title: Redesigning a large-scale clinical trial in response to negative external trial results: the CAMUS study of phytotherapy for benign prostatic hyperplasia.
abstract: BACKGROUND
  Benign prostatic hyperplasia (BPH), a common condition among older men, confers its morbidity through potentially bothersome lower urinary tract symptoms. Treatments for BPH include drugs such as alpha-adrenergic receptor blockers and 5-alpha reductase inhibitors, minimally invasive therapies that use heat to damage or destroy prostate tissue, and surgery including transurethral resection of the prostate. Complementary and alternative medicines are gaining popularity in the US. Two phytotherapies commonly used for BPH are extracts of the fruit of Serenoa repens, the Saw palmetto dwarf palm that grows in the Southeastern US, and extracts of the bark of Pygeum africanum, the African plum tree.
  
  
  OBJECTIVE
  The objective of the Complementary and Alternative Medicines for Urological Symptoms (CAMUS) clinical trial is to determine if phytotherapy is superior to placebo in the treatment of BPH.
  
  
  METHODS
  CAMUS was originally designed as a 3300-participant, four-arm trial of S. repens, P. africanum, an alpha-adrenergic blocking drug, and placebo with time to clinical progression of BPH, a measure of long-term efficacy, as the primary endpoint. Before enrollment started, a randomized, double-blind, placebo-controlled, single institution clinical trial showed that S. repens at the usual dose did not demonstrate any benefit over placebo with respect to symptom relief at 1 year. Consequently, the focus of CAMUS shifted from evaluating long-term efficacy to determining if any short-term (6-18 months) symptom relief could be achieved with increasing doses of S. repens, the phytotherapy most commonly used in the US for BPH.
  
  
  RESULTS
  Results are anticipated in 2011.
  
  
  CONCLUSIONS
  Trial design occurs in an environment of continually evolving information. In this case, emerging results from another trial suggested that a study of long-term efficacy was premature, and that an effective dose and preparation of S. repens had to be established before proceeding to a long-term clinical trial.
authors.affiliation: Department of Biostatistics, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA. jylee@uams.edu
authors.forename: Jeannette
authors.initials: J
authors.lastname: Lee
authors.forename: Gerald
authors.initials: G
authors.lastname: Andriole
authors.forename: Andrew
authors.initials: A
authors.lastname: Avins
authors.forename: E David
authors.initials: ED
authors.lastname: Crawford
authors.forename: Harris
authors.initials: H
authors.lastname: Foster
authors.forename: Steven
authors.initials: S
authors.lastname: Kaplan
authors.forename: Karl
authors.initials: K
authors.lastname: Kreder
authors.forename: John
authors.initials: J
authors.lastname: Kusek
authors.forename: Andrew
authors.initials: A
authors.lastname: McCullough
authors.forename: Kevin
authors.initials: K
authors.lastname: McVary
authors.forename: Sreelatha
authors.initials: S
authors.lastname: Meleth
authors.forename: Michael
authors.initials: M
authors.lastname: Naslund
authors.forename: J Curtis
authors.initials: JC
authors.lastname: Nickel
authors.forename: Leroy
authors.initials: L
authors.lastname: Nyberg
authors.forename: Claus
authors.initials: C
authors.lastname: Roehrborn
authors.forename: O
authors.initials: O
authors.lastname: Dale Williams
authors.forename: Michael
authors.initials: M
authors.lastname: Barry
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005638:Fruit; D006801:Humans; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic / Q000379:methods; D008517:Phytotherapy / Q000379:methods*; D024301:Plant Bark; D010936:Plant Extracts; D011470:Prostatic Hyperplasia / Q000188:drug therapy*; D000068218:Prunus africana; D016032:Randomized Controlled Trials as Topic / Q000379:methods*; D012107:Research Design; D028024:Serenoa
chemical_list: D000317:Adrenergic alpha-Antagonists; D010936:Plant Extracts