PONE-D-21-39043Reproducible disease phenotyping at scale: example of coronary artery disease in UK BiobankPLOS ONE

Dear Dr. Denaxas,

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We look forward to receiving your revised manuscript.

Kind regards,

Dylan A Mordaunt, MB ChB, FRACP, FAIDH

Academic Editor

PLOS ONE

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Thank you for your submission. With specific regards to the criteria for publication:

1. The study appears to present the results of original research.

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Reviewers' comments:

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Comments to the Author

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Reviewer #1: No

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: No

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Reviewer #1: Yes

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Reviewer #1: Yes

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5. Review Comments to the Author

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Reviewer #1: This paper seeks to provide an algorithm for the classification of incident and prevalent CAD primarily using EHR coded data, supported by other coded data sources. There are several issues that need to be addressed to improve the utility of this work.

There was no comparison of the algorithm's classification to a "gold standard" classification. Hence, there was no "validation" in the understanding of most readers of this literature. It is not clear why the recommended approach of separating the dataset into the traditional testing and validation cohorts was not undertaken. I do recognise that the classifications lead to outcome profiles that have some "fidelity" with the expected outcomes of incident and prevalent MI, and therefore provides some assurance, but this still remains a single sample problem, and does not meet there standards of using the term validation.

Please see and apply principles from the TRIPOD recommendations

The use of coded data, rather than primary data sources (and the lack of validation) is problematic for the real clinical use of this algorithm. This should be recognised. This use of this algorithm is therefore useably for only cohort level or population level activities, rather than clinical (patient level) functions.

The inclusion of patient reported disease states is of uncertain value in this report. Some rationale for their inclusion should be provided.

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Reviewer #1: No

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Reproducible disease phenotyping at scale: example of coronary artery disease in UK Biobank

PONE-D-21-39043R1

Dear Dr. Denaxas,

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.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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Kind regards,

Dylan A Mordaunt, MB ChB, MPH, MHLM, FRACP, FAIDH

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Thank you for your resubmission. This now meets the criteria for publication.

Reviewers' comments: