PONE-D-25-18621Unveiling Aducanumab's Safety Profile: A Comprehensive Pharmacovigilance AnalysisPLOS ONE

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Reviewers' comments:

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Reviewer #1: Yes

Reviewer #2: Partly

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: No

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5. Review Comments to the Author

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Reviewer #1: The manuscript by Zongren Zhao et. al entitled “Unveiling Aducanumab's Safety Profile: A Comprehensive Pharmacovigilance Analysis” describes the detailed pharmacovigilance study related to adverse events of Aducanumab. The authors have described very well about methodology they used. The manuscript is well written. Incorporating the minor suggestions listed below will further enhance the quality and clarity of the manuscript.

1. The authors have not discussed whether the incidence or severity of adverse events of Aducanumab varies by stage of Alzheimer’s disease, such as in patients with mild cognitive impairment (MCI) versus those with moderate to severe Alzheimer’s disease. It is important to understand the safety profile of Aducanumab across different stages of disease progression. Describe adverse events in this context.

2. The authors have not reported any significant adverse drug interactions between aducanumab and other medications. Are there known or potential drug-drug interactions involving Aducanumab?

Reviewer #2: Causality Limitations Not Adequately Emphasized:

Although the authors have admitted that the FAERS (FDA Adverse Event Reporting System) data has limitations, sometimes they still write in a way that makes it seem like one thing causes another. This is misleading because FAERS data can't prove cause and effect—it can only show associations (possible links or patterns). The authors should be more careful and consistent, always describing their results as potential signals or associations, not as solid proof that one thing causes another.

Overstatement of Significance for Rare Events:

Some of the reported high ROR/PT values (a measure used to detect potential drug-event associations) are based on only a few cases—for example, subdural hematoma is mentioned with just 3 reports. Because the sample size is so small, the findings might not be reliable. The authors should clearly point out the limited number of cases and be careful not to make these results seem more important or certain than they really are, unless there's stronger evidence to support them.

Clarity and English Language Issues:

While the manuscript is mostly readable, several sections suffer from awkward phrasing, grammatical errors, and overly complex sentence structures. A thorough language revision is recommended to improve clarity and professionalism.

Lack of Comparative Context:

It would strengthen the paper to compare Aducanumab’s AE profile with similar biologics (e.g., lecanemab or other anti-amyloid monoclonal antibodies) if such data are available in FAERS.

Ethical and Data Transparency Considerations:

The ethics statement is marked as "N/A", which is appropriate for FAERS studies. However, the manuscript should explicitly state this in the methods section to pre-empt reviewer concerns.

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Reviewer #1: No

Reviewer #2: Yes:  Prof. Priyatosh Ranjan

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Unveiling Aducanumab's Safety Profile: A Comprehensive Pharmacovigilance Analysis

PONE-D-25-18621R1

Dear Dr. Zhao,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

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Kind regards,

Ashima Nayyar

Academic Editor

PLOS ONE

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