Effects of Music Intervention on Pain, Mood, Sleep, and Heart Rate Variability in Patients with Chronic Pain: A Randomized Controlled Trial [Response to LETTER]

Dear editor

We sincerely thank Satwinder Kaur et al for their close attention to and valuable feedback on our recently published article, “Effects of Music Intervention on Pain, Mood, Sleep, and Heart Rate Variability in Patients with Chronic Pain: A Randomized Controlled Trial”. The methodological concerns raised in their letter are highly pertinent and offer important guidance for improving the rigor of future research in this field.

Based on the contents of our published original manuscript, below are our detailed and rigorous responses to the five key issues raised by the reviewers:

Regarding the Asymmetry of Assessment Time Points

Reviewer’s Concern: The experimental group (EG) included three evaluation points (baseline, immediate post-intervention, and two-week mark), whereas the control group (CG) only had two (baseline and two-week mark). This discrepancy makes it difficult to compare results between groups and increases the risk of error.

Our Response: The inclusion of an “immediate post-intervention” assessment point for the EG was solely designed to monitor the acute physiological responses to a single music intervention session, such as changes in heart rate variability (HRV). However, to ensure methodological rigor, when evaluating the final efficacy of the intervention and conducting between-group comparisons (EG vs CG), we strictly utilized only the standardized time points available for both groups: baseline and the two-week follow-up. Therefore, in our core efficacy comparisons, the assessment time points are completely symmetrical, and no systematic error was introduced due to timing discrepancies.

Regarding the Lack of Standardized Intervention Dosage

Reviewer’s Concern: Patients in the EG listened to music at variable times (afternoon, evening, and night) and with variable frequencies (three to four sessions per day). This inconsistent dosage reduces internal validity.

Our Response: In our study design, we actually stipulated a clear foundational standard dose: 10 minutes per session, three times a day. The protocol’s provision that “if patients felt comfortable, the session could be repeated once more as desired” was intended to maximize adherence to the principles of a Pragmatic Randomized Controlled Trial (Pragmatic RCT) in a home-based self-management setting. We acknowledge that this flexibility introduces some variability in dosage. We agree that for future studies investigating exact mechanisms, a stricter and more standardized exposure protocol should be adopted.

Regarding Sample Heterogeneity and the Lack of Subgroup Analysis

Reviewer’s Concern: The study evaluated a mixed group of chronic pain patients without categorizing them by pain type, duration, or severity, which limits the applicability of the findings to specific patient populations.

Our Response: We completely agree with the reviewers’ perspective. As we explicitly stated in the “Limitations” section of our original manuscript: “CP encompasses a wide range of conditions, and this study did not focus on a single disease entity, which may limit the specificity of its findings”. The primary objective of this study was to explore the overall feasibility and safety of music therapy as a “broad-spectrum” non-pharmacological adjunctive intervention. Due to sample size constraints, we were unable to conduct adequately powered subgroup analyses. Future large-scale studies specifically targeting categorized pain types (eg, neuropathic or nociceptive) are certainly necessary.

Regarding the Absence of Effect Size and Clinical Significance

Reviewer’s Concern: The study reported statistical significance but lacked effect size measurements (such as Cohen’s d) and the minimal clinically important difference (MCID) to establish true clinical significance.

Our Response: We appreciate you pointing out this reporting omission. Although we did not explicitly present effect size metrics like Cohen’s d in the manuscript, the data results demonstrate that the intervention provides tangible clinical value. For instance, after two weeks of treatment, the Present Pain Intensity (PPI) score in the EG not only decreased significantly from baseline but was also significantly lower than that of the CG. This significant reduction in PPI scores reflects a substantial alleviation in the patients’ immediate perception of pain intensity, which holds positive clinical significance in chronic pain management. Furthermore, we calculated the Cohen’s d value for PPI, yielding a result of 0.74, which represents a moderate-to-large effect size. We support the recommendation to establish effect size and MCID as standard reporting requirements in future pain research.

Regarding Attrition Bias and Intention-to-Treat (ITT) Analysis Reporting

Reviewer’s Concern: The CONSORT flow diagram indicates that seven participants were lost to follow-up. The study does not clearly report whether an intention-to-treat (ITT) analysis was performed, increasing the risk of attrition bias.

Our Response: We would like to make an important clarification here: According to the CONSORT flow diagram provided, 86 patients were initially randomized (43 in each group). Five patients in the EG and two in the CG were lost to follow-up. The final number of patients actually analyzed was 79 (38 in the EG and 41 in the CG). This clearly indicates that the data analysis in our study utilized a “Per-Protocol (PP)” or “Complete Case Analysis” approach, rather than an Intention-to-Treat (ITT) analysis. It was an oversight on our part not to explicitly state the omission of an ITT strategy in the methodology section. Nevertheless, the overall dropout rate in this study was relatively low (7 out of 86, approximately 8.1%), which is within an acceptable range for clinical trials. We believe this did not have a fundamentally disruptive impact on the robustness of our core conclusions.

We once again thank our peers for their rigorous review. This constructive feedback will greatly contribute to refining the clinical trial designs of our team and the broader pain research field in the future.