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The standards of obstetrics and gynecology core outcome sets: A scoping review

Background Core outcome sets (COSs) are the minimum outcomes which should be measured and reported by researchers investigating a specific condition. The definition of standards of COSs vary across different health-related areas. This investigated the characteristics of COSs regarding obstetrics and gynecology (OG) and examined the reports and designs of standards of OG COSs. Methods A comprehensive search was conduced on the COMET database on December 20, 2019 to identify systematic reviews on COSs. Two reviewers independently evaluated whether the reported OG COS met the reporting requirements as stipulated in the Core Outcome Set-STAndards for Reporting (COS-STAR) statement checklist and the minimum design recommendations as outlined in the Core Outcome Set-STAndards for Development (COS-STAD) checklist. Results Forty-four OG COSs related to 26 topics were identified. None of them met all the 25 standards of COS-STAR statement which representing 18 items considered essential for transparent and complete reporting list for all COS studies (range: 6.0-24.0, median: 14.0). The compliance rates to 16 standards of methods and result sections ranged from 27.3%–68.2%. Total COS-STAR compliance items for OG COSs with the prior protocol was significantly higher than without prior protocol (MD = 3.846, 95% CI: 0.835–6.858, P = 0.012). None of the OG COSs met all the 12 criteria in the COS-STAD minimum standards (range: 3.0-11.0, median: 5.0). The compliance rates for all three standards of stakeholders involved and all four standards of the consensus process were lower than 60%. Conclusions Methodological and reporting standards of OG COSs should be improved.


Introduction
Selection of outcomes that adequately reflect issues relevant to patients and health care professionals is essential when designing clinical trials to directly compare the effects of different interventions. 1 , 2 Core outcome sets (COSs) represent the minimum im-ing process and a consensus process that involves muti-stakeholder groups. [14][15][16] However, studies have not explored whether the published COSs undertook a systematic review of existing outcomes or fully considered the views of different stakeholder groups on the COSs. 17 The Core Outcome Set-STAndards for Development (COS-STAD) project explored aspects of COSs development to establish minimum standards and apply them regardless of the consensus method chosen. 15 Recommendations have been established to improve the methodological approach for developing COSs and help users assess applicability of a particular COSs. 15 In addition, the Core Outcome Set-STAndards for Reporting (COS-STAR) statement was established using the recommended approach for developing medical reporting guidelines. 18 COS-STAD focuses on the principles of design associated with COSs development, whereas the COS-STAR focuses on reporting of COSs development studies. A recent pilot study used COS-STAD standards to assess the design quality of cancer COSs and reported that the scoping process and consensus process of cancer COSs were not reliable. 19 Moreover, none of the studies met all the 12 standards representing the 11 minimum standards assessed. Therefore, it is important to explore ways of improving the existing standards of COSs development.
Obstetrics and gynecology (OG) is a field in clinical medicine that focuses on physiological and pathological changes of the female reproductive system, and fertility regulation. [20][21][22] Accuratelydeveloped COSs should ensure that outcomes in OG trials prioritize relevant issues for both patients and health care professionals over other disciplines. [21][22][23][24][25] The primary aim of the current study was to use COS-STAD and COS-STAR checklists to assess the methodological and reporting standards of OG COSs. Secondary objectives of the study included exploring factors that affect quality of developed COSs standards and exploring approaches for improving baseline standards for obstetrics and gynecology COSs development.

Inclusion criteria
OG COSs that had developed or applied methodologies to determine which outcome areas or outcomes should be measured, or OG COSs important in clinical trials or other forms of health research were included in the current study. We identified the OG diseases according to the ICD-11 criteria. The latest updated version of COSs was used. Studies that; only reported use of a COS, were systematic reviews of clinical trials, focused on systematic reviews and surveys of outcomes measured in clinical trials or quantitative descriptions (such as frequency) of outcomes, or protocol of COS, were excluded from the study. The inclusion criteria did not include limitations on the year of publication, language, age of participants, and types of interventions.

