PONE-D-24-52964

The challenges of replication: a worked example of methods reproducibility using electronic health record data

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Reviewer #1: Partly

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Reviewer #1: No

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Reviewer #1: Yes

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5. Review Comments to the Author

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Reviewer #1: I congratulate the authors on their interesting paper on a working example of a reproducibility study with electronic health record (EHR) data.

I found the paper very well written and IMO the paper discusses very important challenges and possible solutions, especially for the problem of data reproducibility. In the worked example, the challenge of reproducing the results is not in the data analysis or statistical analysis part, as all the scripts relevant for these analyses are available and applicable, provided that the data tables are set up exactly as in the study for which a replication study is planned. The challenge is to obtain the data in the same structure from different databases. The conclusions are summarised in 12 recommendations for so-called Trusted Research Environments (TREs) and Secure Data Environments (SDEs) to manage such replication studies.

A drawback of the paper is certainly that the example study presented is very much tailored to how the UK system (NHS) manages access to EHR data. However, I think that the recommendations can be applied in a similar way to health systems in many countries, i.e. I suspect that there is also value in reading about the challenges for research groups not based in the UK.

I suggest that the authors write a paragraph on how they think their 12 recommendations can be generalised to other health systems (although they have described this problem in a limitation paragraph). This would add value to the paper.

A second drawback is that the data are not publicly available, but the authors have done some effort to describe the necessary procedures. I think it is an open question whether other researchers from countries other than the UK will be able to get access to the data since only accredited researchres were allowed to have access.

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Reviewer #1: No

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The challenges of replication: a worked example of methods reproducibility using electronic health record data

PONE-D-24-52964R1

Dear Dr. Richard Williams,

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,

Youssef El Khatib, Ph.D.

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

In my view, the revised version of the paper is suitable for publication.

Reviewers' comments: