Reporting quality of randomized, controlled trials evaluating immunotherapy for ovarian cancer: cross-sectional study

Reporting quality of randomized, controlled trials evaluating immunotherapy for ovarian cancer: cross-sectional study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Reporting quality of randomized, controlled trials evaluating immunotherapy for ovarian cancer: cross-sectional study Mingwei Liang, Xinxin Zhang, Wenli Wu, Ruijie Yu, Zhiruo Liao, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9020902/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 17 You are reading this latest preprint version Abstract Background Incorporating immunotherapy effectively remains a priority in therapeutic research of ovarian cancer, making it essential to conduct and report randomized, controlled trials (RCTs) with high quality. The purpose of this study is to assess the reporting quality of RCTs on immunotherapy for ovarian cancer. Methods This was a cross-sectional, meta-epidemiological study. Two researchers searched Pubmed.gov and embase.com for RCTs published before 25th July 2025 for trials on immunotherapy for ovarian cancer. The 37-point overall quality score (OQS) derived from the 2025 CONSORT statement was adopted to estimate the reporting quality of the contained trials. Linear regression analyses were conducted to explore associations between trial characteristics and overall quality of reporting. Detailed data on blinding, allocation concealment, implementation of the intention-to-treat (ITT) principle, follow-up, endpoint setting and adverse event reporting was collected for a further investigation. Results Totally fifty-three relevant RCTs including 12346 participants (range, 14-1301) were analyzed in this study. The mean OQS was 19.08 (s.d. = 6.07, 95% CI = 17.40, 20.75), reflecting more than 46% of the items were inadequately stated in more than half of the studies. As the key methodological factors, allocation concealment, blinding and intention-to-treat principle were reported in 11 (21%), 22 (42%) and 30 (57%) of the 53 RCTs. Although some trials reported their registration status, none provided details on the registration date; additionally, patient and public involvement (PPI) as well as the inclusion criteria for research centers and intervention implementers were not mentioned in any article. Consequently, all 53 trials scored 0 for these three items, and the next most poorly reported aspect was the handling of missing data, with only 2% (n = 1) of the trials documenting this. Publication after 2010 and completely or partially funded by industry remained independent significant factors of improved OQS in multivariate analysis. Conclusions Randomized controlled trials (RCTs) of immunotherapy for ovarian cancer demonstrate poor reporting of the newly added items in the CONSORT 2025 Statement, while simultaneously exhibiting suboptimal reporting quality of items adhering to previous versions of the Statement—despite the fact that most of the included articles were published after 2010. In order to enhance transparency, minimize resource waste, and avoid misleading clinical decision-making, enhancing reporting of key methodological factors, full trial protocol and adverse events is of primary importance. Trial registration: Not applicable. CONSORT statement ovarian cancer immunotherapy reporting quality randomized controlled trial Figures Figure 1 Figure 2 Figure 3 Introduction Randomized controlled trials (RCTs) have long been regarded as the superior study design in the evidence hierarchy of evidence-based medicine determined by its rigorous attributes to minimize biases[1], which has a direct impact on results of systematic reviews and the development of clinical guidelines. However, RCTs may still exhibit bias if they are conducted with defective methods, and inferior reporting of the trials hinders evaluation of their methodological quality[2]. Moreover, inadequately reported RCTs may lead to misinterpretation of trial results and erroneous clinical decisions[3, 4]. Due to the costly nature of RCTs, poor reporting can also result in significant financial waste[5]. The Consolidated Standards of Reporting Trials (CONSORT) is a valid exploration to promote transparent and clear reporting of RCTs[6]. Ovarian cancer remains the eighth leading cause of cancer-related mortality in women worldwide [7, 8]. Due to the deficiency of early detection, around 70% of ovarian cancers are at advanced stages at the time of diagnosis[9-11], entailing an urgent need for novel therapies apart from surgery and chemotherapy, which are still the mainstay treatment but succumb to recurrence and chemoresistance in most situations[12, 13] . To date, immunotherapy has become a distinct pillar of cancer treatment with validated efficacy[14-16]. Since the immunogenic nature of ovarian cancer, great hopes have been placed on immunotherapeutic approaches, and a number of trials of immune checkpoint inhibitors[17-19], tumor vaccines[20, 21], adoptive cell therapies[22, 23], monoclonal antibodies[24, 25] and so on have been conducted[26, 27]. Despite the response remains modest[28], statistically significant improvements or promising trends were identified in some trials[20, 29], especially in certain predefined subgroups[30]. With deepening understanding of immunobiology of ovarian cancer[31], newly-developed immunotherapeutic strategies and synergistic combinations are heatedly investigated[32, 33], and many trials are ongoing[34]. Effective incorporation of immunotherapy remains a priority in therapeutic research of ovarian cancer[12], so high-quality RCTs are urgently needed for this field. Whereas, there is a lack of investigations to comprehensively evaluate reporting quality of RCTs for immunotherapy of ovarian cancer. This evaluation would be valuable to reveal existing deficiencies for researchers to improve reporting of their as-yet-unpublished trials, thereby facilitating communication and interpretation of the latest advances and reducing waste of funds. And the assessment can provide a reference for bias estimation. Accordingly, the objective of this study is to evaluate the reporting quality of RCTs investigating immunotherapy for ovarian cancer based on the CONSORT statement, rather than to synthesize their clinical outcomes. Methods Study selection As a cross-sectional, meta-epidemiological study, the subjects of this study were published RCTs on immunotherapy for ovarian cancer. We retrieved RCTs from Pubmed.gov and embase.com to find all of the published RCTs that focus on immunotherapy for ovarian cancer from January 1, 1980 to July 25, 2025. The keywords used in the literature search were "ovarian neoplasms", "immunotherap*", "PD-1", "PD-L1", "CTLA-4", "CAR-T" , "vaccine*" and "monoclonal antibody" , with "randomized controlled trials" as limitation. Inclusion and exclusion criteria We collected articles that evaluate immunotherapy alone, compared with other therapies (such as radiation or chemotherapy) on their own or in combination with immunotherapy, and articles comparing different strategies for immunotherapy in combination with other therapies. The RCTs only about therapies other than immunotherapy or not focus on ovarian cancer were eliminated. The literatures which were non-English, not focused on immunotherapy of ovarian cancer, not RCTs, incomplete trials, incomplete articles which only have abstract, secondary study of published trials, and repeated articles were also excluded. For RCTs that published twice or more, we chose the article that published its main results. So the articles we chose were all independent. (Figure 1) Overall Reporting Quality The overall quality score (OQS) [35, 36]was adopted to estimate the reporting quality of the contained trials. The OQS includes 37 items for appraising, which is a standardized checklist derived from the 2025 CONSORT statement (Table 1). Then, two investigators marked the articles independently: If an item is described accurately in an article, it scored "1". If an item is poorly described or isn't reported, it scored "0". The problem of scoring deviation caused by inconsistent understanding of CONSORT was solved by discussion and correction. Statistical Analysis The scores of the 37 items were analyzed, and the ratio and 95% CI confidence interval of each scoring item were calculated respectively. Cohen's κ Statistics evaluation was carried out on the scores of the two raters : κ> 0.5 is qualified; 0.6< κ< 0.8 is considerable; 0.8< κ< 1 is excellent; κ= 1 is perfect. Data on AE was analyzed with the same standard. To explore potential predictive factors of overall quality of reporting, OQS was used as the dependent variable which was modeled by linear regression. In consideration of possible with-in journal correlation of articles which were published in the same journal, generalized estimating equations were used[37]. Journal was regarded as the cluster variable, and an exchangeable structure was adopted for the correlation matrix. Univariate analyses were done firstly and factors included were funding sources, published year, region, main results, phase of the trial, sample size and journal impact factor. Variables with a significance of 10% were included in multivariate analyses. Significant variables ( p <0.05) in the multivariate model were considered as independent determinants of reporting quality. All statistical analyses were conducted using the SPSS software version 25.0. Further collection of data on trial reporting To further estimate the reporting quality of some specific sections, we collected detailed data on key methodological factors (blinding, allocation concealment, analysis followed by the intention-to-treat (ITT) principle), endpoint setting, follow-up and adverse event (AE) reporting [see Table S1~Table S4, Additional file 1]. Other details The elaboration of search strategy, selection and appraisal process and other details of our study methods are reported in Additional file 1. Results Trial Characteristics There are totally fifty-three trials included and systematically analyzed in our study. The basic characteristics of each trial included, such as publication year, region and journal are collected. The data of trial characteristics is displayed in Table 2. The trials are all published in 1980 or later, in which most of them were published after 2010 (n=41). Most of the trials took place in Europe or North America (n = 46) and were phase Ⅱ (n = 24) or phase Ⅲ (n = 14). 12346 participants were randomly allocated among the trials. The median participant number was 100 , with a range of 14 to 1301. The inter-rater agreements of all of the items between the two researchers involved in the marking process were considerable, excellent or perfect. Overall Reporting Quality OQS of the studies ranged from 7 to 30 on a scale of 0 to 37. The mean OQS was 19.08 (s.d. = 6.07, 95%CI = 17.40，20.75). The median OQS was 20.00, reflecting more than 46% of the items were inadequately stated in more than half of the studies (Figure 2). According to specific items, although some trials reported their registration status, none provided details on the registration date. Additionally, patient and public involvement (PPI) as well as the inclusion criteria for research centers and intervention implementers were not mentioned in any article. Consequently, all 53 trials scored 0 for these three items, and the next most poorly reported aspect was the handling of missing data, with only 2% (n = 1) of the trials documenting this. Besides, reporting for settings and location, sample size calculation, randomized sequence generation, methods of allocation concealment, blinding, methods of ancillary analysis, flow diagram, results of ancillary analysis, registration and full trial protocol were poor in more than half of the articles. Associations between Trial Characteristics and Overall Quality of Reporting In univariate analyses, published after 2010, completely or partially funded by industry, phase Ⅱ or phase Ⅲ, sample size of more than 500, and impact factor of more than 10 were associated with an increased OQS. In multivariate analyses, published after 2010 and completely or partially funded by industry remained independent significant factors of overall reporting quality (Table 2). To further elaborate on the results of the multivariate model, we explored the interrelationships among key predictors. Non-parametric correlation analysis revealed a significant positive correlation between sample size and journal impact factor (Spearman's ρ = 0.475, P = 0.000, P 0.05). Additionally, cross-tabulation reveals that no significant associations were observed between funding sources and year, sample size, impact factor, trial phase, or primary outcomes. Key Methodological Factors, Endpoint Setting, Follow-up and AE Reporting When it comes to key methodologic factors (Table S1, Additional file 1), allocation concealment is only reported in 21% (n = 11) of the trials, 10 of which used centralized randomization, while the remainder used envelopes that are non-transparent, sealed and numbered in sequence. Blinding is reported in 42% (n = 22) of the trials, where data monitor or statistical analyst was stated to be blinded in only 4 trials. 57% (n = 30) of the trials adequately adhered to the ITT principle. But another 13% (n = 7) mentioned ITT but did not keep to it in practical analysis, or used items like "modified ITT", making the term "ITT" confusing. A variety of endpoints were used in the including trials (Table S2, Additional file 1). The most commonly used endpoint (85%, n = 45) was overall survival, and the most favorable primary endpoint (47%, n = 25) was progression-free survival (PFS). In the follow-up measurement (Table S3, Additional file 1), the longest and shortest period was reported in only 8% (n = 4) of the trials. The median items adequately followed among the 16 items evaluating reporting of AE was 6 (Table S4, Additional file 1). The worst item in AE reporting is non-prespecified harm outcomes, estimated effect sizes and precision of each adverse event. Discussion This study is the first reporting quality evaluation pertaining to immunotherapy of ovarian cancer. The CONSORT statement, as our benchmark, was recently updated on April 14, 2025, introducing a new "Open Science" section that for the first time incorporates items such as data sharing, conflicts of interest, patient and public involvement, eligibility criteria for implementation sites and implementers, harm assessment, handling of missing data, and concomitant care[38]. The introduction of these new items, along with revisions to existing ones, reflects a forward-looking approach aimed at providing a reference and targets for improving the reporting quality of future randomized controlled trials. Only one of our included articles was published after the update of the CONSORT Statement—specifically on June 4, 2025. Given the time typically required for peer review and editorial processing in academic publishing[39], it can be inferred that the included trials (n=53) had virtually no opportunity to reference the newly released CONSORT Statement during trial conduct or manuscript drafting. Therefore, the generally poor and inadequate reporting quality of the newly introduced or revised CONSORT items may be deemed a reasonable outcome. Meanwhile, we found that although most of the articles included are published after 2010, reporting quality based on items retained from the 2010 version in CONSORT 2025 is still suboptimal. A concerning discovery was the significant variation in reporting quality, with the worst-reported study only completely reporting 13% of all items, and none of the included studies fully adhered to the CONSORT checklist. Articles with low scores diminish their evidential quality, and their findings should be treated prudently. Multivariate analysis revealed that publication after 2010 was significantly associated with improved reporting quality. This indicates the positive role of the update and promotion of the CONSORT Statement in enhancing reporting quality and facilitating openness and transparency, and also predicts the potential of the latest 2025 update following its widespread promotion and adoption in the academic community. Additionally, being completely or partly funded by industry was also an independent and significant factor in improving reporting quality. Further analysis revealed that there was no significant association between funding sources and sample size, trial phase, primary outcomes, or impact factor—even presenting an opposite distribution to the prior research conclusions of industry funding's preference for small sample sizes, Phase I trials, and positive results[40, 41], or its negative effect on reporting quality[36]. This anomalous phenomenon may be attributed to the small number of randomized controlled clinical trials (RCTs) on ovarian cancer immunotherapy (n=53), which failed to establish a significant pattern. Additionally, literature examining funding sources for oncology clinical trials indicates that industry funding shows a significant preference for innovative therapies and drugs. Specifically, the odds ratio (OR) of industry funding for trials using immuno-oncology drugs reaches 11.22 (95% CI: 6.64–18.97)[42], which raises a new possibility: given the potential advantages of ovarian cancer immunotherapy, the influx of industry funding (70%, n=37) may have broken the constraint of its preference for small sample sizes and Phase I trials[42]. Meanwhile, industry-funded trials are also subject to strict requirements from journals and review bodies, which may thus improve their reporting quality—for instance, by engaging professionals, among other measures. As government investment in basic scientific research continues to decline, industry funding has become a key source of funding for biomedical research[43]. This suggests that we should re-examine the impact of industry funding on the design, conduct, and reporting of randomized controlled trials. Poor CONSORT adherence is linked to a higher risk of bias[44]. Among all of the items, particular attention should be paid to the key methodological factors (allocation concealment, blinding, ITT), which are widely proved to be mostly related to the generation of bias and may impair the internal validity if they are insufficiently reported[45, 46]. Although a long-standing emphasis was placed[4], reporting of sequence generation of randomization, allocation concealment and blinding implementation was far from adequate, which is only sufficient in 36%, 15% and 36% of included trials. Although open-label design may be conducive to judgment and management of irAEs, blinding can also be applied to outcome assessors and data analysts, but it was reported only in a few studies. This deficiency is consistent with other recent appraisal literatures on RCTs in varied medical fields[47-50], demonstrating it as a pervasive problem that urgently needs to be addressed. This may lead to confusion when readers try to estimate the credibility of the results, and some of the deficiencies may represent a deficient trial design and a more biased result. Since the number of studies is still small for reference, this may produce more adverse effects on research and clinical practices and retard the interpretation of the findings to other researchers.