title: The impact of PLCO control arm contamination on perceived PSA screening efficacy.
abstract: OBJECTIVE
  To quantify the extent to which a clinically significant prostate cancer mortality reduction due to screening could have been masked by control arm screening (contamination) in the Prostate, Lung, Colorectal, and Ovarian (PLCO) trial.
  
  
  METHODS
  We used three independently developed models of prostate cancer natural history to conduct a virtual PLCO trial. Simulated participants underwent pre-trial screening based on population patterns. The intervention arm followed observed compliance during the trial then resumed population screening. A contaminated control arm followed observed contamination during the trial then resumed population screening, while an uncontaminated control arm discontinued screening upon entry. We assumed a clinically significant screening benefit, applied population treatments and survival patterns, and calculated mortality rate ratios relative to the contaminated and uncontaminated control arms.
  
  
  RESULTS
  The virtual trial reproduced observed incidence, including stage and grade distributions, and control arm mortality after 10 years of complete follow-up. Under the assumed screening benefit, the three models found that contamination increased the mortality rate ratio from 0.68-0.77 to 0.86-0.91, increased the chance of excess mortality in the intervention arm from 0-4 % to 15-28 %, and decreased the power of the trial to detect a mortality difference from 40-70 % to 9-25 %.
  
  
  CONCLUSIONS
  Our computer simulation models indicate that contamination substantially limited the ability of the PLCO to identify a clinically significant screening benefit. While the trial shows annual screening does not reduce mortality relative to population screening, contamination prevents concluding whether screening reduces mortality relative to no screening.
authors.affiliation: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N., Seattle, WA 98109-1024, USA. rgulati@fhcrc.org
authors.forename: Roman
authors.initials: R
authors.lastname: Gulati
authors.forename: Alex
authors.initials: A
authors.lastname: Tsodikov
authors.forename: Elisabeth M
authors.initials: EM
authors.lastname: Wever
authors.forename: Angela B
authors.initials: AB
authors.lastname: Mariotto
authors.forename: Eveline A M
authors.initials: EA
authors.lastname: Heijnsdijk
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Katcher
authors.forename: Harry J
authors.initials: HJ
authors.lastname: de Koning
authors.forename: Ruth
authors.initials: R
authors.lastname: Etzioni
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000401:mortality; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis / Q000401:mortality; D008297:Male; D008403:Mass Screening; D008875:Middle Aged; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000175:diagnosis / Q000401:mortality; D017430:Prostate-Specific Antigen / Q000032:analysis*; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000401:mortality*; D018426:SEER Program; D014481:United States / Q000453:epidemiology
chemical_list: D017430:Prostate-Specific Antigen