Venous Cannulation Pain as a Marker of Postoperative Pain Vulnerability: A Pre-Specified Secondary Analysis of a Randomized Controlled Trial

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The study is interesting but presents some significant inconsistencies that must be corrected. Below are our observations:
- There is an inconsistency between the stated objective and the conclusion. The objective aims to demonstrate the predictive capacity of VCP for APOP. However, the results do not seem to fully support this, while in the conclusion the authors appear to affirm it. We recommend that the authors carefully review the results and draw their conclusion based on them.

- The meaning of "predictor" is not clearly established in the text. For this reason, we question whether the authors are referring to a statistical difference, discriminatory values ​​such as sensitivity and specificity, or what they mean by the term "predictive"?

- Significant limitations are observed regarding the multivariate analysis, particularly the stepwise model, mainly due to overfitting and model instability. Furthermore, the selection of the study variables is not clearly justified.

- The sample size is also not justified. While the study sample size is relatively large, it may not be sufficient for multivariate analysis.

- From our perspective, the cutoff value of 2 VAS does not appear to be well justified. It would be worthwhile to include information justifying this, perhaps literature, ROC analysis, etc., to clarify the matter.

- Are the statistical differences found in this study clinically significant? Why? Explain this in the discussion.

- Is gender the only significant predictive factor? Were the influences of the hormonal cycle, psychosocial factors, and biological factors considered?

-Could you discuss why patients with different anesthetic strategies were included and what influence this might have on the results? Could it act as a confounding factor?

-The study is well-intentioned; however, we believe it should be given a more realistic interpretation. Therefore, we invite the authors to revise the text.

Author Response

Please see the attachment

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

This study represents a secondary analysis examining the relationship between venous cannulation pain (VCP) and postoperative pain using data derived from a randomized controlled trial (RCT). As the data were not originally collected with this specific research question as the primary objective, the main findings are negative. However, the parent study was well designed, and the objectivity and reliability of the collected data are adequately ensured. Therefore, the authors’ intention to explore the association between VCP and postoperative pain as a novel analytical perspective is well understood.

The positioning of the manuscript and the analytical approach to the results are appropriate, and although the findings are negative, the discussion is sufficiently cautious and convincingly presented. The only point of concern is the statement in the Abstract: “The aim of the study was to evaluate VCP as a method for postoperative pain prediction in a randomized cohort.” Clarifying this point would improve consistency between the stated aim and the secondary, exploratory nature of the analysis.

Author Response

Please see attachment. 

Author Response File: Author Response.pdf

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

The authors have addressed each of the points of the previous review; therefore, we recommend the acceptance of this version.