Association of industry sponsorship and positive outcome in randomised controlled trials in general and abdominal surgery: protocol for a systematic review and empirical study
- Pascal Probst1, 2,
- Kathrin Grummich2,
- Alexis Ulrich1,
- Markus W Büchler1,
- Phillip Knebel†1, 2 and
- Markus K Diener†1, 2Email author
© Probst et al.; licensee BioMed Central Ltd. 2014
Received: 8 October 2014
Accepted: 11 November 2014
Published: 27 November 2014
Industry sponsorship has been identified as a factor correlating with positive research findings in several fields of medical science. To date, the influence of industry sponsorship in general and abdominal surgery has not been fully studied. This protocol describes the rationale and planned conduct of a systematic review to determine the association between industry sponsorship and positive outcome in randomised controlled trials in general and abdominal surgery.
A literature search in the Cochrane Library, MEDLINE and EMBASE and additional hand searches in relevant citations will be conducted. In order to cover all relevant areas of general and abdominal surgery, a new literature search strategy called multi-PICO search strategy (MPSS) has been developed. No language restriction will be applied. The search will be limited to publications between January 1985 and July 2014. Information on funding source, outcome, study characteristics and methodological quality will be extracted.
The association between industry sponsorship and positive outcome will be tested by a chi-squared test. A multivariate logistic regression analysis will be performed to control for possible confounders, such as number of study centres, multinational trials, methodological quality, journal impact factor and sample size.
This study was designed to clarify whether industry-sponsored trials report more positive outcomes than non-industry trials. It will be the first study to evaluate this topic in general and abdominal surgery. The findings of this study will enable surgical societies, in particular, to give advice about cooperation with the industry and disclosure of funding source based on empirical evidence.
Systematic review registration
KeywordsIndustry bias Industry sponsorship General and abdominal surgery Randomised controlled trial Medical devices Systematic review Science study Health care research
The debate about the presence and extent of inappropriate industry influence on medical professionals began in the 1980s [1, 2]. Shortly thereafter, a positive association between industry funding and positive research outcomes was first shown for pharmaceutical clinical trials . This topic, referred to as industry bias, has meanwhile been studied in many different medical disciplines, and in 2012, a Cochrane review showed a relative risk of 1.32 (95% confidence interval 1.21–1.44) for industry-funded studies to report a positive outcome in a meta-analysis of 48 primary studies. One possible explanation for this difference between industry-funded trials and those with independent funding was found to be conclusions not justified by the study data. Other quality characteristics, such as risk of bias, did not differ between the two groups .
Summary of 11 studies of the association between industry funding and positive research outcome across different surgical disciplines
Included study type (n)
Positive outcomes industry vs. independent
12 months (1999–2000)
All (n = 301)
79% vs. 64% p = 0.0390
3 journals, 2 congresses
12 months (2001–2002)
All (n = 173)
86% vs. 24% p < 0.0001
Different fields of surgery
18 months (1999–2001)
RCT (n = 87)
81% vs. 68% p = 0.4385
19 months (2002–2003)
All (n = 527)
73% vs. 44% p < 0.0001
1 journal (submitted manuscripts)
17 months (2004–2005)
All (n = 208)
74% vs. 70% p = 0.7070
2001 + 2002
All (n = 494)
98% vs. 88% p = 0.0258
CCT/RCT (n = 23)
100% vs. 86% p = 0.6637
60 months (2000–2005)
RCT (n = 202)
81% vs. 79% p = 0.8538
24 months (2002–2004)
RCT (n = 100)
85% vs. <45% p < 0.0001
15 years (1990–2005)
CCT/RCT (n = 63)
74% vs. 64% p = 0.5900
MEDLINE, EMBASE, CINAHL, CENTRAL
RCT (n = 118)
35% vs. 51% p = 0.2067
General and abdominal surgery comprises a large field of different operations. Abdominal surgery involves operations on organs like stomach, liver, pancreas and gut. Whereas, general surgery involves an inhomogeneous spectrum of operations, e.g. surgery of the thyroid gland, hernias and proctology. Surgery is a field with high potential for innovation because of the constant development of new interventions, especially with regard to medical devices. Implementation of new interventions is commonly justified on the basis of clinical trials. Thus, any industry bias would have a relevant impact on surgical practice. This protocol describes the methods to perform a systematic literature search to find a representative sample of trials for a primary statistical analysis. The influence of industry sponsorship in general and abdominal surgery will be evaluated for the first time.
This study will firstly aim to determine whether there is an association between industry sponsorship and positive outcome in randomised controlled trials (RCTs) in the field of general and abdominal surgery.
Second, methodological differences between industry- and non-industry-funded RCT will be evaluated in order to explore potential sources of industry bias.
Systematic literature search methodology
–First, the preliminary PICO question served as the “master PICO”.
Based on the minor PICOs, a systematic literature search will be performed independently by two reviewers following the recommendations of the Cochrane Collaboration . The following databases will be searched: Cochrane Library, MEDLINE (via PubMed) and EMBASE. A search strategy based on a vocabulary thesaurus (MeSH or Emtree) in combination with text words will be used. Additionally, a hand search in relevant citations will be performed. The search will be limited to the period from January 1985 to July 2014, with the rationale that disclosure of funding source was not demanded before 1985. No language restrictions will be applied.