Identification and selection of COSs
COMET is a repository for international COS literature ( http://www.comet-initiative.org/studies/search ). 8 A comprehensive search of COMET database was conducted on December 20, 2019. Two reviewers (Y.G. and J.Y.S.) independently exported all registered COS study records from the COMET database. Full-text publications that met the inclusion criteria were then filtered. A regularly updated systematic review of COSs and the search result of other published articles were screened to identify OG COSs as a supplement (selected by Y.G. and J.Y.S. independently). 8 , 9 Reference lists from eligible COSs and related reviews were reviewed for additional eligible studies. Any disagreement of the final list of COSs was solved by a COS/methodology expert (J.H.Z). Eligible studies published in any language were included.

Data extraction and management
All authors involved in this study performed a pilot study on a random sample of five included COSs to ensure the agreement among interpretation of data items, prior to the actual study. One reviewer (J.Y.S., M.L.Y., or Z.W.S.) extracted data from included COSs using a data extraction sheet from included COSs, and a second reviewer (Y.G., Y.M.C., or M.M.N) verified extracted data. Any disagreements were adjudicated by a third reviewer (J.H.T). Extracted data included: number of authors, countries which coauthors came from, whether the COS protocol was registered, journals where the studies were published and impact factors, number of databases searched (Chinese, English, or both), funding source (industry, government, unfunded, or not reported), and impact factors of journals in which COSs included were retrieved by searching 2018 Journal Citation Reports (Thomson Reuters, 2018) through Web of Science. Details on data extraction table is shown in Supplement 1A.

Reporting quality assessment
COS-STAR was developed using a recommended approach for guiding minimal COS study reporting. The reporting standards of included COSs were explored using COS-STAR which contains 18 items (including 25 checklist criteria) spread over six domains including; title/abstract, introduction, methods, results, discussion, and other information. Responses for each item included; "Yesitem fully compliant, partial -item not fully compliant, or Noitem not compliant. Reporting standards assessment using COS-STAR tool was independently conducted by two independent reviewers (J.Y.S. and M.L.Y.) (Supplement 1B), conflicts were adjudicated by a third reviewer (J.H.Z.).

Methodological quality assessment
Methodological standards of included COSs was evaluated using COS-STAD, which contains 12 checklist criteria spread over three domains namely; scope specification, stakeholders involved, and consensus process (Supplement 1C). The three domains are considered the minimum design recommendations for development of all COSs. To indicate the degree of compliance, each checklist item was defined as: Yes -for fully addressed; Partial -for partially addressed; and No -for not addressed. Assessments were compared, and three authors (J.Y.S. M.L.Y., and Y.G.) deliberated on how the process should be applied. Methodological standards assessment using the COS-STAD checklist was independently conducted by two reviewers (J.Y.S and Y.G). Conflicts were adjudicated by a third reviewer (J.H.Z.).

Statistical analysis
Continuous data was expressed as median and range, whereas categorical data was summarized as frequency and percentages. This article is not intended to criticize the quality of the published COSs. Therefore, the study only reports compliance rates of items included in literature, but it does not score the standards of individual studies. The frequency of "Yes" response was summarized for individual items of the COS-STAD and COS-STAR for all included COSs. Chi-square test and odds ratio (OR) was calculated with 95% confidence intervals (95% CIs), and P -value for each item compared between group one (COSs with statistician or epidemiologist, funding, and with prior protocol) and group two (without statistician or epidemiologist, non-funding, and without protocol) was obtained. Moreover, Chi-square test was used to determine compliance for each item of COS-STAD between OG COSs and cancer COSs (the result of cancer COSs assessment was extracted from a previous study conducted by Elizabeth G). 19 The mean compliance items and standard deviation (SD) were calculated for each of the COS-STAR and COS-STAD checklist items. Mean difference (MD) and 95% CI were calculated for each item to compare the overall compliance items between groups. MD value represented the difference in the mean total compliance items between group one and group two. Analyzes were conducted using STATA (13.0; Stata Corporation, College Station, Texas, USA), and statistical significance was set at P < 0.05. The complete compliance rate of the methodological quality was calculated with the acquired number. Spear-man correlation coefficient (r) was estimated to determine the linear association between average citations per year (dates from Web of Science) and the total complete compliance rates of COS-STAD and COS-STAR for each OG COS. Correlation analyzes were conducted using IBM SPSS Statistics v. 24.0 (IBM Corp., Armonk, NY, USA), and statistical significance was set at P < 0.05. We created bubble plots with Microsoft Excel 2016 (Microsoft Corp, Redmond, WA; www.microsoft.com ) to present the compliance rate. Considering bubble plots according to the compliance rate, the bubble size represented the number of compliance rate, the x-axis represented the COS-STAR or COS-STAD items, and the y-axis represented the compliance rate of each item.

