretation, which may affect the taxonomy of outcomes and outcome measures into domains. Finally, quality assessments using MOMENT and JADAD criteria may carry inherent weaknesses of these two methods. On some occasions consensus among the appraisers had to be established.

The process for the development of COS and COMS should be patient centred aiming to enhance patient centred clinical care. For this reason insights gained from qualitative research should also be documented and inform the process. In parallel to reviewing quantitative evidence prior to developing Delphi surveys and consensus meetings, CHORUS working groups perform qualitative evidence synthesis and conduct meta-synthesis studies in order to enrich our understanding on patient perspectives and priorities.

There is a need to increase comparability of RCTs. Reporting standardized outcomes included in a COS for conservative interventions for POP will facilitate the comparability across RCTs. While the process of developing COS is in progress, we propose the interim use of the three most commonly reported outcomes in each domain: patient-reported outcomes (symptom distress including bowel and urinary symptoms, sexual function), stage of prolapse and quality of life parameters using validated questionnaires (Pelvic Floor Distress Inventory 20 (PFDI-20), Pelvic Floor Impact Questionnaire/Health related quality of life (PFIQ-7/HRQOL) and Pelvic Organ Prolapse Impact Questionnaire (POPIQ-7).

Hagen S, Stark D. Conservative prevention and management of pelvic organ prolapse in women. Cochrane Database Syst Rev 2011. https://doi.org/10.1002/14651858.cd003882.pub4
About CHORUS - CHORUS n.d. https://www.chorusaccess.org/about/about-chorus/ (accessed November 16, 2020)
Williamson PR, Altman DG, Bagley H, Barnes KL, Blazeby JM, Brookes ST, et al. The COMET Handbook: Version 1.0. Trials 2017;18:1–50. https://doi.org/10.1186/s13063-017-1978-4