The method of MPSS allowed the creation of a specific search for every subfield of investigation.
Articles gathered by the MPSS will be screened for eligibility according to the following criteria.
RCT assessing the efficacy or effectiveness of medical devices and perioperative pharmacological and nutritional interventions with direct relation to the surgical procedure in human patient populations in the field of general and abdominal surgery will be eligible.
RCT without funding information.
RCT assessing neurosurgical, urological, orthopaedic, dental, plastic, cardiothoracic, gynaecologic, dermal, vascular or paediatric surgery and otorhinolaryngological or endoscopic interventions.
Thus, a systematic search for surgical RCT in general and abdominal surgery with potential risk for industry bias will yield a broad and representative sample to answer the primary research question.
Extracted information to evaluate the research question
Experimental intervention is reported to be superior to the control intervention
Exact p value of the primary endpoint
Year of publication
Impact factor of journal
Number of study centres
Concluded superiority without statisticalsignificance of primary endpoint
Risk of bias for primary endpoint according to Cochrane Collaboration’s tool for assessing risk of bias
A trial will be classed as industry funded if any funding is explicitly stated, regardless of whether the funding took the form of direct financial support, supply of products for use in the study or the conduct of trial tasks, e.g. data analysis. Trials will be dichotomised according to whether the authors conclude the experimental intervention to be superior to the control intervention. The conclusions drawn by the authors will be compared to the data presented. A conclusion in favour of the experimental intervention based on non-significant differences between groups will be recorded. Risk of bias will be assessed according to the Cochrane Collaboration’s tool for assessing risk of bias . Further study characteristics will be captured for multivariate analysis as stated in the “Statistical analysis” section below.
Data extraction will be performed by two reviewers independently for quality assurance purposes . Discrepancies between the two reviewers will be resolved by a third reviewer, and a final extraction sheet will be determined for database entry. A database monitoring will be performed of 100% of data necessary to evaluate the primary endpoint and a randomly selected 20% of remaining data. Finally, the database will be closed and made available for statistical analysis.
A primary statistical analysis will be performed to answer the primary research question regarding the association of industry sponsorship and positive outcome as well as the magnitude of this association. Therefore, trials will be divided into those funded by industry and those not funded by industry. Further, trials will be dichotomised according to whether or not the experimental intervention is reported to be superior to the control group. The chance that industry-funded trials report more positive outcomes is expressed as odds ratio (OR). The null hypothesis (H0) is that industry funding is not associated with a positive trial outcome. The alternative hypothesis (H1) is that industry funding is associated with a positive trial outcome. The significance of association will be tested by means of Fisher’s exact test if at least one value in the contingency table is 5 or below. Pearson’s chi-squared test with Yates’s correction will be used if the total sample size is 60 or less. In all other cases, significance of association will be tested using Pearson’s chi-squared test without Yates’s correction at a level of significance of 5%. Furthermore, a multivariate logistic regression with factors (multinational trials, methodological quality) and covariates (number of study centres, journal impact factor, sample size) will be conducted. An additional analysis will be performed for the three subgroups medical devices, pharmaceuticals and nutrition.
Moreover, by comparison of reported p values of primary endpoints from industry-funded and independently funded trials, a possible industry bias will be quantified. Student’s t-test or the Wilcoxon rank-sum test will be used for exact p values. If 20% of p values are not reported exactly, the p values will be classified and Fisher’s exact test or a chi-squared test will be performed.
Additional data extracted will be presented descriptively. Publication bias will be explored using a funnel plot separately for industry-sponsored trials and non-industry- sponsored trials. Statistical analysis will be performed with R.
Existing literature about association of industry sponsorship and positive outcome in surgery has major limitations due to the approach to primary trials as mentioned above. Therefore, the presence and extent of such association in randomised controlled trials in general and abdominal surgery remains unexplored.
In the case of the hypothesised association of industry sponsorship and positive outcome, this study will investigate by a multivariate statistical analysis whether industry involvement biases result via standard risk domains or if industry involvement is an independent source of bias as assumed by several studies [4, 20].
The conduct of this study is important, because the detection of an industry bias in surgery would have an impact on future research. The findings of this study will enable surgical societies, in particular, to give advice about cooperation with industry and disclosure of funding source based on empirical evidence.
PP is a surgical resident and holds an MSc in clinical trial management. KG is a methodological specialist and core member of the surgical systematic review group at the Study Center of the German Surgical Society. PK is a board certified surgeon and head of the surgical clinical trial unit. AU is chief consultant in the surgical department and head of surgical oncology. MWB is full professor of the department of general, visceral and transplantation surgery. MKD is a consultant in the surgical department and head of the Study Center of the German Surgical Society.
controlled clinical trial
multi-PICO search strategy
Participants Interventions, Comparisons and Outcomes
Randomised controlled trials.
No additional funding source is available. However, the resources and facilities of the University of Heidelberg were used in conducting this review.
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