Industry sponsorship and research outcome

TLDR: The analyses suggest the existence of an industry bias that cannot be explained by standard 'Risk of bias' assessments.

Abstract: Background Clinical research affecting how doctors practice medicine is increasingly sponsored by companies that make drugs and medical devices. Previous systematic reviews have found that pharmaceutical industry sponsored studies are more often favorable to the sponsor’s product compared with studies with other sources of sponsorship. This review is an update using more stringent methodology and also investigating sponsorship of device studies. Objectives To investigate whether industry sponsored drug and device studies have more favorable outcomes and differ in risk of bias, compared with studies having other sources of sponsorship. Search methods We searched MEDLINE (1948 to September 2010), EMBASE (1980 to September 2010), the Cochrane Methodology Register (Issue 4, 2010) and Web of Science (August 2011). In addition, we searched reference lists of included papers, previous systematic reviews and author files. Selection criteria Cross-sectional studies, cohort studies, systematic reviews and meta-analyses that quantitatively compared primary research studies of drugs or medical devices sponsored by industry with studies with other sources of sponsorship. We had no language restrictions. Data collection and analysis Two assessors identified potentially relevant papers, and a decision about final inclusion was made by all authors. Two assessors extracted data, and we contacted authors of included papers for additional unpublished data. Outcomes included favorable results, favorable conclusions, effect size, risk of bias and whether the conclusions agreed with the study results. Two assessors assessed risk of bias of included papers. We calculated pooled risk ratios (RR) for dichotomous data (with 95% confidence intervals). Main results Forty-eight papers were included. Industry sponsored studies more often had favorable efficacy results, risk ratio (RR): 1.32 (95% confidence interval (CI): 1.21 to 1.44), harms results RR: 1.87 (95% CI: 1.54 to 2.27) and conclusions RR: 1.31 (95% CI: 1.20 to 1.44) compared with non-industry sponsored studies. Ten papers reported on sponsorship and effect size, but could not be pooled due to differences in their reporting of data. The results were heterogeneous; five papers found larger effect sizes in industry sponsored studies compared with non-industry sponsored studies and five papers did not find a difference in effect size. Only two papers (including 120 device studies) reported separate data for devices and we did not find a difference between drug and device studies on the association between sponsorship and conclusions (test for interaction, P = 0.23). Comparing industry and non-industry sponsored studies, we did not find a difference in risk of bias from sequence generation, allocation concealment and follow-up. However, industry sponsored studies more often had low risk of bias from blinding, RR: 1.32 (95% CI: 1.05 to 1.65), compared with non-industry sponsored studies. In industry sponsored studies, there was less agreement between the results and the conclusions than in non-industry sponsored studies, RR: 0.84 (95% CI: 0.70 to 1.01). Authors' conclusions Sponsorship of drug and device studies by the manufacturing company leads to more favorable results and conclusions than sponsorship by other sources. Our analyses suggest the existence of an industry bias that cannot be explained by standard 'Risk of bias' assessments.

Figures

Figure 1. Study flow diagram.

Table 1. Effect size in industry and non-industry sponsored studies.

Figure 2. ’Risk of bias’ graph: review authors’ judgements about each risk of bias item presented as percentages across all included papers.

Figure 3. ’Risk of bias’ summary: review authors’ judgements about each risk of bias item for each included paper.

Full text

University of Southern Denmark
Industry sponsorship and research outcome
Lundh, Andreas; Lexchin, Joel; Mintzes, Barbara; Schroll, Jeppe B; Bero, Lisa
Published in:
Cochrane Database of Systematic Reviews
DOI:
10.1002/14651858.MR000033.pub3
Publication date:
2017
Document version:
Final published version
Citation for pulished version (APA):
Lundh, A., Lexchin, J., Mintzes, B., Schroll, J. B., & Bero, L. (2017). Industry sponsorship and research outcome.
Cochrane Database of Systematic Reviews
,
2
(2), [MR000033].
https://doi.org/10.1002/14651858.MR000033.pub3
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Cochrane Database of Systematic Reviews
Industry sponsorship and research outcome (Review)
Lundh A, Lexchin J, Mintzes B, Schroll JB, Bero L
Lundh A, Lexchin J, Mintzes B, Schroll JB, Bero L.
Industry sponsorship and research outcome.
Cochrane Database of Systematic Reviews 2017, Issue 2. Art. No.: MR000033.
DOI: 10.1002/14651858.MR000033.pub3.
www.cochranelibrary.com
Industry sponsorship and research outcome (Review)
Copyright © 2017 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

