This Article  • Full text  • PDF  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on ISI (133)  • Contact me when this article is cited  Related Content  • Similar articles in JAMA  Topic Collections  • Drug Therapy, Other  • Statistics and Research Methods  • Conflict of Interest  • Randomized Controlled Trial  • Adverse Effects  • Alert me on articles by topic

A Reflection of Treatment Effect or Adverse Events?

Bodil Als-Nielsen, MD; Wendong Chen, MD; Christian Gluud, MD, DMSc; Lise L. Kjaergard, MD

JAMA. 2003;290:921-928.

Context  Previous studies indicate that industry-sponsored trials tend to draw proindustry conclusions.

Objective  To explore whether the association between funding and conclusions in randomized drug trials reflects treatment effects or adverse events.

Design  Observational study of 370 randomized drug trials included in meta-analyses from Cochrane reviews selected from the Cochrane Library, May 2001. From a random sample of 167 Cochrane reviews, 25 contained eligible meta-analyses (assessed a binary outcome; pooled at least 5 full-paper trials of which at least 1 reported adequate and 1 reported inadequate allocation concealment). The primary binary outcome from each meta-analysis was considered the primary outcome for all trials included in each meta-analysis. The association between funding and conclusions was analyzed by logistic regression with adjustment for treatment effect, adverse events, and additional confounding factors (methodological quality, control intervention, sample size, publication year, and place of publication).

Main Outcome Measure  Conclusions in trials, classified into whether the experimental drug was recommended as the treatment of choice or not.

Results  The experimental drug was recommended as treatment of choice in 16% of trials funded by nonprofit organizations, 30% of trials not reporting funding, 35% of trials funded by both nonprofit and for-profit organizations, and 51% of trials funded by for-profit organizations (P<.001; ² test). Logistic regression analyses indicated that funding, treatment effect, and double blinding were the only significant predictors of conclusions. Adjusted analyses showed that trials funded by for-profit organizations were significantly more likely to recommend the experimental drug as treatment of choice (odds ratio, 5.3; 95% confidence interval, 2.0-14.4) compared with trials funded by nonprofit organizations. This association did not appear to reflect treatment effect or adverse events.

Conclusions  Conclusions in trials funded by for-profit organizations may be more positive due to biased interpretation of trial results. Readers should carefully evaluate whether conclusions in randomized trials are supported by data.

Author Affiliations: The Copenhagen Trial Unit, Center for Clinical Intervention Research, Copenhagen University Hospital, Copenhagen, Denmark.

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Treatment Success in Cancer: New Cancer Treatment Successes Identified in Phase 3 Randomized Controlled Trials Conducted by the National Cancer Institute-Sponsored Cooperative Oncology Groups, 1955 to 2006
Djulbegovic et al.
Arch Intern Med 2008;168:632-642.
ABSTRACT | FULL TEXT  

An Ethical View of the Ranibizumab and Bevacizumab Controversy
Packer and Jampol
Arch Ophthalmol 2008;126:286-286.
FULL TEXT  

Financial ties and concordance between results and conclusions in meta-analyses: retrospective cohort study
Yank et al.
BMJ 2007;335:1202-1205.
ABSTRACT | FULL TEXT  

State of the Evidence on Acute Asthma Management in Children: A Critical Appraisal of Systematic Reviews
Boluyt et al.
Pediatrics 2007;120:1334-1343.
ABSTRACT | FULL TEXT  

First-Line Chemotherapy for HER-2 Negative Metastatic Breast Cancer Patients Who Received Anthracyclines as Adjuvant Treatment
Morabito et al.
The Oncologist 2007;12:1288-1298.
ABSTRACT | FULL TEXT  

Strengthening the Reporting of Observational Studies in Epidemiology (STROBE): Explanation and Elaboration
Vandenbroucke et al.
ANN INTERN MED 2007;147:W-163-W-194.
ABSTRACT | FULL TEXT  

Disclosure of Conflicts of Interest by Authors of Clinical Trials and Editorials in Oncology
Riechelmann et al.
JCO 2007;25:4642-4647.
ABSTRACT | FULL TEXT  

Association Between Funding and Quality of Published Medical Education Research
Reed et al.
JAMA 2007;298:1002-1009.
ABSTRACT | FULL TEXT  

Attitudes Toward Research Participation and Investigator Conflicts of Interest Among Advanced Cancer Patients Participating in Early Phase Clinical Trials
Gray et al.
JCO 2007;25:3488-3494.
ABSTRACT | FULL TEXT  

Quality of Prospective Controlled Randomized Trials. Analysis of Trials of Treatment for Lateral Epicondylitis as an Example
Cowan et al.
JBJS 2007;89:1693-1699.
ABSTRACT | FULL TEXT  

Measurement of long-term outcomes in observational and randomised controlled trials
Hodgson et al.
Br. J. Psychiatry 2007;191:s78-s84.
ABSTRACT | FULL TEXT  

Blinded trials taken to the test: an analysis of randomized clinical trials that report tests for the success of blinding
Hrobjartsson et al.
Int J Epidemiol 2007;36:654-663.
ABSTRACT | FULL TEXT  

Use and Perceptions of Clinical Practice Guidelines by Internal Medicine Physicians
Shea et al.
American Journal of Medical Quality 2007;22:170-176.
ABSTRACT  

Publication bias in the medical literature: a review by a Canadian Research Ethics Board: [Biais de publication dans la litterature medicale : un compte rendu d'un Comite d'ethique de recherche canadien]
Hall et al.
Canadian J. Anesthesia 2007;54:380-388.
ABSTRACT | FULL TEXT  

Commercially Funded and United States-Based Research Is More Likely to Be Published; Good-Quality Studies with Negative Outcomes Are Not
Lynch et al.
JBJS 2007;89:1010-1018.
ABSTRACT | FULL TEXT  

