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Efficacy and safety of traditional chemotherapies for patients with ovarian neoplasm: a network meta-analysis · 10.18632/oncotarget.16729

Name: Verified Rigor Record — Efficacy and safety of traditional chemotherapies for patients with ovarian neoplasm: a network meta-analysis · 10.18632/oncotarget.16729
Item: Efficacy and safety of traditional chemotherapies for patients with ovarian neoplasm: a network meta-analysis · 10.18632/oncotarget.16729
Rating: 71
Author: Αlpha¹

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Αlpha¹ Editorial

This rigor review was examined and confirmed by Αlpha¹ Editorial · July 6, 2026

Αlpha¹ Rigor Review

Rigor Reviewed

WARN

Warnings to address · Meta-Analysis / Systematic Review

Eight dimensions — click a segment for details

Critical

High-priority

Model-reported confidence: moderateReviewer agreement: moderateEngine: 7.6.0Source: full text

Not verified in this report

No reported statistical tests were found to recompute.
No data or code availability links were detected to verify.

This Αlpha¹ Rigor Review uses AI Rigor Reviewers trained on a curated corpus of high-fidelity and retracted papers, with expert supervision and curation. It can still make mistakes; verify each finding against the source before relying on it.

This published network meta-analysis has a sound scientific premise and adequately reports most core outcomes, but it is undermined by several methodological reporting gaps and the absence of a data/code availability statement. The most consequential gaps are the lack of a risk-of-bias assessment for the included RCTs, incomplete specification of the Bayesian model (no priors/convergence diagnostics), and no reference to a reporting guideline (PRISMA-NMA). The paper also contains a major copyedit issue (a duplicate sentence in Methods) and the integrity check uncovered a striking 9-year date discrepancy between the header (2026) and the received/accepted dates (2017), which must be resolved.

Seven dimensions were applicable (ethical approvals and biological variables partial — biological variables is scored as applicable because patient demographics from included trials are standard to report). The reviewers agreed on most dimensions but diverged on study design (1 pass vs 2 warn) and key resources/statistical analysis (1 warn vs 2 pass). The statistics component could not recompute any test statistics, leaving the numerical results unverified.

12 major claims checked against the paper's own evidence: all adequately supported.

2 integrity concerns flagged (1 high).

Rigor

Eight Dimensions3 pass · 2 warn · 2 fail

12 major claims2 partial10 supported

The introduction cites risk factors, treatment options, and prior trials. It explicitly identifies gaps: a previous NMA (Jiang 2017) did not assess adverse effects and did not use hazard ratios for time-specific outcomes. The present study's aim is to fill these gaps by including both efficacy and safety outcomes using HR at multiple time points.

Sub-criteria

prior work citedADEQUATE

premise rationaleADEQUATE

limitations addressedADEQUATE

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 92% conf

The paper clearly establishes its scientific foundation by citing prior research, providing a logical rationale, and describing how limitations of prior work are addressed.

Evidence

direct quote[Introduction, paragraph 5]

“though there existed one network meta-analysis (NMA) study [], it only focused on eight different chemotherapy regimens and didn't analyze hazard ratio concerning time period, it also neglected the adverse effects of chemotherapies”

direct quote[Introduction, final paragraph]

“the aim of our study is to complete a NMA using current outcomes from analysis of MA and RCTs, therefore every two therapies with or without direct comparison can be rationally evaluated”

direct quote[Discussion, paragraph 1]

“our study has its necessity and accuracy in addressing these unresolved problems”

PASSReviewer 2· 90% conf

The paper clearly establishes its premise by citing prior research and addressing the limitations of a previous network meta-analysis.

Evidence

direct quote[Introduction, paragraph 4]

“though there existed one network meta-analysis (NMA) study [16], it only focused on eight different chemotherapy regimens and didn't analyze hazard ratio concerning time period, it also neglected the adverse effects of chemotherapies.”

direct quote[Introduction, paragraph 4]

“Thus, the aim of our study is to complete a NMA using current outcomes from analysis of MA and RCTs, therefore every two therapies with or without direct comparison can be rationally evaluated.”

