Is the reported benefit of the Endo-App truly sustained?

Dear Editor,

I read with interest the real-world analysis by Nigdelis et al., reporting improvements in selected outcomes among Endo-App users [1]. Although digital interventions may complement multimodal pain management, several analytical and clinical considerations warrant caution when interpreting these findings as evidence of a sustained, clinically meaningful, and app-specific effect.

First, the 3-month and 6–7-month results do not represent a clearly defined longitudinal trajectory. Analyses were conducted separately among participants with paired T0–T1 or T0–T2 observations, and the authors state that only “some overlap may have occurred” between respondents at the two follow-up points. Because T1 and T2 were not directly compared, the 6–7-month findings cannot demonstrate persistence or further improvement beyond month 3; they may instead reflect a different, highly self-selected subgroup. This distinction is particularly important given the reduction from 143 respondents at 3 months to only 55 at 6–7 months.

Second, self-reported average pain improved modestly, by 0.80 points at 3 months and 0.85 points at 6–7 months, corresponding to relative decreases of approximately 14% and small effect sizes (Cohen’s d = 0.28 at both time points). At 6–7 months, sick days (p = 0.04) and days requiring medical assistance (p = 0.03) also decreased significantly; however, these are indirect measures of disease burden rather than direct measures of symptom intensity, and their nominal significance should be considered in light of the multiple outcomes tested. In chronic pain research, a reduction of approximately 2 points or 30% on a numerical rating scale has commonly corresponded to clinically important improvement [2], although a specific threshold for endometriosis-related pain is not well established. Thus, the observed mean pain reduction appears modest at the group level, while not excluding the possibility that individual patients may derive meaningful benefit from the app as part of a multimodal management approach.

Moreover, counting only the number of days on which pain medication was required does not establish comparable analgesic exposure. Nonsteroidal anti-inflammatory drugs may differ substantially in duration of action, dose, dosing frequency, and anti-inflammatory potency, while the broad term “pain medication” may also include paracetamol, which has no clinically meaningful anti-inflammatory activity. Thus, one treatment day was counted identically regardless of the agent or cumulative exposure. Because analgesics and hormonal therapies are established components of endometriosis pain management [3], unmeasured differences or changes in these treatments could confound a small change in subjective pain.

The underlying pain phenotype was also insufficiently characterized. Fibromyalgia and other chronic overlapping pain conditions may coexist with endometriosis and are associated with greater pain severity, interference, and overall burden [4]. Without documenting fibromyalgia, central sensitization, or other independent sources of pain, a single global pain score cannot confidently be interpreted as reflecting improvement specifically in endometriosis-related pain. The original authors appropriately acknowledged important limitations, including attrition, the lack of a concurrent control group, and limited information on concomitant treatments. These limitations nevertheless remain relevant to causal interpretation, because expectancy effects, self-monitoring, natural symptom fluctuation, regression to the mean, and treatment changes cannot be distinguished from an app-specific effect.

Finally, six outcomes were examined at two follow-up points without adjustment for multiplicity. The nominally significant 6–7-month findings (p = 0.02–0.04) would not remain significant under a simple Bonferroni threshold of approximately 0.004. Although such a correction may be conservative, the clustering of borderline p values warrants an explicitly exploratory interpretation. A reanalysis restricted to participants with observations at all three timepoints could better characterize within-patient trajectories. In addition, a responder analysis using a prespecified threshold, such as a ≥ 30% or ≥ 2-point reduction on the NPRS, would complement mean changes, while multiplicity-adjusted analyses or an explicitly exploratory framing would provide a more cautious assessment of the secondary outcomes.

Taken together, the available data suggest a modest improvement in selected outcomes but do not yet establish that the Endo-App produces a sustained, clinically meaningful, or app-specific effect. Longitudinal within-patient and responder analyses would help clarify the durability and clinical relevance of the observed changes.

Author contributions

Z.K. conceived the correspondence, reviewed the relevant literature, drafted and critically revised the manuscript, and approved the final version.

Funding

No funding was received for this work.

Data availability statement

No datasets were generated or analysed during the current study.

Declarations

Conflict of interest

The author declares no competing interests.