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  • Najibah Galadanci 1,
  • Calia Torres 2 and
  • Julie Kanter 1,*
  • et al.

Reviewer 1: Alexander Leonardo Silva-Junior Reviewer 2: Anonymous Reviewer 3: Anonymous

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The submitted manuscript " A Qualitative Phenomenological Study of Treatment Options for Patients with SCD and Chronic Pain: Buprenorphine-Naloxone or Full-agonist Therapy" shows very interesting data regarding the use of Buprenorphine-Naloxone for opioid use among patients with sickle cell disease.

Authors brough a quite good manuscript, with interesting data over patients’ overview and quality of life with/without Buprenorphine-Naloxone. I believe the manuscript is well written and could be suitable for publication with some adjustments. Here follows my considerations.

 

General reviews:

  1. The authors can insert number lines to help reviewers and authors on review process.

 

Major reviews:

  1. Authors reported in Abstract that “Those receiving bup-nal consistently reported improved daily function, greater independence, enhanced mood, and reduced healthcare utilization. In contrast, those who declined bup-nal described ongoing pain interference, functional limitations, and reliance on acute care services.”. Authors must standardize the terms applied to both groups (receiving bup-nal and not receiving). For example, the “daily functional improvement” (from those who receive bup-nal) stand for the same “functional limitations” (from those who did not take bup-nal)? Or is is in general?
  2. Some paragraphs from Introduction have no reference. To mention, the end of the second paragraph and the fifth. Could authors add references that support the statements?
  3. Although I believe Figure 1 is very clear and interesting, how authors reached these experiences from patients? How authors know that “Will it Work?” and “Stigma of Use” are relevant concerns from patients to decide whether try or not bup-nal? I do see the relevance, but I believe clarify the importance of exactly these questions.
  4. Reading the Results (Participants Characteristics), I was curious about some points that I ask authors to respond to, or at least clarify: i) The patients had a different profile among bup-nal users vs non-bup-nal users, regarding degree or annual income? I question this once usually people with higher degree or annual income are less likely to be involved with addiction (and as I believe, with less requirement for bup-nal), compared to those with less degree and/or annual income. Could authors split table 1 column into two, and show proportion of demographics between these two groups? I believe there is no need for statistical analysis here, but just to clarify this would be very interesting.

    ii) Among these 26, could authors clarify that all of them were under use of opioids? I question this once some patients may not even experience opioids (and subsequently bup-nal requirement), but I couldn’t find this description in inclusion criteria.

    iii) Could authors describe whether the 26 patients were homozygous or heterozygous? It is known that homozygous have a more severe condition and so, I believe they would be more likely to use opioids, rather than heterozygous. I believe this should be stated in the text or at least, in Discussion section.
  5. In patients’ statement, please author add the group patients, whether they are using bup-nal or not. Some indicate a better improvement of life (Participants 8, 9 and 17, for example), but it would be interesting if we could match their report in many questions, if it was possible.

 

Minor reviews:

  1. In abstract authors mentioned “Importantly, participants emphasized function and stability, not pain elimination as the most meaningful outcome.”. Patients emphasized improvement in functional and stability, right?
  2. Still in Abstract, I believe the phrase “that allows participation in daily life” is quite confusing. Authors meant the participation of bup-nal in patient’s drug therapy? Why would it be an issue?
  3. Not sure what authors meant in “These challenges are further compounded by structural and racial inequities. In the United States, SCD predominantly affects Black individuals, who are more likely to be suspected of opioid misuse, subjected to heightened monitoring, and referred to substance use treatment services when receiving opioids for pain.”. I am quite confused about the discussion here. What is the connection between black (SCD or not) individuals, their abuse of opioids and SCD? Are these black individuals (who misuse of opioids) SCD patients?
  4. In Materials and Methods (Study Design, Sample and Setting), authors must standardize whether “Bup-nal” or “suboxone”.
  5. Not sure why, but please standardize the letters among the text. In the same topic as above, “participants’” is in a different letter type.
  6. Please standardize the names of the month in “Participants were recruited between August, 2024 and Nov 2024 from the Lifespan Comprehensive SCD center at the University of Alabama at Birmingham.”, and add the city, state and country, for clarification.
  7. “Verbal consent was confirmed following the investigator reading an introductory statement.” Could authors please state if patients accepted to participate after an “introductory statement”, or after being presented the full statement.
  8. For clarification, any of these patients were under other treatment (Hydroxyurea, folic acid…)?
  9. In patients’ response, authors please review the use of “ “ in the beginning and in the end of the response.
  10. “Seeking pain relief, but unclear what pain is being treated”. Authors meant “which pain is being treated”, no?
Comments on the Quality of English Language

English review is required, especially to transcription from the patients. This will improve comprehension of patients’ response.

Author Response

Thank you for the insightful comments, we have carefully revised the manuscript in response to all suggestions. Our responses are provided as attachment here

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

Reviewer Summary

Thank you for the opportunity to review this manuscript. This study addresses a timely and important topic: patients’ experiences and perceptions of chronic pain and buprenorphine–naloxone (bup-nal) treatment using qualitative interview methods. Although the study is based on a small sample recruited from a single SCD center, the findings offer valuable insights into patients’ experiences, goals, barriers to bup-nal use, and the misalignment between the medication’s mechanism and patients’ expectations, particularly among those who discontinued treatment. However, this limitation regarding generalizability, including the young age of the participants, should be stated more clearly in the Limitations section.

