Letter: Clinical Trial: Treatment of Functional Dyspepsia According to Subtype Compared With Empirical Proton Pump Inhibitor

Abstract

The study by Chuah et al. [1] offers valuable insight that can significantly influence daily outpatient practice. The findings, while valuable, suggest that certain aspects of the study's design and scope could benefit from further refinement to guide future research effectively.

First, the absence of blinding and a placebo group may have contributed to an overestimation of the observed efficacy in both intervention and control arms due to the well documented influence of placebo and nocebo effects in patients with functional dyspepsia (FD) [2]. While the authors stated that both groups received active medical therapy, and thus any placebo or nocebo effects might have been distributed similarly, this assumption requires further investigation. Open-label designs can lead to psychological biases and may confound results.

Second, patients with severe anxiety or depression, defined as requiring medication or experiencing daily functional impairment, were excluded. However, the criteria for exclusion were not clearly defined. This lack of clarity raises concerns about potential bias, particularly if patients with mild symptoms were excluded. As FD is frequently associated with coexisting mental health conditions [3], understanding the proportions of patients with mild mental health problems in both groups would have provided valuable context. The lack of this information may limit the interpretation of the study's findings and applicability to real-world clinical settings.

Third, the post hoc analysis provides useful insights into responder rates by subtype, particularly in those with epigastric pain syndrome and postprandial distress syndrome (EPS-PDS) overlap. However, the lack of detailed statistical considerations for this analysis may limit the clarity and reliability of these findings. As with all post hoc analyses, spurious associations are possible, so these results should be interpreted with care.

Furthermore, the small sample size of certain subtypes, such as EPS, may have influenced the statistical power and reliability of the outcomes. Future studies could benefit from incorporating randomised allocation within subtypes or using stratified analyses to better explore subtype-specific effects. Increasing the sample size would also strengthen the findings and provide a clearer understanding of the role of subtypes in treatment outcomes.

In conclusion, this study has the potential to significantly influence routine FD care. Addressing the four points discussed above could further enhance its impact and contribute significantly to shaping future strategies for the treatment of FD in clinical practice.

Shoko Miyahara: conceptualization, writing – original draft, writing – review and editing, formal analysis. Takeshi Yamashina: writing – review and editing, formal analysis, supervision. Takehiro Ohyama: writing – review and editing, formal analysis, supervision. Masahiro Banno: writing – review and editing, formal analysis, supervision.

The authors declare no conflicts of interest.

This article is linked to Chuah et al. papers. To view these articles, visit https://doi.org/10.1111/apt.18418 and https://doi.org/10.1111/apt.70025.