[2] In some previous studies[51, 52], researchers found that the procedures to avoid bias (such as allocation concealment and blinding) which weren't reported in the article may be performed in the trial actually in even a large proportion. In one of the studies[51], allocation concealment wasn't reported in 55% of the articles but was actually performed in 96% of the articles which didn't report it. There may be a similar situation in the articles investigated in our study, causing underestimation of possibly valuable findings. It could be an alert to the clinical researchers to transparently document their procedures to mitigate bias in the reports to enhance the credibility of their studies. Another problem that needs to be stressed is the reporting of AEs. Due to the specific mechanism of immunotherapy deeply rooted in immune activation, a specific range of adverse events known as immune-related adverse events (irAEs) can occur not limited to the drug exposure period, but rather may persist for a long time alongside immune memory. These events can occur rapidly in the early stage of treatment[53], and can also manifest delayed in the middle to late stages of treatment, or even months to years after treatment discontinuation[54, 55]. irAEs differ in presentation from the adverse events of other well-investigated therapies (e.g., chemotherapy), and some irAEs can even be life-threatening. They can involve nearly all organ systems throughout the body, with a scope of involvement that far exceeds the limited set of systems—such as the hematological, gastrointestinal, and mucosal systems—usually affected by the toxicity of traditional chemotherapy[54]. Furthermore, the irAE spectra of different types of immunotherapies—such as CTLA-4 inhibitors, PD-(L)1 inhibitors, and CAR-T cell therapies—exhibit significant differences[53]. Additionally, the same type of immunotherapy also demonstrates variations in its toxicity spectrum across different tumor types[54, 55]. Despite grave consequences irAEs may lead to, the mechanisms underlying them are still poorly understood[54]. Although categories of common irAEs vary depending on particular immunotherapy strategies, meticulous documentation and adequate follow-up for AEs are essential for all immunotherapeutic regimens[56]. But reporting of these items is far from sufficient. Only 53% of the studies reported the timetable assessing AEs, and only 36% reported all AEs in their studies. Merely reporting AEs of interest is inadvisable in view of uncertain knowledge of irAEs. As long-term effects of these therapies remain unknown, it is favorable to extend monitoring to long-term post-treatment follow-up to further collect this data. The limited space for reporting in high impact factor journals is one of the reasons for incomplete reporting. The available full trial protocol in the supplementary material is a favorable measure to elaborate their methodological considerations and it can reduce nonadherence to the methods and outcome assessment standards regulated in the initial protocol as well, which is also recommended as a new checklist item in the CONSORT statement 2010 and Strengthened in CONSORT statement 2025 with statistical analysis plan. [38]. But only 8 of the 53 trials provided the full trial protocol and statistical analysis plan, making it the fifth worst reported item in our study. Although there are limitations, a full trial protocol is needed to be provided for a better interpretation of the study. There are several weaknesses in our study. Immunotherapy is a newly-developed field, so the trials evaluating immunotherapy of ovarian cancer are few, in comparison with similar studies focused on other therapies[35, 57, 58], which may contribute to the failure to establish significant patterns. Besides, the CONSORT checklist isn't designed as an evaluation criteria initially, so we adopted OQS based on CONSORT to quantify the reporting quality. However, OQS has its limitations. Each item is treated equally in OQS, neglecting the different importance of the items. As a remedy, we collected detailed data in some of the significant parts, including the key methodological factors and some other information associated with quality of the studies. Moreover, the discussion section is not included in our study because its quality is hard to value in a quantitative way[59]. Some of the items such as title and sample size are less reported than some similar studies conducted before[6, 35, 36]. It may because we didn't restrict the phase of the RCTs, and these items are most likely to be poorly reported in phase Ⅰ, Ⅰ/Ⅱ trials and in those not distinguishing the phase of the trial. The multivariate analysis revealed an improvement in reporting quality over time, consistent with a previous study examining the methodology of 176,620 RCTs[60]. This trend can be attributed to increased awareness of the importance of complete reporting and the growing adoption of CONSORT guidelines by a greater number of journals. Items such as interventions, eligibility criteria and baseline data are sufficiently reported in all or most of the studies, enhancing replication and comparison with other studies or specific patients. However, as stated above, there are still numerous issues that urgently need improvement and should be taken seriously by all investigators who attempt to report their RCTs. The improvement of trial reporting still has a long way to go, and it relies a lot on the awareness of the significance of a complete and transparent reporting among clinical trial conductors. The CONSORT statement should be popularized among clinical trial conductors and training could be useful, especially on the key methodological factors and the additional items in CONSORT 2025. There should be more journals accepting the CONSORT statement and setting a higher request for authors to follow it. The meticulous scrutiny of journal editors is also essential in this process. Conclusions Based on the CONSORT Statement 2025, the overall reporting quality of randomized controlled trials (RCTs) focusing on immunotherapy for ovarian cancer is suboptimal. Previously published trials have shown poor reporting of newly added items such as Patient and Public Involvement (PPI) and trial registration, which may be attributed to time constraints. Although some items are well-reported, the reporting of key methodological items remains inadequate and requires great attention. Considering the particularity of immune-related adverse events (irAEs), meticulous documentation and adequate follow-up of adverse events (AEs) are necessary. The full trial protocol should be provided, especially when there is insufficient space in the article to specify the methods used to reduce bias. Publication after 2010 and complete or partial industry funding are independent and significant factors for improving reporting quality. However, the new finding that industry funding may promote reporting quality requires further verification. To enhance reporting quality, the awareness of clinical trial conductors is crucial; additionally, higher requirements and rigorous scrutiny from journals and editors for authors to comply with CONSORT guidelines are also an essential part of this process. Abbreviations RCTs: Randomized controlled trials; OQS: Overall quality score; CONSORT: Consolidated Standards of Reporting Trials; ITT: intention to treat; AE: Adverse events. Declarations Ethics approval and consent to participate Not applicable. Consent for publication Not applicable. Availability of data and materials The data generated in this article can be accessed upon reasonable request to the corresponding author. Competing interests The authors declare that they have no competing interests. Funding This research is funded by Medical Science Foundation of Beijing Bethune (6010224017) and Foundation of Science and Technology Research Institute of Shandong University (6010224010). The funding agency played no role in the research or the writing of the manuscript. Authors' contributions XXZ, MWL and JHW designed the study. XXZ, MWL, WLW, RJY, ZRL, XYS and JL extracted the data. XXZ, MWL and WLW did the statistical analyses. MWL and XYS prepared the figure. XXZ and MWL wrote the manuscript. XXZ, MWL, YJY, QQC and JHW reviewed and edited the paper. Acknowledgments Not applicable. References Djulbegovic B, Guyatt GH: Progress in evidence-based medicine: a quarter century on . Lancet (London, England) 2017, 390 (10092):415-423. Glasziou P, Altman DG, Bossuyt P, Boutron I, Clarke M, Julious S, Michie S, Moher D, Wager E: Reducing waste from incomplete or unusable reports of biomedical research . Lancet (London, England) 2014, 383 (9913):267-276. Dwan K, Altman DG, Arnaiz JA, Bloom J, Chan AW, Cronin E, Decullier E, Easterbrook PJ, Von Elm E, Gamble C et al : Systematic review of the empirical evidence of study publication bias and outcome reporting bias . PLoS One 2008, 3 (8):e3081. Schulz KF: Assessing allocation concealment and blinding in randomised controlled trials: why bother? Equine Vet J 2005, 37 (5):394-395. Moore TJ, Zhang H, Anderson G, Alexander GC: Estimated Costs of Pivotal Trials for Novel Therapeutic Agents Approved by the US Food and Drug Administration, 2015-2016 . JAMA internal medicine 2018, 178 (11):1451-1457. Dal-Ré R, Caplan AL: SPIRIT 2025 and CONSORT 2025 Statements: Guidance Tools to Ensure Clinical Trial Transparency . Archivos de bronconeumologia 2025. Kuroki L, Guntupalli SR: Treatment of epithelial ovarian cancer . BMJ (Clinical research ed) 2020, 371 :m3773. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F: Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries . CA Cancer J Clin 2021, 71 (3):209-249. Liang L, Zhang Y, Li C, Liao Y, Wang G, Xu J, Li Y, Yuan G, Sun Y, Zhang R et al : Plasma cfDNA methylation markers for the detection and prognosis of ovarian cancer . EBioMedicine 2022, 83 :104222. Hurwitz LM, Pinsky PF, Trabert B: General population screening for ovarian cancer . Lancet (London, England) 2021, 397 (10290):2128-2130. Siegel RL, Miller KD, Fuchs HE, Jemal A: Cancer Statistics, 2021 . CA Cancer J Clin 2021, 71 (1):7-33. Konstantinopoulos PA, Matulonis UA: Clinical and translational advances in ovarian cancer therapy . Nat Cancer 2023, 4 (9):1239-1257. Kielbik M, Przygodzka P, Szulc-Kielbik I, Klink M: Snail transcription factors as key regulators of chemoresistance, stemness and metastasis of ovarian cancer cells . Biochim Biophys Acta Rev Cancer 2023, 1878 (6):189003. Labanieh L, Mackall CL: CAR immune cells: design principles, resistance and the next generation . Nature 2023, 614 (7949):635-648. Dagher OK, Schwab RD, Brookens SK, Posey AD, Jr.: Advances in cancer immunotherapies . Cell 2023, 186 (8):1814-1814.e1811. Baker DJ, Arany Z, Baur JA, Epstein JA, June CH: CAR T therapy beyond cancer: the evolution of a living drug . Nature 2023, 619 (7971):707-715. Moore KN, Bookman M, Sehouli J, Miller A, Anderson C, Scambia G, Myers T, Taskiran C, Robison K, Mäenpää J et al : Atezolizumab, Bevacizumab, and Chemotherapy for Newly Diagnosed Stage III or IV Ovarian Cancer: Placebo-Controlled Randomized Phase III Trial (IMagyn050/GOG 3015/ENGOT-OV39) . Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2021, 39 (17):1842-1855. Monk BJ, Colombo N, Oza AM, Fujiwara K, Birrer MJ, Randall L, Poddubskaya EV, Scambia G, Shparyk YV, Lim MC et al : Chemotherapy with or without avelumab followed by avelumab maintenance versus chemotherapy alone in patients with previously untreated epithelial ovarian cancer (JAVELIN Ovarian 100): an open-label, randomised, phase 3 trial . Lancet Oncol 2021, 22 (9):1275-1289. Kurtz JE, Pujade-Lauraine E, Oaknin A, Belin L, Leitner K, Cibula D, Denys H, Rosengarten O, Rodrigues M, de Gregorio N et al : Atezolizumab Combined With Bevacizumab and Platinum-Based Therapy for Platinum-Sensitive Ovarian Cancer: Placebo-Controlled Randomized Phase III ATALANTE/ENGOT-ov29 Trial . Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2023, 41 (30):4768-4778. Rocconi RP, Grosen EA, Ghamande SA, Chan JK, Barve MA, Oh J, Tewari D, Morris PC, Stevens EE, Bottsford-Miller JN et al : Gemogenovatucel-T (Vigil) immunotherapy as maintenance in frontline stage III/IV ovarian cancer (VITAL): a randomised, double-blind, placebo-controlled, phase 2b trial . Lancet Oncol 2020, 21 (12):1661-1672. Brown TA, Byrd K, Vreeland TJ, Clifton GT, Jackson DO, Hale DF, Herbert GS, Myers JW, Greene JM, Berry JS et al : Final analysis of a phase I/IIa trial of the folate-binding protein-derived E39 peptide vaccine to prevent recurrence in ovarian and endometrial cancer patients . Cancer Med 2019, 8 (10):4678-4687. Kershaw MH, Westwood JA, Parker LL, Wang G, Eshhar Z, Mavroukakis SA, White DE, Wunderlich JR, Canevari S, Rogers-Freezer L et al : A phase I study on adoptive immunotherapy using gene-modified T cells for ovarian cancer . Clin Cancer Res 2006, 12 (20 Pt 1):6106-6115. Chen J, Hu J, Gu L, Ji F, Zhang F, Zhang M, Li J, Chen Z, Jiang L, Zhang Y et al : Anti-mesothelin CAR-T immunotherapy in patients with ovarian cancer . Cancer Immunol Immunother 2023, 72 (2):409-425. Berek J, Taylor P, McGuire W, Smith LM, Schultes B, Nicodemus CF: Oregovomab maintenance monoimmunotherapy does not improve outcomes in advanced ovarian cancer . Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2009, 27 (3):418-425. Herzog TJ, Pignata S, Ghamande SA, Rubio MJ, Fujiwara K, Vulsteke C, Armstrong DK, Sehouli J, Coleman RL, Gabra H et al : Randomized phase II trial of farletuzumab plus chemotherapy versus placebo plus chemotherapy in low CA-125 platinum-sensitive ovarian cancer . Gynecol Oncol 2023, 170 :300-308. Revythis A, Limbu A, Mikropoulos C, Ghose A, Sanchez E, Sheriff M, Boussios S: Recent Insights into PARP and Immuno-Checkpoint Inhibitors in Epithelial Ovarian Cancer . International journal of environmental research and public health 2022, 19 (14). Awada A, Ahmad S, McKenzie ND, Holloway RW: Immunotherapy in the Treatment of Platinum-Resistant Ovarian Cancer: Current Perspectives . OncoTargets and therapy 2022, 15 :853-866. Barber E, Matei D: Immunotherapy in ovarian cancer: we are not there yet . The Lancet Oncology 2021, 22 (7):903-905. Brewer M, Angioli R, Scambia G, Lorusso D, Terranova C, Panici PB, Raspagliesi F, Scollo P, Plotti F, Ferrandina G et al : Front-line chemo-immunotherapy with carboplatin-paclitaxel using oregovomab indirect immunization in advanced ovarian cancer: A randomized phase II study . Gynecol Oncol 2020, 156 (3):523-529. Rocconi RP, Monk BJ, Walter A, Herzog TJ, Galanis E, Manning L, Bognar E, Wallraven G, Stanbery L, Aaron P et al : Gemogenovatucel-T (Vigil) immunotherapy demonstrates clinical benefit in homologous recombination proficient (HRP) ovarian cancer . Gynecol Oncol 2021, 161 (3):676-680. Kandalaft LE, Dangaj Laniti D, Coukos G: Immunobiology of high-grade serous ovarian cancer: lessons for clinical translation . Nat Rev Cancer 2022, 22 (11):640-656. Xie G, Dong H, Liang Y, Ham JD, Rizwan R, Chen J: CAR-NK cells: A promising cellular immunotherapy for cancer . EBioMedicine 2020, 59 :102975. Wang Q, Bergholz JS, Ding L, Lin Z, Kabraji SK, Hughes ME, He X, Xie S, Jiang T, Wang W et al : STING agonism reprograms tumor-associated macrophages and overcomes resistance to PARP inhibition in BRCA1-deficient models of breast cancer . Nat Commun 2022, 13 (1):3022. Morand S, Devanaboyina M, Staats H, Stanbery L, Nemunaitis J: Ovarian Cancer Immunotherapy and Personalized Medicine . International journal of molecular sciences 2021, 22 (12). Toulmonde M, Bellera C, Mathoulin-Pelissier S, Debled M, Bui B, Italiano A: Quality of randomized controlled trials reporting in the treatment of sarcomas . Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2011, 29 (9):1204-1209. Chen YP, Chen L, Li WF, Lee AWM, Vermorken JB, Wee J, O'Sullivan B, Eisbruch A, Lin JC, Mai HQ et al : Reporting Quality of Randomized, Controlled Trials Evaluating Combined Chemoradiotherapy in Nasopharyngeal Carcinoma . International journal of radiation oncology, biology, physics 2017, 98 (1):170-176. Ito T, Sugasawa S: Grouped generalized estimating equations for longitudinal data analysis . Biometrics 2023, 79 (3):1868-1879. Hopewell S, Chan AW, Collins GS, Hróbjartsson A, Moher D, Schulz KF, Tunn R, Aggarwal R, Berkwits M, Berlin JA et al : CONSORT 2025 statement: updated guideline for reporting randomised trials . Lancet (London, England) 2025. Andersen MZ, Fonnes S, Rosenberg J: Time from submission to publication varied widely for biomedical journals: a systematic review . Current medical research and opinion 2021, 37 (6):985-993. Lazar Neto F, de Melo MAZ, Hidalgo Filho CMT, Mathias-Machado MC, Testa L, Campolina AG: Global representativeness and impact of funding sources in cost-effectiveness research on systemic therapies for advanced breast cancer: A systematic review . Breast (Edinburgh, Scotland) 2024, 75 :103727. Hirsch BR, Califf RM, Cheng SK, Tasneem A, Horton J, Chiswell K, Schulman KA, Dilts DM, Abernethy AP: Characteristics of oncology clinical trials: insights from a systematic analysis of ClinicalTrials.gov . JAMA internal medicine 2013, 173 (11):972-979. Giacalone NJ, Milani N, Rawal B, Catalano PJ, Nguyen PL, Schoenfeld JD, Tishler RB, Margalit DN: Funding Support and Principal Investigator Leadership of Oncology Clinical Trials Using Radiation Therapy . International journal of radiation oncology, biology, physics 2018, 102 (1):34-43. Yoo SK, Ahmed AA, Ileto J, Zaorsky NG, Deville C, Holliday EB, Wilson LD, Jagsi R, Thomas CR, Jr.: Industry Funding Among Leadership in Medical Oncology and Radiation Oncology in 2015 . International journal of radiation oncology, biology, physics 2017, 99 (2):280-285. Sponchiado-Júnior EC, Vieira WA, Frozoni M, Herkrath FJ, de-Jesus-Soares A: CONSORT Compliance in Randomized Clinical Trials of Regenerative Endodontic Treatments of Necrotic Immature Teeth: A Scoping Review . J Endod 2021, 47 (11):1751-1766. Moher D, Pham B, Jones A, Cook DJ, Jadad AR, Moher M, Tugwell P, Klassen TP: Does quality of reports of randomised trials affect estimates of intervention efficacy reported in meta-analyses? Lancet (London, England) 1998, 352 (9128):609-613. Savović J, Jones HE, Altman DG, Harris RJ, Jüni P, Pildal J, Als-Nielsen B, Balk EM, Gluud C, Gluud LL et al : Influence of reported study design characteristics on intervention effect estimates from randomized, controlled trials . Annals of internal medicine 2012, 157 (6):429-438. Demetriades AK, Tiefenbach J, Park JJ, Anwar MM, Raza SM: What is the quality of reporting in randomized controlled trials in spinal conditions . J Craniovertebr Junction Spine 2023, 14 (4):404-411. Yang J, Yu F, Lin K, Qu H, He Y, Zhao J, Feng F, Pan L, Kui Y: Assessment of Reporting Quality in Randomized Controlled Trials of Acupuncture for Primary Insomnia with CONSORT Statement and STRICTA Guidelines . Evid Based Complement Alternat Med 2022, 2022 :5157870. Yang Y, Han Y, Zou G, Sui Y, Jin J, Liu L: Reporting quality of randomized controlled trials evaluating non-vitamin K oral anticoagulants in atrial fibrillation: a systematic review . BMC Cardiovasc Disord 2023, 23 (1):229. Bachelet VC, Navarrete MS, Barrera-Riquelme C, Carrasco VA, Dallaserra M, Díaz RA, Ibarra Á A, Lizana FJ, Meza-Ducaud N, Saavedra MG et al : A multiyear systematic survey of the quality of reporting for randomised trials in dentistry, neurology and geriatrics published in journals of Spain and Latin America . BMC Med Res Methodol 2021, 21 (1):153. Devereaux PJ, Choi PT, El-Dika S, Bhandari M, Montori VM, Schünemann HJ, Garg AX, Busse JW, Heels-Ansdell D, Ghali WA et al : An observational study found that authors of randomized controlled trials frequently use concealment of randomization and blinding, despite the failure to report these methods . Journal of clinical epidemiology 2004, 57 (12):1232-1236. Soares HP, Daniels S, Kumar A, Clarke M, Scott C, Swann S, Djulbegovic B: Bad reporting does not mean bad methods for randomised trials: observational study of randomised controlled trials performed by the Radiation Therapy Oncology Group . BMJ (Clinical research ed) 2004, 328 (7430):22-24. Santomasso BD, Nastoupil LJ, Adkins S, Lacchetti C, Schneider BJ, Anadkat M, Atkins MB, Brassil KJ, Caterino JM, Chau I et al : Management of Immune-Related Adverse Events in Patients Treated With Chimeric Antigen Receptor T-Cell Therapy: ASCO Guideline . Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2021, 39 (35):3978-3992. Brahmer JR, Abu-Sbeih H, Ascierto PA, Brufsky J, Cappelli LC, Cortazar FB, Gerber DE, Hamad L, Hansen E, Johnson DB et al : Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immune checkpoint inhibitor-related adverse events . J Immunother Cancer 2021, 9 (6). Yin Q, Wu L, Han L, Zheng X, Tong R, Li L, Bai L, Bian Y: Immune-related adverse events of immune checkpoint inhibitors: a review . Frontiers in immunology 2023, 14 :1167975. Xie T, Zhang Z, Qi C, Lu M, Zhang X, Li J, Shen L, Peng Z: The Inconsistent and Inadequate Reporting Of Immune-Related Adverse Events in PD-1/PD-L1 Inhibitors: A Systematic Review of Randomized Controlled Clinical Trials . The oncologist 2021, 26 (12):e2239-e2246. Lai R, Chu R, Fraumeni M, Thabane L: Quality of randomized controlled trials reporting in the primary treatment of brain tumors . Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2006, 24 (7):1136-1144. Kloukos D, Papageorgiou SN, Doulis I, Petridis H, Pandis N: Reporting quality of randomised controlled trials published in prosthodontic and implantology journals . Journal of oral rehabilitation 2015, 42 (12):914-925. Krzyzanowska MK, Pintilie M, Brezden-Masley C, Dent R, Tannock IF: Quality of abstracts describing randomized trials in the proceedings of American Society of Clinical Oncology meetings: guidelines for improved reporting . Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2004, 22 (10):1993-1999. Vinkers CH, Lamberink HJ, Tijdink JK, Heus P, Bouter L, Glasziou P, Moher D, Damen JA, Hooft L, Otte WM: The methodological quality of 176,620 randomized controlled trials published between 1966 and 2018 reveals a positive trend but also an urgent need for improvement . PLoS Biol 2021, 19 (4):e3001162. Tables Table 1 Overall reporting quality: Assessment based on the 2025 CONSORT statement items (n=53) Item Criteria Description No. of positive trials ％ 95％CI Cohen’s k coefficient 1 Title Whether it is clearly stated in the title as a randomized trial 38 72 60,84 1.000 2 Abstract A structured abstract summarizing the trial's design, methods, results, and conclusions 41 77 66,89 0.948 3 Registration The trial registry's name, identification number (including URL), and the date of registration 0 0 0,0 NA 4 Protocol Access details for the trial protocol and the statistical analysis plan 8 15 5,25 0.662 5 Data sharing The location and procedure for accessing de-identified individual participant data (including a data dictionary), statistical code, and other relevant materials 18 34 21,47 0.879 6 Funding Sources of funding and additional support, alongside the role of founders in the trial's design, conduct, analysis, and reporting 20 38 25,51 0.921 7 Conflicts of interest Disclosure of financial and non-financial conflicts of interest for all manuscript authors 43 81 71,92 0.741 8 Background Presentation of the scientific background and rationale for the study 48 91 83,98 0.739 9 Objectives Specific objectives pertaining to both benefits and harms 21 40 26,53 0.771 10 Patient and public involvement Details regarding the involvement of patients or the public in the trial's design, conduct, and reporting 0 0 0,0 NA 11 Trial design Description of the trial design, encompassing its type (eg, parallel group, crossover), allocation ratio, and framework (eg, superiority, equivalence, non-inferiority, exploratory) 35 66 53,79 0.875 12 Settings and location Settings (eg, community, hospital) and geographical locations (eg, countries, sites) where the trial was conducted 27 51 37,64 0.887 13 Participants Eligibility criteria for participant enrolment 52 98 94,102 0.658 14 Administrator If applicable, eligibility criteria for participating sites and individuals administering the interventions (eg, surgeons, physiotherapists) 0 0 0,0 NA 15 Intervention and comparator Sufficiently detailed descriptions of the interventions and comparators to permit replication, including, if relevant, access to supplementary materials (eg, an intervention manual) 35 66 53,79 0.636 16 Outcome measures Pre-specified primary and secondary outcomes, detailing for each: the specific measurement variable (eg, systolic blood pressure), metric for analysis (eg, change from baseline, final value, time to event), method of aggregation (eg, median, proportion), and time point 33 62 49,75 0.642 17 Adverse event classification Definitions and assessment methods for harms (eg, systematic, non-systematic) 45 85 75,95 0.756 18 Sample size Justification for the sample size, including all underlying assumptions for its calculation 32 60 47,74 0.881 19 Randomization, Sequence generation Identity of the individual(s) who generated the random allocation sequence and the method employed 19 36 23,49 0.836 20 Randomization, restriction Type of randomization utilized and specifics of any restrictions applied (eg, stratification, blocking, block size) 33 62 49,75 0.920 21 Allocation concealment Mechanism employed to implement the random allocation sequence (eg, central computer/telephone; sequentially numbered, opaque, sealed containers), including steps taken to conceal the sequence until intervention assignment 8 15 5,25 0.733 22 Access to allocation Indication of whether personnel enrolling participants and those assigning interventions had access to the random allocation sequence 35 66 53,79 0.654 23 Blinding，group Specification of who was blinded following intervention assignment (eg, participants, care providers, outcome assessors, data analysts) 46 87 78,96 0.638 24 Blinding，implement If blinding was implemented, the method used to achieve it and a description of the similarity between interventions 19 36 23,49 0.748 25 Statistical methods Statistical methods applied for comparing groups regarding primary and secondary outcomes, including harms 47 89 80,97 0.912 26 Analysis population definition Definition of the analysis population(s) (eg, all randomized participants) and their group assignments 22 42 28,55 0.883 27 Missing data Methods employed for handling missing data within the analyses 1 2 -2,6 1.000 28 Methods of Ancillary analysis Methods for any supplementary analyses (eg, subgroup, sensitivity), clearly distinguishing between pre-specified and post hoc analyses 15 28 16,40 0.858 29 Diagram Presentation of a participant flow diagram adhering to CONSORT specifications 25 47 34,61 1.000 30 Participant flow For each group, the numbers of participants who were randomly assigned, received the intended intervention, and were analyzed for the primary outcome, along with details of exclusions 46 87 78,96 1.000 31 Recruitment Dates defining the recruitment period and the follow-up period for assessing beneficial and harmful outcomes 37 70 57,82 0.914 32 Outcomes and estimation Description of the interventions and comparators as actually administered (including, if applicable, details on who delivered them, participant adherence, and fidelity to the intended protocol) 16 30 18,43 0.821 33 Concomitant care Concomitant care received by each group during the trial period 17 32 20,45 0.957 34 Baseline data Table presenting baseline demographic and clinical characteristics for each group 50 94 88,101 1.000 35 Outcomes For each primary and secondary outcome, by group: (i) number of participants included in the analysis; (ii) number of participants with available data at the outcome time point; (iii) results for each group, including estimated effect size and its precision (eg, 95% confidence interval); (iv) for binary outcomes, presentation of both absolute and relative effect sizes 9 17 7,27 0.726 36 Harms or unintended events All instances of harms or unintended events observed in each group 42 79 68,90 0.844 37 Ancillary analyses Reporting of any other analyses performed (eg, subgroup, sensitivity), clearly distinguishing pre-specified from post hoc analyses 28 53 39,66 0.887 Abbreviations ： CI ＝ confidence interval ； CONSORT ＝ Consolidated Standards of Reporting Trials ； NA ＝ not available. * We could not calculate the Cohen’s k indices because the positive rate awarded by a investigator was 100 ％ for the item. Table 2 Univariate and multivariable analysis of overall quality score (OQS) with trial characteristics Univariate analyses Multivariable analyses Trial characteristic Mean OQS (95% CI) Estimate (95% CI)* P Estimate (95% CI)* P Published year Before 2010 13.0(9.3 to 16.7) Reference Reference After 2010 20.9(19.3 to 22.4) 8.9(4.5 to 11.2) .000 4.9(2.8 to 7.1) .000 Region Europe and North America 19.1(17.4 to 20.8) Reference Not included Others 18.9(11.0 to 26.7) -0.3(-5.2 to 4.7) .920 Funding Sources Government/foundation 13.7(10.4 to 17.0) Reference Reference Partially funded by industry 20.6(18.4 to 22.8) 7.0(1.1 to 12.9) .015 4.5(2.8 to 6.2) .000 Completely funded by industry 21.7(19.3 to 24.1) 8.0(2.7 to 13.4) .001 5.3(2.7 to 7.8) .000 Funding not reported 14.1(8.6 to 19.7) 0.5(-6.4 to -7.3) .998 2.3(0.4 to 4.2) .015 Main results Positive 17.9(15.6 to 20.2) Reference Not included Negative 20.2(17.7 to 22.7) 2.3(-1.1 to 5.6) .177 Phase of the trial Ⅰ 16.0(11.3 to 20.7) Reference Reference Ⅱ 20.4(18.7 to 22.1) 4.4(-2.3 to 11.1) .352 3.6(0.2 to 6.9) .038 Ⅲ 23.3(19.8 to 26.7) 7.3(-0.2 to 14.3) .040 6.1(1.3 to 10.9) .013 Ⅰ/Ⅱ 16.7(11.5 to 21.8) 0.7(-8.8 to 10.2) 1.000 2.0(-1.9 to 5.9) .315 Unclear 10.1(7.9 to 12.3) -5.9(-13.5 to 1.8) .203 -0.7(-3.7 to 2.3) .654 Sample size 500 24.4（20.7 to 28.1） 7.1(1.6 to 12.7) .008 0.2(-3.4 to 3.8) .903 Journal impact factor 10 22.7（20.8 to 24.6） 7.6(2.1 to 13.0) .004 1.3(-2.4 to 5.1) .482 Overall quality score rated on a scale of 0 to 37. *The estimates show the advantage observed in comparison to the reference. A positive value indicates additional benefit compared to the reference, while a negative value indicates a disadvantage compared to the reference. Additional Declarations No competing interests reported. Supplementary Files Additionalfile.docx SupplementaryTable1.docx SupplementaryTable2.docx SupplementaryTable3.docx SupplementaryTable4.docx Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 06 May, 2026 Reviewers agreed at journal 27 Apr, 2026 Reviews received at journal 26 Apr, 2026 Reviewers agreed at journal 25 Apr, 2026 Reviews received at journal 24 Apr, 2026 Reviews received at journal 23 Apr, 2026 Reviewers agreed at journal 20 Apr, 2026 Reviewers agreed at journal 20 Apr, 2026 Reviews received at journal 17 Apr, 2026 Reviewers agreed at journal 17 Apr, 2026 Reviewers agreed at journal 16 Apr, 2026 Reviewers agreed at journal 14 Apr, 2026 Reviewers invited by journal 14 Apr, 2026 Editor assigned by journal 13 Apr, 2026 Editor invited by journal 25 Mar, 2026 Submission checks completed at journal 16 Mar, 2026 First submitted to journal 16 Mar, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9020902","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":626751738,"identity":"ed846ff8-7d12-40e0-9902-75725a971124","order_by":0,"name":"Mingwei Liang","email":"","orcid":"","institution":"Shandong University","correspondingAuthor":false,"prefix":"","firstName":"Mingwei","middleName":"","lastName":"Liang","suffix":""},{"id":626751739,"identity":"f0ad99f2-597e-4022-935a-6eaa0dbfac3e","order_by":1,"name":"Xinxin Zhang","email":"","orcid":"","institution":"The Second Hospital of Shandong University","correspondingAuthor":false,"prefix":"","firstName":"Xinxin","middleName":"","lastName":"Zhang","suffix":""},{"id":626751740,"identity":"33a46ad5-ab8d-4de6-9c3c-86dcb576fa34","order_by":2,"name":"Wenli Wu","email":"","orcid":"","institution":"Jining Medical University","correspondingAuthor":false,"prefix":"","firstName":"Wenli","middleName":"","lastName":"Wu","suffix":""},{"id":626751741,"identity":"b25e43f5-698e-4d61-9d5b-f27e1354cd76","order_by":3,"name":"Ruijie Yu","email":"","orcid":"","institution":"Shandong University","correspondingAuthor":false,"prefix":"","firstName":"Ruijie","middleName":"","lastName":"Yu","suffix":""},{"id":626751743,"identity":"4cbfd688-3d60-4e26-a75f-17e1e9a1800b","order_by":4,"name":"Zhiruo Liao","email":"","orcid":"","institution":"The Second Hospital of Shandong University","correspondingAuthor":false,"prefix":"","firstName":"Zhiruo","middleName":"","lastName":"Liao","suffix":""},{"id":626751749,"identity":"9899ca9b-b7cf-4a78-8243-e8c32922a904","order_by":5,"name":"Qianqian Cao","email":"","orcid":"","institution":"The Second Hospital of Shandong University","correspondingAuthor":false,"prefix":"","firstName":"Qianqian","middleName":"","lastName":"Cao","suffix":""},{"id":626751750,"identity":"af1641b1-4060-43af-a4f1-541323d46b7e","order_by":6,"name":"Xiyue Su","email":"","orcid":"","institution":"Shandong University","correspondingAuthor":false,"prefix":"","firstName":"Xiyue","middleName":"","lastName":"Su","suffix":""},{"id":626751751,"identity":"f2c32183-eb26-4a11-acff-c46b93b020a5","order_by":7,"name":"Jia lu","email":"","orcid":"","institution":"The Second Hospital of Shandong University","correspondingAuthor":false,"prefix":"","firstName":"Jia","middleName":"","lastName":"lu","suffix":""},{"id":626751752,"identity":"66890fff-aee5-427e-a439-fd2d01b97fb4","order_by":8,"name":"Jihua Wang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA6ElEQVRIiWNgGAWjYLACCYMDDAzszQcffDCwsSNBC8+xZMMZBWnJxNoD1CLhoybM8+EQYwMhtQbHzx5+YVFwJ7F/Bg8bs43BAWYG9sNHN+DVciYvzULC4FnijNu9xx7nGNzhY+BJS7uBT4vZgRwzAwmDw4kNd86lG+cYPGNmkOAxw6/l/BuIlvk3csykLQwOMzYQ1HIjx/gBSMsGkBYGYrTY33hjBgzkw8YbzwADuccgLZmNkF8k+3OMP0v8OSw77zgwKn/8sbHjZz98DK8WIGCTlkDhElAOAswfPxChahSMglEwCkYwAAAMM1PN1EyiFAAAAABJRU5ErkJggg==","orcid":"","institution":"The Second Hospital of Shandong University","correspondingAuthor":true,"prefix":"","firstName":"Jihua","middleName":"","lastName":"Wang","suffix":""}],"badges":[],"createdAt":"2026-03-03 13:53:17","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9020902/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9020902/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":107614964,"identity":"2c70f465-63da-4ef1-bca0-af00c9c7c474","added_by":"auto","created_at":"2026-04-23 09:10:39","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":187806,"visible":true,"origin":"","legend":"\u003cp\u003eDiagram flow of the process for selecting randomized controlled trials.\u003c/p\u003e","description":"","filename":"Figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-9020902/v1/9e27f08f2be3772ac9989a27.jpg"},{"id":107615073,"identity":"4043e389-8926-4e49-acaa-51a4141ff893","added_by":"auto","created_at":"2026-04-23 09:10:53","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":71744,"visible":true,"origin":"","legend":"\u003cp\u003eTrial characteristics (n=53)\u003c/p\u003e","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-9020902/v1/4dc9fd907194e637566f846b.jpg"},{"id":107615318,"identity":"6c7912bc-d674-4c7d-b86d-0f5f3a9c99f5","added_by":"auto","created_at":"2026-04-23 09:11:21","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":1030076,"visible":true,"origin":"","legend":"\u003cp\u003ePercentage of studies meeting CONSORT criteria grouped by study section.