Breakthrough and Episodic Cancer Pain from a Palliative Care Perspective

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The authors address the important topic of breakthrough pain in cancer but unfortunately don’t tell us anything new despite the multiple calculations. Their conclusion “Large pain flares were associated with inferior pain relief” is something we’re confronted with on a daily basis .

For me, the authors fail to demonstrate the clinical added value of introducing absolute and relative pain peak intensities. In addition, they do not make sufficiently clear why the relative pain peak intensity in particular has added value, after all, you can also see if a peak is really a peak, I don't need a number above 1 for that. Also, you may wonder whether when the difference between mean pain and a peak is only 1 point on the NRS you can speak of a peak: to me, that is a normal fluctuation that may also be related to mood, distraction, etc.

In more detail:

-          The authors could only include 131 patients out of 256 potential candidates. I presume over 51% of patients had a NRS ≥ 1 when admitted to the APCU so the missings are because of lack of “reported worst and average PI at admission, and average PI at discharge”: Doesn't missing half the patients generate too much bias?

-          What is the surplus of paragraph 3.3? see above

-          Paragraph 3.4: “The patients with controlled background pain reported mean average PI 174 worsening of 0.1” 0.1 is not at all clinically relevant: you cannot speak of worsening. The only thing what the paragraph says: during hospitalization in the APCU: background pain is managed better (of course).

-          - Discussion: You say: “We demonstrated that palliative care cancer patients with high pain spikes at admission experienced less improvement of average PI during hospitalization compared to patients with low pain spikes or no pain spikes. ”I wonder if that is true: possibly the existence of severe peaks makes the subjective interpretation of the background pain worse.

Please let’s keep things simple and ask patients whether their pain (background and breakthrough) is acceptable, without all kinds of new calculations with unknown cut-off points.

Author Response

Shared response for both reviewers.

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

Congratulations on conducting a comprehensive study and presenting your findings; your work adds valuable insights to the field. The manuscript is well-articulated; however, some aspects could benefit from further refinement for clarity and coherence.

The abstract provides a good overview of the study and its findings. However, it could benefit from more concise sentences and clearer definitions of the terms used.

It would be helpful to briefly mention the significance of studying the relationship between pain flares and background pain in palliative care.

Providing more details on the methodology and statistical analysis will enhance the reader's understanding of how the study was conducted and how the results were obtained.

The introduction lays a solid foundation, introducing the context of pain management in palliative cancer care and presenting the concepts of BTCP and pain flares. However, expanding on the background, particularly the limitations of current methodologies or findings, will enhance the reader's understanding of the study's significance.

Further clarification of the study's objectives and the specific gaps or challenges it aims to address would be beneficial. Additionally, consider providing more details from the referenced studies directly related to the research question.

Lastly, ensure that all terms are clearly defined and consider providing more specifics about pain management in palliative care to emphasize the need for the study.

Method:

The prospective longitudinal observation study design is appropriate for this research as it allows for observing variations in pain intensity (PI) over time among cancer patients admitted to the APCU. Conducting a secondary analysis of a primary study enhances the depth of the research and allows for the exploration of new dimensions related to pain flares and background PI.

The methods section provides a detailed and systematic description of the study design, patient selection, assessments, statistical analysis, and ethical considerations. However, further clarification on the selection criteria and details on the interventions and symptom relief reported in the primary study would be beneficial. The statistical analysis subsection is well-detailed, but clarification on the rationale behind grouping the NRS 0-10 differences and the choice of statistical tests would enhance understanding.

Provide more details on primary study: Since this is a secondary analysis, providing more details or a summary of the interventions and symptom relief reported in the primary study would help better contextualize the current research.

Rationale behind statistical choices: Clarify the rationale for the chosen groupings of the NRS 0-10 differences and the selection of specific statistical tests. This would help readers understand the appropriateness and relevance of the analytical approach.

Ensure ethical considerations are addressed: While the ethics section mentions that explicit informed consent from the patients was unnecessary, further elaboration on how patient confidentiality and data privacy were maintained would be reassuring.

The authors provide a detailed account of the demographics of the patient sample and their characteristics, the pain alleviation observed in patients with and without pain flares, and insights into the relationship between absolute and relative pain spike intensity and pain relief. The results are structured logically, and data are presented in tables to aid understanding.

One potential improvement could be summarising the results to aid reader understanding. While the detailed results are presented clearly, a concise summary highlighting the key findings and their implications might make the presentation even clearer, especially for readers who may not be experts in the field.

Discussion/conclusion

The authors have discussed their findings thoroughly and compared them with previous work. They have clearly stated the principal findings and acknowledged their study's limitations, including its retrospective nature and the limitations in the data collection. The comparison with previous studies and the integration of earlier research give context to their results, allowing readers to understand the significance of the findings.

The conclusion briefly summarizes the study's main findings, emphasizing the implications of high pain spikes and variations in pain intensity (PI) for pain management outcomes. The conclusion also reiterates the findings regarding patients with and without controlled background pain. However, it might be improved by more explicitly connecting the results to their implications for clinical practice and future research.

Author Response

Shared response letter for both reviewers

Author Response File: Author Response.pdf

Round 2

Reviewer 2 Report

Comments and Suggestions for Authors

I appreciate the time and effort you have taken to address each point raised. Here's my assessment based on your response:

Abstract:

• I appreciate your effort revising the abstract to make the definitions more transparent and the language more consistent. This will likely enhance readers' understanding of your work from the outset.

Introduction:

• Your inclusion of new literature and the emphasis on the clinical importance of BTCP, along with the added nuances and reformulated text, show that you have taken my feedback seriously. The elaboration on the significance of the relationship between pain flares and background pain is also a welcome addition.

Materials and Methods:

• I commend your efforts in providing a more detailed context for the current research. Clarifying the NRS 0-10 differences and the rationale behind your statistical choices is crucial for readers. Additionally, the expansion of ethical considerations is essential and appreciated.

Results:

• Your reference to the "Statement of principal findings" as a summary, the clarity you've provided on patient numbers, and the clinical relevance of a PI worsening of 0.1 addresses my feedback comprehensively.

Discussion:

• Your clarification on the introduction of pain spike intensities and the shared clinical experience gives depth to the discussion. The elaboration on biases, assessment methods, and considerations for a patient's subjective experience of pain shows a well-thought-out revision process.

Conclusion:

• I am pleased you've revised the "Implications" and "Conclusions" sections to clarify the results, their implications for clinical practice, and future research directions.

In conclusion, your response indicates a thorough effort to address the feedback provided.