Calibration of quality-adjusted life years for oncology clinical trials

Jeff A Sloan, Daniel J. Sargent, Paul J. Novotny, Paul A. Decker, Randolph Stuart Marks, Heidi Nelson

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Context Quality-adjusted life year (QALY) estimation is a well-known but little used technique to compare survival adjusted for complications. Lack of calibration and interpretation guidance hinders implementation of QALY analyses. Objectives We conducted simulation studies to assess the impact of differences in survival, toxicity rates, and utility values on QALY results. Methods Survival comparisons used both log-rank and Wilcoxon testing. We examined power considerations for a North Central Cancer Treatment Group Phase III lung cancer clinical trial (89-20-52). Results Sample sizes of 100 events per treatment have low power to generate a statistically significant difference in QALYs unless the toxicity rate is 44% higher in one arm. For sample sizes of 200 per arm and equal survival times, toxicity needs to be at least 38% more in one arm for the result to be statistically significant, using a utility of 0.3 for days with toxicity. Sample sizes of 300 (500)/arm provide 80% power if there is a 31% (25%) toxicity difference. If the overall survival hazard ratio between the two treatment arms is 1.25, then samples of at least 150 patients and 13% increased toxicity are necessary to have 80% power to detect QALY differences. In study 89-20-52, there was only 56% power to determine the statistical significance of the observed QALY differences, clarifying the enigmatic conclusion of no statistically significant difference in QALY despite an observed 14.5% increase in toxicity between treatments. Conclusion This calibration allows researchers to interpret the clinical significance of QALY analyses and facilitates QALY inclusion in clinical trials through improved study design.

Original languageEnglish (US)
JournalJournal of Pain and Symptom Management
Volume47
Issue number6
DOIs
StatePublished - 2014

Fingerprint

Quality-Adjusted Life Years
Calibration
Clinical Trials
Sample Size
Survival
Therapeutics
Lung Neoplasms
Survival Rate
Research Personnel

Keywords

  • Q-TWiST
  • QALY
  • QOL
  • quality of life
  • quality-adjusted life year
  • simulation

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine
  • Clinical Neurology
  • Nursing(all)

Cite this

Calibration of quality-adjusted life years for oncology clinical trials. / Sloan, Jeff A; Sargent, Daniel J.; Novotny, Paul J.; Decker, Paul A.; Marks, Randolph Stuart; Nelson, Heidi.

In: Journal of Pain and Symptom Management, Vol. 47, No. 6, 2014.

Research output: Contribution to journalArticle

@article{089adba344014b9d9e8405d360ad5f35,
title = "Calibration of quality-adjusted life years for oncology clinical trials",
abstract = "Context Quality-adjusted life year (QALY) estimation is a well-known but little used technique to compare survival adjusted for complications. Lack of calibration and interpretation guidance hinders implementation of QALY analyses. Objectives We conducted simulation studies to assess the impact of differences in survival, toxicity rates, and utility values on QALY results. Methods Survival comparisons used both log-rank and Wilcoxon testing. We examined power considerations for a North Central Cancer Treatment Group Phase III lung cancer clinical trial (89-20-52). Results Sample sizes of 100 events per treatment have low power to generate a statistically significant difference in QALYs unless the toxicity rate is 44{\%} higher in one arm. For sample sizes of 200 per arm and equal survival times, toxicity needs to be at least 38{\%} more in one arm for the result to be statistically significant, using a utility of 0.3 for days with toxicity. Sample sizes of 300 (500)/arm provide 80{\%} power if there is a 31{\%} (25{\%}) toxicity difference. If the overall survival hazard ratio between the two treatment arms is 1.25, then samples of at least 150 patients and 13{\%} increased toxicity are necessary to have 80{\%} power to detect QALY differences. In study 89-20-52, there was only 56{\%} power to determine the statistical significance of the observed QALY differences, clarifying the enigmatic conclusion of no statistically significant difference in QALY despite an observed 14.5{\%} increase in toxicity between treatments. Conclusion This calibration allows researchers to interpret the clinical significance of QALY analyses and facilitates QALY inclusion in clinical trials through improved study design.",
keywords = "Q-TWiST, QALY, QOL, quality of life, quality-adjusted life year, simulation",
author = "Sloan, {Jeff A} and Sargent, {Daniel J.} and Novotny, {Paul J.} and Decker, {Paul A.} and Marks, {Randolph Stuart} and Heidi Nelson",
year = "2014",
doi = "10.1016/j.jpainsymman.2013.07.016",
language = "English (US)",
volume = "47",
journal = "Journal of Pain and Symptom Management",
issn = "0885-3924",
publisher = "Elsevier Inc.",
number = "6",