Characteristics of included COSs
The first COS was published in 20 0 0; most COSs were published from 2018-2019 (Supplement 2A). Forty-four COSs focused on 26 topics mainly with most reporting on pelvic organ prolapse (9%) and maternity care (9%) (Supplement 2B). Corresponding authors of included studies were from nine countries, with the UK (38.6%), USA (13.6%), Canada (11.4%), and Australia (9%) having the highest number (Supplement 2C). The main characteristics of included COSs are presented in Table 1 showed the main characteristics of the included COSs, including e.g., correspondence author, impact journal factor, prior protocol, and COS development process.

Results of reporting quality
Compliance rates of 8 standards were > 85%, mainly focusing on introduction and discussion sections; among them, the compliance rates of items 2b, 3a, and 3b were 100.0%. However, compliance rates of the 11 standards on the COS-STAR assessment were less than 55%, including items 1a, 5, 7, 8, 9a, 9b, 10, 11, 12, 13a, 13b ( Fig. 1 ). Further more, total COS-STAR compliance standards of OG COSs with the priori protocol were significantly higher compared those for OG COSs without protocol ( Table 2 ). The compliance for each of the 25 criteria was analyzed and the findings showed significant differences between COSs with priori protocol and those without a priori protocol based on the items 1a, 4, 6a, 6b, and 17.

Results of methodological quality
Compliance rates of four criteria related to "scope specification" were above 95%. However, the compliance rates of eight items related to "stakeholders involved" and "consensus process" were less than 60%. ( Fig. 2 ). The findings showed that there was no significant difference in total COS-STAR compliance standards of OG COSs between group one and group two. Studies with a priori protocol or registered details showed higher compliance rates of the items 9a, 9b, and 10 compared with COSs without prior protocol or registered details. COSs which involved statistician, or epidemiologist authors showed higher compliance rates on item 6 compared with those COSs not involve statistician, or epidemiologist author. Moreover, funding COSs and non-funding COSs related to the item 7 showed significant differences ( Table 3 ).

Summary of characteristics of included COSs
Overall, the reporting of statistical analysis methods was suboptimal, and the reporting quality and methodological quality were low. Compliance rates were insufficient for most of the items of COS-STAD and COS-STAR checklists.
A total of 44 OG COSs were identified from 26 research topics. Identification of an inclusive list of outcomes from the existing literature is important in development of a core outcome set. 7 Main data sources included systematic reviews of published studies, reviews of published qualitative work, and interviews with key stakeholders. 16 , 26 However, only three COSs interviewed key stakeholders to understand their views of important outcomes, whereas 16% of COSs did not conduct systematic/literature review to identify existing knowledge on outcomes. Comprehensiveness of the results of a systematic review is highly dependent on the results of the underlying data, therefore, it is important to carry out a thorough verification of reported results. Notably, only 34.1% of COSs searched more than three databases. A systematic review of the results aggregates the opinions of previous researchers. Therefore, it is important to subsequently strike a consensus with the wider community of stakeholders on outcomes to be included in a COS. In the present study, only twenty COSs (45.5%) conducted two or more rounds of Delphi survey. Notably, 40.9% of COSs used the consensus meeting method whereas 36.4% of studies used both systematic review and consensus methods.

Reporting standards of included COSs
For the COS-STAR checklist, only 34.1% of studies reported the title that the paper reports the development of a COS, future researcher should identify their report as a COS development study in the title. COS developers should provide a clear and transparent report of the methods they used, but the compliance rates of 9 criteria in the methods section ranged from 27.3%-68.2%, which is not conducive to improving the transparency of COS, nor is it conducive for COS users to judge whether the development process of COS is rigorous. No study met the item 11 criterion (describe any changes from the protocol), therefore, further analysis should explore whether COS not deviating from the protocol should report this item. This would improve the applicability and suitability of this criterion. Characteristics of participants involved were not presented in 61.4% of included studies, and all outcomes considered at the start of the consensus process and descriptions of any other outcomes introduced/dropped during the consensus process were absent in more than half of the studies, which makes it impossible for readers to assess whether the decisions were made in an unbiased way. Recommended outcomes in 43.2% of COSs were unclear or ambiguous, which may limit their application. Only twenty-four (54.5%) COSs met all the other two information criteria (sources of funding and conficts of Interest), future COS developer should clearly report funding information and describe any conflicts of interest within the study team. Moreover, total COS-STAR compliance criteria of OG COSs was significantly positively correlated with prior protocol, indicating that COS developer may improve the quality of COS by publishing protocol or registry details in advance.