\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-9020902/v1/b1583cb9e4abc19376a58782.png"},{"id":107616232,"identity":"021780df-abea-4cc1-8e44-b259e48c786f","added_by":"auto","created_at":"2026-04-23 09:12:54","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3921229,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9020902/v1/e0508dff-88eb-481c-833a-15e43611b3de.pdf"},{"id":107614952,"identity":"c492bd04-9684-47b7-82b7-7a90083f9763","added_by":"auto","created_at":"2026-04-23 09:10:36","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":49662,"visible":true,"origin":"","legend":"","description":"","filename":"Additionalfile.docx","url":"https://assets-eu.researchsquare.com/files/rs-9020902/v1/5b2ef15546319cc8b04fcb35.docx"},{"id":107614947,"identity":"e92675ba-49ca-497c-8bf3-c89a77c571aa","added_by":"auto","created_at":"2026-04-23 09:10:36","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":14963,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryTable1.docx","url":"https://assets-eu.researchsquare.com/files/rs-9020902/v1/e374c62f1c6b9c0f2d8dbd69.docx"},{"id":107615072,"identity":"549905b3-964a-4c1b-8a55-0d5abd31aff7","added_by":"auto","created_at":"2026-04-23 09:10:53","extension":"docx","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":25113,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryTable2.docx","url":"https://assets-eu.researchsquare.com/files/rs-9020902/v1/4b4850620b85b488fc102527.docx"},{"id":107614971,"identity":"846f7902-cf80-48b6-bc73-0148c592efed","added_by":"auto","created_at":"2026-04-23 09:10:39","extension":"docx","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":14747,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryTable3.docx","url":"https://assets-eu.researchsquare.com/files/rs-9020902/v1/ee0d183e33b7066be5d56e24.docx"},{"id":107615683,"identity":"5a241b63-d784-4b63-8b58-cf7c2477860c","added_by":"auto","created_at":"2026-04-23 09:12:08","extension":"docx","order_by":5,"title":"","display":"","copyAsset":false,"role":"supplement","size":24354,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryTable4.docx","url":"https://assets-eu.researchsquare.com/files/rs-9020902/v1/516507a931b52bdeb2aea5a3.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Reporting quality of randomized, controlled trials evaluating immunotherapy for ovarian cancer: cross-sectional study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eRandomized controlled trials (RCTs) have long been regarded as the superior study design in the evidence hierarchy of evidence-based medicine determined by its rigorous attributes to minimize biases[1], which has a direct impact on results of systematic reviews and the development of clinical guidelines. However, RCTs may still exhibit bias if they are conducted with defective methods, and inferior reporting of the trials hinders evaluation of their methodological quality[2]. Moreover, inadequately reported RCTs may lead to misinterpretation of trial results and erroneous clinical decisions[3, 4]. Due to the costly nature of RCTs, poor reporting can also result in significant financial waste[5]. The Consolidated Standards of Reporting Trials (CONSORT) is a valid exploration to promote transparent and clear reporting of RCTs[6].\u003c/p\u003e\n\u003cp\u003eOvarian cancer remains the eighth leading cause of cancer-related mortality in women worldwide [7, 8]. Due to the deficiency of early detection, around 70% of ovarian cancers are at advanced stages at the time of diagnosis[9-11], entailing an urgent need for novel therapies apart from surgery and chemotherapy, which are still the mainstay treatment but succumb to recurrence and chemoresistance in most situations[12, 13] . To date, immunotherapy has become a distinct pillar of cancer treatment with validated efficacy[14-16]. Since the immunogenic nature of ovarian cancer, great hopes have been placed on immunotherapeutic approaches, and a number of trials of immune checkpoint inhibitors[17-19], tumor vaccines[20, 21], adoptive cell therapies[22, 23], monoclonal antibodies[24, 25] and so on have been conducted[26, 27]. Despite the response remains modest[28], statistically significant improvements or promising trends were identified in some trials[20, 29], especially in certain predefined subgroups[30]. With deepening understanding of immunobiology of ovarian cancer[31], newly-developed immunotherapeutic strategies and synergistic combinations are heatedly investigated[32, 33], and many trials are ongoing[34].\u003c/p\u003e\n\u003cp\u003eEffective incorporation of immunotherapy remains a priority in therapeutic research of ovarian cancer[12], so high-quality RCTs are urgently needed for this field. Whereas, there is a lack of investigations to comprehensively evaluate reporting quality of RCTs for immunotherapy of ovarian cancer. This evaluation would be valuable to reveal existing deficiencies for researchers to improve reporting of their as-yet-unpublished trials, thereby facilitating communication and interpretation of the latest advances and reducing waste of funds. And the assessment can provide a reference for bias estimation. Accordingly, the objective of this study is to evaluate the reporting quality of RCTs investigating immunotherapy for ovarian cancer based on the CONSORT statement, rather than to synthesize their clinical outcomes.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cstrong\u003eStudy selection\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAs a cross-sectional,\u003cem\u003e\u0026nbsp;meta-epidemiological\u003c/em\u003e study, the subjects of this study were published RCTs on immunotherapy for ovarian cancer. We retrieved RCTs from \u003cem\u003ePubmed.gov\u003c/em\u003e and \u003cem\u003eembase.com\u003c/em\u003e to\u0026nbsp;find all of the published RCTs that focus on immunotherapy for ovarian cancer from January 1, 1980 to July 25, 2025. The keywords used in the literature search were \u0026quot;ovarian neoplasms\u0026quot;, \u0026quot;immunotherap*\u0026quot;, \u0026quot;PD-1\u0026quot;, \u0026quot;PD-L1\u0026quot;, \u0026quot;CTLA-4\u0026quot;, \u0026quot;CAR-T\u0026quot; , \u0026quot;vaccine*\u0026quot; and \u0026quot;monoclonal antibody\u0026quot; , with \u0026quot;randomized controlled trials\u0026quot; as limitation.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInclusion and exclusion criteria\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe collected articles that evaluate immunotherapy alone, compared with other therapies (such as radiation or chemotherapy) on their own or in combination with immunotherapy, and articles comparing different strategies for immunotherapy in combination with other therapies.\u003c/p\u003e\n\u003cp\u003eThe RCTs only about therapies other than immunotherapy or not focus on ovarian cancer were eliminated. The literatures which were non-English, not focused on immunotherapy of ovarian cancer, not RCTs, incomplete trials, incomplete articles which only have abstract, secondary study of published trials, and repeated articles were also excluded. For RCTs that published twice or more, we chose the article that published its main results. So the articles we chose were all independent. (Figure 1)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eOverall Reporting Quality\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe overall quality score (OQS) [35, 36]was adopted to estimate the reporting quality of the contained trials. The OQS includes 37 items for appraising, which is a standardized checklist derived from the 2025 CONSORT statement (Table 1). Then, two investigators marked the articles independently: If an item is described accurately in an article, it scored \u0026quot;1\u0026quot;. If an item is poorly described or isn\u0026apos;t reported, it scored \u0026quot;0\u0026quot;. The problem of scoring deviation caused by inconsistent understanding of CONSORT was solved by discussion and correction.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical Analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe scores of the 37 items were analyzed, and the ratio and 95% CI confidence interval of each scoring item were calculated respectively. Cohen\u0026apos;s \u0026kappa; Statistics evaluation was carried out on the scores of the two raters : \u0026kappa;\u0026gt; 0.5 is qualified; 0.6\u0026lt; \u0026kappa;\u0026lt; 0.8 is considerable; 0.8\u0026lt; \u0026kappa;\u0026lt; 1 is excellent; \u0026kappa;= 1 is perfect. Data on AE was analyzed with the same standard.\u003c/p\u003e\n\u003cp\u003eTo explore potential predictive factors of overall quality of reporting, OQS was used as the dependent variable which was modeled by linear regression. In consideration of possible with-in journal correlation of articles which were published in the same journal, generalized estimating equations were used[37]. Journal was regarded as the cluster variable, and an exchangeable structure was adopted for the correlation matrix.\u003c/p\u003e\n\u003cp\u003eUnivariate analyses were done firstly and factors included were funding sources, published year, region, main results, phase of the trial, sample size and journal impact factor. Variables with a significance of 10% were included in multivariate analyses. Significant variables (\u003cem\u003ep\u003c/em\u003e\u0026lt;0.05) in the multivariate model were considered as independent determinants of reporting quality.\u003c/p\u003e\n\u003cp\u003eAll statistical analyses were conducted using the SPSS software version 25.0.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFurther collection of data on trial reporting\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTo further estimate the reporting quality of some specific sections, we collected detailed data on key methodological factors (blinding, allocation concealment, analysis followed by the intention-to-treat (ITT) principle), endpoint setting, follow-up and adverse event (AE) reporting [see Table S1~Table S4, Additional file 1].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eOther details\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe elaboration of search strategy, selection and appraisal process and other details of our study methods are reported in Additional file 1.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003eTrial Characteristics\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThere are totally fifty-three trials included and systematically analyzed in our study. The basic characteristics of each trial included, such as publication year, region and journal are collected. The data of trial characteristics is displayed in Table 2. The trials are all published in 1980 or later, in which most of them were published after 2010 (n=41). Most of the trials took place in Europe or North America (n = 46) and were phase Ⅱ (n = 24) or phase Ⅲ (n = 14). 12346 participants were randomly allocated among the trials. The median participant number was 100 , with a range of 14 to 1301. The inter-rater agreements of all of the items between the two researchers involved in the marking process were considerable, excellent or perfect.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eOverall Reporting Quality\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOQS of the studies ranged from 7 to 30 on a scale of 0 to 37. The mean OQS was 19.08 (s.d. = 6.07, 95%CI = 17.40，20.75). The median OQS was 20.00, reflecting more than 46% of the items were inadequately stated in more than half of the studies (Figure 2). According to specific items, although some trials reported their registration status, none provided details on the registration date. Additionally, patient and public involvement (PPI) as well as the inclusion criteria for research centers and intervention implementers were not mentioned in any article. Consequently, all 53 trials scored 0 for these three items, and the next most poorly reported aspect was the handling of missing data, with only 2% (n = 1) of the trials documenting this. Besides, reporting for settings and location, sample size calculation, randomized sequence generation, methods of allocation concealment, blinding, methods of ancillary analysis, flow diagram, results of ancillary analysis, registration and full trial protocol were poor in more than half of the articles.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAssociations between Trial Characteristics and Overall Quality of Reporting\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn univariate analyses, published after 2010, completely or partially funded by industry, phase Ⅱ or phase Ⅲ, sample size of more than 500, and impact factor of more than 10 were associated with an increased OQS. In multivariate analyses, published after 2010 and completely or partially funded by industry remained independent significant factors of overall reporting quality (Table 2).\u003c/p\u003e\n\u003cp\u003eTo further elaborate on the results of the multivariate model, we explored the interrelationships among key predictors. Non-parametric correlation analysis revealed a significant positive correlation between sample size and journal impact factor (Spearman\u0026apos;s \u0026rho; = 0.475, P = 0.000, P \u0026lt; 0.01), while no significant correlation was observed between sample size and publication year (Spearman\u0026rsquo;s \u0026rho; = 0.057, P = 0.685, P \u0026gt; 0.05). Additionally, cross-tabulation reveals that no significant associations were observed between funding sources and year, sample size, impact factor, trial phase, or primary outcomes.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eKey Methodological Factors, Endpoint Setting, Follow-up and AE Reporting\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWhen it comes to key methodologic factors (Table S1, Additional file 1), allocation concealment is only reported in 21% (n = 11) of the trials, 10 of which used centralized randomization, while the remainder used envelopes that are non-transparent, sealed and numbered in sequence. Blinding is reported in 42% (n = 22) of the trials, where data monitor or statistical analyst was stated to be blinded in only 4 trials. 57% (n = 30) of the trials adequately adhered to the ITT principle. But another 13% (n = 7) mentioned ITT but did not keep to it in practical analysis, or used items like \u0026quot;modified ITT\u0026quot;, making the term \u0026quot;ITT\u0026quot; confusing. A variety of endpoints were used in the including trials (Table S2, Additional file 1). The most commonly used endpoint (85%, n = 45) was overall survival, and the most favorable primary endpoint (47%, n = 25) was progression-free survival (PFS). In the follow-up measurement (Table S3, Additional file 1), the longest and shortest period was reported in only 8% (n = 4) of the trials. The median items adequately followed among the 16 items evaluating reporting of AE was 6 (Table S4, Additional file 1). The worst item in AE reporting is non-prespecified harm outcomes, estimated effect sizes and precision of each adverse event.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study is the first reporting quality evaluation pertaining to immunotherapy of ovarian cancer. The CONSORT statement, as our benchmark, was recently updated on April 14, 2025, introducing a new \u0026quot;Open Science\u0026quot; section that for the first time incorporates items such as data sharing, conflicts of interest, patient and public involvement, eligibility criteria for implementation sites and implementers, harm assessment, handling of missing data, and concomitant care[38]. The introduction of these new items, along with revisions to existing ones, reflects a forward-looking approach aimed at providing a reference and targets for improving the reporting quality of future randomized controlled trials. Only one of our included articles was published after the update of the CONSORT Statement\u0026mdash;specifically on June 4, 2025. Given the time typically required for peer review and editorial processing in academic publishing[39], it can be inferred that the included trials (n=53) had virtually no opportunity to reference the newly released CONSORT Statement during trial conduct or manuscript drafting. Therefore, the generally poor and inadequate reporting quality of the newly introduced or revised CONSORT items may be deemed a reasonable outcome. Meanwhile, we found that although most of the articles included are published after 2010, reporting quality based on items retained from the 2010 version in CONSORT 2025 is still suboptimal. A concerning discovery was the significant variation in reporting quality, with the worst-reported study only completely reporting 13% of all items, and none of the included studies fully adhered to the CONSORT checklist. Articles with low scores diminish their evidential quality, and their findings should be treated prudently.\u003c/p\u003e\n\u003cp\u003eMultivariate analysis revealed that publication after 2010 was significantly associated with improved reporting quality. This indicates the positive role of the update and promotion of the CONSORT Statement in enhancing reporting quality and facilitating openness and transparency, and also predicts the potential of the latest 2025 update following its widespread promotion and adoption in the academic community. Additionally, being completely or partly funded by industry was also an independent and significant factor in improving reporting quality. Further analysis revealed that there was no significant association between funding sources and sample size, trial phase, primary outcomes, or impact factor\u0026mdash;even presenting an opposite distribution to the prior research conclusions of industry funding\u0026apos;s preference for small sample sizes, Phase I trials, and positive results[40, 41], or its negative effect on reporting quality[36]. This anomalous phenomenon may be attributed to the small number of randomized controlled clinical trials (RCTs) on ovarian cancer immunotherapy (n=53), which failed to establish a significant pattern. Additionally, literature examining funding sources for oncology clinical trials indicates that industry funding shows a significant preference for innovative therapies and drugs. Specifically, the odds ratio (OR) of industry funding for trials using immuno-oncology drugs reaches 11.22 (95% CI: 6.64\u0026ndash;18.97)[42], which raises a new possibility: given the potential advantages of ovarian cancer immunotherapy, the influx of industry funding (70%, n=37) may have broken the constraint of its preference for small sample sizes and Phase I trials[42]. Meanwhile, industry-funded trials are also subject to strict requirements from journals and review bodies, which may thus improve their reporting quality\u0026mdash;for instance, by engaging professionals, among other measures. As government investment in basic scientific research continues to decline, industry funding has become a key source of funding for biomedical research[43]. This suggests that we should re-examine the impact of industry funding on the design, conduct, and reporting of randomized controlled trials.