Peer Review History

Original SubmissionJanuary 18, 2020
Decision Letter - Adya Misra, Editor

Dear Dr Wilkinson,

Thank you for submitting your manuscript entitled "Robust Prediction of Incident Diabetes Using Quantitative Clinical Data and a Bayesian Logistic Model for Cardiometabolic Disease Staging" for consideration by PLOS Medicine.

Your manuscript has now been evaluated by the PLOS Medicine editorial staff [as well as by an academic editor with relevant expertise] and I am writing to let you know that we would like to send your submission out for external peer review.

However, before we can send your manuscript to reviewers, we need you to complete your submission by providing the metadata that is required for full assessment. To this end, please login to Editorial Manager where you will find the paper in the 'Submissions Needing Revisions' folder on your homepage. Please click 'Revise Submission' from the Action Links and complete all additional questions in the submission questionnaire.

Please re-submit your manuscript within two working days, i.e. by .

Login to Editorial Manager here: https://www.editorialmanager.com/pmedicine

Once your full submission is complete, your paper will undergo a series of checks in preparation for peer review. Once your manuscript has passed all checks it will be sent out for review.

Feel free to email us at plosmedicine@plos.org if you have any queries relating to your submission.

Kind regards,

Adya Misra, PhD,

Senior Editor

PLOS Medicine

Revision 1
Decision Letter - Adya Misra, Editor

Dear Dr. Wilkinson,

Thank you very much for submitting your manuscript "Robust Prediction of Incident Diabetes Using Quantitative Clinical Data and a Bayesian Logistic Model for Cardiometabolic Disease Staging" (PMEDICINE-D-20-00156R1) for consideration at PLOS Medicine.

Your paper was evaluated by a senior editor and discussed among all the editors here. It was also discussed with an academic editor with relevant expertise, and sent to independent reviewers, including a statistical reviewer. The reviews are appended at the bottom of this email and any accompanying reviewer attachments can be seen via the link below:

[LINK]

In light of these reviews, I am afraid that we will not be able to accept the manuscript for publication in the journal in its current form, but we would like to consider a revised version that addresses the reviewers' and editors' comments. Obviously we cannot make any decision about publication until we have seen the revised manuscript and your response, and we plan to seek re-review by one or more of the reviewers.

In revising the manuscript for further consideration, your revisions should address the specific points made by each reviewer and the editors. Please also check the guidelines for revised papers at http://journals.plos.org/plosmedicine/s/revising-your-manuscript for any that apply to your paper. In your rebuttal letter you should indicate your response to the reviewers' and editors' comments, the changes you have made in the manuscript, and include either an excerpt of the revised text or the location (eg: page and line number) where each change can be found. Please submit a clean version of the paper as the main article file; a version with changes marked should be uploaded as a marked up manuscript.

In addition, we request that you upload any figures associated with your paper as individual TIF or EPS files with 300dpi resolution at resubmission; please read our figure guidelines for more information on our requirements: http://journals.plos.org/plosmedicine/s/figures. While revising your submission, please upload your figure files to the PACE digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email us at PLOSMedicine@plos.org.

We expect to receive your revised manuscript by May 29 2020 11:59PM. Please email us (plosmedicine@plos.org) if you have any questions or concerns.

***Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out.***

We ask every co-author listed on the manuscript to fill in a contributing author statement, making sure to declare all competing interests. If any of the co-authors have not filled in the statement, we will remind them to do so when the paper is revised. If all statements are not completed in a timely fashion this could hold up the re-review process. If new competing interests are declared later in the revision process, this may also hold up the submission. Should there be a problem getting one of your co-authors to fill in a statement we will be in contact. YOU MUST NOT ADD OR REMOVE AUTHORS UNLESS YOU HAVE ALERTED THE EDITOR HANDLING THE MANUSCRIPT TO THE CHANGE AND THEY SPECIFICALLY HAVE AGREED TO IT. You can see our competing interests policy here: http://journals.plos.org/plosmedicine/s/competing-interests.

Please use the following link to submit the revised manuscript:

https://www.editorialmanager.com/pmedicine/

Your article can be found in the "Submissions Needing Revision" folder.

To enhance the reproducibility of your results, we recommend that you deposit your laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. For instructions see http://journals.plos.org/plosmedicine/s/submission-guidelines#loc-methods.

Please ensure that the paper adheres to the PLOS Data Availability Policy (see http://journals.plos.org/plosmedicine/s/data-availability), which requires that all data underlying the study's findings be provided in a repository or as Supporting Information. For data residing with a third party, authors are required to provide instructions with contact information for obtaining the data. PLOS journals do not allow statements supported by "data not shown" or "unpublished results." For such statements, authors must provide supporting data or cite public sources that include it.

