Concerns regarding methodological and interpretive aspects in the evaluation of <scp>BTHC</scp> ‐ <scp>PAGGSM</scp> red cell storage

We read with great interest the recent article by Vermeulen et al. [1] titled ‘Clinical evaluation of red cell concentrates in non-DEHP plasticized containers compared with standard DEHP plasticized containers: A quasi-randomized observational multicentre study’. The authors address a timely and clinically relevant topic—the transition from di-ethyl-hexyl-phthalate (DEHP)-containing to non-DEHP blood storage systems. Although their contribution to haemovigilance is commendable, several aspects of methodology, statistical interpretation and data integration merit further consideration. This publication represents the second phase of a broader evaluation by the same group. Their earlier in vitro study [2] suggested that 1,2-cyclohexane dicar-boxylic acid diisononyl ester - N-butyryl-n-hexyl citrate containers, combined with the phosphate-adenine-glucose-guanosine-saline-mannitol (PAGGSM) additive solution, provided improved red cell quality based on haemolysis and adenosine triphosphate retention. Consequently, a haemovigilance study was initiated in two Dutch hospitals, where the initial analysis reported a transfusion reaction rate (TRR) of 0.24% for BTHC-PAGGSM compared with 0.44% for DEHP-saline-adenine-glucose-mannitol (SAGM), supporting further evaluation [2]. The recently published study expands the analysis to 32,878 red cell concentrate (RCC) transfusions across eight hospitals. Contrary to the earlier findings, the TRR associated with BTHC-PAGGSM in this larger dataset was 0.35%, compared with 0.20% for DEHP-SAGM, indicating a statistically and clinically significant difference (odds ratio [OR] 1.76; 95% confidence interval [CI]: 1.10–2.81). While the authors primarily report Bayesian intervals, our comments refer to complementary frequentist analyses (e.g., Fisher's exact test, p = 0.029) to illustrate the robustness of this difference. However, this outcome is not explicitly discussed in the study's interpretation. To mitigate the observed discrepancy, the authors pooled data from the current and previous haemovigilance studies, reporting a combined OR of 1.36 (95% CI: 0.90–2.08) concluding that TRRs were ‘consistent’ between the two groups. The validity of such pooling warrants reconsideration. The DEHP-SAGM group demonstrated significantly different adverse event rates between study phases (Fisher's exact test; p = 0.002), indicating heterogeneity of effects rather than simple variance differences. Future analyses could address this heterogeneity through stratified reporting, random-effects or hierarchical modelling or formal interaction testing to assess consistency across phases. We further note the marked imbalance in group sizes (25,371 for DEHP-SAGM vs. 7507 for BTHC-PAGGSM). This disparity reduces power and increases uncertainty in the smaller cohort. Weighted analyses, regression adjustment or presentation of both absolute and relative risk differences could improve interpretability and mitigate the effects of unequal sample sizes. The limited description of statistical methods in the original article also deserves mention. Although Bayesian principles were cited for sample size determination, the operational details of model specification, priors and computational implementation were not provided. Greater transparency would strengthen reproducibility and facilitate a more informed evaluation of the reported results. We acknowledge that the post hoc analysis restricted to high-imputability reactions (definite, probable or possible) showed attenuated differences (0.23% vs. 0.16%). Nonetheless, the broader pattern of higher TRR in the BTHC-PAGGSM group across a larger dataset warrants careful interpretation. In conclusion, while we appreciate the authors' contributions to advancing haemovigilance research, we believe that methodological transparency, stratified analyses and statistical approaches accounting for heterogeneity and sample imbalance will be crucial for future evaluations. Continued haemovigilance surveillance and registry-based monitoring would further support patient safety during the ongoing transition to non-DEHP blood storage systems. We thank the authors for their valuable contributions to the field of haemovigilance and hope our comments support future refinement in study design and data interpretation. The authors declare no conflicts of interest. The data that support the findings of this study are available from the corresponding author upon reasonable request.