Please find my comments below:

  1. Introduction
  2. Citations are not presented in numeric order, which makes it difficult to assess the relevance and completeness of the references. For example, the first sentence cites references 10 and 15. This raises concerns about whether all references are properly cited and whether the reference list is complete and final.
  3. Reference 11 does not appear to be a guideline, although the sentence refers to guideline recommendations.
  4. Regarding the unique barriers faced by individuals with SCD in accessing effective acute pain management, more recent quantitative study, such as the one published in JAMA showing the impact of CDC opioid guidelines on reduced opioid prescribing in SCD, should be considered to be added to strengthen the argument.
  5. Figure 1:
  • In the first box, it is unclear whether the three bullet points are intended to support “Chronic Pain,” as they describe acute SCD pain crises rather than chronic pain.
  • In the second box, consider adding the word “pain” between “Limited” and “Relief” in the third bullet point.
  • The relationship between “Outcomes” and “Ongoing reassessment and treatment decisions” is unclear due to the lack of an arrow on the dotted line.
  1. Materials and Methods
  • The terms “bup-nal” and “Suboxone” are used interchangeably without clear explanation. Please clarify their relationship and use terms consistently.
  • The authors described that they used purposive sampling with an estimate of 14 bup-nal users and 14 non-users, but the final sample included 16 users and 10 non-users. An explanation for this discrepancy would be helpful.
  • More detail on the interview process is needed. For example, were all interviews conducted 1:1, or were any group interviews performed?
  1. Results
  • The study population is very young (mean age 29.4 years; IQR 23–32). This should be acknowledged as a limitation when discussing generalizability, including how having only younger adults in the study may have impacted on the findings.
  • Some statements are interpretive rather than descriptive and may not be appropriate for the Results section. For example, “This mix allowed for rich exploration of perspectives…”
  • Table 1 and its corresponding description in the text are not fully aligned (e.g., “half had some college education” in the text vs. “High school/some college” in the table), which creates confusion. Please ensure consistency between the table and text.
  • Given the small sample size, please report absolute numbers alongside proportions (e.g., “over one-third (n=9)” and “nearly half (n=12)”).
  • Theme 1 focuses on acute SCD pain, rather than chronic pain, which is not the primary focus of the study. The rationale for including the questions that generated it should be clearly explained.
  • The final quote in section 3.2.1.2 contains a double negative (“you can’t do nothing”), which is confusing and does not clearly support the theme. Please review and revise as needed.
  • In section 3.2.4, the meaning of “uncertainty” is unclear before reading the subthemes. Please consider clarifying this in the summary statement.
  • In subtheme 3.2.7.2, the latter portion does not align with the title “Emotional relief and restoration of motivation,” as it describes negative emotional effects. Please consider revising for consistency.
  • In Theme 8, “side effects” are mentioned in the summary but not reflected in the supporting patient quotes. Please provide more detail on side effects, either in the summary, the quotations, or both.

Overall:

  • The research objectives are repeated throughout the manuscript; reducing redundancy would improve readability.
  • Please carefully check for missing letters and typos throughout the manuscript.
Comments on the Quality of English Language

Please carefully check for missing letters and typos throughout the manuscript.

Author Response

Thank you for your comments. We have carefully revised the manuscript in response to all suggestions. Our responses are provided as attachment below

Author Response File: Author Response.pdf

Reviewer 3 Report

Comments and Suggestions for Authors

The study addresses a clinically important question and the participant voices are genuinely rich, but the manuscript currently reads too much as an endorsement of buprenorphine-naloxone. Please see other comments below:

  • The framing throughout (abstract, results synthesis, conclusion) is consistently positive about bup-nal and reads as advocacy; the language should be moderated and the experiences of those who declined or discontinued given equal interpretive weight rather than positioned as "non-alignment"
  • The Results section is disproportionately weighted toward the lived experience of chronic pain (themes 1–5) and gives relatively little space to the treatment experience, which is the actual core of the study; themes 6–8 on bup-nal should be expanded with more participant voice
  • A reflexivity statement is needed: the interviewing hematologist and senior authors are part of the team that prescribes bup-nal at the recruiting center, which raises selection and social-desirability concerns
  • The inclusion criterion of ≥6 months on bup-nal structurally selects for tolerators and likely inflates the positive signal; justify and acknowledge as a limitation
  • The planned 14 + 14 design ended up as 16 + 10
  • The chronic pain definition (most days for ≥3 months) does not align with the AAPT criteria for chronic SCD pain
  • Excluding non-English-speaking participants should be discussed as a limitation
  • Replace the brand name "suboxone" with the generic throughout
  • Explain the mechanism of bup-nal properly in the introduction; partial mu-agonist plus naloxone antagonist, why this matters for chronic vs acute pain
  • Clarify in the introduction whether bup-nal is being proposed as first-line or after COT
  • The sentence about vaso-occlusive pain "traditionally conceptualized as episodic" implies chronic pain is also vaso-occlusive; SCD chronic pain is multifactorial and should be described accordingly
  • "Despite these promising findings bup-nal remains more commonly as a treatment for opioid use disorder..." - sentence is grammatically broken
  • Several quotes are very short (three to five words) and do not function as phenomenological evidence; provide longer, contextualized excerpts
  • The Discussion is short relative to the data and does not engage seriously with why participants declined or discontinued treatment
  • The Conclusion overstates benefits and reads as a treatment recommendation; revise to reflect the more mixed phenomenology
  • Minor: female n=17 (65%) in text but n=18 (69.2%) in Table 1

Author Response

Thank you for your comments. We have carefully revised the manuscript in response to all suggestions. Our responses are provided as attachment below.

Author Response File: Author Response.pdf

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

First I would like to thank the authors for the responses and the changes, I believe the thematic is very interesting and the data shown has a very promising quality.

I would like to ask, and I will ask this only as a minor review, for authors to double check the format of the text, regarding the italic in the responses. I noticed that some patient's responses are not in italic. Again, I don't think this is a major issue, just adjustments for the final text.

In any case, congratulations!