Conflict of Interest in Orthopaedic Research. An Association Between Findings and Funding in Scientific Presentations
Okike et al.
JBJS 2007;89:608-613.
ABSTRACT | FULL TEXT  

Opprobrium or opportunity?
Glick
Journal of the American Dental Association 2006;137:1484-1486.
FULL TEXT  

Comparative effectiveness of second-generation antipsychotics and haloperidol in acute schizophrenia
McCUE et al.
Br. J. Psychiatry 2006;189:433-440.
ABSTRACT | FULL TEXT  

Cochrane reviews compared with industry supported meta-analyses and other meta-analyses of the same drugs: systematic review
Jorgensen et al.
BMJ 2006;333:782.
ABSTRACT | FULL TEXT  

Comparative Effectiveness of Antipsychotic Drugs: A Commentary on Cost Utility of the Latest Antipsychotic Drugs in Schizophrenia Study (CUtLASS 1) and Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE).
Lieberman
Arch Gen Psychiatry 2006;63:1069-1072.
FULL TEXT  

A piece of my mind. Swan's way.
Blank
JAMA 2006;296:1041-1042.
FULL TEXT  

Symposium. Relationships with Industry: Critical for New Technology or an Unnecessary Evil?
Jacobs et al.
JBJS 2006;88:1650-1663.
FULL TEXT  

Reported outcomes in major cardiovascular clinical trials funded by for-profit and not-for-profit organizations: 2000-2005.
Ridker and Torres
JAMA 2006;295:2270-2274.
ABSTRACT | FULL TEXT  

Bias in Clinical Intervention Research
Gluud
Am J Epidemiol 2006;163:493-501.
ABSTRACT | FULL TEXT  

Lessons From and Cautions About Noninferiority and Equivalence Randomized Trials
Gotzsche
JAMA 2006;295:1172-1174.
FULL TEXT  

Why Olanzapine Beats Risperidone, Risperidone Beats Quetiapine, and Quetiapine Beats Olanzapine: An Exploratory Analysis of Head-to-Head Comparison Studies of Second-Generation Antipsychotics
Heres et al.
Am. J. Psychiatry 2006;163:185-194.
ABSTRACT | FULL TEXT  

Pharmacists' perceptions of the pharmaceutical industry
Farthing-Papineau and Peak
Am J Health Syst Pharm 2005;62:2401-2409.
FULL TEXT  

Mortality from cirrhosis: lack of progress over the last 35 years
Gluud
Gut 2005;54:1523-1526.
FULL TEXT  

Selling Sickness: How the World's Pharmaceutical Companies Are Turning Us All Into Patients; Selling Sickness
Yom
JAMA 2005;294:1114-1116.
FULL TEXT  

The Effect of Conflict of Interest on Biomedical Research and Clinical Practice Guidelines: Can We Trust the Evidence in Evidence-Based Medicine?
Abramson and Starfield
J Am Board Fam Med 2005;18:414-418.
FULL TEXT  

When Health Policy Is the Problem: A Report from the Field
Spitz and Abramson
Journal of Health Politics, Policy and Law 2005;30:327-366.
ABSTRACT  

Evaluation of New Treatments in Radiation Oncology: Are They Better Than Standard Treatments?
Soares et al.
JAMA 2005;293:970-978.
ABSTRACT | FULL TEXT  

Selective serotonin reuptake inhibitors (SSRIs) and suicide in adults: meta-analysis of drug company data from placebo controlled, randomised controlled trials submitted to the MHRA's safety review
Gunnell et al.
BMJ 2005;330:385.
ABSTRACT | FULL TEXT  

The availability of references and the sponsorship of original research cited in pharmaceutical advertisements
Cooper and Schriger
CMAJ 2005;172:487-491.
ABSTRACT | FULL TEXT  

Comparing estimates of cost effectiveness submitted to the National Institute for Clinical Excellence (NICE) by different organisations: retrospective study
Miners et al.
BMJ 2005;330:65.
ABSTRACT | FULL TEXT  

Implications of Pharmaceutical Industry Funding on Clinical Research
Lexchin
The Annals of Pharmacotherapy 2005;39:194-197.
ABSTRACT | FULL TEXT  

The Ethical Conduct of Clinical Research Involving Critically Ill Patients in the United States and Canada: Principles and Recommendations
Am. J. Respir. Crit. Care Med. 2004;170:1375-1384.
FULL TEXT  

Users' guide to detecting misleading claims in clinical research reports
Montori et al.
BMJ 2004;329:1093-1096.
FULL TEXT  

Antidepressants and suicide: what is the balance of benefit and harm
Gunnell and Ashby
BMJ 2004;329:34-38.
FULL TEXT  

Satisfaction of the uncertainty principle in cancer clinical trials: retrospective cohort analysis
Joffe et al.
BMJ 2004;328:1463.
ABSTRACT | FULL TEXT  

Randomized clinical trials: What gets published, and when?
Hirsch
CMAJ 2004;170:481-483.
FULL TEXT  

Results of Clinical Trials Sponsored by For-Profit vs Nonprofit Entities
Waldorff
JAMA 2003;290:3071-3071.
FULL TEXT  

Results of Clinical Trials Sponsored by For-Profit vs Nonprofit Entities
Palmer
JAMA 2003;290:3070-3070.
FULL TEXT  

Results of Clinical Trials Sponsored by For-Profit vs Nonprofit Entities
Rosefsky
JAMA 2003;290:3070-3071.
FULL TEXT  

ABSTRACTS
Obstet Gynecol 2003;102:1410-1413.
FULL TEXT  

Pricing Drugs
Graham and Morgan
Health Aff (Millwood) 2003;22:284-285.
FULL TEXT