Liposomal Bupivacaine Infiltration and Postoperative Pain Outcomes in Lumbar Fusion: A Prospective Randomized Controlled Trial [Response to Letter]

Dear editor

We thank the Editor for the opportunity to respond to the comments by Wu and Jiang regarding our publication “Liposomal Bupivacaine Infiltration and Postoperative Pain Outcomes in Lumbar Fusion: A Prospective Randomized Controlled Trial”. We also appreciate their interest in our work. We would also like to thank the authors for their interest in our paper and for taking the time to express their views, here are our responses to each of the suggestions they raised.

The Prespecified 24-Hour Resting VAS Endpoint

Wu and Jiang state that the prespecified primary endpoint, the 24-hour resting VAS score, was not directly reported as a between-group comparison. This assertion is not supported by the published record. The article explicitly identified the resting VAS score at 24 hours postoperatively as the prespecified primary endpoint used for sample-size determination, while repeated postoperative pain assessments were described separately as secondary or exploratory outcomes.

The corresponding 24-hour contrast was reported in Supplementary Table S2. The estimated marginal mean resting VAS score was 1.14 (95% CI, 0.92–1.37) in the LB+B group and 1.30 (95% CI, 1.01–1.58) in the RH group, with a between-group difference of 0.15 points (95% CI, −0.21 to 0.52; P = 0.406; Holm-adjusted p = 1.000). These findings show neither a statistically significant difference nor a clinically meaningful separation between groups. The primary endpoint was therefore not omitted; it was reported in the supplementary material, which forms part of the published article.

Longitudinal Modeling and Endpoint Interpretation

We do not agree that endpoint switching occurred. The longitudinal generalized estimating equation models were used to describe pain trajectories across repeated postoperative assessments, account for within-subject correlation, and avoid overinterpretation of isolated time-point contrasts. These analyses complemented, rather than replaced, the prespecified 24-hour resting VAS endpoint.

The findings were concordant: the 24-hour resting VAS contrast was not significant, the overall GEE treatment effect was not significant, and the treatment-by-time interaction was not significant. The conclusion was therefore based on consistent evidence across prespecified and longitudinal analyses, not on a selective shift in endpoint interpretation.

Attrition and Missing Data, and Power

Figure 1 reported discontinuation and missing follow-up separately by treatment group, with 44 patients in the LB+B group and 39 in the RH group included in the mITT analysis.¹ The longitudinal models used all available postoperative observations rather than complete cases only.

We agree that missing data in patient-reported outcomes can introduce bias, particularly when missingness is not random.² This limitation was acknowledged in the article. However, the observed between-group differences were small, and the pain findings were not accompanied by opioid-sparing effects, improved recovery quality, shorter hospitalization, or fewer adverse events.

We also agree that pilot-derived effect sizes from very small samples are imprecise and may overestimate the true effect.³ This issue was explicitly noted in our Statistical Analysis section. Importantly, our trial was not presented as an equivalence or noninferiority study. It was a superiority trial, and the appropriate interpretation is that LB+B did not demonstrate a statistically significant or clinically meaningful advantage over ropivacaine infiltration within the multimodal analgesic regimen used in this study.

Typographical Correction

We agree that “BH group” in the Results section was a typographical error and should read “RH group.” This error was confined to the narrative text and did not affect the dataset, analyses, tables, figures, or conclusions.

We thank Wu and Jiang again for their comments and carefully consider their recommendations to continuously refine our study protocol and reporting.