\u003c/p\u003e\n\u003cp\u003ePoor CONSORT adherence is linked to a higher risk of bias[44]. Among all of the items, particular attention should be paid to the key methodological factors (allocation concealment, blinding, ITT), which are widely proved to be mostly related to the generation of bias and may impair the internal validity if they are insufficiently reported[45, 46]. Although a long-standing emphasis was placed[4], reporting of\u0026nbsp;sequence generation\u0026nbsp;of randomization,\u0026nbsp;allocation concealment and blinding implementation was far from adequate, which is only sufficient in 36%, 15% and 36% of included trials. Although open-label design may be conducive to judgment and management of irAEs, blinding can also be applied to outcome assessors and data analysts, but it was reported only in a few studies. This deficiency is consistent with other recent appraisal literatures on RCTs in varied medical fields[47-50], demonstrating it as a pervasive problem that urgently needs to be addressed. This may lead to confusion when readers try to estimate the credibility of the results, and some of the deficiencies may represent a deficient trial design and a more biased result. Since the number of studies is still small for reference, this may produce more adverse effects on research and clinical practices and retard the interpretation of the findings to other researchers.[2]\u003c/p\u003e\n\u003cp\u003eIn some previous studies[51, 52], researchers found that the procedures to avoid bias (such as allocation concealment and blinding) which weren\u0026apos;t reported in the article may be performed in the trial actually in even a large proportion. In one of the studies[51], allocation concealment wasn\u0026apos;t reported in 55% of the articles but was actually performed in 96% of the articles which didn\u0026apos;t report it. There may be a similar situation in the articles investigated in our study, causing underestimation of possibly valuable findings. It could be an alert to the clinical researchers to transparently document their procedures to mitigate bias in the reports to enhance the credibility of their studies.\u003c/p\u003e\n\u003cp\u003eAnother problem that needs to be stressed is the reporting of AEs. Due to the specific mechanism of immunotherapy deeply rooted in immune activation, a specific range of adverse events known as immune-related adverse events (irAEs) can occur not limited to the drug exposure period, but rather may persist for a long time alongside immune memory. These events can occur rapidly in the early stage of treatment[53], and can also manifest delayed in the middle to late stages of treatment, or even months to years after treatment discontinuation[54, 55]. irAEs differ in presentation from the adverse events of other well-investigated therapies (e.g., chemotherapy), and some irAEs can even be life-threatening. They can involve nearly all organ systems throughout the body, with a scope of involvement that far exceeds the limited set of systems\u0026mdash;such as the hematological, gastrointestinal, and mucosal systems\u0026mdash;usually affected by the toxicity of traditional chemotherapy[54]. Furthermore, the irAE spectra of different types of immunotherapies\u0026mdash;such as CTLA-4 inhibitors, PD-(L)1 inhibitors, and CAR-T cell therapies\u0026mdash;exhibit significant differences[53]. Additionally, the same type of immunotherapy also demonstrates variations in its toxicity spectrum across different tumor types[54, 55]. Despite grave consequences irAEs may lead to, the mechanisms underlying them are still poorly understood[54]. Although categories of common irAEs vary depending on particular immunotherapy strategies, meticulous documentation and adequate follow-up for AEs are essential for all immunotherapeutic regimens[56]. But reporting of these items is far from sufficient. Only 53% of the studies reported the timetable assessing AEs, and only 36% reported all AEs in their studies. Merely reporting AEs of interest is inadvisable in view of uncertain knowledge of irAEs. As long-term effects of these therapies remain unknown, it is favorable to extend monitoring to long-term post-treatment follow-up to further collect this data.\u003c/p\u003e\n\u003cp\u003eThe limited space for reporting in high impact factor journals is one of the reasons for incomplete reporting. The available full trial protocol in the supplementary material is a favorable measure to elaborate their methodological considerations and it can reduce nonadherence to the methods and outcome assessment standards regulated in the initial protocol as well, which is also recommended as a new checklist item in the CONSORT statement 2010 and Strengthened in CONSORT statement 2025 with statistical analysis plan. [38]. But only 8 of the 53 trials provided the full trial protocol and statistical analysis plan, making it the fifth worst reported item in our study. Although there are limitations, a full trial protocol is needed to be provided for a better interpretation of the study.\u003c/p\u003e\n\u003cp\u003eThere are several weaknesses in our study. Immunotherapy is a newly-developed field, so the trials evaluating immunotherapy of ovarian cancer are few, in comparison with similar studies focused on other therapies[35, 57, 58], which may contribute to the failure to establish significant patterns. Besides, the CONSORT checklist isn\u0026apos;t designed as an evaluation criteria initially, so we adopted OQS based on CONSORT to quantify the reporting quality. However, OQS has its limitations. Each item is treated equally in OQS, neglecting the different importance of the items. As a remedy, we collected detailed data in some of the significant parts, including the key methodological factors and some other information associated with quality of the studies. Moreover, the discussion section is not included in our study because its quality is hard to value in a quantitative way[59].\u003c/p\u003e\n\u003cp\u003eSome of the items such as title and sample size are less reported than some similar studies conducted before[6, 35, 36]. It may because we didn\u0026apos;t restrict the phase of the RCTs, and these items are most likely to be poorly reported in phase Ⅰ, Ⅰ/Ⅱ trials and in those not distinguishing the phase of the trial. The multivariate analysis revealed an improvement in reporting quality over time, consistent with a previous study examining the methodology of 176,620 RCTs[60]. This trend can be attributed to increased awareness of the importance of complete reporting and the growing adoption of CONSORT guidelines by a greater number of journals. Items such as interventions, eligibility criteria and baseline data are sufficiently reported in all or most of the studies, enhancing replication and comparison with other studies or specific patients. However, as stated above, there are still numerous issues that urgently need improvement and should be taken seriously by all investigators who attempt to report their RCTs.\u003c/p\u003e\n\u003cp\u003eThe improvement of trial reporting still has a long way to go, and it relies a lot on the awareness of the significance of a complete and transparent reporting among clinical trial conductors. The CONSORT statement should be popularized among clinical trial conductors and training could be useful, especially on the key methodological factors and the additional items in CONSORT 2025. There should be more journals accepting the CONSORT statement and setting a higher request for authors to follow it. The meticulous scrutiny of journal editors is also essential in this process.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eBased on the CONSORT Statement 2025, the overall reporting quality of randomized controlled trials (RCTs) focusing on immunotherapy for ovarian cancer is suboptimal. Previously published trials have shown poor reporting of newly added items such as Patient and Public Involvement (PPI) and trial registration, which may be attributed to time constraints. Although some items are well-reported, the reporting of key methodological items remains inadequate and requires great attention. Considering the particularity of immune-related adverse events (irAEs), meticulous documentation and adequate follow-up of adverse events (AEs) are necessary. The full trial protocol should be provided, especially when there is insufficient space in the article to specify the methods used to reduce bias. Publication after 2010 and complete or partial industry funding are independent and significant factors for improving reporting quality. However, the new finding that industry funding may promote reporting quality requires further verification. To enhance reporting quality, the awareness of clinical trial conductors is crucial; additionally, higher requirements and rigorous scrutiny from journals and editors for authors to comply with CONSORT guidelines are also an essential part of this process.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eRCTs: Randomized controlled trials; OQS: Overall quality score; CONSORT: Consolidated Standards of Reporting Trials; ITT: intention to treat; AE: Adverse events.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data generated in this article can be accessed upon reasonable request to the corresponding author.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research is funded by Medical Science Foundation of Beijing Bethune (6010224017) and Foundation of Science and Technology Research Institute of Shandong University (6010224010). The funding agency played no role in the research or the writing of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eXXZ, MWL and JHW designed the study. XXZ, MWL, WLW, RJY, ZRL, XYS and JL extracted the data. XXZ, MWL and WLW did the statistical analyses. MWL and XYS prepared the figure. XXZ and MWL wrote the manuscript. XXZ, MWL, YJY, QQC and JHW reviewed and edited the paper.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eDjulbegovic B, Guyatt GH: \u003cstrong\u003eProgress in evidence-based medicine: a quarter century on\u003c/strong\u003e. \u003cem\u003eLancet (London, England) \u003c/em\u003e2017, \u003cstrong\u003e390\u003c/strong\u003e(10092):415-423.\u003c/li\u003e\n\u003cli\u003eGlasziou P, Altman DG, Bossuyt P, Boutron I, Clarke M, Julious S, Michie S, Moher D, Wager E: \u003cstrong\u003eReducing waste from incomplete or unusable reports of biomedical research\u003c/strong\u003e. \u003cem\u003eLancet (London, England) \u003c/em\u003e2014, \u003cstrong\u003e383\u003c/strong\u003e(9913):267-276.\u003c/li\u003e\n\u003cli\u003eDwan K, Altman DG, Arnaiz JA, Bloom J, Chan AW, Cronin E, Decullier E, Easterbrook PJ, Von Elm E, Gamble C\u003cem\u003e et al\u003c/em\u003e: \u003cstrong\u003eSystematic review of the empirical evidence of study publication bias and outcome reporting bias\u003c/strong\u003e. \u003cem\u003ePLoS One \u003c/em\u003e2008, \u003cstrong\u003e3\u003c/strong\u003e(8):e3081.\u003c/li\u003e\n\u003cli\u003eSchulz KF: \u003cstrong\u003eAssessing allocation concealment and blinding in randomised controlled trials: why bother?\u003c/strong\u003e \u003cem\u003eEquine Vet J \u003c/em\u003e2005, \u003cstrong\u003e37\u003c/strong\u003e(5):394-395.\u003c/li\u003e\n\u003cli\u003eMoore TJ, Zhang H, Anderson G, Alexander GC: \u003cstrong\u003eEstimated Costs of Pivotal Trials for Novel Therapeutic Agents Approved by the US Food and Drug Administration, 2015-2016\u003c/strong\u003e. \u003cem\u003eJAMA internal medicine \u003c/em\u003e2018, \u003cstrong\u003e178\u003c/strong\u003e(11):1451-1457.\u003c/li\u003e\n\u003cli\u003eDal-R\u0026eacute; R, Caplan AL: \u003cstrong\u003eSPIRIT 2025 and CONSORT 2025 Statements: Guidance Tools to Ensure Clinical Trial Transparency\u003c/strong\u003e. \u003cem\u003eArchivos de bronconeumologia \u003c/em\u003e2025.\u003c/li\u003e\n\u003cli\u003eKuroki L, Guntupalli SR: \u003cstrong\u003eTreatment of epithelial ovarian cancer\u003c/strong\u003e. \u003cem\u003eBMJ (Clinical research ed) \u003c/em\u003e2020, \u003cstrong\u003e371\u003c/strong\u003e:m3773.\u003c/li\u003e\n\u003cli\u003eSung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F: \u003cstrong\u003eGlobal Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries\u003c/strong\u003e. \u003cem\u003eCA Cancer J Clin \u003c/em\u003e2021, \u003cstrong\u003e71\u003c/strong\u003e(3):209-249.\u003c/li\u003e\n\u003cli\u003eLiang L, Zhang Y, Li C, Liao Y, Wang G, Xu J, Li Y, Yuan G, Sun Y, Zhang R\u003cem\u003e et al\u003c/em\u003e: \u003cstrong\u003ePlasma cfDNA methylation markers for the detection and prognosis of ovarian cancer\u003c/strong\u003e. \u003cem\u003eEBioMedicine \u003c/em\u003e2022, \u003cstrong\u003e83\u003c/strong\u003e:104222.\u003c/li\u003e\n\u003cli\u003eHurwitz LM, Pinsky PF, Trabert B: \u003cstrong\u003eGeneral population screening for ovarian cancer\u003c/strong\u003e. \u003cem\u003eLancet (London, England) \u003c/em\u003e2021, \u003cstrong\u003e397\u003c/strong\u003e(10290):2128-2130.\u003c/li\u003e\n\u003cli\u003eSiegel RL, Miller KD, Fuchs HE, Jemal A: \u003cstrong\u003eCancer Statistics, 2021\u003c/strong\u003e. \u003cem\u003eCA Cancer J Clin \u003c/em\u003e2021, \u003cstrong\u003e71\u003c/strong\u003e(1):7-33.\u003c/li\u003e\n\u003cli\u003eKonstantinopoulos PA, Matulonis UA: \u003cstrong\u003eClinical and translational advances in ovarian cancer therapy\u003c/strong\u003e. \u003cem\u003eNat Cancer \u003c/em\u003e2023, \u003cstrong\u003e4\u003c/strong\u003e(9):1239-1257.\u003c/li\u003e\n\u003cli\u003eKielbik M, Przygodzka P, Szulc-Kielbik I, Klink M: \u003cstrong\u003eSnail transcription factors as key regulators of chemoresistance, stemness and metastasis of ovarian cancer cells\u003c/strong\u003e. \u003cem\u003eBiochim Biophys Acta Rev Cancer \u003c/em\u003e2023, \u003cstrong\u003e1878\u003c/strong\u003e(6):189003.\u003c/li\u003e\n\u003cli\u003eLabanieh L, Mackall CL: \u003cstrong\u003eCAR immune cells: design principles, resistance and the next generation\u003c/strong\u003e. \u003cem\u003eNature \u003c/em\u003e2023, \u003cstrong\u003e614\u003c/strong\u003e(7949):635-648.\u003c/li\u003e\n\u003cli\u003eDagher OK, Schwab RD, Brookens SK, Posey AD, Jr.: \u003cstrong\u003eAdvances in cancer immunotherapies\u003c/strong\u003e. \u003cem\u003eCell \u003c/em\u003e2023, \u003cstrong\u003e186\u003c/strong\u003e(8):1814-1814.e1811.\u003c/li\u003e\n\u003cli\u003eBaker DJ, Arany Z, Baur JA, Epstein JA, June CH: \u003cstrong\u003eCAR T therapy beyond cancer: the evolution of a living drug\u003c/strong\u003e. \u003cem\u003eNature \u003c/em\u003e2023, \u003cstrong\u003e619\u003c/strong\u003e(7971):707-715.\u003c/li\u003e\n\u003cli\u003eMoore KN, Bookman M, Sehouli J, Miller A, Anderson C, Scambia G, Myers T, Taskiran C, Robison K, M\u0026auml;enp\u0026auml;\u0026auml; J\u003cem\u003e et al\u003c/em\u003e: \u003cstrong\u003eAtezolizumab, Bevacizumab, and Chemotherapy for Newly Diagnosed Stage III or IV Ovarian Cancer: Placebo-Controlled Randomized Phase III Trial (IMagyn050/GOG 3015/ENGOT-OV39)\u003c/strong\u003e. \u003cem\u003eJournal of clinical oncology : official journal of the American Society of Clinical Oncology \u003c/em\u003e2021, \u003cstrong\u003e39\u003c/strong\u003e(17):1842-1855.\u003c/li\u003e\n\u003cli\u003eMonk BJ, Colombo N, Oza AM, Fujiwara K, Birrer MJ, Randall L, Poddubskaya EV, Scambia G, Shparyk YV, Lim MC\u003cem\u003e et al\u003c/em\u003e: \u003cstrong\u003eChemotherapy with or without avelumab followed by avelumab maintenance versus chemotherapy alone in patients with previously untreated epithelial ovarian cancer (JAVELIN Ovarian 100): an open-label, randomised, phase 3 trial\u003c/strong\u003e. \u003cem\u003eLancet Oncol \u003c/em\u003e2021, \u003cstrong\u003e22\u003c/strong\u003e(9):1275-1289.\u003c/li\u003e\n\u003cli\u003eKurtz JE, Pujade-Lauraine E, Oaknin A, Belin L, Leitner K, Cibula D, Denys H, Rosengarten O, Rodrigues M, de Gregorio N\u003cem\u003e et al\u003c/em\u003e: \u003cstrong\u003eAtezolizumab Combined With Bevacizumab and Platinum-Based Therapy for Platinum-Sensitive Ovarian Cancer: Placebo-Controlled Randomized Phase III ATALANTE/ENGOT-ov29 Trial\u003c/strong\u003e. \u003cem\u003eJournal of clinical oncology : official journal of the American Society of Clinical Oncology \u003c/em\u003e2023, \u003cstrong\u003e41\u003c/strong\u003e(30):4768-4778.\u003c/li\u003e\n\u003cli\u003eRocconi RP, Grosen EA, Ghamande SA, Chan JK, Barve MA, Oh J, Tewari D, Morris PC, Stevens EE, Bottsford-Miller JN\u003cem\u003e et al\u003c/em\u003e: \u003cstrong\u003eGemogenovatucel-T (Vigil) immunotherapy as maintenance in frontline stage III/IV ovarian cancer (VITAL): a randomised, double-blind, placebo-controlled, phase 2b trial\u003c/strong\u003e. \u003cem\u003eLancet Oncol \u003c/em\u003e2020, \u003cstrong\u003e21\u003c/strong\u003e(12):1661-1672.\u003c/li\u003e\n\u003cli\u003eBrown TA, Byrd K, Vreeland TJ, Clifton GT, Jackson DO, Hale DF, Herbert GS, Myers JW, Greene JM, Berry JS\u003cem\u003e et al\u003c/em\u003e: \u003cstrong\u003eFinal analysis of a phase I/IIa trial of the folate-binding protein-derived E39 peptide vaccine to prevent recurrence in ovarian and endometrial cancer patients\u003c/strong\u003e. \u003cem\u003eCancer Med \u003c/em\u003e2019, \u003cstrong\u003e8\u003c/strong\u003e(10):4678-4687.\u003c/li\u003e\n\u003cli\u003eKershaw MH, Westwood JA, Parker LL, Wang G, Eshhar Z, Mavroukakis SA, White DE, Wunderlich JR, Canevari S, Rogers-Freezer L\u003cem\u003e et al\u003c/em\u003e: \u003cstrong\u003eA phase I study on adoptive immunotherapy using gene-modified T cells for ovarian cancer\u003c/strong\u003e. \u003cem\u003eClin Cancer Res \u003c/em\u003e2006, \u003cstrong\u003e12\u003c/strong\u003e(20 Pt 1):6106-6115.\u003c/li\u003e\n\u003cli\u003eChen J, Hu J, Gu L, Ji F, Zhang F, Zhang M, Li J, Chen Z, Jiang L, Zhang Y\u003cem\u003e et al\u003c/em\u003e: \u003cstrong\u003eAnti-mesothelin CAR-T immunotherapy in patients with ovarian cancer\u003c/strong\u003e. \u003cem\u003eCancer Immunol Immunother \u003c/em\u003e2023, \u003cstrong\u003e72\u003c/strong\u003e(2):409-425.\u003c/li\u003e\n\u003cli\u003eBerek J, Taylor P, McGuire W, Smith LM, Schultes B, Nicodemus CF: \u003cstrong\u003eOregovomab maintenance monoimmunotherapy does not improve outcomes in advanced ovarian cancer\u003c/strong\u003e. \u003cem\u003eJournal of clinical oncology : official journal of the American Society of Clinical Oncology \u003c/em\u003e2009, \u003cstrong\u003e27\u003c/strong\u003e(3):418-425.