Methodological and Statistical Concerns Regarding “Nanofiber Matrix Dressing for Split-Thickness Skin Graft Donor Sites” [Letter]

Dear editor

We read with interest the randomized comparative study by Biskupski et al¹ evaluating a nanofiber matrix dressing for split-thickness skin graft donor sites. The authors concluded that the nanofiber matrix reduced early postoperative pain and shortened healing time compared with conventional dressing. While the topic is clinically relevant and the translational potential of electrospun nanofiber technology is promising, we have identified several methodological and statistical issues that substantially affect the validity of the reported findings.²

A second concern relates to the inappropriate use of parametric tests for ordinal data. The authors employed Student’s t-test to compare pain scores measured on a 0–10 numeric rating scale across multiple time points. This scale is ordinal, not interval-level, and the t-test assumes normality and equal variances—assumptions unlikely to hold for such bounded, skewed data. Indeed, the reported standard deviations (eg, Day 1 pain: study group 0.85 ± 0.99, control group 3.16 ± 1.26) suggest heterogeneity and potential non-normality. The correct analytical approach would have been the Mann–Whitney U-test or other non-parametric methods, which the authors inconsistently applied to other variables.³

Third, we noted a biologically implausible data pattern that warrants clarification. On postoperative day 14, the control group had a mean pain score of 0.00 with a standard deviation of 0.00—indicating that all 20 patients reported zero pain. While complete pain resolution is possible, such absolute uniformity is extremely unusual in clinical research and raises questions about measurement granularity, ceiling effects, or potential reporting bias. The study group had a mean of 0.10 ± 0.45, suggesting minimal variability. The authors did not provide medians, interquartile ranges, or frequency distributions for these scores, which prevents readers from assessing the clinical significance and variability of the data.⁴

Fourth, the handling of missing data is inadequate. For late scar outcomes, the analysis was performed on a reduced subset (n=19 in the study group, n=17 in the control group), but the authors did not explain why these patients were lost to follow-up, nor did they compare baseline characteristics between completers and non-completers. More critically, they did not specify whether an intention-to-treat analysis was performed or whether missing data were handled using appropriate methods such as multiple imputation or sensitivity analysis. Attrition of approximately 10–15% is non-negligible, and if missingness is related to the outcome, the results may be severely biased. As Sterne et al noted, the handling of missing data in clinical trials requires careful prespecification and transparent reporting.⁵

Fifth, the exudate analysis is statistically underpowered and overinterpreted. Mild exudate occurred in 3 patients in the nanofiber group and none in the control group, yet the authors concluded that this difference was not significant (p=0.12). With such low event counts, no relative risk or effect size was reported. Moreover, the association between exudate and longer healing time (p=0.048) is based on only 3 patients and should not be interpreted causally. Recent evidence suggests that exudate burden is a significant predictor of delayed wound healing and should be analyzed with appropriate statistical rigor.⁶

In summary, while we applaud the authors for addressing an important clinical question using a randomized design, the methodological and statistical issues outlined above cast doubt on the robustness of their conclusions. We urge the authors to provide additional analyses (eg, non-parametric tests for pain scores, individual-level data for Day 14 pain, imputation for missing data, and a formal sample size justification) and to revise their interpretation accordingly. We hope this constructive critique will stimulate further discussion and lead to more rigorous evaluations of nanofiber-based wound dressings in future research.

Disclosure

The author reports no conflicts of interest in this communication.