PONE-D-19-16726

“Chasing the pain relief, not the high”: experiences managing pain after opioid reductions among patients with HIV and a history of substance use

PLOS ONE

Dear Ms. Behar,

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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PLOS ONE

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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: Yes

Reviewer #2: Yes

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

Reviewer #1: Yes

Reviewer #2: N/A

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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: This is a qualitative analysis of interviews with individuals with HIV who experienced after long term opioid pain medication reduction or discontinuation. This is an important contribution to the field and is generally a well-done analysis with an accompanying well-written manuscript . A few comments for the authors to consider:

1)

Abstract:

Consider reporting Ns rather than percentages in the results paragraph (see related comment regarding Results below).

Intro:

-The final paragraph in the introduction (line 49) would benefit from introducing the participant population as having a history of illicit substance use in addition to HIV and chronic pain, as this is an important differentiating factor for the sample.

Methods:

-Please provide a citation for the longitudinal COPING study cohort, if one exists.

-Please provide additional information about how OPR dose reduction or discontinuation was defined? Participant self report vs chart review?

-Please provide some additional information about how/when interim analyses were conducted, which would allow the investigators to know when thematic saturation was reached.

-Please provide citations for content analysis methods (line 79).

Results:

-Given that this is a qualitative analysis with an appropriately small N, I would recommend reporting the Ns for each demographic characteristic (ie 11 were male) rather than reporting percentages, which may suggest to readers that these findings are more representative/generalizable to a wider population, which we are not sure they are.

-Are you able to provide information regarding how many participants experienced dose reductions vs those who experienced discontinuation? Are you able to provide any info regarding average size of the dose reduction or discontinuation?

-Consider expanding discussion of the fact that HIV-related factors are not included in the qualitative analysis (line 95). Was it necessary to enroll HIV infected participants or do you believe that the results would have been similar with a non-HIV infected population. Please provide further justification one way or the other.

-Please remove marijuana from the non-pharmacologic therapies section, as cannabis and its derivatives are increasingly used in medical/pharmacologic contexts. Consider referring to the substance as cannabis, which may have fewer stigmatizing connotations relative to marijuana.

-Some participants quotes (participant F, for example, in the non-pharmacologic section) seem over-represented. If possible, consider diversifying the participants whose quotes are provided in the manuscript to provide a more comprehensive overview of perspectives.

Conclusions:

-I would encourage the authors do use the conclusion to further contextualize their work given how unique it is for them to be providing detailed perspectives from individuals with substance use/HIV. These are individuals whose voices are not commonly heard in the research literature, making this a particularly important contribution.

-Seems worth revisiting here the fact that the common tropes were unrelated to HIV infection or HIV-specific care. Can you please provide some additional context to the brief discussion of this in the results section (line 95), see comment above.

-Can the authors please provide some further clarification and summarization about the respective rationales, facilitators, and barriers to the pharmacologic, non-pharmacologies and illicit substance use self-management strategies participants reported?

Reviewer #2: Overall this was an excellent paper and interesting to review. I learned a lot about the patient experience following opioid taper or cessiation that will impact my clinical practice. I do have some suggestions prior to publication for the authors. One thing that struck me was that there was no mention of fentanyl in the participant quotes. In other parts of North America the risk of fatal overdose is so great as the heroin supply has been replaced by fentanyl. This makes the results of your study even more compelling. I am not sure how to fit this in but it is an observation I wanted to share.

General comments:

Is the period supposed to be before or after the reference parenthesis? I would check with the journal, usually I have seen the period before.

Abstract:

In the background or methods please state the aim of the study.

Background

Line 21-24: I think justified is a strong word. Additionally, there is also epidemiological evidence that showed as the rate of opioid prescriptions increase so too did the rate of opioid misuse. This also supported this public health strategy

Line 24: suggest rephrasing “However, reduction in prescribing also carry risks:” to “However, decreasing the opioid dose or prescription cessation also carries risks:”

Line 27: why is it paradoxical?

Line 43-47: The first sentence is slightly repetitive from the sentence in line 24 and could be removed or included above in 24. It is reasonable to end paragraph starting on line 30, with the second sentence of this small paragraph.

Overall comment for the background: Has there been any other qualitative research in this area? If so how does your work build or add to this? If not, it is reasonable to say this, and would strongly support the need for this work. To accommodate these extra sentences you could consider paring down the second paragraph.

Methods

Data collection and analysis

Line 62: Could you say what the COPING study was about or at least what the acronym stands for and a reference to the original publication or study protocol?

Line 71: Please describe how the interview guides were developed. Was it a flexible guide etc?

General comment: How was language addressed? Were non-English speakers included?

Results

The table and quantitative summary were clear and helpful. Overall the results were presented very clearly and the quotes chosen highlight the themes very well.