Methodological standards of included COSs
Four standards for scope specification for the COS-STAD checklist were well met. All stakeholders involved in the COS development should be reported to ascertain whether the COS fully reflects the views of important outcomes for the target population in the forthcoming research, which will improves utilization and promotion of the COS. 23 However, only fourteen COSs (31.8%) met all the three standards for the domain of stakeholders involved. Judging the standards of COS-STAD in the consensus process that was set in advance is challenging, analysis was performed to determine whether the studies that met this standard relied on registration information and published protocol. 19 But only 27.3% of COSs priori described a consensus protocol, and some registration information was inadequately reported, making it challenging to judge whether some standards were set prior. The registration platform can improve the standards for COS registration, thus promoting integrity and transparency of COS developed. Analysis showed that 92.1% of COSs did not report whether the patient representatives received a glossary of terms before completing the survey, which may cause ambiguity in language. Futher more, Spearman's correlation analysis showed a statistically significant positive correlation between average citations per year and compliance rates of COS-STAD for OG COSs, which indicates that improving the quality of COS may contribute to the promotion and application of COS.

Comparisons between cancer COSs and OG COSs
A previous study conducted by Elizabeth G on the minimum standard assessments of cancer COSs reported that compliance rates for both four standards in scope domain were above 95%, which was consistent with that of OG COSs. 19 Cancer COSs showed similar low compliance rate for all five standards in consensus process standards, but had lower compliance rates for items 9a and 10 compared with OG COSs, which indicates that future researchers should pay more attention to these items (Supplement 3). Overall, OG COSs had a similar low compliance rate for COS-STAD items compared with cancer COSs, further research needs to explore whether this problem exists in COS for other fields.

Suggestions for future work
This study indicated that both the reporting and methodological standards of OG COSs were of low quality according to COS-STAD and COS-STAR checklists, and many items had low compliance rates. Future OG COS makers should address these identified shortcomings, and conducted COS according to the reporting and methodological guidelines. The results of this study also found that writing a protocol is of great help in improving the quality of OG COS, future OG COS developer need to increase the transparency and robustness of the methods by drafting of high-quality protocols according to the Core Outcome Set-STAndardised Protocol Items (COS-STAP) statement. 3 Moreover, future researcher should fully consider the need for COS updating, including updating the SR and consensus progress.

Strengths and limitations
This work had a few limitations. First, some studies assessed were published before development of COS-STAR and COS-STAD standards, therefore they could not have been informed by the development standards. However, the current study focused on investigating the current issues of COSs and explored ways of improving the COS standards instead of criticizing quality of existing COSs, thus circumventing this limitation. Second, some included COSs were published before the COMET initiative was set up, thus they were not registered. Therefore, the definition of COSs developed with the protocol was not limited to this website, but was also based on other registration platforms, and protocols published in peer-reviewed journals that met the set criteria. Third, the same COS-STAD criteria was used to compare the standards between OG COSs with cancer COSs based on previous research. Notably, variation in standards for item compliance may exist in the assessment progress between different reviewers. COS-STAD and COS-STAR did not provide a standard to score the overall quality of COSs, therefore, analysis in the current study was limited to the compliance rate. Further studies should be conducted to explore the appropriate statistical methods for estimating an average value of the quality scores of multiple COSs.

Conclusion
Compliance of COS-STAD and COS-STAR criteria in OG COSs are not optimistic. Therefore, reporting and methodological standards of OG COSs should be further improved, mainly design of important stakeholders involved and consensus process; and reporting standards in methods, results, and other information specifications. OG COS developed with the prior protocol is reliable for improving the reporting standards.