Informative censoring — a neglected cause of bias in oncology trials

Informative censoring occurs when progression-free survival is the primary end point of a randomized clinical trial and unequal patient dropout is observed between treatment arms owing to poorer tolerance of experimental treatment. Herein we discuss how informative censoring in the experimental arm before criteria for disease progression are met causes bias towards a positive result.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1.

    Ranganathan, P. & Pramesh, C. S. Censoring in survival analysis: potential for bias. Perspect. Clin. Res. 3, 40 (2012).

  2. 2.

    Stone, A. M. et al. Research outcomes and recommendations for the assessment of progression in cancer clinical trials from a PhRMA working group. Eur. J. Cancer 47, 1763–1771 (2011).

  3. 3.

    Fleming, T. R., Rothmann, M. D. & Lu, H. L. Issues in using progression-free survival when evaluating oncology products. J. Clin. Oncol. 27, 2874–2880 (2009).

  4. 4.

    Shih, W. Problems in dealing with missing data and informative censoring in clinical trials. Curr. Control Trials Cardiovasc. Med. 3, 4 (2002).

  5. 5.

    Baselga, J. et al. Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer. N. Engl. J. Med. 366, 520–529 (2012).

  6. 6.

    Piccart, M. et al. Everolimus plus exemestane for hormone-receptor-positive, human epidermal growth factor receptor-2-negative advanced breast cancer: overall survival results from BOLERO-2. Ann. Oncol. 25, 2357–2362 (2014).

  7. 7.

    Templeton, A. J. et al. Influence of censoring on conclusions of trials for women with metastatic breast cancer. Eur. J. Cancer 51, 721–724 (2015).

  8. 8.

    Sun, J. The Statistical Analysis of Interval-Censored Failure Time Data: Statistics for Biology and Health. (Springer, 2006).

  9. 9.

    Sparano, J. A. et al. Adjuvant chemotherapy guided by a 21-gene expression assay in breast cancer. N. Engl. J. Med. 379, 111–121 (2018).

  10. 10.

    Ethier, J.L. et al. Influence of competing risks of death on the interpretation of adjuvant endocrine therapy trials for breast cancer. Cancer Res. 79, Abstract P4-14-03 (2019).

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to Ian F. Tannock.

Ethics declarations

Competing interests

The authors declare no competing interests.

Supplementary Information

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Templeton, A.J., Amir, E. & Tannock, I.F. Informative censoring — a neglected cause of bias in oncology trials. Nat Rev Clin Oncol 17, 327–328 (2020). https://doi.org/10.1038/s41571-020-0368-0

Download citation