Clinical trial design in small cell lung cancer: Surrogate end points and statistical evolution

Myles Nickolich, Shahab Babakoohi, Pingfu Fu, Afshin Dowlati

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Background Small-cell lung cancer (SCLC) is a disease for which few recent therapeutic advances have been achieved. SCLC trial design and reporting may have an impact on the interpretation of studies. Furthermore, the use of surrogate end points in SCLC has not been explored. Material and Methods Through examining SCLC trials published in the Journal of Clinical Oncology (JCO) (8471 patients from 66 trials between 1983 and 2010), we examined how SCLC trial reporting and design has evolved, determining if the type I error, power, and sample size calculations were provided. We assessed primary end points for all trials and sought to discover surrogate end points for overall survival (OS). Results There was increased reporting of statistical design in power (16.7% in 1986-1996 to 77.8% in 2006-2010; P =.001) and type I error (22.2% in 1986-1996 to 72.2% in 2006-2010; P =.005). Of trials published in 1986 to 1996, 72.2% failed to report a primary end point, whereas only 5.56% of trials conducted in 2006 to 2010 failed to do so (P =.004). Of phase II trials, primary end points were identified as response rate (RR) in 65%, OS in 25%, and progression-free survival (PFS) in 10%. Conclusion There is a strong correlation between RR and both PFS (P =.013) and OS (P =.012) in extensive disease (ED). RR (P =.029) exhibits a negative trend over time, with a dramatic and significant decrease in RR across all studies starting in 2005. A strong correlation exists between PFS and OS for limited disease (LD) (P =.036) and ED (P =.058). We found no change in OS (P =.383) over time.

Original languageEnglish (US)
Pages (from-to)207-212
Number of pages6
JournalClinical Lung Cancer
Volume15
Issue number3
DOIs
StatePublished - Jan 1 2014

Fingerprint

Small Cell Lung Carcinoma
Biomarkers
Clinical Trials
Survival
Disease-Free Survival
Medical Oncology
Sample Size

All Science Journal Classification (ASJC) codes

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research

Cite this

Nickolich, Myles ; Babakoohi, Shahab ; Fu, Pingfu ; Dowlati, Afshin. / Clinical trial design in small cell lung cancer : Surrogate end points and statistical evolution. In: Clinical Lung Cancer. 2014 ; Vol. 15, No. 3. pp. 207-212.
@article{8f601500334f4cbe90adbad2ce9e14eb,
title = "Clinical trial design in small cell lung cancer: Surrogate end points and statistical evolution",
abstract = "Background Small-cell lung cancer (SCLC) is a disease for which few recent therapeutic advances have been achieved. SCLC trial design and reporting may have an impact on the interpretation of studies. Furthermore, the use of surrogate end points in SCLC has not been explored. Material and Methods Through examining SCLC trials published in the Journal of Clinical Oncology (JCO) (8471 patients from 66 trials between 1983 and 2010), we examined how SCLC trial reporting and design has evolved, determining if the type I error, power, and sample size calculations were provided. We assessed primary end points for all trials and sought to discover surrogate end points for overall survival (OS). Results There was increased reporting of statistical design in power (16.7{\%} in 1986-1996 to 77.8{\%} in 2006-2010; P =.001) and type I error (22.2{\%} in 1986-1996 to 72.2{\%} in 2006-2010; P =.005). Of trials published in 1986 to 1996, 72.2{\%} failed to report a primary end point, whereas only 5.56{\%} of trials conducted in 2006 to 2010 failed to do so (P =.004). Of phase II trials, primary end points were identified as response rate (RR) in 65{\%}, OS in 25{\%}, and progression-free survival (PFS) in 10{\%}. Conclusion There is a strong correlation between RR and both PFS (P =.013) and OS (P =.012) in extensive disease (ED). RR (P =.029) exhibits a negative trend over time, with a dramatic and significant decrease in RR across all studies starting in 2005. A strong correlation exists between PFS and OS for limited disease (LD) (P =.036) and ED (P =.058). We found no change in OS (P =.383) over time.",
author = "Myles Nickolich and Shahab Babakoohi and Pingfu Fu and Afshin Dowlati",
year = "2014",
month = "1",
day = "1",
doi = "10.1016/j.cllc.2013.12.001",
language = "English (US)",
volume = "15",
pages = "207--212",
journal = "Clinical Lung Cancer",
issn = "1525-7304",
publisher = "Elsevier",
number = "3",

}

Clinical trial design in small cell lung cancer : Surrogate end points and statistical evolution. / Nickolich, Myles; Babakoohi, Shahab; Fu, Pingfu; Dowlati, Afshin.

