Example

 

“The study is funded by the National Health and Medical Research Council (NHMRC) of Australia by a project grant (1140756). RNB is supported by an NHMRC Research Fellowship (1037220)" [47].

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“Funding Information

The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the Pfizer Global Investigator-Initiated Research Grant (grant no. GA6120A8) and Blue Cross Blue Shield of Michigan Foundation, Investigator-Initiated Grant (grant no. 002607.II) [101].

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A randomised trial requires considerable funding, typically from drug or device companies (i.e., “industry-funded”), or from scientific or private foundations, or governmental or non-governmental organisations (“non-industry-funded” [102]. One study estimated the median cost per phase 3 industry-funded trial to be $US 21.4 million, [103] with substantial variation. The mean cost of clinical trials funded by the National Institute for Health and Care Research in the United Kingdom was lower, but still sizeable, at approximately £ 1.3 million and also with considerable variation [104]. The various types of funders differ in their overall agenda, their reasons for funding a trial, and their propensity to influence the trial.

 

Funding of a trial typically involves direct monetary support, but financial support may also be provided indirectly in the form of free trial drugs, equipment, or services (e.g., statistical analysis or use of medical writers) [105]. Although both industry-funded and non-industry-funded trials are susceptible to bias, industry funding is associated with conclusions that favour the intervention. A systematic review of 75 methodological studies, comparing industry-funded with non-industry-funded studies (mostly randomised trials), reported that industry studies more often had favourable conclusions (risk ratio 1.34 (1.19 to 1.51), compared with non‐industry studies [106].

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Industry-funded trials may also report more favourable results (i.e., estimates of intervention effects) than comparable trials that are funded by other sources, though the evidence is less certain. One review of eight published meta-epidemiological studies reported that, on average, odds ratios from industry-funded trials did not differ significantly from non-industry-funded trials. However, in the subset of trials with a high risk of industry funder influence (for example on trial design, conduct, and analysis), the difference was 12% (3% to 19%) [52]. Undue influence on trials from non-industry funders with a strong interest in a specific trial result has been described [107] but has been studied much less.

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No clear consensus exists for a threshold for when funding from a source with conflicting interest becomes problematic, nor on the characteristics of a possible “dose-response” relationship. It is also debated whether industry funding per se is less important than the degree and type of funder influence on trial design, conduct, analysis, and reporting (Item 3c). Indirect financial support, such as provision of various medical services, will impact differently on various stages of a trial. For example, use of industry paid medical statisticians will impact on analysis, and use of industry paid medical writers will influence reporting.

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Reviews of two samples of 108 and 292 trial protocols from 2016 found that 91% and 83% respectively described funding sources [9, 10]. A systematic review of five studies compared funding sources reported in protocols or trial registries with funding sources declared in the corresponding publications of results. It found discrepancies in a median of 45% of protocol–publication pairs (range: 4% to 80%) (not exclusively randomised trials [64].

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Reporting the funding source, and the role of the trial funder (Item 3c), provides important context for readers of a protocol when ascertaining the feasibility of the trial as well as its overall methodological quality (e.g., relevance of the type of comparator intervention and eligibility criteria for patients) and risk of bias (e.g., risk of selective reporting of favourable results). At a minimum, the protocol should identify the sources of direct and indirect financial support and the specific type (e.g., funds, equipment, drugs, services).

 

Summary of key elements to address

For each funding source:

• Name of funder

• Type of funding:

  • Direct monetary support

  • Indirect support (free trial drugs, equipment, or services such as statistical analysis or use of medical writers)