Response to “Trial design, conflict of interest, and evidence independence in the JASMINE trial and its economic evaluations”

The JASMINE study was designed as a multicenter, randomized Phase III registration trial (jRCT2031210384) conducted under the Japanese Good Clinical Practice (GCP) framework to evaluate the safety and efficacy of an exclusive human milk diet (EHMD) in Japanese very low birth weight (VLBW) infants. Because the intervention consisted of different nutritional products requiring distinct preparation and administration procedures, blinding of treating clinicians was not practically feasible. Several design elements were implemented to minimize potential observer bias.

Randomization was performed centrally using a permuted-block scheme stratified by study site and birth weight, with allocation concealment maintained until assignment. Clinical management followed predefined protocols across participating NICUs, and major outcomes, including body weight, time to full enteral feeding, and adverse events, were prospectively defined. Although blinded endpoint adjudication was not incorporated into the study design, randomization, protocol standardization, prospective data collection, and GCP-compliant monitoring, including on-site source data verification, were implemented to safeguard data integrity.

We nevertheless recognize that the open-label design and absence of blinded endpoint adjudication are limitations of the trial and should be considered when interpreting outcomes that may be influenced by clinical management decisions. The correspondents raise important questions regarding sponsor involvement in the trial and the interpretation of the competing-interest statement. Industry sponsorship is a standard model for pivotal Phase III clinical trials conducted to support regulatory approval of a new drug.

Such trials require substantial resources for multicenter trial conduct, data management, pharmacovigilance, quality assurance, statistical analysis, and preparation of regulatory submissions. In this context, we believe it is important to distinguish the fact of sponsor funding from the separate question of the sponsor’s role in the analysis and interpretation of the trial results. As disclosed in the published article, Prolacta Bioscience funded the study and contributed to its statistical design.

However, the statistical analyses of the trial data were performed by a third-party contract research organization (CRO), Innovative Analytics, according to the prespecified statistical analysis plan (SAP), and not by Prolacta Bioscience personnel. The statistical workflow was as follows: Pre-specification of the analysis. The protocol and SAP were finalized before database lock and before any unblinded efficacy analysis.

The SAP prespecified the primary endpoint (weight gain velocity), the non-inferiority margin, sample size calculation, intent-to-treat and per-protocol analysis sets, and the testing hierarchy in which superiority was tested only after non-inferiority was established [1]. Allocation was performed centrally using a permuted-block scheme stratified by study site and birth weight, with allocation concealment maintained until assignment [1]. Data management and monitoring.