We look forward to receiving your revised manuscript.

Sincerely,

Adya Misra, PhD

Senior Editor

PLOS Medicine

plosmedicine.org

-----------------------------------------------------------

Requests from the editors:

Please revise your title according to PLOS Medicine's style. Your title must be nondeclarative and not a question. It should begin with main concept if possible. "Effect of" should be used only if causality can be inferred, i.e., for an RCT. Please place the study design ("A randomized controlled trial," "A retrospective study," "A modelling study," etc.) in the subtitle (ie, after a colon).

Abstract

Please provide brief participant demographics from both cohorts

If you meant T2D, please do replace instances of “diabetes” with Type 2 diabetes or T2D.

Last sentence of the methods and findings section should be a limitation of your study design/methodology

Conclusions

Please start this section with “our results show” or similar

Please avoid overreaching conclusions and use of adjectives such as “superior” to describe the predictive model

Author Summary

At this stage, we ask that you include a short, non-technical Author Summary of your research to make findings accessible to a wide audience that includes both scientists and non-scientists. The Author Summary should immediately follow the Abstract in your revised manuscript. This text is subject to editorial change and should be distinct from the scientific abstract. Please see our author guidelines for more information: https://journals.plos.org/plosmedicine/s/revising-your-manuscript#loc-author-summary

Prospective analysis plan

Did your study have a prospective protocol or analysis plan? Please state this (either way) early in the Methods section.

a) If a prospective analysis plan (from your funding proposal, IRB or other ethics committee submission, study protocol, or other planning document written before analyzing the data) was used in designing the study, please include the relevant prospectively written document with your revised manuscript as a Supporting Information file to be published alongside your study, and cite it in the Methods section. A legend for this file should be included at the end of your manuscript.

b) If no such document exists, please make sure that the Methods section transparently describes when analyses were planned, and when/why any data-driven changes to analyses took place.

c) In either case, changes in the analysis-- including those made in response to peer review comments-- should be identified as such in the Methods section of the paper, with rationale.

Please ensure that the study is reported according to TRIPOD guideline, and include the completed checklist as Supporting Information. When completing the checklist, please use section and paragraph numbers, rather than page numbers. Please add the following statement, or similar, to the Methods: "This study is reported as per the Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis guideline (S1 Checklist)."

Please report your study according to the relevant guideline, which can be found here: http://www.equator-network.org/

Introduction

Could you add a reference at lines 67-68?

Could you please add a space between the text and reference brackets throughout, followed by a full stop.

Please introduce NHANES on first view

Line 105- please introduce HDL

Methods

Line 130- please can you add United States here?

Please provide the full name of the ethics committee that approved the protocol(s)

Line 142- it would be useful to have a bit more information regarding what analyses/measurements were carried out even if brief. You may wish to add a citation in addition, if this has been previously published

Please format your bibliography to Vancouver style

Comments from the reviewers:

Reviewer #1: The stated purpose of this analysis is to create a tool using quantitative predictors available in real-world clinical practice that identifies individuals who are most likely to benefit from therapies to prevent diabetes.

Comments:

Is the REGARDS dataset (2003-2007), collected for stroke patients, representative of the wider population in order to analyse T2DM incidence?

How do the baseline population characteristics compare to the wider population, in order to extrapolate results?

"External validation was performed using 9,710 participants from Atherosclerotic Risk in Communities (ARIC) (1987-1989), observed through 1996-1998."

Is this population an unbiased sampling frame for T2DM?

"...Atherosclerotic Risk in Communities (ARIC)[11] cohorts to predict incident diabetes with specificity for sex and race. CMDS was developed using quantitative measures of metabolic syndrome traits (i.e., ATP-III criteria)[12], with the limitation that these cohorts were not designed as nationally representative."

Are the authors referring to the same cohort that they are using for their external validation?

How did the authors cope with any potential changes in definition or testing methods of T2DM over time between baseline and follow up?

The authors use a Bayesian logistic model using full-information continuous predictors. The novelty of this research piece is in its' application of continuous variables and interactions.

The method of Bayesian logistic modelling, and the means of measuring and comparing performance, seem appropriate given the context of this research question.

"Between the first and second visit, 5,713 individuals died, and 8,532 withdrew from further follow-up, leaving a population of 15,938 with follow-up data available."

What was cause of death (i.e. were any T2DM related?)? Were reasons for withdrawing from follow up provided (in order to understand if this missing data can be considered to be missing at random)?