PASSReviewer 3· 95% conf

Prior research is well cited, the rationale for the NMA is clearly justified by shortcomings of a previous NMA, and the study addresses those limitations.

Evidence

direct quote[Introduction, paragraph 5]

“the aim of our study is to complete a NMA using current outcomes from analysis of MA and RCTs, therefore every two therapies with or without direct comparison can be rationally evaluated.”

paraphrase[Discussion, paragraph 1]

“The paper states that its study includes both efficacy and safety outcomes and uses HR to evaluate survival at different time points, addressing shortcomings of the prior NMA.”

The paper reports clear inclusion/exclusion criteria for study selection. However, no risk-of-bias tool is applied to the included RCTs, and no power analysis or search completeness assessment (e.g., funnel plot) is reported, both of which are expected for a meta-analysis.

Sub-criteria

controlsNOT REPORTED

power analysisNOT REPORTED

blinding levelsN/A

outlier handlingN/A

randomization unitN/A

inclusion exclusionADEQUATE

randomization methodN/A

replicate distinctionN/A

independent replicationN/A

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 85% conf

The study design is appropriate for a network meta-analysis: it describes a systematic search, prespecified selection criteria, and a Bayesian NMA framework. Applicable sub-criteria are well covered.

Evidence

direct quote[Materials and Methods, Selection criteria]

“all RCTs evaluating the efficacy and safety of drug therapies for ovarian neoplasm and including at least one pair of direct control group were potentially eligible”

direct quote[Materials and Methods, Selection criteria]

“duplicates; articles based on the same clinical trials; RCTs could not form a network; data was insufficient or unavailable”

direct quote[Materials and Methods, Data extraction]

“Data extraction of characteristics and data from the included trials was accomplished independently by two reviewers”

WARNReviewer 2· 80% conf

Inclusion/exclusion criteria are well-defined, but the paper lacks a risk-of-bias assessment and a formal evaluation of search completeness.

Evidence

direct quote[Methods, Selection criteria]

“all RCTs evaluating the efficacy and safety of drug therapies for ovarian neoplasm and including at least one pair of direct control group were potentially eligible. Furthermore, many trials were excluded for the following reasons: (1) duplicates; (2) articles based on the same clinical trials; (3) RCTs could not form a network; (4) data was insufficient or unavailable.”

absence[Methods]

No risk-of-bias assessment reported.

WARNReviewer 3· 75% conf

Study selection criteria are adequately described, but the paper does not report a risk-of-bias assessment or how outliers/handling of heterogeneity were addressed, which are expected for a meta-analysis.

Evidence

direct quote[Materials and Methods, Selection criteria]

“For the NMA, all RCTs evaluating the efficacy and safety of drug therapies for ovarian neoplasm and including at least one pair of direct control group were potentially eligible.”

absence[Materials and Methods]

No risk-of-bias assessment is reported.

absence[Materials and Methods, Statistical analysis]

No method for handling outliers or heterogeneity is described.

Table 1 lists study characteristics (author, follow-up, sample size, comparisons) but contains no information on patient age, sex, race, or health status. Sex is implied (ovarian cancer) but never explicitly stated. Age and other biological variables are not reported.

Sub-criteria

demographicsNOT REPORTED

sex reportedNOT REPORTED

sex justifiedN/A

age weight healthNOT REPORTED

housing conditionsN/A

species strain sourceN/A

Per reviewer (3) — the votes behind the verdict

N/AReviewer 1· 98% conf

This is a meta-analysis of published trials; individual participant-level biological variables are not directly reported or analyzed. The paper extracts aggregate outcome data from included trials, not subject-level metadata.

Evidence

paraphrase[Materials and Methods, Data extraction]

“The data extracted are aggregate trial characteristics and outcomes, not individual participant demographics.”

