title: Prognostic enrichment design in clinical trials for autosomal dominant polycystic kidney disease: the HALT-PKD clinical trial.
abstract: BACKGROUND
  Patients with mild autosomal dominant polycystic kidney disease (ADPKD) are less likely to be informative in randomized clinical trials (RCTs). We previously developed an imaging classification of ADPKD (typical diffuse cyst distribution Class 1A-E and atypical cyst distribution Class 2) for prognostic enrichment design in RCTs. We investigated whether using this classification would have increased the power to detect a beneficial treatment effect of rigorous blood pressure (BP) control on HALT-PKD participants with early disease (Study A).
  
  
  METHODS
  Post hoc analysis of the early disease HALT-PKD study, an RCT that studied the effect of rigorous versus standard BP control on rates of total kidney volume (TKV) increase and estimated glomerular filtration rate (eGFR) decline in ADPKD patients with eGFR >60 mL/min/1.73 m2.
  
  
  RESULTS
  Five hundred and fifty-one patients were classified by two observers (98.2% agreement) into Class 1A (6.2%), 1B (20.3%), 1C (34.1%), 1D (22.1%), 1E (11.8%) and 2 (5.4%). The TKV increase and eGFR decline became steeper from Class 1A through 1E. Rigorous BP control had been shown to be associated with slower TKV increase, without a significant overall effect on the rate of eGFR decline (faster in the first 4 months and marginally slower thereafter). Merging Classes 1A and 2 (lowest severity), 1B and 1C (intermediate severity) and 1D and 1E (highest severity) detected stronger beneficial effects on TKV increase and eGFR decline in Class 1D and E with a smaller number of patients.
  
  
  CONCLUSIONS
  Strategies for prognostic enrichment, such as image classification, should be used in the design of RCTs for ADPKD to increase their power and reduce their cost.
authors.affiliation: Division of Nephrology and Hypertension, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA.
authors.forename: María V
authors.initials: MV
authors.lastname: Irazabal
authors.affiliation: University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: Kaleab Z
authors.initials: KZ
authors.lastname: Abebe
authors.affiliation: University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: Kyongtae Ty
authors.initials: KT
authors.lastname: Bae
authors.affiliation: Tufts Medical Center, Boston, MA, USA.
authors.forename: Ronald D
authors.initials: RD
authors.lastname: Perrone
authors.affiliation: Division of Nephrology, University of Chicago, Chicago, IL, USA.
authors.forename: Arlene B
authors.initials: AB
authors.lastname: Chapman
authors.affiliation: University of Colorado, Denver, CO, USA.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Schrier
authors.affiliation: Kansas University Medical Center, Kansas City, KS, USA.
authors.forename: Alan S
authors.initials: AS
authors.lastname: Yu
authors.affiliation: Cleveland Clinic, Cleveland, OH, USA.
authors.forename: William E
authors.initials: WE
authors.lastname: Braun
authors.affiliation: Beth Israel Deaconess Medical Center, Boston, MA, USA.
authors.forename: Theodore I
authors.initials: TI
authors.lastname: Steinman
authors.affiliation: Division of Nephrology and Hypertension, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA.
authors.forename: Peter C
authors.initials: PC
authors.lastname: Harris
authors.affiliation: National Institutes of Health, Bethesda, MD, USA.
authors.forename: Michael F
authors.initials: MF
authors.lastname: Flessner
authors.affiliation: Division of Nephrology and Hypertension, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA.
authors.forename: Vicente E
authors.initials: VE
authors.lastname: Torres
mesh_terms: D000328:Adult; D001794:Blood Pressure; D018450:Disease Progression; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D007668:Kidney / Q000503:physiopathology; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D016891:Polycystic Kidney, Autosomal Dominant / Q000000981:diagnostic imaging* / Q000503:physiopathology / Q000628:therapy*; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome; D055815:Young Adult
keywords: HALT-PKD study; autosomal dominant polycystic kidney disease; eGFR; image classification; total kidney volume