"Diabetes was defined by having a fasting blood glucose level ≥126mg/dL, a non-fasting blood glucose ≥ 200mg/dL, self-reported diabetes or on diabetes medication"

Is there a risk of misclassification for cases of self diagnosed T2DM? This is part of the published ARIC protocol, but what is the potential impact in this setting?

There are some grammatical errors in the text, for example the statistical methods section."Cauchy priors, which has advantage of providing"

Did the authors assess correlation between parameters in the model, and the effect this might have on the model outcome and interpretation?

The authors provide a clear description of findings in the results section, aligned with informative tables and figures.

"additional reason for greater predictive value is that the previous models did not include age.[19] "

Can the authors compare their model with previous models updated to include age (albeit dichotomously), in order to compare how much uplift in the model performance is down to the inclusion of this variable, and how much is due to the novel application of Bayesian modelling?

Reviewer #2: This is a well-conducted study that developed a Bayesian logistic model using full-information continuous predictors to predict T2DM risk. This tool can be used for diabetes prevention efforts including weight loss therapy by allowing clinicians to target high risk individuals in a manner that could be used to optimize outcomes.

The authors developed the model in REGARDS and validated it in ARIC, two large national cohorts including both White and Black men and women. They compared the Bayesian method with several other predictive modeling methods, including lasso, generalized additive model, random forests, and support vector machine learning, and found that the Bayesian logistic model outperformed these alternative approaches.

They further compared the AUC from the Bayesian logistic model to the CMDS model, the Framingham and American Diabetes Association risk scores. The AUC for the Bayesian logistic model was superior at AUC 0.79 to other models or scores, such as the CMDS model (AUC 0.75), the Framingham scoring system (AUC 0.76) and American Diabetes Association scoring system (AUC 0.64).

Reviewer #3: This manuscript conducted a Bayesian logistic model using the full-information continuous analysis with the nationally sampled data from white and black American adults to predict T2DM risk. The manuscript is well written and provides a powerful predictive tool to used for diabetes prevention. There were some issues related to this manuscript.

1. As the authors indicated that there were 8,532 participants withdrew from further follow-up in the REGARDS. Since that the REGARDS is a nationally sampled longitudinal survey, are there any differences between these 8,532 participants and the participants remained for the further analysis in the present study?

2. Line 230, age (45-92) should be age (45-92 y).

3. In the Table A2, the min value of BMI, waist circumference, blood glucose, and HDL are extremely low. it is better to exclude these participants with outlier. Also, the unit (kg/m2) for BMI and cm for waist circumference should add in this table.

4. The mean age of the REGARDS survey is 63.12 years. Therefore, generalizability to younger population also requires caution.

Any attachments provided with reviews can be seen via the following link:

[LINK]

Revision 2

Attachments
Attachment
Submitted filename: Response to Reviewers.docx
Decision Letter - Adya Misra, Editor

Dear Dr. Wilkinson,

Thank you very much for re-submitting your manuscript "Development and Validation of a Model for Predicting Incident Type-2 Diabetes Using Quantitative Clinical Data and a Bayesian Logistic Model: A Nationwide Cohort and Modelling Study" (PMEDICINE-D-20-00156R2) for review by PLOS Medicine.

I have discussed the paper with my colleagues and the academic editor and it was also seen again by reviewers. I am pleased to say that provided the remaining editorial and production issues are dealt with we are planning to accept the paper for publication in the journal.

The remaining issues that need to be addressed are listed at the end of this email. Any accompanying reviewer attachments can be seen via the link below. Please take these into account before resubmitting your manuscript:

[LINK]

Our publications team (plosmedicine@plos.org) will be in touch shortly about the production requirements for your paper, and the link and deadline for resubmission. DO NOT RESUBMIT BEFORE YOU'VE RECEIVED THE PRODUCTION REQUIREMENTS.

***Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out.***

In revising the manuscript for further consideration here, please ensure you address the specific points made by each reviewer and the editors. In your rebuttal letter you should indicate your response to the reviewers' and editors' comments and the changes you have made in the manuscript. Please submit a clean version of the paper as the main article file. A version with changes marked must also be uploaded as a marked up manuscript file.

Please also check the guidelines for revised papers at http://journals.plos.org/plosmedicine/s/revising-your-manuscript for any that apply to your paper. If you haven't already, we ask that you provide a short, non-technical Author Summary of your research to make findings accessible to a wide audience that includes both scientists and non-scientists. The Author Summary should immediately follow the Abstract in your revised manuscript. This text is subject to editorial change and should be distinct from the scientific abstract.