\u003c/li\u003e\n\u003cli\u003eHerzog TJ, Pignata S, Ghamande SA, Rubio MJ, Fujiwara K, Vulsteke C, Armstrong DK, Sehouli J, Coleman RL, Gabra H\u003cem\u003e et al\u003c/em\u003e: \u003cstrong\u003eRandomized phase II trial of farletuzumab plus chemotherapy versus placebo plus chemotherapy in low CA-125 platinum-sensitive ovarian cancer\u003c/strong\u003e. \u003cem\u003eGynecol Oncol \u003c/em\u003e2023, \u003cstrong\u003e170\u003c/strong\u003e:300-308.\u003c/li\u003e\n\u003cli\u003eRevythis A, Limbu A, Mikropoulos C, Ghose A, Sanchez E, Sheriff M, Boussios S: \u003cstrong\u003eRecent Insights into PARP and Immuno-Checkpoint Inhibitors in Epithelial Ovarian Cancer\u003c/strong\u003e. \u003cem\u003eInternational journal of environmental research and public health \u003c/em\u003e2022, \u003cstrong\u003e19\u003c/strong\u003e(14).\u003c/li\u003e\n\u003cli\u003eAwada A, Ahmad S, McKenzie ND, Holloway RW: \u003cstrong\u003eImmunotherapy in the Treatment of Platinum-Resistant Ovarian Cancer: Current Perspectives\u003c/strong\u003e. \u003cem\u003eOncoTargets and therapy \u003c/em\u003e2022, \u003cstrong\u003e15\u003c/strong\u003e:853-866.\u003c/li\u003e\n\u003cli\u003eBarber E, Matei D: \u003cstrong\u003eImmunotherapy in ovarian cancer: we are not there yet\u003c/strong\u003e. \u003cem\u003eThe Lancet Oncology \u003c/em\u003e2021, \u003cstrong\u003e22\u003c/strong\u003e(7):903-905.\u003c/li\u003e\n\u003cli\u003eBrewer M, Angioli R, Scambia G, Lorusso D, Terranova C, Panici PB, Raspagliesi F, Scollo P, Plotti F, Ferrandina G\u003cem\u003e et al\u003c/em\u003e: \u003cstrong\u003eFront-line chemo-immunotherapy with carboplatin-paclitaxel using oregovomab indirect immunization in advanced ovarian cancer: A randomized phase II study\u003c/strong\u003e. \u003cem\u003eGynecol Oncol \u003c/em\u003e2020, \u003cstrong\u003e156\u003c/strong\u003e(3):523-529.\u003c/li\u003e\n\u003cli\u003eRocconi RP, Monk BJ, Walter A, Herzog TJ, Galanis E, Manning L, Bognar E, Wallraven G, Stanbery L, Aaron P\u003cem\u003e et al\u003c/em\u003e: \u003cstrong\u003eGemogenovatucel-T (Vigil) immunotherapy demonstrates clinical benefit in homologous recombination proficient (HRP) ovarian cancer\u003c/strong\u003e. \u003cem\u003eGynecol Oncol \u003c/em\u003e2021, \u003cstrong\u003e161\u003c/strong\u003e(3):676-680.\u003c/li\u003e\n\u003cli\u003eKandalaft LE, Dangaj Laniti D, Coukos G: \u003cstrong\u003eImmunobiology of high-grade serous ovarian cancer: lessons for clinical translation\u003c/strong\u003e. \u003cem\u003eNat Rev Cancer \u003c/em\u003e2022, \u003cstrong\u003e22\u003c/strong\u003e(11):640-656.\u003c/li\u003e\n\u003cli\u003eXie G, Dong H, Liang Y, Ham JD, Rizwan R, Chen J: \u003cstrong\u003eCAR-NK cells: A promising cellular immunotherapy for cancer\u003c/strong\u003e. \u003cem\u003eEBioMedicine \u003c/em\u003e2020, \u003cstrong\u003e59\u003c/strong\u003e:102975.\u003c/li\u003e\n\u003cli\u003eWang Q, Bergholz JS, Ding L, Lin Z, Kabraji SK, Hughes ME, He X, Xie S, Jiang T, Wang W\u003cem\u003e et al\u003c/em\u003e: \u003cstrong\u003eSTING agonism reprograms tumor-associated macrophages and overcomes resistance to PARP inhibition in BRCA1-deficient models of breast cancer\u003c/strong\u003e. \u003cem\u003eNat Commun \u003c/em\u003e2022, \u003cstrong\u003e13\u003c/strong\u003e(1):3022.\u003c/li\u003e\n\u003cli\u003eMorand S, Devanaboyina M, Staats H, Stanbery L, Nemunaitis J: \u003cstrong\u003eOvarian Cancer Immunotherapy and Personalized Medicine\u003c/strong\u003e. \u003cem\u003eInternational journal of molecular sciences \u003c/em\u003e2021, \u003cstrong\u003e22\u003c/strong\u003e(12).\u003c/li\u003e\n\u003cli\u003eToulmonde M, Bellera C, Mathoulin-Pelissier S, Debled M, Bui B, Italiano A: \u003cstrong\u003eQuality of randomized controlled trials reporting in the treatment of sarcomas\u003c/strong\u003e. \u003cem\u003eJournal of clinical oncology : official journal of the American Society of Clinical Oncology \u003c/em\u003e2011, \u003cstrong\u003e29\u003c/strong\u003e(9):1204-1209.\u003c/li\u003e\n\u003cli\u003eChen YP, Chen L, Li WF, Lee AWM, Vermorken JB, Wee J, O\u0026apos;Sullivan B, Eisbruch A, Lin JC, Mai HQ\u003cem\u003e et al\u003c/em\u003e: \u003cstrong\u003eReporting Quality of Randomized, Controlled Trials Evaluating Combined Chemoradiotherapy in Nasopharyngeal Carcinoma\u003c/strong\u003e. \u003cem\u003eInternational journal of radiation oncology, biology, physics \u003c/em\u003e2017, \u003cstrong\u003e98\u003c/strong\u003e(1):170-176.\u003c/li\u003e\n\u003cli\u003eIto T, Sugasawa S: \u003cstrong\u003eGrouped generalized estimating equations for longitudinal data analysis\u003c/strong\u003e. \u003cem\u003eBiometrics \u003c/em\u003e2023, \u003cstrong\u003e79\u003c/strong\u003e(3):1868-1879.\u003c/li\u003e\n\u003cli\u003eHopewell S, Chan AW, Collins GS, Hr\u0026oacute;bjartsson A, Moher D, Schulz KF, Tunn R, Aggarwal R, Berkwits M, Berlin JA\u003cem\u003e et al\u003c/em\u003e: \u003cstrong\u003eCONSORT 2025 statement: updated guideline for reporting randomised trials\u003c/strong\u003e. \u003cem\u003eLancet (London, England) \u003c/em\u003e2025.\u003c/li\u003e\n\u003cli\u003eAndersen MZ, Fonnes S, Rosenberg J: \u003cstrong\u003eTime from submission to publication varied widely for biomedical journals: a systematic review\u003c/strong\u003e. \u003cem\u003eCurrent medical research and opinion \u003c/em\u003e2021, \u003cstrong\u003e37\u003c/strong\u003e(6):985-993.\u003c/li\u003e\n\u003cli\u003eLazar Neto F, de Melo MAZ, Hidalgo Filho CMT, Mathias-Machado MC, Testa L, Campolina AG: \u003cstrong\u003eGlobal representativeness and impact of funding sources in cost-effectiveness research on systemic therapies for advanced breast cancer: A systematic review\u003c/strong\u003e. \u003cem\u003eBreast (Edinburgh, Scotland) \u003c/em\u003e2024, \u003cstrong\u003e75\u003c/strong\u003e:103727.\u003c/li\u003e\n\u003cli\u003eHirsch BR, Califf RM, Cheng SK, Tasneem A, Horton J, Chiswell K, Schulman KA, Dilts DM, Abernethy AP: \u003cstrong\u003eCharacteristics of oncology clinical trials: insights from a systematic analysis of ClinicalTrials.gov\u003c/strong\u003e. \u003cem\u003eJAMA internal medicine \u003c/em\u003e2013, \u003cstrong\u003e173\u003c/strong\u003e(11):972-979.\u003c/li\u003e\n\u003cli\u003eGiacalone NJ, Milani N, Rawal B, Catalano PJ, Nguyen PL, Schoenfeld JD, Tishler RB, Margalit DN: \u003cstrong\u003eFunding Support and Principal Investigator Leadership of Oncology Clinical Trials Using Radiation Therapy\u003c/strong\u003e. \u003cem\u003eInternational journal of radiation oncology, biology, physics \u003c/em\u003e2018, \u003cstrong\u003e102\u003c/strong\u003e(1):34-43.\u003c/li\u003e\n\u003cli\u003eYoo SK, Ahmed AA, Ileto J, Zaorsky NG, Deville C, Holliday EB, Wilson LD, Jagsi R, Thomas CR, Jr.: \u003cstrong\u003eIndustry Funding Among Leadership in Medical Oncology and Radiation Oncology in 2015\u003c/strong\u003e. \u003cem\u003eInternational journal of radiation oncology, biology, physics \u003c/em\u003e2017, \u003cstrong\u003e99\u003c/strong\u003e(2):280-285.\u003c/li\u003e\n\u003cli\u003eSponchiado-J\u0026uacute;nior EC, Vieira WA, Frozoni M, Herkrath FJ, de-Jesus-Soares A: \u003cstrong\u003eCONSORT Compliance in Randomized Clinical Trials of Regenerative Endodontic Treatments of Necrotic Immature Teeth: A Scoping Review\u003c/strong\u003e. \u003cem\u003eJ Endod \u003c/em\u003e2021, \u003cstrong\u003e47\u003c/strong\u003e(11):1751-1766.\u003c/li\u003e\n\u003cli\u003eMoher D, Pham B, Jones A, Cook DJ, Jadad AR, Moher M, Tugwell P, Klassen TP: \u003cstrong\u003eDoes quality of reports of randomised trials affect estimates of intervention efficacy reported in meta-analyses?\u003c/strong\u003e \u003cem\u003eLancet (London, England) \u003c/em\u003e1998, \u003cstrong\u003e352\u003c/strong\u003e(9128):609-613.\u003c/li\u003e\n\u003cli\u003eSavović J, Jones HE, Altman DG, Harris RJ, J\u0026uuml;ni P, Pildal J, Als-Nielsen B, Balk EM, Gluud C, Gluud LL\u003cem\u003e et al\u003c/em\u003e: \u003cstrong\u003eInfluence of reported study design characteristics on intervention effect estimates from randomized, controlled trials\u003c/strong\u003e. \u003cem\u003eAnnals of internal medicine \u003c/em\u003e2012, \u003cstrong\u003e157\u003c/strong\u003e(6):429-438.\u003c/li\u003e\n\u003cli\u003eDemetriades AK, Tiefenbach J, Park JJ, Anwar MM, Raza SM: \u003cstrong\u003eWhat is the quality of reporting in randomized controlled trials in spinal conditions\u003c/strong\u003e. \u003cem\u003eJ Craniovertebr Junction Spine \u003c/em\u003e2023, \u003cstrong\u003e14\u003c/strong\u003e(4):404-411.\u003c/li\u003e\n\u003cli\u003eYang J, Yu F, Lin K, Qu H, He Y, Zhao J, Feng F, Pan L, Kui Y: \u003cstrong\u003eAssessment of Reporting Quality in Randomized Controlled Trials of Acupuncture for Primary Insomnia with CONSORT Statement and STRICTA Guidelines\u003c/strong\u003e. \u003cem\u003eEvid Based Complement Alternat Med \u003c/em\u003e2022, \u003cstrong\u003e2022\u003c/strong\u003e:5157870.\u003c/li\u003e\n\u003cli\u003eYang Y, Han Y, Zou G, Sui Y, Jin J, Liu L: \u003cstrong\u003eReporting quality of randomized controlled trials evaluating non-vitamin K oral anticoagulants in atrial fibrillation: a systematic review\u003c/strong\u003e. \u003cem\u003eBMC Cardiovasc Disord \u003c/em\u003e2023, \u003cstrong\u003e23\u003c/strong\u003e(1):229.\u003c/li\u003e\n\u003cli\u003eBachelet VC, Navarrete MS, Barrera-Riquelme C, Carrasco VA, Dallaserra M, D\u0026iacute;az RA, Ibarra \u0026Aacute; A, Lizana FJ, Meza-Ducaud N, Saavedra MG\u003cem\u003e et al\u003c/em\u003e: \u003cstrong\u003eA multiyear systematic survey of the quality of reporting for randomised trials in dentistry, neurology and geriatrics published in journals of Spain and Latin America\u003c/strong\u003e. \u003cem\u003eBMC Med Res Methodol \u003c/em\u003e2021, \u003cstrong\u003e21\u003c/strong\u003e(1):153.\u003c/li\u003e\n\u003cli\u003eDevereaux PJ, Choi PT, El-Dika S, Bhandari M, Montori VM, Sch\u0026uuml;nemann HJ, Garg AX, Busse JW, Heels-Ansdell D, Ghali WA\u003cem\u003e et al\u003c/em\u003e: \u003cstrong\u003eAn observational study found that authors of randomized controlled trials frequently use concealment of randomization and blinding, despite the failure to report these methods\u003c/strong\u003e. \u003cem\u003eJournal of clinical epidemiology \u003c/em\u003e2004, \u003cstrong\u003e57\u003c/strong\u003e(12):1232-1236.\u003c/li\u003e\n\u003cli\u003eSoares HP, Daniels S, Kumar A, Clarke M, Scott C, Swann S, Djulbegovic B: \u003cstrong\u003eBad reporting does not mean bad methods for randomised trials: observational study of randomised controlled trials performed by the Radiation Therapy Oncology Group\u003c/strong\u003e. \u003cem\u003eBMJ (Clinical research ed) \u003c/em\u003e2004, \u003cstrong\u003e328\u003c/strong\u003e(7430):22-24.\u003c/li\u003e\n\u003cli\u003eSantomasso BD, Nastoupil LJ, Adkins S, Lacchetti C, Schneider BJ, Anadkat M, Atkins MB, Brassil KJ, Caterino JM, Chau I\u003cem\u003e et al\u003c/em\u003e: \u003cstrong\u003eManagement of Immune-Related Adverse Events in Patients Treated With Chimeric Antigen Receptor T-Cell Therapy: ASCO Guideline\u003c/strong\u003e. \u003cem\u003eJournal of clinical oncology : official journal of the American Society of Clinical Oncology \u003c/em\u003e2021, \u003cstrong\u003e39\u003c/strong\u003e(35):3978-3992.\u003c/li\u003e\n\u003cli\u003eBrahmer JR, Abu-Sbeih H, Ascierto PA, Brufsky J, Cappelli LC, Cortazar FB, Gerber DE, Hamad L, Hansen E, Johnson DB\u003cem\u003e et al\u003c/em\u003e: \u003cstrong\u003eSociety for Immunotherapy of Cancer (SITC) clinical practice guideline on immune checkpoint inhibitor-related adverse events\u003c/strong\u003e. \u003cem\u003eJ Immunother Cancer \u003c/em\u003e2021, \u003cstrong\u003e9\u003c/strong\u003e(6).\u003c/li\u003e\n\u003cli\u003eYin Q, Wu L, Han L, Zheng X, Tong R, Li L, Bai L, Bian Y: \u003cstrong\u003eImmune-related adverse events of immune checkpoint inhibitors: a review\u003c/strong\u003e. \u003cem\u003eFrontiers in immunology \u003c/em\u003e2023, \u003cstrong\u003e14\u003c/strong\u003e:1167975.\u003c/li\u003e\n\u003cli\u003eXie T, Zhang Z, Qi C, Lu M, Zhang X, Li J, Shen L, Peng Z: \u003cstrong\u003eThe Inconsistent and Inadequate Reporting Of Immune-Related Adverse Events in PD-1/PD-L1 Inhibitors: A Systematic Review of Randomized Controlled Clinical Trials\u003c/strong\u003e. \u003cem\u003eThe oncologist \u003c/em\u003e2021, \u003cstrong\u003e26\u003c/strong\u003e(12):e2239-e2246.\u003c/li\u003e\n\u003cli\u003eLai R, Chu R, Fraumeni M, Thabane L: \u003cstrong\u003eQuality of randomized controlled trials reporting in the primary treatment of brain tumors\u003c/strong\u003e. \u003cem\u003eJournal of clinical oncology : official journal of the American Society of Clinical Oncology \u003c/em\u003e2006, \u003cstrong\u003e24\u003c/strong\u003e(7):1136-1144.\u003c/li\u003e\n\u003cli\u003eKloukos D, Papageorgiou SN, Doulis I, Petridis H, Pandis N: \u003cstrong\u003eReporting quality of randomised controlled trials published in prosthodontic and implantology journals\u003c/strong\u003e. \u003cem\u003eJournal of oral rehabilitation \u003c/em\u003e2015, \u003cstrong\u003e42\u003c/strong\u003e(12):914-925.\u003c/li\u003e\n\u003cli\u003eKrzyzanowska MK, Pintilie M, Brezden-Masley C, Dent R, Tannock IF: \u003cstrong\u003eQuality of abstracts describing randomized trials in the proceedings of American Society of Clinical Oncology meetings: guidelines for improved reporting\u003c/strong\u003e. \u003cem\u003eJournal of clinical oncology : official journal of the American Society of Clinical Oncology \u003c/em\u003e2004, \u003cstrong\u003e22\u003c/strong\u003e(10):1993-1999.\u003c/li\u003e\n\u003cli\u003eVinkers CH, Lamberink HJ, Tijdink JK, Heus P, Bouter L, Glasziou P, Moher D, Damen JA, Hooft L, Otte WM: \u003cstrong\u003eThe methodological quality of 176,620 randomized controlled trials published between 1966 and 2018 reveals a positive trend but also an urgent need for improvement\u003c/strong\u003e. \u003cem\u003ePLoS Biol \u003c/em\u003e2021, \u003cstrong\u003e19\u003c/strong\u003e(4):e3001162.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e1\u003c/strong\u003e Overall reporting quality: Assessment based on the 2025 CONSORT statement items (n=53)\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" align=\"\" width=\"718\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003eItem\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003eCriteria\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.1667%;\"\u003e\n \u003cp\u003eDescription\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003eNo. of positive trials\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e％\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e95％CI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003eCohen\u0026rsquo;s k coefficient\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.8056%;\"\u003e\n \u003cp\u003eTitle\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.1667%;\"\u003e\n \u003cp\u003eWhether it is clearly stated in the title as a randomized trial\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e72\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e60,84\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e1.000\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.8056%;\"\u003e\n \u003cp\u003eAbstract\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.1667%;\"\u003e\n \u003cp\u003eA structured abstract summarizing the trial\u0026apos;s design, methods, results, and conclusions\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e77\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e66,89\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e0.948\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.8056%;\"\u003e\n \u003cp\u003eRegistration\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.1667%;\"\u003e\n \u003cp\u003eThe trial registry\u0026apos;s name, \u0026nbsp;identification number (including URL), and the date of registration\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e0,0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.8056%;\"\u003e\n \u003cp\u003eProtocol\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.1667%;\"\u003e\n \u003cp\u003eAccess details for the trial protocol and the statistical analysis plan\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e5,25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e0.662\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.8056%;\"\u003e\n \u003cp\u003eData sharing\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.1667%;\"\u003e\n \u003cp\u003eThe location and procedure for accessing de-identified individual participant data (including a data dictionary), statistical code, and other relevant materials\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e21,47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e0.879\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.8056%;\"\u003e\n \u003cp\u003eFunding\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.1667%;\"\u003e\n \u003cp\u003eSources of funding and additional support, alongside the role of founders in the trial\u0026apos;s design, conduct, analysis, and reporting\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e25,51\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e0.921\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.8056%;\"\u003e\n \u003cp\u003eConflicts of interest\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.1667%;\"\u003e\n \u003cp\u003eDisclosure of financial and non-financial conflicts of interest for all manuscript authors\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e81\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e71,92\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e0.741\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.8056%;\"\u003e\n \u003cp\u003eBackground\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.1667%;\"\u003e\n \u003cp\u003ePresentation of the scientific background and rationale for the study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e91\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e83,98\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e0.739\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.8056%;\"\u003e\n \u003cp\u003eObjectives\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.1667%;\"\u003e\n \u003cp\u003eSpecific objectives pertaining to both benefits and