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Exaggeration of PFS by blinded, independent, central review (BICR)
- Source :
- Stone, A, Gebski, V, Davidson, R, Bloomfield, R, Bartlett, J W & Sabin, A 2019, ' Exaggeration of PFS by blinded, independent, central review (BICR) ', Annals of Oncology, vol. 30, no. 2, mdy514, pp. 332-338 . https://doi.org/10.1093/annonc/mdy514
- Publication Year :
- 2019
-
Abstract
- Background Recent published studies have shown meaningful discrepancies between local investigator and blinded, independent, central review (BICR) assessed median progression-free survival (PFS). When the local review but not BICR shows progression, generally, no further assessments are carried out and patients are censored in the BICR analysis, leading to violation of the statistical assumptions of independence between censoring and outcome used in survival analysis methods. Methods We carried out a simulation study to assess methodological reasons behind these discrepancies and corroborated our findings in a case study of three BRCA-mutated ovarian cancer trials. We briefly outline possible methodological solutions that may lead to improved estimation of the BICR medians. Results The Kaplan–Meier (KM) curve for the BICR PFS can often be exaggerated. The degree of bias is largest when there is reasonably strong correlation between BICR and local PFS, especially when PFS is long compared with assessment frequency. This can result in an exaggeration of the medians and their difference; however, the hazard ratio (HR) is much less susceptible to bias. Our simulation shows that when the true BICR median PFS was 19 months, and patients assessed every 12 weeks, the estimated KM curves were materially biased whenever the correlation between BICR and local PFS was 0.4 or greater. This was corroborated by case studies where, in the active arm, the BICR median PFS was between 6 and 11 months greater than the local median PFS. Further research is required to find improved methods for estimating BICR survival curves. Conclusions In general, when there is a difference between local and BICR medians, the true BICR KM curve is likely to be exaggerated and its true median will probably lie somewhere between the observed local and BICR medians. Presentation of data should always include both BICR and local results whenever a BICR is carried out.
- Subjects :
- 0301 basic medicine
Oncology
medicine.medical_specialty
Poly(ADP-ribose) Polymerase Inhibitors
Informative censoring
03 medical and health sciences
0302 clinical medicine
SDG 3 - Good Health and Well-being
Internal medicine
medicine
Humans
Computer Simulation
Single-Blind Method
Survival analysis
Ovarian Neoplasms
business.industry
BRCA1 Protein
Hazard ratio
Kaplan-meier
Progression-free survival
Hematology
Parp inhibitors
Progression-Free Survival
Bicr
Survival Rate
030104 developmental biology
030220 oncology & carcinogenesis
Censoring (clinical trials)
Mutation
Disease Progression
Female
business
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Stone, A, Gebski, V, Davidson, R, Bloomfield, R, Bartlett, J W & Sabin, A 2019, ' Exaggeration of PFS by blinded, independent, central review (BICR) ', Annals of Oncology, vol. 30, no. 2, mdy514, pp. 332-338 . https://doi.org/10.1093/annonc/mdy514
- Accession number :
- edsair.doi.dedup.....881896ea17c9b1bbefe82f98ec6b3558