In Reply:
In Reply: We greatly appreciate the suggestions laid forth in the Letter to the Editor from Drs. Liang and Fan regarding the statistical analysis of our trial, published in the January 2025 issue.1 We are also grateful to the Editor for the opportunity to respond and clarify our rationale. This study was designed and powered from the outset as a cross-sectional randomized controlled trial, with the primary objective of comparing pain scores immediately after the biopsy. Pain scores collected at other time points, particularly those assessed twice after the biopsy, were intended to evaluate the stability of the transcutaneous electrical nerve simulation (TENS) device's effect over time. This was proposed as a secondary aim of the original study design. In their Letter, Drs. Liang and Fan propose the use of repeated measures analysis of variance (ANOVA) to account for potential correlation of repeated measures. We agree that this approach could be a valuable statistical consideration for future trials. However, in the context of this trial, we believe it is unlikely to substantively affect our results or their interpretation. For our primary endpoint—pain immediately after endometrial biopsy—we observed a statistically significant but clinically insignificant reduction in pain. The box plots in Figure 2 demonstrate no appreciable difference in pain scores at any other time point. These data reinforce our conclusion that, for participants enrolled in the trial, TENS did not result in a clinically significant reduction in pain compared with placebo, regardless of the statistical method employed. Additional statistical testing that might yield a numerically greater estimate of the difference between groups, potentially meeting our prespecified clinically significant threshold of 15 mm, would not alter our overall interpretation of the results. Conversely, a reduction in the estimated difference would add little new information to what is already a negative trial. It is also worth noting that the use of repeated measures ANOVA likely would require a larger sample size to achieve adequate power. Although we do not believe additional testing is warranted in the current trial, we greatly appreciate the thoughtful consideration of our work by the authors of the Letter. We will certainly consider incorporating a longitudinal model in future studies to address similar concerns and further refine our methodology.
Authors
- Shakthi Unnithan (ORCID: https://orcid.org/0000-0002-7863-8712)
- Alaattin Erkanli
- Jonas J. Swartz (ORCID: https://orcid.org/0000-0002-9726-965X)
- Laura Jean Havrilesky (ORCID: https://orcid.org/0000-0002-4259-5992)
- Jenny Wu (ORCID: https://orcid.org/0000-0003-1424-544X)
Institutions
- Duke University (US)
Publication Details
- Journal
- Obstetrics and Gynecology
- Published
- 2025-03-20
- DOI
- https://doi.org/10.1097/aog.0000000000005876
- Primary Topic
- Advances in Oncology and Radiotherapy
- Type
- article
- Field-Weighted Citation Impact
- 0.00