title: Correcting the Results of the Wrong Model: Treatment Effects under Early Detection of Cancer.
abstract: Early detection of cancer leads to variability of the point of diagnosis advanced by the amount of the so-called lead time, a random variable. Estimated treatment effects by the proportional hazards (PH) model may be biased if this variability is ignored. We study how true and PH-estimated treatment effects differ in screened vs. unscreened populations and offer an approximate correction for the reported PH-based estimate that does not require raw data, targeting a meta-analysis-type application. We rely on a joint cancer incidence and survival model of prostate cancer to furnish key information for the correction. The procedure is applied to a series of prostate cancer data analyses using the PH models reported in the literature. Simulations are used for assessing the quality of the method and sensitivity analyses.
authors.affiliation: Millennium Pharmaceuticals, 35 Landsdowne Street, Cambridge, MA 02139. Connie.Lee@MPI.com.
authors.forename: Shih-Yuan
authors.initials: SY
authors.lastname: Lee
authors.forename: Alex
authors.initials: A
authors.lastname: Tsodikov
keywords: Bias; Early detection; Lead time; Misspecified model; Proportional hazards
references.citation: Urology. 2006 Dec;68(6):1268-74
references.pmid: 17169648
references.citation: Stat Med. 2006 Aug 30;25(16):2846-66
references.pmid: 16397859
references.citation: J R Stat Soc Series B Stat Methodol. 2003 Aug 1;65(3):759-774
references.pmid: 21127741
references.citation: N Engl J Med. 2005 May 12;352(19):1977-84
references.pmid: 15888698
references.citation: Biometrics. 1984 Dec;40(4):1037-48
references.pmid: 6534407
references.citation: Cancer Causes Control. 2008 Mar;19(2):175-81
references.pmid: 18027095
references.citation: Cancer. 2007 May 1;109(9):1877-86
references.pmid: 17372918
references.citation: Stat Med. 1987 Oct-Nov;6(7):773-84
references.pmid: 3423500
references.citation: J Urol. 2007 Mar;177(3):932-6
references.pmid: 17296379