title: Lessons Learned from EVOLVE for Planning of Future Randomized Trials in Patients on Dialysis.
abstract: The effect of the calcimimetic cinacalcet on cardiovascular disease in patients undergoing hemodialysis with secondary hyperparathyroidism was assessed in the Evaluation of Cinacalcet Hydrochloride Therapy to Lower Cardiovascular Events trial. This was the largest (in size) and longest (in duration) randomized controlled clinical trial undertaken in this population. During planning, execution, analysis, and reporting of the trial, many lessons were learned, including those related to the use of a composite cardiovascular primary endpoint, definition of endpoints (particularly heart failure and severe unremitting hyperparathyroidism), importance of age for optimal stratification at randomization, use of unadjusted and adjusted intention-to-treat analysis for the primary outcome, how to respond to a lower-than-predicted event rate during the trial, development of a prespecified analytic plan that accounted for nonadherence and for cointerventions that diminished the power of the trial to observe a treatment effect, determination of the credibility of a subgroup effect, use of adverse effects database to investigate rare diseases, collection of blood for biomarker measurement not designated before trial initiation, and interpretation of the benefits-to-harms ratio for individual patients. It is likely that many of these issues will arise in the planning of future trials in CKD.
authors.affiliation: Due to the number of contributing authors, the affiliations are provided in the Supplemental Material. pparfrey@mun.ca.
authors.forename: Patrick S
authors.initials: PS
authors.lastname: Parfrey
authors.affiliation: Due to the number of contributing authors, the affiliations are provided in the Supplemental Material.
authors.forename: Geoffrey A
authors.initials: GA
authors.lastname: Block
authors.affiliation: Due to the number of contributing authors, the affiliations are provided in the Supplemental Material.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Correa-Rotter
authors.affiliation: Due to the number of contributing authors, the affiliations are provided in the Supplemental Material.
authors.forename: Tilman B
authors.initials: TB
authors.lastname: Drüeke
authors.affiliation: Due to the number of contributing authors, the affiliations are provided in the Supplemental Material.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Floege
authors.affiliation: Due to the number of contributing authors, the affiliations are provided in the Supplemental Material.
authors.forename: Charles A
authors.initials: CA
authors.lastname: Herzog
authors.affiliation: Due to the number of contributing authors, the affiliations are provided in the Supplemental Material.
authors.forename: Gerard M
authors.initials: GM
authors.lastname: London
authors.affiliation: Due to the number of contributing authors, the affiliations are provided in the Supplemental Material.
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Mahaffey
authors.affiliation: Due to the number of contributing authors, the affiliations are provided in the Supplemental Material.
authors.forename: Sharon M
authors.initials: SM
authors.lastname: Moe
authors.affiliation: Due to the number of contributing authors, the affiliations are provided in the Supplemental Material.
authors.forename: David C
authors.initials: DC
authors.lastname: Wheeler
authors.affiliation: Due to the number of contributing authors, the affiliations are provided in the Supplemental Material.
authors.forename: Glenn M
authors.initials: GM
authors.lastname: Chertow
mesh_terms: D057966:Calcimimetic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000209:etiology / Q000517:prevention & control*; D000069449:Cinacalcet / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology; D016032:Randomized Controlled Trials as Topic / Q000379:methods*; D006435:Renal Dialysis / Q000009:adverse effects*; D051436:Renal Insufficiency, Chronic / Q000150:complications / Q000175:diagnosis / Q000628:therapy*; D012107:Research Design; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D057966:Calcimimetic Agents; D000069449:Cinacalcet
keywords: cardiovascular disease; cardiovascular diseases; chronic kidney disease; cinacalcet; hemodialysis; humans; hyperparathyroidism; parathyroid hormone; randomized controlled trials as topic