Adjudication of Self-reported Symptomatic Stone Recurrence in the Prevention of Urinary Stones With Hydration Trial

Abstract

Objective: To assess accuracy of self-reported stone events in a large clinical trial by adjudication against the weight of documentation for spontaneous stone passage or surgical intervention.

Methods: Participants in the Prevention of Urinary Stones with Hydration (PUSH) trial were randomized to a multi-component behavioral intervention or control arm to increase and maintain high fluid intake. The primary endpoint was urinary stone events including symptomatic stone passage or procedural intervention. An independent adjudication committee blinded to randomization assignments reviewed all events. Confirmed clinical stone events required typical stone symptoms and documentation of stone passage (eg, via photograph, clinical record) and/or surgical intervention. Events with typical symptoms and self-described stone passage but without objective documentation of passage were also considered as meeting the primary endpoint and classified separately as patient-reported passage. Non-events did not meet either criteria.

Results: At time of this blinded analysis, a total of 1658 participants were randomized and had a median follow-up of 19 months. Self-reported stone events (n = 217) were adjudicated by the committee as either confirmed clinical events (134; 61.8%), patient-reported passage (71; 32.7%), or non-events (12; 5.5%). Confirmed clinical events consisted of stone passage in 66/134 and procedural interventions in 68/134 (53 for symptoms and 15 without symptoms).

Conclusion: Rigorous adjudication revealed that self-reported stone events in the PUSH trial overwhelmingly represented clinically documented passage, surgical intervention, and patient-reported passage outside healthcare settings, with only 5.5% failing to satisfy adjudication criteria. Similar adjudication and classification processes warrant consideration for implementation in future stone trials.

Clinical trials registration: NCT03244189.

Figure 1.

Schematic for outcomes adjudicated from a self-reported clinical urinary stone event including non-event, patient reported passage, or confirmed clinical stone event. Although the primary study endpoint is analyzed as a time to event analysis in which the participant was censored after the first confirmed stone event, subsequent events are also reported and adjudicated.

Figure 2.

Flow diagram showing the PUSH Adjudication Committee workflow process triggered by a self-reported primary outcome event. Note that an event report in the electronic database eCOS could be initiated by the study participant or research coordinator. Elements prior to “Phase 1 Review” represent administrative steps to prepare data for review. LCRA: Lead Clinical Research Associate. eCOS: electronic Clinical Operating System. PAC: PUSH Adjudication Committee.

Figure 3.

Kaplan Meier curves for the first 217 events adjudicated by the PUSH Adjudication Committee.

Figure 4.

Examples of participant submitted photographs leading to a confirmed clinical stone event.