T A B L E O F C O N T E N T S
1HEADER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2PLAIN LANGUAGE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3SUMMARY OF FINDINGS FOR THE MAIN COMPARISON . . . . . . . . . . . . . . . . . . .
5BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
5OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
5METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
9RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Figure 1. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
Figure 2. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
Figure 3. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
17DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
21AUTHORS’ CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
21ACKNOWLEDGEMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
21REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
34CHARACTERISTICS OF STUDIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
91DATA AND ANALYSES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 1.1. Comparison 1 Results: Industry sponsored versus non-industry sponsored studies, O utcome 1 Number of
studies with favorable efficacy results. . . . . . . . . . . . . . . . . . . . . . . . . . . 95
Analysis 1.2. Comparison 1 Results: Industry sponsored versus non-industry sponsored studies, O utcome 2 Number of
studies with favorable harms results. . . . . . . . . . . . . . . . . . . . . . . . . . . 96
Analysis 2.1. Comparison 2 Results: Industry sponsorship by test treatment company versus sponsorship by comparator
treatment company, Outcome 1 Number of studies with favorable test treatment efficacy results. . . . . . 97
Analysis 3.1. Comparison 3 Conclusions: industry sponsored versus non-industry sponsored studies, Outcome 1 Number
of studies with favorable conclusions. . . . . . . . . . . . . . . . . . . . . . . . . . . 98
Analysis 4.1. Comparison 4 Conclusions: Industry sponsorship by test treatment company versus sponsorship by
comparator treatment company, Outcome 1 Number of studies with favorable test treatment conclusions. . . 99
Analysis 5.1. Comparison 5 Risk of bias: industry sponsored versus non-industry sponsored studies, Outcome 1 Number of
studies with low risk of bias from sequence generation. . . . . . . . . . . . . . . . . . . . . 100
Analysis 5.2. Comparison 5 Risk of bias: industry sponsored versus non-industry sponsored studies, Outcome 2 Number of
studies with low risk of bias from concealment of allocation. . . . . . . . . . . . . . . . . . . 101
Analysis 5.3. Comparison 5 Risk of bias: industry sponsored versus non-industry sponsored studies, Outcome 3 Number of
studies with low risk of bias from blinding-overall. . . . . . . . . . . . . . . . . . . . . . 102
Analysis 5.4. Comparison 5 Risk of bias: industry sponsored versus non-industry sponsored studies, Outcome 4 Number of
studies with low risk from blinding-performance bias. . . . . . . . . . . . . . . . . . . . . 103
Analysis 5.5. Comparison 5 Risk of bias: industry sponsored versus non-industry sponsored studies, Outcome 5 Number of
studies with low risk from blinding-detection bias. . . . . . . . . . . . . . . . . . . . . . 104
Analysis 5.6. Comparison 5 Risk of bias: industry sponsored versus non-industry sponsored studies, Outcome 6 Number of
studies with low risk of bias from loss to f ol low-up. . . . . . . . . . . . . . . . . . . . . . 105
Analysis 5.7. Comparison 5 Risk of bias: industry sponsored versus non-industry sponsored studies, Outcome 7 Number of
studies with low risk of bias from selective outcome reporting. . . . . . . . . . . . . . . . . . 106
Analysis 6.1. Comparison 6 Concordance between study results and conclusions: industry sponsored versus non-industry
sponsored studies, Outcome 1 Number of studies with concordant study results and conclusions. . . . . . 107
Analysis 7.1. Comparison 7 Subgroup analysis, Outcome 1 Number of studies with favorable efficacy results, stratified by
risk of bias. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 108
Analysis 7.2. Comparison 7 Subgroup analysis, Outcome 2 Number of studies with favorable harms results, stratified by
risk of bias. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 110
Analysis 7.3. Comparison 7 Subgroup analysis, Outcome 3 Number of studies with favorable conclusions, stratified by risk
of bias. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 111
Analysis 7.4. Comparison 7 Subgroup analysis, Outcome 4 Number of studies with favorable efficacy results, stratified by
type of intervention. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 113
iIndustry sponsorship and research outco me (Review)
Copyright © 2017 The Cochrane Coll a boration. Published by John Wiley & Sons, Ltd.

