Quality, Evolution, and Clinical Implications of Randomized, Controlled Trials on the Treatment of Lung Cancer

A Lost Opportunity for Meta-analysis

Antonio Nicolucci, Roberto Grilli, Alessandro A. Alexanian, Giovanni Apolone, Valter Torri, Alessandro Liberati

Research output: Contribution to journalArticle

70 Citations (Scopus)

Abstract

A review of 150 published randomized trials on the treatment of lung cancer showed serious methodological drawbacks. Handling of withdrawals (only 7 trials had no dropouts), a priori estimates of sample size (only 9 trials specified the required number of patients), blinding of randomization (only 22 trials had a satisfactory procedure), and information on eligible nonrandomized patients (only 13 studies reported it precisely) were areas of major concern. Although trial quality improved over time both in design/execution (study size estimation and analysis by prognostic factors became more frequent) and reporting (information on patients’ characteristics and side effects were more thoroughly reported), their evolution was inconsistent. For non—small-cell lung cancer—despite the persistent lack of proof of efficacy of any active treatment—an untreated control arm was prematurely abandoned and a wide variety of tested regimens prevailed even in better-quality studies. Slightly more promising is the picture for small-cell lung cancer, where research indicates somewhat more reliable—though limited—progress. While clinical research in lung cancer has contributed little to defining the best standard care, we conclude that its heterogeneity makes it unlikely that quantitative meta-analysis of existing trials will be constructive.

Original languageEnglish
Pages (from-to)2101-2107
Number of pages7
JournalJournal of the American Medical Association
Volume262
Issue number15
DOIs
Publication statusPublished - Oct 20 1989

Fingerprint

Meta-Analysis
Lung Neoplasms
Randomized Controlled Trials
Small Cell Lung Carcinoma
Random Allocation
Research
Sample Size
Therapeutics
Lung

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Quality, Evolution, and Clinical Implications of Randomized, Controlled Trials on the Treatment of Lung Cancer : A Lost Opportunity for Meta-analysis. / Nicolucci, Antonio; Grilli, Roberto; Alexanian, Alessandro A.; Apolone, Giovanni; Torri, Valter; Liberati, Alessandro.

In: Journal of the American Medical Association, Vol. 262, No. 15, 20.10.1989, p. 2101-2107.

Research output: Contribution to journalArticle

@article{8def0949e412439e8c2a553870de129d,
title = "Quality, Evolution, and Clinical Implications of Randomized, Controlled Trials on the Treatment of Lung Cancer: A Lost Opportunity for Meta-analysis",
abstract = "A review of 150 published randomized trials on the treatment of lung cancer showed serious methodological drawbacks. Handling of withdrawals (only 7 trials had no dropouts), a priori estimates of sample size (only 9 trials specified the required number of patients), blinding of randomization (only 22 trials had a satisfactory procedure), and information on eligible nonrandomized patients (only 13 studies reported it precisely) were areas of major concern. Although trial quality improved over time both in design/execution (study size estimation and analysis by prognostic factors became more frequent) and reporting (information on patients’ characteristics and side effects were more thoroughly reported), their evolution was inconsistent. For non—small-cell lung cancer—despite the persistent lack of proof of efficacy of any active treatment—an untreated control arm was prematurely abandoned and a wide variety of tested regimens prevailed even in better-quality studies. Slightly more promising is the picture for small-cell lung cancer, where research indicates somewhat more reliable—though limited—progress. While clinical research in lung cancer has contributed little to defining the best standard care, we conclude that its heterogeneity makes it unlikely that quantitative meta-analysis of existing trials will be constructive.",
author = "Antonio Nicolucci and Roberto Grilli and Alexanian, {Alessandro A.} and Giovanni Apolone and Valter Torri and Alessandro Liberati",
year = "1989",
month = "10",
day = "20",
doi = "10.1001/jama.1989.03430150069028",
language = "English",
volume = "262",
pages = "2101--2107",
journal = "JAMA - Journal of the American Medical Association",
issn = "0002-9955",
publisher = "American Medical Association",
number = "15",

}

TY - JOUR

T1 - Quality, Evolution, and Clinical Implications of Randomized, Controlled Trials on the Treatment of Lung Cancer

T2 - A Lost Opportunity for Meta-analysis

AU - Nicolucci, Antonio

AU - Grilli, Roberto

AU - Alexanian, Alessandro A.

AU - Apolone, Giovanni

AU - Torri, Valter

AU - Liberati, Alessandro

PY - 1989/10/20

Y1 - 1989/10/20

N2 - A review of 150 published randomized trials on the treatment of lung cancer showed serious methodological drawbacks. Handling of withdrawals (only 7 trials had no dropouts), a priori estimates of sample size (only 9 trials specified the required number of patients), blinding of randomization (only 22 trials had a satisfactory procedure), and information on eligible nonrandomized patients (only 13 studies reported it precisely) were areas of major concern. Although trial quality improved over time both in design/execution (study size estimation and analysis by prognostic factors became more frequent) and reporting (information on patients’ characteristics and side effects were more thoroughly reported), their evolution was inconsistent. For non—small-cell lung cancer—despite the persistent lack of proof of efficacy of any active treatment—an untreated control arm was prematurely abandoned and a wide variety of tested regimens prevailed even in better-quality studies. Slightly more promising is the picture for small-cell lung cancer, where research indicates somewhat more reliable—though limited—progress. While clinical research in lung cancer has contributed little to defining the best standard care, we conclude that its heterogeneity makes it unlikely that quantitative meta-analysis of existing trials will be constructive.

AB - A review of 150 published randomized trials on the treatment of lung cancer showed serious methodological drawbacks. Handling of withdrawals (only 7 trials had no dropouts), a priori estimates of sample size (only 9 trials specified the required number of patients), blinding of randomization (only 22 trials had a satisfactory procedure), and information on eligible nonrandomized patients (only 13 studies reported it precisely) were areas of major concern. Although trial quality improved over time both in design/execution (study size estimation and analysis by prognostic factors became more frequent) and reporting (information on patients’ characteristics and side effects were more thoroughly reported), their evolution was inconsistent. For non—small-cell lung cancer—despite the persistent lack of proof of efficacy of any active treatment—an untreated control arm was prematurely abandoned and a wide variety of tested regimens prevailed even in better-quality studies. Slightly more promising is the picture for small-cell lung cancer, where research indicates somewhat more reliable—though limited—progress. While clinical research in lung cancer has contributed little to defining the best standard care, we conclude that its heterogeneity makes it unlikely that quantitative meta-analysis of existing trials will be constructive.

UR - http://www.scopus.com/inward/record.url?scp=0024332944&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0024332944&partnerID=8YFLogxK

U2 - 10.1001/jama.1989.03430150069028

DO - 10.1001/jama.1989.03430150069028

M3 - Article

VL - 262

SP - 2101

EP - 2107

JO - JAMA - Journal of the American Medical Association

JF - JAMA - Journal of the American Medical Association

SN - 0002-9955

IS - 15

ER -