Response to letter regarding - Impact of opioid-free anesthesia on the overall benefit of analgesia score

Sep 30, 2026

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Letter to the editor responding to comments on a published multicenter trial protocol comparing opioid-free anesthesia with opioid-based anesthesia after laparoscopic cholecystectomy. The authors address concerns about defining and assessing chronic postsurgical pain (CPSP), explain the primary endpoint of the 24-hour Overall Benefit of Analgesia Score (OBAS), and describe sample size justification and sensitivity analyses for OBAS variability. They confirm CPSP was not used for power, outline a planned post-hoc sensitivity analysis using a stricter NRS threshold, and acknowledge limitations of relying on NRS intensity alone.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages3

Reading Time8 min

AccessFree to download

Primary endpoint of the 24-h OBAS

Sample size justification and sensitivity analysis for OBAS variability

Definition and assessment of CPSP

Multidimensional pain assessment

Clinical and methodological implications

AnnAls of Medicine 2026, Vol. 58, no. 1, 2614127 [https://doi.org/10.1080/07853890.2026.2614127](https://doi.org/10.1080/07853890.2026.2614127) LETTER TO THE EDITOR Response to letter regarding [Impact of opioid-free anesthesia on the overall benefit of analgesia score after laparoscopiccholecystectomy] We thank Dr. Lv and Dr. Xuan for their interest in our published trial protocol comparing opioid-free anesthesia (OFA) with opioid-based anesthesia on Overall Benefit of Analgesia Score (OBAS) after laparoscopiccholecystectomy [1] . We appreciate their recognition of the methodological rigor and clinical relevance of our trial design. Their thoughtful comments mainly focus on the definition and assessment of chronic postsurgical pain (CPSP), which is a secondary endpoint in our trial. Here, we address their specific concerns regarding CPSP definition, assessment, and sample size justification, while also reaffirming the primary focus of our study. 1. Primary endpoint of the 24-h OBAS This trial is powered to detect a 1-point between-group difference in the OBAS at 24 h postoperatively, which is the prespecified primary endpoint. OBAS is a validated composite measure that integrates pain intensity, opioid-related adverse effects, and patient satisfaction, providing a holistic evaluation of perioperative analgesic quality. This patient-centered endpoint aligns with contemporary multimodal recovery paradigms and represents the core clinical question of our trial. 2. Sample size justification and sensitivity analysis for OBAS variability The assumed standard deviation (SD) of 3.0 for OBAS was derived from a synthesis of previous studies in abdominal and endocrine surgery. To ensure transparency and robustness, we have conducted the sensitivity power analysis using the PASS 2023 software. With an SD of 2.7, 155 patients per group would provide 90% power to detect a difference in means of 1 point. With an SD of 3.3, however, 172 patients per group would be required to achieve 80% power for a 1-point difference; under our recruited sample size of 159 evaluable patients per arm, the corresponding power is 76% . While this falls just below the conventional 80% threshold, we consider that it is also acceptable. 3. Definition and assessment of CPSP We defined CPSP as pain in the surgical area with a Numerical Rating Scale (NRS) score ≥ 1 at 90 days postoperatively, consistent with several contemporary trials to capture all levels of persistent pain [2,3] . However, we acknowledge that this threshold may include mild symptoms of limited clinical relevance. In response to the suggestion, we will perform a post-hoc sensitivity analysis using a more stringent threshold (NRS ≥ 3) for CPSP incidence. This will allow us to distinguish clinically significant pain and enhance the interpretability of our secondary outcome. 4. Multidimensional pain assessment We agree that comprehensive pain assessment should ideally incorporate quality of life and functional impact measures, such as the McGill Pain Questionnaire or Brief Pain Inventory. For pragmatic reasons with this multicenter design, our protocol currently relies on NRS intensity scores. We acknowledge this as a limitation and thus recommend that future trials integrate multidimensional tools to better characterize CPSP phenotype after laparoscopic cholecystectomy. 2 D. WANG ET AL. 5. Clinical and methodological implications The primary superiority comparison of OBAS at 24 h remains unaffected by the refinement of CPSP definition, as CPSP was not used for sample size calculation. The addition of sensitivity analyses for CPSP (NRS ≥ 3) and OBAS variability will strengthen the secondary findings without compromising the primary objective. We believe that these additional analyses will improve the validity, interpretability, and clinical applicability of our trial results. In summary, we thank Dr. Lv and Dr. Xuan again for their valuable feedback, which will h

FAQs

What is the primary endpoint used in the trial?

The primary endpoint is the Overall Benefit of Analgesia Score (OBAS) at 24 hours postoperatively.

How was the sample size and power for OBAS determined?

The analysis uses an assumed OBAS standard deviation of 3.0; with an SD of 2.7, 155 patients per group provide 90% power, while with an SD of 3.3, 172 per group would be needed for 80% power, yielding 76% with 159 evaluable patients per arm.

How is chronic postsurgical pain (CPSP) defined and what refinement is planned?

CPSP is defined as pain in the surgical area with Numerical Rating Scale (NRS) score ≥ 1 at 90 days. The authors plan a post-hoc sensitivity analysis using a stricter threshold of NRS ≥ 3 to better distinguish clinically significant pain.

Sep 30, 2026

Uploaded by Bulrr