PONE-D-20-34374

Experiences from Six Years of Quality Assured Model of End Stage Liver Disease (MELD) Diagnostics

PLOS ONE

Dear Dr. Kaiser,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please submit your revised manuscript by Mar 05 2021 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

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We look forward to receiving your revised manuscript.

Kind regards,

Pal Bela Szecsi, M.D. D.M.Sci.

Academic Editor

PLOS ONE

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Additional Editor Comments:

I find the manuscript of some value, even though one reviewer recommend rejection.

Anyhow, I’ll allow a major revision.

You should emphasize more on the laboratory errors around reporting the MELD score.

Being in a laboratory myself, I wonder why you system does not automatically request all three parameters when MELD is ordered and why it not automatically substitute MELD with PELD when the age is <12yrs?

In table 2, several of the errors seems belonging to the same group, missing material, wrong material, lithium instead of serum. “Confusion of patients in the process of blood withdrawal” is that the code for incorrect ID? “Incorrect labeling of monovettes (wrong material)” is that patient label og a producer error?

Some details concerning the analytic methods would be nice, calibration CV, QC.

SPSS is not originating in Ehningen, the correct citation should be “IBM Corp. Released 2016. IBM SPSS Statistics for Windows, Version 24.0. Armonk, NY: IBM Corp”, or some abbreviation hereof.

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Partly

Reviewer #2: Yes

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

Reviewer #1: Yes

Reviewer #2: Yes

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3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: No

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4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: The paper is reviewing the experience of a quality assurance system of validation and report of MELD score. All the results shows the good performance of this system to detect invalid MELD scores due to different reasons .

I think these results should be submitted to a different type of journal more focused in Clinical Chemistry and/or Laboratory

In the discussion , it should be emphasized to interpret this MELD score in the clinical context of patients . The clinician must understand , before sending the data , the intrinsic limitations of MELD . This score is NOT design for patient under dialysis or under anticoagulation therapy .

All this scores must be validated before and/or after the results of the laboratory to the final use of allocation of patients in a waiting list . There is a some exceptions for MELD and also some limitations that make essential the evaluation of the physician. All this aspects must be discussed in the paper

Reviewer #2: The significance of this study, and what exactly was accomplished, needs to be more strongly justified. The introduction should provide more clarification as to what kinds of laboratory errors this diagnostic review algorithm is supposed to address. Additionally, while a recent laboratory validation controversy in Germany is mentioned, further support for the need for a validation algorithm would strengthen the study. The manuscript as a whole also would benefit to referring to the "laboratory diagnostic" as a verification algorithm, or some similar terminology, because as it is written, it initially appeared that the study was on a new form of laboratory test that somehow calculates MELD directly from a sample.

A more granular and clearly labeled diagram of the verification algorithm should be included. It is hard to tell what types of findings would trigger review by the laboratory medicine group in this "diagnostic", and therefore these findings are, as yet, not applicable to other centers. As this is an implementation/quality improvement type project, a clear algorithm would be helpful, or at least examples: for example, where you state that "conspicuous constellations" in Figure 1 trigger a review, suggest some of these conspicuous constellations.

Page 11, line 105: "blood takings" should be "blood draws" or "blood samples needed to be procured". Line 111 on the same page should have "the" before "ethics committee". Note that in line 163, you state there were cases in which further blood draws were performed if the original sample was inadequate; please change line 105's statement to reflect that this study did not require further blood draws beyond those needed for adequate MELD determination.

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Reviewer #1: No

Reviewer #2: No

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Attachments

Attachment

Submitted filename: PONE-D-20-34374_reviewer.pdf

PONE-D-20-34374R1

Experiences from Six Years of Quality Assured Model of End Stage Liver Disease (MELD) Diagnostics

PLOS ONE

Dear Dr. Kaiser,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

A few issues still need to be addressed. Please correct and the MS will shortly be accepted.

Please submit your revised manuscript by Jul 05 2021 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

• A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Pal Bela Szecsi, M.D. D.M.Sci.

Academic Editor

PLOS ONE

Journal Requirements:

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #2: (No Response)

Reviewer #3: All comments have been addressed

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2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #2: Yes

Reviewer #3: Yes

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

Reviewer #2: Yes

Reviewer #3: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #2: Yes

Reviewer #3: Yes

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5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #2: Yes

Reviewer #3: Yes

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6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #2: Line 22: add “the” before “laboratory MELD diagnostic” or make diagnostics plural, for appropriate grammar

Lines 78-79: correct conventions such as follows: “policy violations; for example, dialysis was stated but not performed, or blood samples were manipulated.”

Lines 79-81: correct conventions such as follows: “These violations had the consequence that for some patients on the waiting list, priority for liver transplantation was falsely increased.”

Lines 90 to 96: Change “constellations may be” to “may include”; change “remarkably” to a more concrete term such as “improbable” or “extreme.” Also, what does “materials of the same order” mean? Do you mean “components”? Change “specifical” to “specifically”. Also, use semi-colons instead of commas to separate list items when list items contain a list – i.e., “deviation in comparison to previous analysis; improbable changes in creatine, bilirubin concentration, or INR values; and preanalytical errors such as hemolysis, or extended time spans between different materials of the same order or between test ordering and arrival at the laboratory.”

Lines 116-117: “confusion of patients” should be restated. I believe you are referring to misidentification of patients – rather than confusion as a mental status.

Lines 123-124: Restate “A notification during the order creation informed ensured the use for this indication.” It appears informed is an extra word here.

Table 2: Does “missing material” refer to a missing blood draw, an incorrect tube used, or something else? Again, as above, use “misidentification” rather than “confusion” to refer to incorrect patient ID

Lines 258-259: Add “the” before “basis”

Line 260: replace the word “embraced” with something more clinical such as “incorporated”; add “a” or “the” before “patient’s specific”

Line 265: add “the” before “relevant patient’s”

Reviewer #3: This is a revised version of a paper that I did not originally review. The information provided is of interest. The authors have addressed all previous comments in a satisfactory way.

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7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #2: No

Reviewer #3: No

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (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. Registration is free. 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 PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

Experiences from Six Years of Quality Assured Model of End Stage Liver Disease (MELD) Diagnostics

PONE-D-20-34374R2

Dear Dr. Kaiser,

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.

An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Pal Bela Szecsi, M.D. D.M.Sci.

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #2: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #2: Yes

**********

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

Reviewer #2: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #2: No

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #2: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #2: All comments from this revision pertained to grammar and conventions, which have all been satisfactorily addressed.

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7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #2: No