The trajectory of a range of commonly captured symptoms with standard care in people with kidney failure receiving haemodialysis: consideration for clinical trial design.

Background: Despite the recognized high symptom prevalence in haemodialysis population, how these symptoms change over time and its implications for clinical practice and research is poorly understood.

Methods: Prevalent haemodialysis patients in the SHAREHD trial reported 17 POS-S Renal symptoms (none, mild, moderate, severe and overwhelming) at baseline, 6, 12 and 18 months. To assess the prevalence change at population level in people reporting moderate or worse symptoms at baseline, the absolute change in prevalence was estimated using multi-level mixed effects probit regression adjusting for age, sex, time on haemodialysis and Charlson Comorbidity Score. To assess changes at individual level, the proportion of people changing their symptom score every 6 months was estimated.

Results: Five hundred fifty-two participants completed 1725 questionnaires at four timepoints. Across all 17 symptoms with moderate or worse symptom severity at baseline, the majority of the change in symptom prevalence at population level occurred in the 'severe' category. The absolute improvement in prevalence of the 'severe' category was ≤ 20% over 18 months in eleven of the seventeen symptoms despite a large degree of relatively balanced movement of individuals in and out of severe category every six months. Examples include depression, skin changes and drowsiness, which had larger proportion (75-80%) moving in and out of severe category each 6 months period but < 5% difference between movement in and out of severe category resulting in relatively static prevalence over time. Meanwhile, larger changes in prevalence of > 20% were observed in six symptoms, driven by a 9 to 18% difference between movement in and movement out of severe category. All symptoms had > 50% of people in severe group changing severity within 6 months.

Conclusions: Changes in the severity of existing symptoms under standard care were frequent, often occurring within six months. Certain symptoms exhibited clinically meaningful shifts at both the population and individual levels. This highlighted the need to consider improvements in symptom severity when determining sample size and statistical power for trials. By accounting for potential symptom improvements with routine care, researchers can design trials capable of robustly detecting genuine treatment effects, distinguishing them from spontaneous changes associated with standard haemodialysis.