Analysis 7.5. Comparison 7 Subgroup analysis, Outcome 5 Number of studies with favorable conclusions, stratified by type
of inter vention. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 115
Analysis 7.6. Comparison 7 Subgroup analysis, Outcome 6 Number of studies with favorable efficacy results, stratified by
type of domain. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 117
Analysis 7.7. Comparison 7 Subgroup analysis, Outcome 7 Number of studies with favorable harms results, stratified by
type of domain. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 119
Analysis 7.8. Comparison 7 Subgroup analysis, Outcome 8 Number of studies with favorable conclusions, stratified by type
of domain. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 120
Analysis 8.1. Comparison 8 Sensitivity analysis, Outcome 1 Number of studies with favorable efficacy results, sponsorship
recoded. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 122
Analysis 8.2. Comparison 8 Sensitivity analysis, Outcome 2 Number of studies with favorable harms results, sponsorship
recoded. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 123
Analysis 8.3. Comparison 8 Sensitivity analysis, Outcome 3 Number of studies with favorable conclusions, sponsorship
recoded. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 124
Analysis 8.4. Comparison 8 Sensitivity analysis, Outcome 4 Number of studies with favorable efficacy results, analysis
adjusted for confounders. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 125
Analysis 8.5. Comparison 8 Sensitivity analysis, Outcome 5 Number of studies with favorable conclusions, analysis adjusted
for confounders. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 126
Analysis 8.6. Comparison 8 Sensitivity analysis, Outcome 6 Number of studies with favorable efficacy results, fixed-effect
model. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 127
Analysis 8.7. Comparison 8 Sensitivity analysis, Outcome 7 Number of studies with favorable harms results, fixed-effect
model. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 128
Analysis 8.8. Comparison 8 Sensitivity analysis, Outcome 8 Number of studies with favorable test treatment efficacy results,
fixed-effect model. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 129
Analysis 8.9. Comparison 8 Sensitivity analysis, Outcome 9 Number of studies with favorable conclusions, fixed-effect
model. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 130
Analysis 8.10. Comparison 8 Sensitivity analysis, Outcome 10 Number of studies with favorable test treatment conclusions,
fixed-effect model. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 131
Analysis 8.11. Comparison 8 Sensitivity analysis, Outcome 11 Number of studies with favorable conclusions, papers with
unpublished studies excluded. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 132
Analysis 8.12. Comparison 8 Sensitivity analysis, Outcome 12 Number of studies with favorable efficacy results, restricted
to specific domains. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 134
Analysis 8.13. Comparison 8 Sensitivity analysis, Outcome 13 Number of studies with favorable harms results, restricted to
specific domains. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 135
Analysis 8.14. Comparison 8 Sensitivity analysis, O utcome 14 Number of studies with favorable test treatment efficacy
results, restricted to specific domains. . . . . . . . . . . . . . . . . . . . . . . . . . . 136
Analysis 8.15. Comparison 8 Sensitivity analysis, Outcome 15 Number of studies with favorable conclusions, restricted to
specific domains. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 137
Analysis 8.16. Comparison 8 Sensitivity analysis, Outcome 16 Number of studies with favorable test treatment conclusions,
restricted to specific domains. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 138
138APPENDICES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
139WHAT’S NEW . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
139CONTRIBUTIONS OF AUTHORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
139DECLARATIONS OF INTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
139SOURCES OF SUPPORT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
140DIFFERENCES BETWEEN PROTOCOL AND REVIEW . . . . . . . . . . . . . . . . . . . . .
140INDEX TERMS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
iiIndustry sponsorship and research out come (Review)
Copyright © 2017 The Cochrane Coll a boration. Published by John Wiley & Sons, Ltd.