FAILReviewer 2· 70% conf

The paper does not report patient demographics (age, sex, health status) across the included studies, which is a significant gap for a meta-analysis synthesizing clinical trial data.

Evidence

direct quote[Table 1]

“Table 1 Study characteristics ... Sample Size ... Comparision ... Primary Outcomes ... Adverse Effects”

absence[Results and Table 1]

Age, weight, and health status are not reported.

WARNReviewer 3· 50% conf

Patient demographic and biological variables (age, sex, health status) are not summarized across the included trials, which limits assessment of the study population.

Evidence

absence[Table 1]

No summary of participant demographics (age, sex, health status) is provided.

absence[Table 1 and text]

Sex of patients is not explicitly reported, though ovarian cancer implies female.

The study reuses data from already published, publicly available RCTs. No new subject-level data were generated. Therefore, no IRB or IACUC approval is required for the meta-analysis. The paper does not claim any new data collection.

Sub-criteria

iacuc statementN/A

informed consentN/A

irb ethics statementN/A

regulatory complianceN/A

Per reviewer (3) — the votes behind the verdict

N/AReviewer 1· 95% conf

The paper is a meta-analysis of published RCTs; it does not involve new data collection from human or animal subjects, so ethics approval is not applicable for the synthesis itself.

Evidence

direct quote[Abstract]

“Eligible randomized controlled trials (RCTs) were retrieved from electronic databases”

N/AReviewer 2· 95% conf

This is a meta-analysis of published RCT data; no new human or animal subject data were collected, so ethical approvals are not applicable.

Evidence

paraphrase[Methods, Search strategy and Selection criteria]

“The paper describes searching electronic databases for published RCTs and extracting data from those trials.”

N/AReviewer 3· 95% conf

This is a meta-analysis of published RCTs; no new human or animal subject data were collected, so ethics approval is not applicable.

Evidence

paraphrase[Methods and Results]

“The paper describes a network meta-analysis of 19 eligible RCTs identified from electronic databases.”

The paper reports using R 3.3.2 and STATA 13.1 for the Bayesian NMA. No other reagents, cell lines, antibodies, or biological materials were used, as this is a literature-based meta-analysis.

Sub-criteria

mycoplasma testingN/A

reagents identifiedN/A

organisms identifiedN/A

antibodies identifiedN/A

cell line authenticationN/A

software tools identifiedADEQUATE

Per reviewer (3) — the votes behind the verdict

WARNReviewer 1· 85% conf

The paper identifies the statistical software (R 3.3.2, STATA 13.1) but does not provide version details, custom code, or a repository. It does not use biological reagents or investigational products directly, but the therapeutics compared are named. The omission of systematic reporting tools (software versions in formal citations, code sharing) warrants a warning.

Evidence

direct quote[Materials and Methods, Statistical analysis]

“R 3.3.2 and STATA 13.1 were applied to conduct the Bayesian NMA”

absence[Materials and Methods, Statistical analysis]

No custom code is shared or repository mentioned.

PASSReviewer 2· 90% conf

The statistical software used (R and STATA) is identified with version numbers; no other biological resources are applicable.

Evidence

direct quote[Methods, Statistical analysis]

“R 3.3.2 and STATA 13.1 were applied to conduct the Bayesian NMA”

PASSReviewer 3· 95% conf

Statistical software (R 3.3.2 and STATA 13.1) is identified by name and version; other biological/chemical resources are not applicable to this meta-analysis.

Evidence

direct quote[Materials and Methods, Statistical analysis]

“R 3.3.2 and STATA 13.1 were applied to conduct the Bayesian NMA”

The paper reports hazard ratios and odds ratios with 95% credible intervals for all comparisons. The statistical software is named with versions. Forest plots and network diagrams are provided. However, the specific Bayesian model (e.g., random-effects, prior distributions, convergence diagnostics) is not described, and no assumption checks (e.g., consistency, heterogeneity) are reported. These are limitations but do not invalidate the pass status as the core elements are adequate.

Sub-criteria

tests namedINADEQUATE

exact p valuesN/A

effect sizes ciADEQUATE

data presentationADEQUATE

software identifiedADEQUATE

assumptions verifiedNOT REPORTED

mathematical plausibilityN/A

Per reviewer (3) — the votes behind the verdict

WARNReviewer 1· 80% conf

Statistical tests (Bayesian NMA, HR, OR, SUCRA) are named, effect sizes with 95% CrI are reported, and software is identified. However, exact p-values are not reported (only CrI), assumptions are not verified (inherent in Bayesian framework but not discussed), and data presentation uses forest plots and tables but does not show individual data points. The mathematical plausibility of the summary statistics cannot be fully verified from the aggregate CrI and SUCRA values alone.

Evidence

direct quote[Materials and Methods, Statistical analysis]

“R 3.3.2 and STATA 13.1 were applied to conduct the Bayesian NMA, and 95% CrI were computed for HR and OR in survival and adverse effect analysis”

direct quote[Table 2]

“Hazard ratio (HR) and corresponding 95% CrI for efficacy outcomes”

absence[Materials and Methods, Statistical analysis]

Assumptions of the Bayesian model (priors, convergence) are not reported.

PASSReviewer 2· 75% conf

Effect sizes with 95% credible intervals are reported, software is identified, and data are presented in forest plots and tables. However, the Bayesian model is not fully specified and assumptions are not verified.

Evidence

direct quote[Methods, Statistical analysis]

“For survival analysis, hazard ratio (HR) and the associated 95% credible interval (CrI) were used to describe efficacy in a comparison under OS and PFS measurements”

direct quote[Methods, Statistical analysis]

“R 3.3.2 and STATA 13.1 were applied to conduct the Bayesian NMA”

paraphrase[Results, Figures 2 and 3]

“Figure 2 is a network diagram; Figure 3 is a forest plot of efficacy outcomes.”

PASSReviewer 3· 60% conf

Effect sizes (HR, OR) with 95% credible intervals are reported, and software is identified. However, the statistical model (priors, convergence) is incompletely described and assumption checks are not reported.

Evidence

direct quote[Results, Table 2]

“Hazard ratio (HR) and corresponding 95% CrI for efficacy outcomes.”

absence[Materials and Methods, Statistical analysis]

Bayesian model details (priors, convergence) are not reported.

absence[Materials and Methods]

Assumption checks (e.g., consistency) are not mentioned.

The paper does not include any statement about where the data (e.g., the extracted data from the 19 trials, the analysis code) can be accessed. For a meta-analysis, a data availability statement and ideally a repository deposit (e.g., GitHub for code, a data repository for extracted data) are expected. The paper lacks all of these.

Sub-criteria

code sharingNOT REPORTED

accession numbersNOT REPORTED

repository depositNOT REPORTED

data availability statementNOT REPORTED

Per reviewer (3) — the votes behind the verdict

FAILReviewer 1· 90% conf

No data availability statement is provided, no repository deposit is mentioned, no accession numbers, and no custom code sharing. All applicable criteria are not_reported, leading to a fail.

Evidence

absence[Entire paper]

No data availability statement is present.

absence[Entire paper]

No code repository or sharing is mentioned.

FAILReviewer 2· 90% conf

No data availability statement is provided, and no data or code are deposited in a repository.

Evidence

absence[Entire paper]

No data availability statement present.

absence[Entire paper]

No code sharing mentioned.

FAILReviewer 3· 40% conf

No data availability statement is provided, and no data or custom code are deposited in a public repository, which is increasingly expected for meta-analyses.

Evidence

absence[Entire manuscript]

No data availability statement is present.

absence[Entire manuscript]

No repository deposition or code sharing is mentioned.

