PONE-D-21-02639

Predictive variables of prescription opioid misuse in patients with chronic non-oncologic pain. Development of a risk detection scale : A registered report protocol

PLOS ONE

Dear Dr. Ramírez-Maestre,

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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We look forward to receiving your revised manuscript.

Kind regards,

Vijayaprakash Suppiah, PhD

Academic Editor

PLOS ONE

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2. We recognize that, as this is a Registered Report Protocol, you do not yet have data available to share. However, as per PLOS' guidelines, we do expect authors to provide a Data Availability Statement and outline your data management plan and/or state how you expect their data to be made available (https://journals.plos.org/plosone/s/criteria-for-publication#loc-7). To this effect, please confirm that you will be able to make your data available when your study is completed and if it is accepted for publication.

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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: Yes

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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: Yes

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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: No

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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: Yes

Reviewer #2: No

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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: No

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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: Major comments

The authors are planning to conduct two studies, each with a different primary objective: (1) conducting a comprehensive study to identify the factors most closely associated with subsequent opioid misuse and, (2) developing a brief, reliable, valid, and useful instrument informed by this research that would enable healthcare providers to make decisions regarding opioid prescription and the needed level of monitoring and follow-up.

In study 1, A battery of questionnaires will also be completed by each participant in the assessment session. These questionnaires will measure the variables that we expect to be related to opioid misuse, and the current misuse of prescription opioids. And then, on the basis of the results of the regression analysis conducted in Study 1, those variables that predict opioid misuse in a sample of 200 patients will be identified. A cross validation of the model will then be conducted with a different sample of 200 patients with the same characteristics.

Subsequently, in study 2, to develop a measure to assess risk of prescribed opioid misuse, and to analyze its reliability and validity, a longitudinal design with three assessment sessions will be applied.

This referee think that this study protocol is well designed and the manuscript is well written, but there are several grammatical errors on the manuscript.

Reviewer #2: The authors have presented a nice presentation of two protocols that will be conducted in order to identify some predictors of opioid misuse and then to develop a scale to be used in clinical practice

The topic is surely important and highly debated and the protocols try to add some important informations to scientific debate

Unfortunately I think that there are some major concerns that should be addressed in order to improve the quality of the manuscript, of the protocols and in order to have a better reproducible dataset.

The first major concern that should be addressed is about the concept of "misuse" defined in the title. Opioids in chronic pain patients can lead not only to misuse but also to abuse. Please discuss better this two problems and define better how authors' protocols can help clinicians to identify the two different problems

The second major concern is about the definition of chronic pain. How do the authors define "chronic pain"?Please provide a definition : temporal definition or pathophysiological definition? It is strange that authors have considered several psychological and demographic factors to be correlated to misuse/abuse but they have not considered if different chronic pain syndromes could be related to different risk for misuse/abuse. Please discuss it and provide explanations (better if you can consider them)

The third concern is about the sample size explanation: the authors stated "the sample size must be: [n = 10 * (k + 1)] (being k= number of variables). In this study we will need at least 180 participants [10 * (16+1) = 160]." How do you decide that K is 16?Please discuss it more in detail

Finally minor concerns

You have stated that there will be limitations to the available data: please provide an explanation

It should be better to revise all the text with a native English speaker

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Reviewer #1: Yes: Young-Chang Arai

Reviewer #2: No

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Predictive variables of prescription opioid misuse in patients with chronic noncancer pain. Development of a risk detection scale : A registered report protocol

PONE-D-21-02639R1

Dear Dr. Ramírez-Maestre,

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,

Vijayaprakash Suppiah, PhD

Academic Editor

PLOS ONE

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: 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: Yes

Reviewer #2: Yes

**********

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: Yes

Reviewer #2: 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 #2: 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: After this referee read this version and found out that the authors amended the manuscript well, the referee is satisfied with the content.

Reviewer #2: The authors have deeply revised the text accordingly reviewers' suggestions improving the quality of the data presented

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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 #1: Yes: Young-Chang Arai

Reviewer #2: No