In: Clinical Lung Cancer, Vol. 15, No. 3, 01.01.2014, p. 207-212.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Clinical trial design in small cell lung cancer

T2 - Surrogate end points and statistical evolution

AU - Nickolich, Myles

AU - Babakoohi, Shahab

AU - Fu, Pingfu

AU - Dowlati, Afshin

PY - 2014/1/1

Y1 - 2014/1/1

N2 - Background Small-cell lung cancer (SCLC) is a disease for which few recent therapeutic advances have been achieved. SCLC trial design and reporting may have an impact on the interpretation of studies. Furthermore, the use of surrogate end points in SCLC has not been explored. Material and Methods Through examining SCLC trials published in the Journal of Clinical Oncology (JCO) (8471 patients from 66 trials between 1983 and 2010), we examined how SCLC trial reporting and design has evolved, determining if the type I error, power, and sample size calculations were provided. We assessed primary end points for all trials and sought to discover surrogate end points for overall survival (OS). Results There was increased reporting of statistical design in power (16.7% in 1986-1996 to 77.8% in 2006-2010; P =.001) and type I error (22.2% in 1986-1996 to 72.2% in 2006-2010; P =.005). Of trials published in 1986 to 1996, 72.2% failed to report a primary end point, whereas only 5.56% of trials conducted in 2006 to 2010 failed to do so (P =.004). Of phase II trials, primary end points were identified as response rate (RR) in 65%, OS in 25%, and progression-free survival (PFS) in 10%. Conclusion There is a strong correlation between RR and both PFS (P =.013) and OS (P =.012) in extensive disease (ED). RR (P =.029) exhibits a negative trend over time, with a dramatic and significant decrease in RR across all studies starting in 2005. A strong correlation exists between PFS and OS for limited disease (LD) (P =.036) and ED (P =.058). We found no change in OS (P =.383) over time.

AB - Background Small-cell lung cancer (SCLC) is a disease for which few recent therapeutic advances have been achieved. SCLC trial design and reporting may have an impact on the interpretation of studies. Furthermore, the use of surrogate end points in SCLC has not been explored. Material and Methods Through examining SCLC trials published in the Journal of Clinical Oncology (JCO) (8471 patients from 66 trials between 1983 and 2010), we examined how SCLC trial reporting and design has evolved, determining if the type I error, power, and sample size calculations were provided. We assessed primary end points for all trials and sought to discover surrogate end points for overall survival (OS). Results There was increased reporting of statistical design in power (16.7% in 1986-1996 to 77.8% in 2006-2010; P =.001) and type I error (22.2% in 1986-1996 to 72.2% in 2006-2010; P =.005). Of trials published in 1986 to 1996, 72.2% failed to report a primary end point, whereas only 5.56% of trials conducted in 2006 to 2010 failed to do so (P =.004). Of phase II trials, primary end points were identified as response rate (RR) in 65%, OS in 25%, and progression-free survival (PFS) in 10%. Conclusion There is a strong correlation between RR and both PFS (P =.013) and OS (P =.012) in extensive disease (ED). RR (P =.029) exhibits a negative trend over time, with a dramatic and significant decrease in RR across all studies starting in 2005. A strong correlation exists between PFS and OS for limited disease (LD) (P =.036) and ED (P =.058). We found no change in OS (P =.383) over time.

UR - http://www.scopus.com/inward/record.url?scp=84898014665&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84898014665&partnerID=8YFLogxK

U2 - 10.1016/j.cllc.2013.12.001

DO - 10.1016/j.cllc.2013.12.001

M3 - Article

C2 - 24485231

AN - SCOPUS:84898014665

VL - 15

SP - 207

EP - 212

JO - Clinical Lung Cancer

JF - Clinical Lung Cancer

SN - 1525-7304

IS - 3

ER -