Methods_completeness is adequate: search strategy, selection criteria, data extraction, and statistical analysis are described. Trial_registration is n/a. Reporting_guideline is not_reported: no mention of PRISMA or any other reporting guideline. All_outcomes_reported seems adequate; the paper reports multiple efficacy and safety outcomes as specified. Limitations_discussed is adequate: the paper openly discusses the lack of direct comparisons, small sample sizes for some therapies, missing safety data for PLD/Pa/Ca, and inability to analyze drug dose. Conclusions_proportional is adequate: the authors recommend therapies with caution and state limitations. Funding_coi is adequate: a conflicts of interest statement is provided; funding sources are not explicitly stated but the COI statement exists. With 1 out of 6 applicable criteria (reporting_guideline) not_reported and the rest adequate, the overall score is warn.

Sub-criteria

funding coiADEQUATE

trial registrationN/A

reporting guidelineNOT REPORTED

methods completenessADEQUATE

all outcomes reportedADEQUATE

limitations discussedADEQUATE

conclusions proportionalADEQUATE

Per reviewer (3) — the votes behind the verdict

WARNReviewer 1· 82% conf

The paper describes methods in sufficient detail for replication (search strategy, selection criteria, statistical analysis). Limitations are discussed. Conclusions are mostly proportional. However, no reporting guideline (PRISMA) is referenced, no trial registration (n/a for NMA), and all outcomes are reported transparently. Funding and COI are stated. The absence of a PRISMA checklist reference is a notable gap.

Evidence

direct quote[Materials and Methods, Search strategy, Selection criteria]

“Electronic databases such as PubMed, EMBASE were utilized to identify relevant trials”

direct quote[Discussion, last paragraph before Conclusions]

“we could not find the adverse effects outcomes of PLD/Pa/Ca, though it was regarded as one of the recommended highly efficacious therapies among all therapies”

absence[Entire paper]

No PRISMA or other reporting guideline is referenced.

WARNReviewer 2· 80% conf

The paper discusses limitations and includes proportional conclusions, but it does not reference a reporting guideline (e.g., PRISMA), provides no funding information, and the methods lack full detail on the Bayesian model.

Evidence

direct quote[Discussion, paragraph 4]

“Although this study was conducted as meticulous as possible, it still had limitations.”

absence[Methods]

No reporting guideline referenced.

direct quote[Conclusions]

“PLD/Pa/Ca, PLD/Ca and Pa/E/Ca were highly recommended as potential choice of therapies for patients with ovarian cancer. But considering the lack of safety data for PLD/Pa/Ca, this intervention should be taken with caution.”

WARNReviewer 3· 65% conf

Outcomes and limitations are well reported, but the paper does not reference a reporting guideline (e.g., PRISMA), and the methods lack sufficient detail for full replication (e.g., Bayesian priors). Funding is not reported.

Evidence

absence[Materials and Methods]

No PRISMA or other reporting guideline is referenced.

absence[Materials and Methods, Statistical analysis]

Methods lack Bayesian model details (priors, convergence).

direct quote[Conflicts of Interest]

“The authors declare no financial interests in the findings described in the manuscript.”

16 copyedit issues flagged (1 major): mostly typo, consistency, grammar.

Checked 30 references: 25 verified — 5 not checked.

Αlpha¹ Rigor Action ItemsFinal pass before journal submission

POST-PUBLICATION AUDIT: An informed reader should consider the publishing date anomaly (header states 2026 but dates are 2017) and the complete lack of a data/code availability statement as serious concerns. The absence of a risk-of-bias assessment and missing Bayesian model details limit confidence in the results. A correction or independent re-analysis would be warranted if the date discrepancy is not resolved through a formal erratum, and the original data and code should be made available to allow verification. The paper's conclusions should be treated as preliminary until these issues are addressed.

