Combining Survival and Toxicity Effect Sizes from Clinical Trials: NCCTG 89-20-52 (Alliance)

Authors

  • Brittny T. Major-Elechi Division of Biomedical Statistics and Bioinformatics, Mayo Clinic, Rochester, MN 55905, USA
  • Paul J. Novotny Division of Biomedical Statistics and Bioinformatics, Mayo Clinic, Rochester, MN 55905, USA
  • Jasvinder A. Singh Birmingham Veterans Affairs Medical Center, and the Department of Medicine and Epidemiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
  • James A. Bonner Department of Radiation Oncology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
  • Amylou C. Dueck Department of Health Sciences Research, Mayo Clinic, Scottsdale, AZ, USA
  • Daniel J. Sargent Division of Biomedical Statistics and Bioinformatics, Mayo Clinic, Rochester, MN 55905, USA
  • Axel Grothey Department of Medical Oncology, Mayo Clinic, Rochester, MN 55905, USA
  • Jeff A. Sloan Department of Medical Oncology, Mayo Clinic, Rochester, MN 55905, USA

DOI:

https://doi.org/10.6000/1929-6029.2018.07.04.4

Keywords:

Survival, toxicity, quality of life, effect size, quality-adjusted life years, QALY.

Abstract

Background: How can a clinician and patient incorporate survival and toxicity information into a single expression of comparative treatment benefit? Sloan et al. recently extended the ½ standard deviation concept for judging the clinical importance of findings from clinical trials to survival and tumor response endpoints. A new method using this approach to combine survival and toxicity effect sizes from clinical trials into a quality-adjusted effect size is presented.

Methods: The quality-adjusted survival effect size (QASES) is calculated as survival effect size (ESS) minus the calibrated toxicity effect sizes (EST) (QASES=ESS-EST). This combined effect size can be weighted to adjust for the relative emphasis placed by the patient on survival and toxicity effects.

Results: As an example, consider clinical trial NCCTG 89-20-52 which randomized patients to once-daily thoracic radiotherapy (ODTRT) versus twice-daily treatment of thoracic radiotherapy (TDRT) for the treatment of lung cancer. The ODTRT vs. TDRT arms had median survival time of 22 vs. 20 months (p=0.49) and toxicity rate of 39% vs. 54%, (p<0.05). The QASES of 0.18 standard deviations translates to a quality-adjusted survival difference of 5.7 months advantage for the ODRT arm over the TDRT treatment arm (22(16.3) months), p<0.05). Similar results are presented for the four possible case combinations of significant/non-significant survival and toxicity benefits using completed clinical trials.

Conclusions: We used a novel approach to re-analyze clinical trial data to produce a single estimate for each treatment that combines survival and toxicity data. The QASES approach is an intuitive and mathematically simple yet robust approach.

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Published

2018-11-16

How to Cite

Major-Elechi, B. T., Novotny, P. J., Singh, J. A., Bonner, J. A., Dueck, A. C., Sargent, D. J., Grothey, A., & Sloan, J. A. (2018). Combining Survival and Toxicity Effect Sizes from Clinical Trials: NCCTG 89-20-52 (Alliance). International Journal of Statistics in Medical Research, 7(4), 137–146. https://doi.org/10.6000/1929-6029.2018.07.04.4

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General Articles