harms\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e26,53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e0.771\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.8056%;\"\u003e\n \u003cp\u003ePatient and public involvement\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.1667%;\"\u003e\n \u003cp\u003eDetails regarding the involvement of patients or the public in the trial\u0026apos;s design, conduct, and reporting\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e0,0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.8056%;\"\u003e\n \u003cp\u003eTrial design\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.1667%;\"\u003e\n \u003cp\u003eDescription of the trial design, encompassing its type (eg, parallel group, crossover), allocation ratio, and framework (eg, superiority, equivalence, non-inferiority, exploratory)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e66\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e53,79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e0.875\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.8056%;\"\u003e\n \u003cp\u003eSettings and location\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.1667%;\"\u003e\n \u003cp\u003eSettings (eg, community, hospital) and geographical locations (eg, countries, sites) where the trial was conducted\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e51\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e37,64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e0.887\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.8056%;\"\u003e\n \u003cp\u003eParticipants\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.1667%;\"\u003e\n \u003cp\u003eEligibility criteria for participant enrolment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e98\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e94,102\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e0.658\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.8056%;\"\u003e\n \u003cp\u003eAdministrator\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.1667%;\"\u003e\n \u003cp\u003eIf applicable, eligibility criteria for participating sites and individuals administering the interventions (eg, surgeons, physiotherapists)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e0,0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.8056%;\"\u003e\n \u003cp\u003eIntervention and comparator\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.1667%;\"\u003e\n \u003cp\u003eSufficiently detailed descriptions of the interventions and comparators to permit replication, including, if relevant, access to supplementary materials (eg, an intervention manual)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e66\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e53,79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e0.636\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.8056%;\"\u003e\n \u003cp\u003eOutcome measures\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.1667%;\"\u003e\n \u003cp\u003ePre-specified primary and secondary outcomes, detailing for each: the specific measurement variable (eg, systolic blood pressure), metric for analysis (eg, change from baseline, final value, time to event), method of aggregation (eg, median, proportion), and time point\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e62\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e49,75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e0.642\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.8056%;\"\u003e\n \u003cp\u003eAdverse event classification\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.1667%;\"\u003e\n \u003cp\u003eDefinitions and assessment methods for harms (eg, systematic, non-systematic)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e85\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e75,95\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e0.756\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.8056%;\"\u003e\n \u003cp\u003eSample size\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.1667%;\"\u003e\n \u003cp\u003eJustification for the sample size, including all underlying assumptions for its calculation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e47,74\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e0.881\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.8056%;\"\u003e\n \u003cp\u003eRandomization, Sequence generation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.1667%;\"\u003e\n \u003cp\u003eIdentity of the individual(s) who generated the random allocation sequence and the method employed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e23,49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e0.836\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.8056%;\"\u003e\n \u003cp\u003eRandomization, restriction\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.1667%;\"\u003e\n \u003cp\u003eType of randomization utilized and specifics of any restrictions applied (eg, stratification, blocking, block size)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e62\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e49,75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e0.920\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.8056%;\"\u003e\n \u003cp\u003eAllocation concealment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.1667%;\"\u003e\n \u003cp\u003eMechanism employed to implement the random allocation sequence (eg, central computer/telephone; sequentially numbered, opaque, sealed containers), including steps taken to conceal the sequence until intervention assignment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e5,25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e0.733\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.8056%;\"\u003e\n \u003cp\u003eAccess to allocation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.1667%;\"\u003e\n \u003cp\u003eIndication of whether personnel enrolling participants and those assigning interventions had access to the random allocation sequence\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e66\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e53,79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e0.654\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.8056%;\"\u003e\n \u003cp\u003eBlinding，group\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.1667%;\"\u003e\n \u003cp\u003eSpecification of who was blinded following intervention assignment (eg, participants, care providers, outcome assessors, data analysts)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e87\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e78,96\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e0.638\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.8056%;\"\u003e\n \u003cp\u003eBlinding，implement\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.1667%;\"\u003e\n \u003cp\u003eIf blinding was implemented, the method used to achieve it and a description of the similarity between interventions\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e23,49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e0.748\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.8056%;\"\u003e\n \u003cp\u003eStatistical methods\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.1667%;\"\u003e\n \u003cp\u003eStatistical methods applied for comparing groups regarding primary and secondary outcomes, including harms\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e89\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e80,97\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e0.912\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.8056%;\"\u003e\n \u003cp\u003eAnalysis population definition\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.1667%;\"\u003e\n \u003cp\u003eDefinition of the analysis population(s) (eg, all randomized participants) and their group assignments\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e28,55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e0.883\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.8056%;\"\u003e\n \u003cp\u003eMissing data\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.1667%;\"\u003e\n \u003cp\u003eMethods employed for handling missing data within the analyses\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e-2,6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e1.000\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.8056%;\"\u003e\n \u003cp\u003eMethods of Ancillary analysis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.1667%;\"\u003e\n \u003cp\u003eMethods for any supplementary analyses (eg, subgroup, sensitivity), clearly distinguishing between pre-specified and post hoc analyses\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e16,40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e0.858\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.8056%;\"\u003e\n \u003cp\u003eDiagram\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.1667%;\"\u003e\n \u003cp\u003ePresentation of a participant flow diagram adhering to CONSORT specifications\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e34,61\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e1.000\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.8056%;\"\u003e\n \u003cp\u003eParticipant flow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.1667%;\"\u003e\n \u003cp\u003eFor each group, the numbers of participants who were randomly assigned, received the intended intervention, and were analyzed for the primary outcome, along with details of exclusions\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e87\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e78,96\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e1.000\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.8056%;\"\u003e\n \u003cp\u003eRecruitment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.1667%;\"\u003e\n \u003cp\u003eDates defining the recruitment period and the follow-up period for assessing beneficial and harmful outcomes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e70\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e57,82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e0.914\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.8056%;\"\u003e\n \u003cp\u003eOutcomes and estimation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.1667%;\"\u003e\n \u003cp\u003eDescription of the interventions and comparators as actually administered (including, if applicable, details on who delivered them, participant adherence, and fidelity to the intended protocol)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e18,43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e0.821\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.8056%;\"\u003e\n \u003cp\u003eConcomitant care\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.1667%;\"\u003e\n \u003cp\u003eConcomitant care received by each group during the trial period\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e20,45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e0.957\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.8056%;\"\u003e\n \u003cp\u003eBaseline data\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.1667%;\"\u003e\n \u003cp\u003eTable presenting baseline demographic and clinical characteristics for each group\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e94\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e88,101\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e1.000\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.8056%;\"\u003e\n \u003cp\u003eOutcomes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.1667%;\"\u003e\n \u003cp\u003eFor each primary and secondary outcome, by group: (i) number of participants included in the analysis; (ii) number of participants with available data at the outcome time point; (iii) results for each group, including estimated effect size and its precision (eg, 95% confidence interval); (iv) for binary outcomes, presentation of both absolute and relative effect sizes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e7,27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e0.726\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.8056%;\"\u003e\n \u003cp\u003eHarms or unintended events\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.1667%;\"\u003e\n \u003cp\u003eAll instances of harms or unintended events observed in each group\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e68,90\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e0.844\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003eAncillary analyses\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.1667%;\"\u003e\n \u003cp\u003eReporting of any other analyses performed (eg, subgroup, sensitivity), clearly distinguishing pre-specified from post hoc analyses\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e39,66\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8056%;\"\u003e\n \u003cp\u003e0.887\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cem\u003eAbbreviations\u003c/em\u003e\u003cem\u003e：\u003c/em\u003e\u003cem\u003eCI\u003c/em\u003e\u003cem\u003e＝\u003c/em\u003e\u003cem\u003econfidence interval\u003c/em\u003e\u003cem\u003e；\u003c/em\u003e\u003cem\u003eCONSORT\u003c/em\u003e\u003cem\u003e＝\u003c/em\u003e\u003cem\u003eConsolidated Standards of Reporting Trials\u003c/em\u003e\u003cem\u003e；\u003c/em\u003e\u003cem\u003eNA\u003c/em\u003e\u003cem\u003e＝\u003c/em\u003e\u003cem\u003enot available.\u003c/em\u003e\u003cem\u003e*\u003c/em\u003e\u003cem\u003e\u0026nbsp;We could not calculate the Cohen\u0026rsquo;s\u0026nbsp;\u003c/em\u003e\u003cem\u003ek\u003c/em\u003e\u003cem\u003e\u0026nbsp;indices because the positive rate awarded by a investigator was 100\u003c/em\u003e\u003cem\u003e％\u003c/em\u003e\u003cem\u003e\u0026nbsp;for the item.\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2\u003c/strong\u003e Univariate and multivariable analysis of overall quality score (OQS) with trial characteristics\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"115%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" style=\"width: 28px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 20px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" colspan=\"2\" style=\"width: 25px;\"\u003e\n \u003cp\u003eUnivariate analyses\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 2px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" colspan=\"2\" style=\"width: 23px;\"\u003e\n \u003cp\u003e\u0026nbsp;Multivariable analyses\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" style=\"width: 28px;\"\u003e\n \u003cp\u003eTrial characteristic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 20px;\"\u003e\n \u003cp\u003eMean OQS (95% CI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 18px;\"\u003e\n \u003cp\u003eEstimate (95% CI)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 6px;\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 2px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 17px;\"\u003e\n \u003cp\u003eEstimate (95% CI)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 5px;\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" style=\"width: 28px;\"\u003e\n \u003cp\u003ePublished year\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 20px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 18px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 6px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 2px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 17px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 5px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" style=\"width: 28px;\"\u003e\n \u003cp\u003eBefore 2010\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 20px;\"\u003e\n \u003cp\u003e13.0(9.3 to 16.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 18px;\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 6px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 2px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 17px;\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 5px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" style=\"width: 28px;\"\u003e\n \u003cp\u003eAfter 2010\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 20px;\"\u003e\n \u003cp\u003e20.9(19.3 to 22.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 18px;\"\u003e\n \u003cp\u003e8.9(4.5 to 11.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 6px;\"\u003e\n \u003cp\u003e.000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 2px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 17px;\"\u003e\n \u003cp\u003e4.9(2.8 to 7.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 5px;\"\u003e\n \u003cp\u003e.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" style=\"width: 28px;\"\u003e\n \u003cp\u003eRegion\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 20px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 18px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 6px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 2px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 17px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 5px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" style=\"width: 28px;\"\u003e\n \u003cp\u003eEurope and North America\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 20px;\"\u003e\n \u003cp\u003e19.1(17.4 to 20.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 18px;\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 6px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 2px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 17px;\"\u003e\n \u003cp\u003eNot included\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 5px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" style=\"width: 28px;\"\u003e\n \u003cp\u003eOthers\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 20px;\"\u003e\n \u003cp\u003e18.9(11.0 to 26.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 18px;\"\u003e\n \u003cp\u003e-0.3(-5.2 to 4.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 6px;\"\u003e\n \u003cp\u003e.920\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 2px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 17px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 5px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" valign=\"top\" style=\"width: 28px;\"\u003e\n \u003cp\u003eFunding Sources\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 20px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 18px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 6px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 2px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 17px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 5px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" style=\"width: 28px;\"\u003e\n \u003cp\u003eGovernment/foundation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 20px;\"\u003e\n \u003cp\u003e13.7(10.4 to 17.