PONE-D-23-09669Effect of accelerated postoperative rehabilitation after tibial tubercle distalisation: a randomised controlled trial protocolPLOS ONE

Dear Dr. Rahnel,

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.

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Ahmed A. Khalifa, M.D., FRCS, MSc.

Academic Editor

PLOS ONE

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3. 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 If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references.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 If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.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. Does the manuscript provide a valid rationale for the proposed study, with clearly identified and justified research questions?

The research question outlined is expected to address a valid academic problem or topic and contribute to the base of knowledge in the field.

Reviewer #1: Yes

Reviewer #2: Partly

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2. Is the protocol technically sound and planned in a manner that will lead to a meaningful outcome and allow testing the stated hypotheses?

The manuscript should describe the methods in sufficient detail to prevent undisclosed flexibility in the experimental procedure or analysis pipeline, including sufficient outcome-neutral conditions (e.g. necessary controls, absence of floor or ceiling effects) to test the proposed hypotheses and a statistical power analysis where applicable. As there may be aspects of the methodology and analysis which can only be refined once the work is undertaken, authors should outline potential assumptions and explicitly describe what aspects of the proposed analyses, if any, are exploratory.

Reviewer #1: Yes

Reviewer #2: Partly

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3. Is the methodology feasible and described in sufficient detail to allow the work to be replicable?

Reviewer #1: Yes

Reviewer #2: Yes

**********

4. Have the authors described where all data underlying the findings will be made available when the study is complete?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception, at the time of publication. 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: No

Reviewer #2: 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 #1: Yes

Reviewer #2: Yes

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6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above and, if applicable, provide comments about issues authors must address before this protocol can be accepted for publication. You may also include additional comments for the author, including concerns about research or publication ethics.

You may also provide optional suggestions and comments to authors that they might find helpful in planning their study.

(Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: The authors reported about the protocol of a prospective, randomised, controlled, single-blinded, single centre trial to evaluate the effect of accelerated postoperative with the traditional rehabilitation after tibial tubercle distalisation with respect to knee ROM measured at 12 weeks.

In general the current protocol is sound and - based on the fact the recruitment is not yet started (according to clintrial.gov) the minor comments can be corrected in the protocol without affecting validity.

Detailed comments:

L95: I think it should be "will be" instead of "has been".

L121: I understand the RO measurement in the supine position is the main outcome measure. However, it is not clear, if the difference between the treatment groups is in flexation direction, or extension direction or the range (of flexation to extension). This should be made clear in the paper.

L166: The stratification /randomization is not clear. As the total sample size 144 falls in two treatment groups and stratified by 2 age groups this calls for 72 per treatment group which is not divisible by 10 the block size. The authors also mentioned, that " Caton-Deschamps index" is another stratification factor. However strata categories are not given. I assume that, according the inclusion criteria, no correspond subgroups are considered. I would not recommend to use blocksizes of 8 to avoid unfilled blocks, but rather to use blocksizes of varying length (6,8,10) or BigStick randomization to mitigate attrition bias.

Please describe how concealment is achieved. Please comment, how detection bias - do to single blinding - is achieved, e.g. by keeping patients records concealed.

L223: It is acceptable to use an unadjusted (unstratified) test as basis for sample size calculation. Please give the name of the test and the name of the statistical software used for calculation. I assume it is a t-Test with equal variances in both groups. (My software tells me 64 per group).

Concerning the dropout rate: The portion of 15% is large and is prone to invalidate study results. If the authors use a multiple imputation (MI) analysis model based on the longitudinal data and the corresponding aggregated analysis for the t-Test, no correction for missing is necessary. This would protect against a under/overpowered study, if the observed missing rate is different from the planned.

L229: The statistical analysis model has to be modified. The primary analysis is a stratified t-Test (Age) mit MI aggregation for missing. The sensitivity analysis may include a mixed model for Repeated measures (MMRM, Mallinckrod et al (2013), "Recent Developments in the Prevention and Treatment of Missing Data")) using the longitudinal observations. The latter should be used for the secondary outcomes as well.

pleas give the statistical software planned to do the analysis.

Reviewer #2: I believe the research question is valid and clinically relevant

Line 29–30

I believe the authors should mention the reasons for holding knee motion and limiting weight-bearing status somewhere in their preamble

Line 34

I’m not sure that I would call their accelerated rehab program ‘novel’ as many surgeons already do it.

However it is never been studied in a prospective randomized way, which is the uniqueness of the study.

Line 40–43

Hypothesis is valid and understandable

Line 71 to 78

I believe the surgery to reduce patella alta, and our measuring techniques does not need to be reviewed for the study, and could be considerably shortened.

Line 80–84

I will repeat what was said above. I believe that the rational why some surgeons limit knee motion and weight-bearing status merits at least one line of explanation. The authors go on to discuss the potential risk of the “traditional” rehab program, but they do not talk about the potential risk of an accelerated program.