[Methodology Review]
Industry sponsorship and resea rch outcome
Andreas Lundh
1
, Joel Lexchin
2
, Barbara Mintzes
3
, Jeppe B Sch r ol l
4
, Lisa Bero
5
1
Center for Evidence-Based Medicine, Odense University Hospital and University of Southern Denmark, O dense, Denmark.
2
School
of Health Policy and Management, York University, Toronto, Canada.
3
Charles Perkins Centre and Faculty of Pharmacy, The University
of Sydney, Sydney, Australia.
4
Department of Obstetrics and Gynaecology, Herlev Hospital, Herlev, Denmark.
5
Charles Perkins Centre
and Faculty of Pharmacy, University of Sydney, Sydney, Australia
Contact address: Andreas Lundh, Center for Evidence-Based Medicine, Odense University Hospital and University of Southern
Denmark, Sdr. Boulevard 29, Entrance 50 ( Videncentret), Odense, 5000, Denmark.
andreas.hover.lundh@rsyd.dk.
Editorial group: Cochrane Methodology Review Group.
Publication status and date: New search for studies and content updated (no change to conclusions), published in Issue 2, 2017.
Citation: Lundh A, Lexchin J, Mintzes B, Schroll JB, Bero L. Industry sponsorship and research outcome. Cochrane Database of
Systematic Reviews 2017, Issue 2. Art. No.: MR000033. DOI: 10.1002/14651858.MR000033.pub3.
Copyright © 2017 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
A B S T R A C T
Background
Clinical research affecting how doctors practice medicine is increasingly sponsored by companies that make drugs and medical de vices.
Previous systematic reviews have found that pharmaceutical-industry sponsored studies are more often favorable to the sponsor’s product
compared with studies with other sources of sponsorship. A similar association between sponsorship and outcomes have been found
for device studies, but th e body of evidence is not as strong as for sponsorship of drug studies. This review is an update of a previous
Cochrane review and includes empirical studies on the association between sponsorship and research outcome.
Objectives
To investigate whether industry sponsored drug and device studies have more favorable outcomes and differ in risk of bias, compared
with studies having other sources of sponsorship.
Search methods
In this update we searched MEDLINE (2010 to February 2015), Embase (2010 to February 2015), the Cochrane Methodology Register
(2015, Issue 2) and Web of Science (June 2015). In addition, we searched reference lists of included papers, previous systematic reviews
and author files.
Selection criteria
Cross-sectional studies, cohort studies, systematic reviews and meta-analyses that quantitatively compared primar y research studies of
drugs or medical devices sponsored by industry with studies with other sources of sponsorship. We had no language restrictions.
Data collection and analysis
Two assessors screened abstracts and identified and included relevant papers. Two assessors extracted data, and we contacted authors
of included papers for additional unpublished data. Outcomes included favorable results, favorable conclusions, effect size, risk of bias
and whether the conclusions agreed with the study results. Two assessors assessed risk of bias of included papers. We calculated pooled
risk ratios (RR) for dichotomous data (with 95% confidence intervals (CIs)).
1Industry sponsorship and research outcome (Review)
Copyright © 2017 The Cochrane Coll a boration. Published by John Wiley & Sons, Ltd.

Frequently asked questions

Q1. What are the future works in this paper?

GRADE Working Group grades of evidence High quality: Further research is very unlikely to change their conf idence in the est imate of ef fect. Moderate quality: Further research is likely to have an important impact on their conf idence in the est imate of ef fect and may change the est imate. Low quality: Further research is very likely to have an important impact on their conf idence in the est imate of ef fect and is likely to change the est imate. 

Q2. What are the contributions in this paper?

Twenty-seven new papers were included in this update and in total the review contains 75 included papers. Comparing industry and non-industry sponsored studies, the authors did not find a difference in risk of bias from sequence generation, allocation concealment, follow-up and selective outcome reporting. This review is an update of a previous review that looked at sponsorship of drug and device studies. The primary aim of the review was to find out whether the published results and overall conclusions of industry sponsored drug and device studies were more likely to favor the sponsors ’ products, compared with studies with other sources of sponsorship. The secondary aim was to find out whether such industry sponsored studies used methods that increase the risk of bias, again compared with studies with other sources of sponsorship. In this update, the authors carried out a comprehensive search of all relevant papers of empirical studies published from 2010 to February 2015 and included 27 new papers, yielding a total of 75 papers included in their review. The authors did not find a difference between industry and non-industry sponsored studies with respect to standard methodological factors that may increase the risk of bias, except for blinding: industry sponsored studies reported satisfactory blinding more often than non-industry sponsored studies. The basis for the assumed risk ( e. g. the median control group risk across studies ) is provided in footnotes. Their analyses suggest the existence of an industry bias that can not be explained by standard ’ Risk of bias ’ assessments. This suggests that industry sponsored studies are biased in favor of the sponsor ’ s products. Their analysis suggests that industry sponsored drug and device studies are more often favorable to the sponsor ’ s products than non-industry sponsored drug and device studies due to biases that can not be explained by standard ’ Risk of bias ’ assessment tools. GRADE Working Group grades of evidence High quality: Further research is very unlikely to change their conf idence in the est imate of ef fect. Moderate quality: Further research is likely to have an important impact on their conf idence in the est imate of ef fect and may change the est imate. Low quality: Further research is very likely to have an important impact on their conf idence in the est imate of ef fect and is likely to change the est imate.