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 18px;\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 6px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 2px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 17px;\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 5px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" style=\"width: 28px;\"\u003e\n \u003cp\u003ePartially funded by industry\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 20px;\"\u003e\n \u003cp\u003e20.6(18.4 to 22.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 18px;\"\u003e\n \u003cp\u003e7.0(1.1 to 12.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 6px;\"\u003e\n \u003cp\u003e.015\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 2px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 17px;\"\u003e\n \u003cp\u003e4.5(2.8 to 6.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 5px;\"\u003e\n \u003cp\u003e.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" style=\"width: 28px;\"\u003e\n \u003cp\u003eCompletely funded by industry\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 20px;\"\u003e\n \u003cp\u003e21.7(19.3 to 24.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 18px;\"\u003e\n \u003cp\u003e8.0(2.7 to 13.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 6px;\"\u003e\n \u003cp\u003e.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 2px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 17px;\"\u003e\n \u003cp\u003e5.3(2.7 to 7.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 5px;\"\u003e\n \u003cp\u003e.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" style=\"width: 28px;\"\u003e\n \u003cp\u003eFunding not reported\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 20px;\"\u003e\n \u003cp\u003e14.1(8.6 to 19.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 18px;\"\u003e\n \u003cp\u003e0.5(-6.4 to -7.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 6px;\"\u003e\n \u003cp\u003e.998\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 2px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 17px;\"\u003e\n \u003cp\u003e2.3(0.4 to 4.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 5px;\"\u003e\n \u003cp\u003e.015\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" style=\"width: 28px;\"\u003e\n \u003cp\u003eMain results\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 20px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 18px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 6px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 2px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 17px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 5px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" style=\"width: 28px;\"\u003e\n \u003cp\u003ePositive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 20px;\"\u003e\n \u003cp\u003e17.9(15.6 to 20.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 18px;\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 6px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 2px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 17px;\"\u003e\n \u003cp\u003eNot included\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 5px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" style=\"width: 28px;\"\u003e\n \u003cp\u003eNegative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 20px;\"\u003e\n \u003cp\u003e20.2(17.7 to 22.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 18px;\"\u003e\n \u003cp\u003e2.3(-1.1 to 5.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 6px;\"\u003e\n \u003cp\u003e.177\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 2px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 17px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 5px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" style=\"width: 28px;\"\u003e\n \u003cp\u003ePhase of the trial\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 20px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 18px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 6px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 2px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 17px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 5px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" style=\"width: 28px;\"\u003e\n \u003cp\u003eⅠ\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 20px;\"\u003e\n \u003cp\u003e16.0(11.3 to 20.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 18px;\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 6px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 2px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 17px;\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 5px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" style=\"width: 28px;\"\u003e\n \u003cp\u003eⅡ\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 20px;\"\u003e\n \u003cp\u003e20.4(18.7 to 22.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 18px;\"\u003e\n \u003cp\u003e4.4(-2.3 to 11.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 6px;\"\u003e\n \u003cp\u003e.352\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 2px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 17px;\"\u003e\n \u003cp\u003e3.6(0.2 to 6.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 5px;\"\u003e\n \u003cp\u003e.038\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" style=\"width: 28px;\"\u003e\n \u003cp\u003eⅢ\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 20px;\"\u003e\n \u003cp\u003e23.3(19.8 to 26.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 18px;\"\u003e\n \u003cp\u003e7.3(-0.2 to 14.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 6px;\"\u003e\n \u003cp\u003e.040\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 2px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 17px;\"\u003e\n \u003cp\u003e6.1(1.3 to 10.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 5px;\"\u003e\n \u003cp\u003e.013\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" style=\"width: 28px;\"\u003e\n \u003cp\u003eⅠ/Ⅱ\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 20px;\"\u003e\n \u003cp\u003e16.7(11.5 to 21.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 18px;\"\u003e\n \u003cp\u003e0.7(-8.8 to 10.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 6px;\"\u003e\n \u003cp\u003e1.000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 2px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 17px;\"\u003e\n \u003cp\u003e2.0(-1.9 to 5.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 5px;\"\u003e\n \u003cp\u003e.315\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" style=\"width: 28px;\"\u003e\n \u003cp\u003eUnclear\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 20px;\"\u003e\n \u003cp\u003e10.1(7.9 to 12.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 18px;\"\u003e\n \u003cp\u003e-5.9(-13.5 to 1.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 6px;\"\u003e\n \u003cp\u003e.203\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 2px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 17px;\"\u003e\n \u003cp\u003e-0.7(-3.7 to 2.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 5px;\"\u003e\n \u003cp\u003e.654\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" style=\"width: 28px;\"\u003e\n \u003cp\u003eSample size\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 20px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 18px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 6px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 2px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 17px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 5px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" style=\"width: 28px;\"\u003e\n \u003cp\u003e\u0026lt;100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 20px;\"\u003e\n \u003cp\u003e17.2（14.8 to 19.6）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 18px;\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 6px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 2px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 17px;\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 5px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" style=\"width: 28px;\"\u003e\n \u003cp\u003e100-500\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 20px;\"\u003e\n \u003cp\u003e19.4（16.6 to 22.1）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 18px;\"\u003e\n \u003cp\u003e2.1(-2.0 to 6.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 6px;\"\u003e\n \u003cp\u003e.428\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 2px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 17px;\"\u003e\n \u003cp\u003e-0.3(-2.5 to 1.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 5px;\"\u003e\n \u003cp\u003e.679\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" style=\"width: 28px;\"\u003e\n \u003cp\u003e\u0026gt;500\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 20px;\"\u003e\n \u003cp\u003e24.4（20.7 to 28.1）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 18px;\"\u003e\n \u003cp\u003e7.1(1.6 to 12.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 6px;\"\u003e\n \u003cp\u003e.008\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 2px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 17px;\"\u003e\n \u003cp\u003e0.2(-3.4 to 3.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 5px;\"\u003e\n \u003cp\u003e.903\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" style=\"width: 28px;\"\u003e\n \u003cp\u003eJournal impact factor\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 20px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 18px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 6px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 2px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 17px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 5px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" style=\"width: 28px;\"\u003e\n \u003cp\u003e\u0026lt;4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 20px;\"\u003e\n \u003cp\u003e15.1（8.3 to 22.0）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 18px;\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 6px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 2px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 17px;\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 5px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" style=\"width: 28px;\"\u003e\n \u003cp\u003e4-10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 20px;\"\u003e\n \u003cp\u003e16.7（14.3 to 19.0）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 18px;\"\u003e\n \u003cp\u003e1.5(-4.0 to 7.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 6px;\"\u003e\n \u003cp\u003e.783\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 2px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 17px;\"\u003e\n \u003cp\u003e-1.1(-3.9 to 1.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 5px;\"\u003e\n \u003cp\u003e.447\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" style=\"width: 28px;\"\u003e\n \u003cp\u003e\u0026gt;10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 20px;\"\u003e\n \u003cp\u003e22.7（20.8 to 24.6）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 18px;\"\u003e\n \u003cp\u003e7.6(2.1 to 13.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 6px;\"\u003e\n \u003cp\u003e.004\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 2px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 17px;\"\u003e\n \u003cp\u003e1.3(-2.4 to 5.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 5px;\"\u003e\n \u003cp\u003e.482\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eOverall quality score rated on a scale of 0 to 37.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e*The estimates show the advantage observed in comparison to the reference. A positive value indicates additional benefit compared to the reference, while a negative value indicates a disadvantage compared to the reference.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcan","sideBox":"Learn more about [BMC Cancer](http://bmccancer.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcan/default.aspx","title":"BMC Cancer","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"CONSORT statement, ovarian cancer, immunotherapy, reporting quality, randomized controlled trial","lastPublishedDoi":"10.21203/rs.3.rs-9020902/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9020902/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eIncorporating immunotherapy effectively remains a priority in therapeutic research of ovarian cancer, making it essential to conduct and report randomized, controlled trials (RCTs) with high quality. The purpose of this study is to assess the reporting quality of RCTs on immunotherapy for ovarian cancer.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThis was a cross-sectional, meta-epidemiological study. Two researchers searched \u003cem\u003ePubmed.gov\u003c/em\u003e and \u003cem\u003eembase.com\u003c/em\u003e for RCTs published before 25th July 2025 for trials on immunotherapy for ovarian cancer. The 37-point overall quality score (OQS) derived from the 2025 CONSORT statement was adopted to estimate the reporting quality of the contained trials. Linear regression analyses were conducted to explore associations between trial characteristics and overall quality of reporting. Detailed data on blinding, allocation concealment, implementation of the intention-to-treat (ITT) principle, follow-up, endpoint setting and adverse event reporting was collected for a further investigation.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eTotally fifty-three relevant RCTs including 12346 participants (range, 14-1301) were analyzed in this study. The mean OQS was 19.08 (s.d. = 6.07, 95% CI\u0026thinsp;=\u0026thinsp;17.40, 20.75), reflecting more than 46% of the items were inadequately stated in more than half of the studies. As the key methodological factors, allocation concealment, blinding and intention-to-treat principle were reported in 11 (21%), 22 (42%) and 30 (57%) of the 53 RCTs. Although some trials reported their registration status, none provided details on the registration date; additionally, patient and public involvement (PPI) as well as the inclusion criteria for research centers and intervention implementers were not mentioned in any article. Consequently, all 53 trials scored 0 for these three items, and the next most poorly reported aspect was the handling of missing data, with only 2% (n\u0026thinsp;=\u0026thinsp;1) of the trials documenting this. Publication after 2010 and completely or partially funded by industry remained independent significant factors of improved OQS in multivariate analysis.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eRandomized controlled trials (RCTs) of immunotherapy for ovarian cancer demonstrate poor reporting of the newly added items in the CONSORT 2025 Statement, while simultaneously exhibiting suboptimal reporting quality of items adhering to previous versions of the Statement\u0026mdash;despite the fact that most of the included articles were published after 2010. In order to enhance transparency, minimize resource waste, and avoid misleading clinical decision-making, enhancing reporting of key methodological factors, full trial protocol and adverse events is of primary importance.\u003c/p\u003e\u003ch2\u003eTrial registration:\u003c/h2\u003e \u003cp\u003eNot applicable.\u003c/p\u003e","manuscriptTitle":"Reporting quality of randomized, controlled trials evaluating immunotherapy for ovarian cancer: cross-sectional study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-23 09:08:32","doi":"10.21203/rs.3.rs-9020902/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2026-05-07T00:55:24+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"161122417427423181564728091429968430611","date":"2026-04-27T06:45:45+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-26T06:44:05+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"102389718427527693936087988221468392812","date":"2026-04-25T10:57:21+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-24T06:54:27+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-23T04:25:15+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"125992846538192155946662070097423695872","date":"2026-04-20T13:16:04+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"135618850723137754588981105837275754238","date":"2026-04-20T10:58:32+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-17T09:58:50+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"113221724022996749181380834873756373122","date":"2026-04-17T06:52:05+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"615732299118921283745409739086229024","date":"2026-04-16T23:01:35+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"190092266203336282542376442766018036280","date":"2026-04-14T21:37:03+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-04-14T14:03:19+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-04-13T06:36:30+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-03-25T17:25:43+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-03-16T11:01:58+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Cancer","date":"2026-03-16T08:12:39+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcan","sideBox":"Learn more about [BMC Cancer](http://bmccancer.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcan/default.aspx","title":"BMC Cancer","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"2f1baa9c-8d21-4e42-9fbd-901906afc5fc","owner":[],"postedDate":"April 23rd, 2026","published":true,"recentEditorialEvents":[{"type":"editorInvitedReview","content":"","date":"2026-05-07T00:55:24+00:00","index":86,"fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-04-23T09:08:38+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-23 09:08:32","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9020902","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9020902","identity":"rs-9020902","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}