title: Opportunities and challenges in incorporating ancillary studies into a cancer prevention randomized clinical trial.
abstract: The Selenium and Vitamin E Cancer Prevention Trial (SELECT) was a randomized, double-blind, placebo-controlled, prostate cancer prevention study funded by the National Cancer Institute and conducted by SWOG (Southwest Oncology Group). A total of 35,533 men were assigned randomly to one of four treatment groups (vitamin E + placebo, selenium + placebo, vitamin E + selenium, placebo + placebo). At the time of the trial's development, NIH had invested substantial resources in evaluating the potential benefits of these antioxidants. To capitalize on the knowledge gained from following a large cohort of healthy, aging males on the effects of selenium and/or vitamin E, ancillary studies with other disease endpoints were solicited.
  
  
  
  Four ancillary studies were added. Each drew from the same population but had independent objectives and an endpoint other than prostate cancer. These studies fell into two categories: those prospectively enrolling and following participants (studies of Alzheimer's disease and respiratory function) and those requiring a retrospective medical record review after a reported event (cataracts/age-related macular degeneration and colorectal screening). An examination of the challenges and opportunities of adding ancillary studies is provided. The impact of the ancillary studies on adherence to SELECT was evaluated using a Cox proportional hazards model.
  
  
  
  While the addition of ancillary studies appears to have improved participant adherence to the primary trial, this did not come without added complexity. Activation of the ancillary studies happened after the SELECT randomizations had begun resulting in accrual problems to some of the studies. Study site participation in the ancillary trials varied greatly and depended on the interest of the study site principal investigator. Procedures for each were integrated into the primary trial and all monitoring was done by the SELECT Data and Safety Monitoring Committee. The impact of the early closure of the primary trial was different for each of the ancillary trials.
  
  
  
  The ancillary studies allowed study sites to broaden the research opportunities for their participants. Their implementation was efficient because of the established infrastructure of the primary trial. Implementation of these ancillary trials took substantial planning and coordination but enriched the overall primary trial.
  
  
  
  NCT00006392-S0000 : Selenium and Vitamin E in Preventing Prostate Cancer (SELECT) (4 October 2000). NCT00780689-S0000A :  Prevention of Alzheimer's Disease by Vitamin E and Selenium (PREADVISE) (25 June 2002). NCT00784225-S0000B : Vitamin E and/or Selenium in Preventing Cataract and Age-Related Macular Degeneration in Men on SELECT SWOG-S0000 (SEE) (31 October 2008). NCT00706121-S0000D : Effect of Vitamin E and/or Selenium on Colorectal Polyps in Men Enrolled on SELECT Trial SWOG-S0000 (ACP) (26 June 2008). NCT00063453-S0000C : Vitamin E and/or Selenium in Preventing Loss of Lung Function in Older Men Enrolled on SELECT Clinical Trial SWOG-S0000 (26 June 2003).
authors: SWOG Statistical Center, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N, M3-C102, Seattle, WA, 98109, USA. pgoodman@fredhutch.org.
authors: Phyllis J
authors: PJ
authors: Goodman
authors: SWOG Statistical Center, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N, M3-C102, Seattle, WA, 98109, USA.
authors: Catherine M
authors: CM
authors: Tangen
authors: SWOG Statistical Center, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N, M3-C102, Seattle, WA, 98109, USA.
authors: Amy K
authors: AK
authors: Darke
authors: SWOG Statistical Center, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N, M3-C102, Seattle, WA, 98109, USA.
authors: Kathryn B
authors: KB
authors: Arnold
authors: SWOG Statistical Center, Cancer Research and Biostatistics, Seattle, WA, USA.
authors: JoAnn
authors: J
authors: Hartline
authors: SWOG Statistical Center, Cancer Research and Biostatistics, Seattle, WA, USA.
authors: Monica
authors: M
authors: Yee
authors: SWOG Statistical Center, Cancer Research and Biostatistics, Seattle, WA, USA.
authors: Karen
authors: K
authors: Anderson
authors: Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA.
authors: Allison
authors: A
authors: Caban-Holt
authors: Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors: William G
authors: WG
authors: Christen
authors: Division of Nutritional Sciences, Cornell University, Ithaca, NY, USA.
authors: Patricia A
authors: PA
authors: Cassano
authors: Arizona Cancer Center, University of Arizona, Phoenix, AZ, USA.
authors: Peter
authors: P
authors: Lance
authors: Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH, USA.
authors: Eric A
authors: EA
authors: Klein
authors: SWOG Statistical Center, Cancer Research and Biostatistics, Seattle, WA, USA.
authors: John J
authors: JJ
authors: Crowley
authors: Division of Cancer Prevention, National Cancer Institute, Bethesda, MD, USA.
authors: Lori M
authors: LM
authors: Minasian
authors: University of California at Irvine, Orange, CA, USA.
authors: Frank L
authors: FL
authors: Meyskens
mesh_terms: D000368:Aged; D016588:Anticarcinogenic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D000975:Antioxidants / Q000008:administration & dosage* / Q000009:adverse effects; D016208:Databases, Factual; D004311:Double-Blind Method; D023381:Endpoint Determination; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000209:etiology / Q000517:prevention & control*; D012107:Research Design; D012189:Retrospective Studies; D012307:Risk Factors; D012643:Selenium / Q000008:administration & dosage* / Q000009:adverse effects; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States; D014810:Vitamin E / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D016588:Anticarcinogenic Agents; D000975:Antioxidants; D014810:Vitamin E; D012643:Selenium
keywords: Ancillary studies; Prostate cancer; Randomized controlled trial; Study implementation