Introduction
Reporting clinical trial funding
Bias introduced from funding
References
Funding for clinical trials comes from a wide variety of sources, including government, private investors, charities, universities, and other research institutions, though the vast majority generally originates from the pharmaceutical company with the greatest financial stake in the completion of the trial, allowing them to produce and market products for which they own the intellectual property.
Government funding is allocated by research councils and other informed bodies that make educated decisions about where funding would be best applied in the face of current medical issues, often with a highly specific scope or at the whim of political forces. This type of funding is more commonly encountered in the early stages of clinical trials, allowing universities and other research institutions to investigate potential new therapeutic leads. Similarly, research funding from charities more often focuses on novel and emerging treatment strategies that have the potential to revolutionize clinical practice, allowing market forces to then secure further investment for those that produce promising results.
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Reporting clinical trial funding
Ideally, all clinical trials should list any funding sources within the report generated, including a breakdown of how the money was spent and the role of each funder in the design, implementation, and authorship. Most governments host health organizations responsible for tracking and overseeing clinical trials, and as a part of clinical trial registration, all funders must be reported in detail. However, several journal papers and other scientific outputs may be produced from a single clinical trial with differing reporting requirements, often obscuring the funding source.
In a meta-study by Hakoum et al. (2017), the reporting of funding sources within 200 clinical trials was assessed. The group found that most clinical studies are funded by just one source, though they ranged as high as 12 independent contributors. 58% of studies were funded by the government, and 40% by private companies, with around a quarter receiving funding from claimed not-for-profit organizations. However, upon further investigation, around half of these non-profit organizations were linked in some way to profit-driven corporations, around half of which again were not reported in the published study.
Only around half of the studies assessed identified the detailed roles of any funders within the study, which mostly consisted of assisting in study design (42%), data analysis (41%), data collection (27%), and manuscript authorship (32%). Interestingly, multivariable regression analysis suggests that those clinical trials with rigorous reporting of funding were more likely to publish in journals with higher impact factors and be affiliated with institutions from high-income countries, though this is likely also related to the influence of higher minimum journal requirements and the larger scale of studies possible given more funding.
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Bias introduced from funding
The finding that half of the non-profit organizations funding clinical trials are actually supported by private companies is likely significantly underestimated, with only around a third of peer-reviewed journals requiring complete disclosure of funding sources and allocation. This is concerning regarding the clear conflict of interest that could result in manipulated or hidden scientific data, obvious examples being the heavy investment of tobacco and fast food industries into researching the adverse health effects of their products. Such funders should be as far removed as possible from the design, implementation, and analysis of clinical trials to ensure that trials are carried out without bias and should not be the only responsible party in the decision to publish.
Even when these factors are minimized as best as possible, funding from a particular source tends to favor the desired outcome of the funding organization regardless. Another 2017 meta-analysis of over 8,000 trials found a risk ratio of 1.27 for producing favorable drug efficacy results and of 1.34 for overall favorable conclusions when a pharmaceutical company primarily funded the trial as compared to any other funder, despite pharmaceutical companies actually often going to greater efforts than other funders to implement blind processes meant to prevent bias. Therefore, the principle issue in bias generated by the source of funding does not necessarily originate from scientific methodological concerns but from systemic bias starting in the initial planning stages, where only studies likely to produce good results are put forward, and ending with the decision only to promote the publication of favorable material.
Pharmaceutical companies often design the clinical trial and then sub-contract laboratories and independent researchers to collect and analyze the data, the latter of which should then go on to publish independently. In many cases, however, pharmaceutical companies tightly control subsequent publication according to pre-set publication plans implemented based on the data expected from the trial, and, arguably, independent researchers are used as a screen to maintain the illusion of independent research.
Anonymous surveys of corruption within the clinical sciences present worrying statistics regarding the number of respondents reporting first-hand knowledge of scientific fraud, as high as 50-92% amongst some of the groups surveyed. Importantly, a third of USA respondents reported having engaged in at least one of ten questionable behaviors previously, 16% of which had changed the design, methodology, or results of a study at the wishes of the funding source.
Is Education Key to Accelerating Clinical Trial Participation?
References:
Further Reading
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