The primary outcome of a study is knee range of motion. I would not expect this to be different and perhaps should not be the primary outcome, but perhaps moved to a secondary outcome.

A secondary outcome is isometric muscle strength. I believe this is a valid outcome, I would put it as a primary outcome.

A third outcome might be time to bone healing, but that might be difficult to distinguish healing time as they are looking at six week intervals.

Line 1 26–1 27

I’m assuming isometric muscle strength is measured at the tibial level as they’re measuring it at different angles of knee motion. This is an open chain test, specific details of where the dynometer is placed should be given i.e. at the proximal tibia, or the lower distal tibia. If I understand the timing of interventions, this will be tested at six weeks with a maximum isometric contraction, which might be difficult to perform maximally at six weeks due to pain, placement of the dynometer, and or risk of torque at the fracture site, depending on where exactly they’re placing the dynometer.

Line 1 40–1 42: inclusion criteria

If I am reading this correctly as they are treating two different patient populations.

One patient group is the more traditional reason for this surgical intervention, (ie) recurrent patellar dislocation.

The second would be anterior knee pain combined with patella alta. This second category of patients is quite a bit smaller in most of our populations, and I am not sure that it adds to the study to combine the reason for the patient seeking surgery. Also no reason for this treatment for this class of patients in given.

Exclusion criteria line 1 47–1 48

Their surgical thresholds are quite low in my opinion, and this would lead to a very small mm (distance) of distalization.

One value that I do not see mentioned in there results would be to factor in the millimeters of displacement, as I think that 2-3mm of distal repostitioning is different than 8-10 mm. This might pose a different element into their outcomes. Since already the surgical threshold is Lower than many Patellofemoral surgeons, I believe some of their patients will be distalized only a few millimeters, and therefore with a more accelerated program, we have would expect fewer complications.

Line to 12–2 22

Complications

And lines 272 to 278

Adverse events

These two sections seem duplicative to me

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Reviewer #1: No

Reviewer #2: No

**********

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PONE-D-23-09669R1Effect of accelerated postoperative rehabilitation after tibial tubercle distalisation: a randomised controlled trial protocolPLOS ONE

Dear Dr. Rahnel,

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 May 08 2024 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: https://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,

Mehrnaz Kajbafvala, Ph.D

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.

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Does the manuscript provide a valid rationale for the proposed study, with clearly identified and justified research questions?

The research question outlined is expected to address a valid academic problem or topic and contribute to the base of knowledge in the field.

Reviewer #1: No

Reviewer #3: Yes

**********

2. Is the protocol technically sound and planned in a manner that will lead to a meaningful outcome and allow testing the stated hypotheses?

The manuscript should describe the methods in sufficient detail to prevent undisclosed flexibility in the experimental procedure or analysis pipeline, including sufficient outcome-neutral conditions (e.g. necessary controls, absence of floor or ceiling effects) to test the proposed hypotheses and a statistical power analysis where applicable. As there may be aspects of the methodology and analysis which can only be refined once the work is undertaken, authors should outline potential assumptions and explicitly describe what aspects of the proposed analyses, if any, are exploratory.

Reviewer #1: No

Reviewer #3: Yes

**********

3. Is the methodology feasible and described in sufficient detail to allow the work to be replicable?

Reviewer #1: No

Reviewer #3: Yes

**********

4. Have the authors described where all data underlying the findings will be made available when the study is complete?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception, at the time of publication. 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: No

Reviewer #3: Yes

**********

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 #1: Yes

Reviewer #3: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above and, if applicable, provide comments about issues authors must address before this protocol can be accepted for publication. You may also include additional comments for the author, including concerns about research or publication ethics.

You may also provide optional suggestions and comments to authors that they might find helpful in planning their study.

(Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: The presented description is not aligned with the specific study, i.e. what method to prove what! Statsistical analysis dos not adress the point of analysis of the primary and secondary endpoint aligned with sample size justification. Analysis population is missing.

I recommended in my first review some aspects: The statistical analysis model has to be modified. The primary analysis is a

stratified t-Test (Age) mit MI aggregation for missing. The sensitivity analysis may

include a mixed model for Repeated measures (MMRM, Mallinckrod et al (2013),

"Recent Developments in the Prevention and Treatment of Missing Data")) using the

longitudinal observations. The latter should be used for the secondary outcomes as

well.

Reviewer #3: congratulation

your manuscript is acceptable............................................................................

**********

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 #1: No

Reviewer #3: Yes: Soheil Mansour Sohani

**********

[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.

Effect of accelerated postoperative rehabilitation after tibial tubercle distalisation: a randomised controlled trial protocol

PONE-D-23-09669R2

Dear Dr. Timo Rahnel

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,

Mehrnaz Kajbafvala, Ph.D

Academic Editor

PLOS ONE

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