Line 281: Suggest starting the sentence at Participants.

Line 288-90: This quote is a bit confusing and does not strongly support the above theme. It almost sounds like he trusts the illicit market more? I re-read it several times. Perhaps it would be clearer if more of the quote was included or the interviewer question? Alternatively, perhaps there is another quote that could be used.

Line 329-336: Does the rest of the quote describe her overdose experience and how she survived? If so would be interesting to include this if it does.

Line 402-407: This quote does not clearly capture the concept of harm reduction techniques of tester shots or cautious dosing. I suggest removing this idea or including more of this quote or another quote that illustrated this concept more clearly.

Line 426: suggest replacing “household chores” with “activities of daily living”.

Line 434: I would rephrase the idea of “education” to “lack of experience with heroin” as this seems to be what the quote supports.

Line 447-452: This part of the quote is very interesting but does not connect to the statement above. I wonder if there is a way to highlight this piece of Narcan training specifically?

Discussion

551-557: This seems like a new theme not previously discussed or supported by the quotes in the paper. Participants did not describe withdrawal as a driver for their using illicit opioids. I suggest this be removed or add some quotes that support this concepts.

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Reviewer #1: Yes: Benjamin Bearnot, MD, MPH, FASAM

Reviewer #2: No

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PONE-D-19-16726R1

“Chasing the pain relief, not the high”: experiences managing pain after opioid reductions among patients with HIV and a history of substance use

PLOS ONE

Dear Ms. Behar,

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.

We would appreciate receiving your revised manuscript by Dec 27 2019 11:59PM. When you are 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.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter.

To enhance the reproducibility of your results, we recommend that if applicable 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/plosone/s/submission-guidelines#loc-laboratory-protocols

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). This letter should be uploaded as separate file and labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. This file should be uploaded as separate file and labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. This file should be uploaded as separate file and labeled 'Manuscript'.

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 look forward to receiving your revised manuscript.

Kind regards,

Leo Beletsky

Academic Editor

PLOS ONE

Additional Editor Comments (if provided):

This piece is much improved after the revision. Acceptance is contingent on the following minor revisions:

A. Overall comment/suggestion: may be useful to get a sense of the general prevalence of perspectives in each category, ie how pervasive the view listed was, and whether there were contrasting views and experiences. Obviously no need to quantify, but something more descriptive than the current "many" could help orient the reader.

B. Overall comment/suggestion: may be enriching to foreground criminalization and punitive measures in the health care system, either in the narratives listed, in the discussion, or both. Feels a bit like the elephant in the room that the manuscript glosses over.

Specific comments:

- Line 37: although certainly useful in some cases, multimodal pain therapies described do not, as a rule, have a more robust evidence base when compared with opioid pharmacotherapy

- Lines 42-43: clarify that transition may, in fact, be facilitated by tapering interventions or other measures to suppress pharmacotherapy access (See, e.g. Larochelle et al, 2019)

- Lines 51-53: what is the prevalence of injection drug use in this population? Injection contributes additional vulnerability to chronic and acute pain

- Line 66: how was Rx history determined in the larger study?

- Line 81: double check Journal formatting rules for citation of software packages

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Reviewers' comments:

[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 to be viewed.]

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 us at figures@plos.org. Please note that Supporting Information files do not need this step.

“Chasing the pain relief, not the high”: experiences managing pain after opioid reductions among patients with HIV and a history of substance use

PONE-D-19-16726R2

Dear Dr. Behar,

We are pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it complies with all outstanding technical requirements.

Within one week, you will receive an e-mail containing information on the amendments required prior to publication. When all required modifications have been addressed, you will receive a formal acceptance letter and your manuscript will proceed to our production department and be scheduled for publication.

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With kind regards,

Leo Beletsky

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Given that the first version was deemed to require only a minor review, and Reviewer 2 has favorably rated the revision, I am satisfied that the authors have adequately met concerns. I am proceeding with accepting the paper, pending additional minor tweaks as suggested by the reviewer's comments.

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)

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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

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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

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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

**********

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: The manuscript was great to read again, I have a few additional minor suggestions for your consideration, but believe it is appropriate to publish at this time

Abstract:

Background: The aim sentence is long, perhaps could end at discontinuations

Methods/results: it is unclear why/how you arrived at 18 interviews, from the paper we know this was because themaptic satuation was reached but this would be helpful to have stated in the abstract.

Methods:

Study sample: again, is there a protocol published for COPING? if so please include this reference, if not ignore this comment.

Results:

Demographics: I echo revierwers 1's comments regading specifics about the patients OPR reductions. Do you know how many of your participants had their OPR stopped, or the mean reudciton amount? From a clinical perspective, this helps providers reading your study understand how specific treatment changes impacted your study participants experiences.

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Reviewer #2: No