1.
HIGHother
Resolve the 9-year date discrepancy: the manuscript header states a 2026 publication date, but the received (2017-01-07) and accepted (2017-02-24) dates are from 2017. Verify the correct publication year and issue a formal correction if already published.
This discrepancy is a high-severity integrity concern that undermines the credibility of the publication record and must be corrected via an erratum or retraction notice.
2.
HIGHdata code
Add a data availability statement specifying where the extracted dataset (e.g., the NMA-ready table of outcomes from the 19 trials) can be accessed, ideally in a repository like Figshare or Zenodo with a DOI.
The paper provides no way for readers to access the underlying data, which is a fundamental failure for reproducibility of a meta-analysis.
3.
HIGHdata code
Deposit the custom analysis code (R and/or STATA scripts for the Bayesian NMA) in a public repository (e.g., GitHub) with a permanent identifier, and reference it in the manuscript.
The Bayesian model is incompletely specified in the text; sharing exact code is the only way to verify the analysis.
4.
HIGHreporting
Reference the PRISMA 2020 checklist for network meta-analyses (PRISMA-NMA) and include the completed checklist as a supplementary file.
No reporting guideline is cited, which is a standard expectation for meta-analyses and would improve completeness of reporting.
5.
HIGHreporting
Report the full Bayesian model specification: prior distributions, number of MCMC chains, iterations, burn-in, and convergence diagnostics (e.g., Gelman-Rubin statistic) in the Statistical analysis section.
Without these details the analysis is not reproducible and the robustness of the credible intervals cannot be assessed.
6.
HIGHreporting
Conduct and report a risk-of-bias assessment for each included RCT using the Cochrane Risk of Bias tool, and present the results in a table or figure.
A meta-analysis without quality assessment of its primary studies leaves the evidence base uncharacterized, which is a major methodological gap.
7.
HIGHreporting
Report funding sources and grant numbers for the study; currently only a conflict-of-interest statement is present.
Funding transparency is a standard ethical requirement for published research.
8.
HIGHreporting
Add a summary table of patient demographics (age, sex, disease stage) from the included trials, either extracted from each study or as a range/median across studies.
Patient demographics are critical for assessing the generalizability and clinical applicability of the meta-analysis results.
9.
HIGHcopyedit
Delete the duplicate sentence in the Methods section (Statistical analysis paragraph: the sentence 'R 3.3.2 and STATA 13.1 were applied...' appears twice verbatim).
This is a major copyedit error that suggests careless formatting and may confuse readers.
10.
MEDIUMreporting
Describe how heterogeneity/inconsistency was assessed (e.g., node-splitting, I² statistic, or at minimum a statement that pairwise heterogeneity was examined) in the Statistical analysis section.
Assessment of inconsistency is a key step in any NMA; its absence reduces confidence in the validity of the network estimates.
11.
MEDIUMreporting
Include a PRISMA flow diagram that shows the exact numbers of records identified, screened, excluded (with reasons), and included, and ensure it follows current PRISMA guidelines fully.
The current Figure 1 may be a flow diagram but its PRISMA compliance is not verifiable from the text.
12.
MEDIUMcopyedit
Fix the typo 'Gordan' to 'Gordon' in Table 1 (author name), and standardize all author spelling throughout the manuscript and reference list.
Incorrect author names undermine the scholarly record and can cause citation errors.
13.
MEDIUMcopyedit
Fix the duplicate word 'the' in Discussion paragraph 2: 'the the significant difference' should read 'the significant difference'.
This is a distracting grammatical error in a published paper.
14.
LOWcopyedit
Standardize all shorthand notation for survival outcomes: use '3y-OS, 5y-OS, 3y-PFS, 5y-PFS' consistently throughout the Results section (currently mixed with '3 year' and '5 year').
Inconsistent abbreviation use can confuse readers and appears unprofessional.
15.
LOWcopyedit
Correct the table note in Table 3: change 'nunbers' to 'numbers' and 'significance difference' to 'significant difference'.
These are typographical errors in a published table legend.

Full text (51,296 chars)Analyzed: Jul 6, 2026

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