We ask every co-author listed on the manuscript to fill in a contributing author statement. If any of the co-authors have not filled in the statement, we will remind them to do so when the paper is revised. If all statements are not completed in a timely fashion this could hold up the re-review process. Should there be a problem getting one of your co-authors to fill in a statement we will be in contact. YOU MUST NOT ADD OR REMOVE AUTHORS UNLESS YOU HAVE ALERTED THE EDITOR HANDLING THE MANUSCRIPT TO THE CHANGE AND THEY SPECIFICALLY HAVE AGREED TO IT.

Please ensure that the paper adheres to the PLOS Data Availability Policy (see http://journals.plos.org/plosmedicine/s/data-availability), which requires that all data underlying the study's findings be provided in a repository or as Supporting Information. For data residing with a third party, authors are required to provide instructions with contact information for obtaining the data. PLOS journals do not allow statements supported by "data not shown" or "unpublished results." For such statements, authors must provide supporting data or cite public sources that include it.

If you have any questions in the meantime, please contact me or the journal staff on plosmedicine@plos.org.

We look forward to receiving the revised manuscript by Jun 15 2020 11:59PM.

Sincerely,

Adya Misra, PhD

Senior Editor

PLOS Medicine

plosmedicine.org

------------------------------------------------------------

Requests from Editors:

COI – can you please say who is a paid employee of Novo Nordisk. I think this needs clarity.

Abstract-could you add some more demographic information, like mean age and maybe BMI ranges.

Line 237 “We found that our Bayesian logistic model outperformed these alternative approaches.” Please can they provide a call out to Table A1 where the comparison is.

Reference call outs should be in square brackets please

Line 101- suggest rephrasing “along ethnic, social, or economic lines”

Throughout- please take care to avoid saying “participants were obese” and instead say “participants suffered from obesity” or similar to avoid the use of stigmatising language. For example Line 258

Please provide exact p-values, for example at line 304 unless the p-value is <0.001 and check that the p-values are provided throughout, where appropriate

Line 337 should say “with improved capability”

Please temper the assertions of primacy by adding “to our knowledge” in the discussion

Please add a sentence in the methods to note the analyses were prespecified and that the analysis plans are provided as SI files

Please remove all iterations of "[Internet]" from the reference list.

I think Table 1 is not visible in the manuscript PDF and may need adjusting

Please remove page numbers from the TRIPOD checklist as these are likely to change. Instead please use paragraphs and sections

Comments from Reviewers:

Any attachments provided with reviews can be seen via the following link:

[LINK]

Revision 3

Attachments
Attachment
Submitted filename: FInal_revisions_RESPONSE.docx
Decision Letter - Adya Misra, Editor

Dear Dr Wilkinson,

On behalf of my colleagues and the academic editor, Dr. Karine Clément, I am delighted to inform you that your manuscript entitled "Development and Validation of a Model for Predicting Incident Type-2 Diabetes Using Quantitative Clinical Data and a Bayesian Logistic Model: A Nationwide Cohort and Modelling Study" (PMEDICINE-D-20-00156R3) has been accepted for publication in PLOS Medicine.

PRODUCTION PROCESS

Before publication you will see the copyedited word document (in around 1-2 weeks from now) and a PDF galley proof shortly after that. The copyeditor will be in touch shortly before sending you the copyedited Word document. We will make some revisions at the copyediting stage to conform to our general style, and for clarification. When you receive this version you should check and revise it very carefully, including figures, tables, references, and supporting information, because corrections at the next stage (proofs) will be strictly limited to (1) errors in author names or affiliations, (2) errors of scientific fact that would cause misunderstandings to readers, and (3) printer's (introduced) errors.

If you are likely to be away when either this document or the proof is sent, please ensure we have contact information of a second person, as we will need you to respond quickly at each point.

PRESS

A selection of our articles each week are press released by the journal. You will be contacted nearer the time if we are press releasing your article in order to approve the content and check the contact information for journalists is correct. If your institution or institutions have a press office, please notify them about your upcoming paper at this point, to enable them to help maximize its impact.

PROFILE INFORMATION

Now that your manuscript has been accepted, please log into EM and update your profile. Go to https://www.editorialmanager.com/pmedicine, log in, and click on the "Update My Information" link at the top of the page. Please update your user information to ensure an efficient production and billing process.

Thank you again for submitting the manuscript to PLOS Medicine. We look forward to publishing it.

Best wishes,

Adya Misra, PhD

Senior Editor

PLOS Medicine

plosmedicine.org

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