}

TY - JOUR

T1 - Calibration of quality-adjusted life years for oncology clinical trials

AU - Sloan, Jeff A

AU - Sargent, Daniel J.

AU - Novotny, Paul J.

AU - Decker, Paul A.

AU - Marks, Randolph Stuart

AU - Nelson, Heidi

PY - 2014

Y1 - 2014

N2 - Context Quality-adjusted life year (QALY) estimation is a well-known but little used technique to compare survival adjusted for complications. Lack of calibration and interpretation guidance hinders implementation of QALY analyses. Objectives We conducted simulation studies to assess the impact of differences in survival, toxicity rates, and utility values on QALY results. Methods Survival comparisons used both log-rank and Wilcoxon testing. We examined power considerations for a North Central Cancer Treatment Group Phase III lung cancer clinical trial (89-20-52). Results Sample sizes of 100 events per treatment have low power to generate a statistically significant difference in QALYs unless the toxicity rate is 44% higher in one arm. For sample sizes of 200 per arm and equal survival times, toxicity needs to be at least 38% more in one arm for the result to be statistically significant, using a utility of 0.3 for days with toxicity. Sample sizes of 300 (500)/arm provide 80% power if there is a 31% (25%) toxicity difference. If the overall survival hazard ratio between the two treatment arms is 1.25, then samples of at least 150 patients and 13% increased toxicity are necessary to have 80% power to detect QALY differences. In study 89-20-52, there was only 56% power to determine the statistical significance of the observed QALY differences, clarifying the enigmatic conclusion of no statistically significant difference in QALY despite an observed 14.5% increase in toxicity between treatments. Conclusion This calibration allows researchers to interpret the clinical significance of QALY analyses and facilitates QALY inclusion in clinical trials through improved study design.

AB - Context Quality-adjusted life year (QALY) estimation is a well-known but little used technique to compare survival adjusted for complications. Lack of calibration and interpretation guidance hinders implementation of QALY analyses. Objectives We conducted simulation studies to assess the impact of differences in survival, toxicity rates, and utility values on QALY results. Methods Survival comparisons used both log-rank and Wilcoxon testing. We examined power considerations for a North Central Cancer Treatment Group Phase III lung cancer clinical trial (89-20-52). Results Sample sizes of 100 events per treatment have low power to generate a statistically significant difference in QALYs unless the toxicity rate is 44% higher in one arm. For sample sizes of 200 per arm and equal survival times, toxicity needs to be at least 38% more in one arm for the result to be statistically significant, using a utility of 0.3 for days with toxicity. Sample sizes of 300 (500)/arm provide 80% power if there is a 31% (25%) toxicity difference. If the overall survival hazard ratio between the two treatment arms is 1.25, then samples of at least 150 patients and 13% increased toxicity are necessary to have 80% power to detect QALY differences. In study 89-20-52, there was only 56% power to determine the statistical significance of the observed QALY differences, clarifying the enigmatic conclusion of no statistically significant difference in QALY despite an observed 14.5% increase in toxicity between treatments. Conclusion This calibration allows researchers to interpret the clinical significance of QALY analyses and facilitates QALY inclusion in clinical trials through improved study design.

KW - Q-TWiST

KW - QALY

KW - QOL

KW - quality of life

KW - quality-adjusted life year

KW - simulation

UR - http://www.scopus.com/inward/record.url?scp=84902463199&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84902463199&partnerID=8YFLogxK

U2 - 10.1016/j.jpainsymman.2013.07.016

DO - 10.1016/j.jpainsymman.2013.07.016

M3 - Article

VL - 47

JO - Journal of Pain and Symptom Management

JF - Journal of Pain and Symptom Management

SN - 0885-3924

IS - 6

ER -