When you look matters: the effect of assessment schedule on progression-free survival.
Progression-free survival (PFS) is increasingly used as an endpoint for cancer clinical trials. Disease progression is typically assessed on the basis of radiologic testing at scheduled time points or after a fixed number of treatment cycles. The date of the radiologic evaluation at which progression is first evident is used as a proxy for the true progression time. The true progression time actually lies somewhere within the time interval between two assessments, a situation that results in interval-censored data. An analysis that ignores this interval censoring and uses the detection date as the date of progression unavoidably results in an overestimation of median PFS. This overestimation can erroneously result in a result being described as clinically significant when in fact a longer median PFS may just be a consequence of the length of the surveillance interval. Furthermore, if surveillance intervals are heterogenous within a disease group, comparisons of median PFS across studies may not be meaningful. The decision to use PFS as a primary endpoint should be made carefully when designing clinical trials, and investigators focused on a particular disease should develop consensus standards and strive for consistent surveillance intervals.
Panageas
Katherine S
KS
Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, 307 East 63rd St, 3rd Fl, New York, NY 10021, USA. panageak@mskcc.org
Ben-Porat
Leah
L
Dickler
Maura N
MN
Chapman
Paul B
PB
Schrag
Deborah
D
D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D000068258:Bevacizumab; D001943:Breast Neoplasms / Q000188:drug therapy / Q000401:mortality*; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D018572:Disease-Free Survival; D000069347:Erlotinib Hydrochloride; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D009369:Neoplasms / Q000401:mortality; D011159:Population Surveillance / Q000379:methods*; D011799:Quinazolines / Q000008:administration & dosage; D012107:Research Design; D018709:Statistics, Nonparametric; D013997:Time Factors
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D011799:Quinazolines; D000068258:Bevacizumab; D000069347:Erlotinib Hydrochloride