Range and Variability of Outcomes Reported in Randomized Trials Conducted in Patients With Polycystic Kidney Disease: A Systematic Review

Abstract

Rationale & objective: Trials in autosomal dominant polycystic kidney disease (ADPKD) have increased, but their impact on decision making has been limited. Because heterogeneity in reported outcomes may be responsible, we assessed their range and variability in ADPKD trials.

Study design: Systematic review.

Setting & study population: Adult participants in clinical trials in ADPKD.

Selection criteria for studies: We included trials that studied adults and were published in English. For trials that enrolled patients without ADPKD, only those enrolling ≥50% of participants with ADPKD were included.

Data extraction: We extracted information on all discrete outcome measures, grouped them into 97 domains, and classified them into clinical, surrogate, and patient-reported categories. For each category, we choose the 3 most frequently reported domains and performed a detailed analysis of outcome measures.

Analytical approach: Frequencies and characteristics of outcome measures were described.

Results: Among 68 trials, 1,413 different outcome measures were reported. 97 domains were identified; 41 (42%) were surrogate, 30 (31%) were clinical, and 26 (27%) were patient reported. The 3 most frequently reported domains were in the surrogate category: kidney function (54; 79% of trials; using 46 measures), kidney and cyst volumes (43; 63% of trials; 52 measures), and blood pressure (27; 40% of trials, 30 measures); in the clinical category: infection (10; 15%; 21 measures), cardiovascular events (9; 13%; 6 measures), and kidney failure requiring kidney replacement therapy (8; 12%; 5 measures); and in the patient-reported category: pain related to ADPKD (16; 24%; 26 measures), pain for other reasons (11; 16%; 11 measures), and diarrhea/constipation/gas (10; 15%; 9 measures).

Limitations: Outcome measures were assessed for only the top 3 domains in each category.

Conclusions: The outcomes in ADPKD trials are broad in scope and highly variable. Surrogate outcomes were most frequently reported. Patient-reported outcomes were uncommon. A consensus-based set of core outcomes meaningful to patients and clinicians is needed for future ADPKD trials.

Keywords: Autosomal dominant polycystic kidney disease (ADPKD); blood pressure; cardiovascular events; cyst volume; end-stage kidney disease (ESKD); epidemiology; hard outcome; infection; kidney function; kidney volume; nephrology; outcome heterogeneity; outcomes; pain; patient-centered research; patient-reported outcome (PRO); surrogate end point; systematic review; trial design.