Item 3c: Role of trial sponsor and funders in design, conduct, analysis, and reporting of trial; including any authority over these activities.

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). The study is sponsored by The University of Queensland. The University of Queensland and the funder have no influence on study design, collection, management, analysis and interpretation of data, writing of the report and the decision to submit for publication [47].

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Explanation

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Trials are typically funded by drug or device companies (“industry-funded”) or by scientific, private, or governmental foundations or organisations (“non-industry-funded”). The various types of funders differ in their overall agenda, reasons for funding a trial, and propensity to influence the trial. A funder will typically provide direct monitory support for a trial, but funding may also be provided indirectly such as free trial drugs, equipment, or services (e.g., statistical analysis or use of medical writers) (Item 7a).

The more direct the influence a trial funder (or sponsor) with a strong interest in a specific study result has on the design, conduct, analysis, and reporting of a trial, the higher is the risk that their interests interfere with the scientific purpose of the trial. Undue influence may result in methodological problems (e.g., inappropriate comparator group or narrow patient eligibility criteria) and bias.

Most industry-initiated trials are controlled by the company sponsoring and funding the trial; this authority is often enforced by contractual agreements signed between the company and trial investigators [38, 48]. Publication restrictions have been imposed by various groups, including industry sponsors [38, 49, 50]. These restrictions are sometimes not fully described in the protocol but rather in separate publication agreements [38, 51].

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Industry-funded trials with greater funder involvement tend to report more favourable results (i.e., larger estimates of intervention effects) than comparable trials without such involvement. One review of eight published meta-epidemiological studies reported that trials with a high risk of industry funder influence (for example on trial design, conduct, and analysis) reported 12% more beneficial effects (odds ratios) (95% confidence interval: 3% to 19%), on average, than comparable trials without high risk of funder influence [52]. Reviews of two samples of 108 and 292 trial protocols from 2016 found that 61% and 39% respectively reported the role of the sponsor and funder [9, 10].

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The protocol should explicitly outline the roles of the sponsor and funders in trial design, conduct, data analysis and interpretation, manuscript writing, and dissemination of results. It is also important to state whether the sponsor or funder makes the final decision regarding any of these aspects of the trial or has the right to review or comment on the trial manuscript. Any restrictions on publications should be disclosed in the protocol for review by research ethics committees and other relevant parties. If any mechanisms were planned to mitigate funder influence, this should be reported. Also, if the funder will have no direct involvement in the trial, the authors should explicitly state this.

Summary of key elements to address

For the sponsor and funders:

• Roles and responsibilities in trial design, conduct, data analysis and interpretation, manuscript writing, and results dissemination

• Who will make final decision regarding the above trial aspects

• Whether the sponsor or funder will have the right to review or comment on the trial manuscript

• Any mechanisms used to mitigate funder influence. If the funder will have no direct involvement in the trial, then this should be explicitly stated.