Brian Gac, Hanna D. Yakubi and Dorie E. Apollonio
This blog post is based on the Evidence & Policy article, ‘Issues arising from the study design, conduct, and promotion of clinical trials funded by opioid manufacturers: a review of internal pharmaceutical industry documents’.
From 1999 to 2021, opioid overdoses caused over one million deaths in the US. The pharmaceutical industry has been held legally responsible in some cases for overstating the benefits and understating the risks of opioid use, leading to overprescribing that contributed to these deaths. Opioid manufacturers sponsor clinical trials to generate scientific evidence that supports use of their products to gain regulatory approval, and to use in commercial materials to promote drug sales. Previous research has found industry sponsored research may use dubious research practices to generate findings that justify use. Three examples of such research practices include inappropriate use of enriched enrollment trial design, ghost authorship, and overstatement of research findings.
In our recently published Evidence and Policy article, we identified research practices used in clinical trials funded by opioid manufacturers that created the perception that opioids were safe, non-addictive and effective in treating pain. Since 2005, confidential documents made public in litigation against pharmaceutical companies have been collected in the Opioid Industry Document Archive (OIDA) at the University of California San Francisco for storage in perpetuity. In January 2020, OIDA made available the first 503 documents that later become part of the larger OIDA, totaling over 62,000 pages, that were released as part of the Oklahoma litigation in a discrete collection named the Oklahoma Opioid Litigation Documents. These documents included clinical trial reports, witness declarations, internal corporate communications and marketing strategies regarding opioids, and served as the primary data source for the study.
We found that initial corporate studies supporting opioid prescribing and use relied on enriched enrollment, in which only people who had the desired response to opioids—meaning that they indicated that opioids addressed their pain—were included in studies, which meant that this research overstated the benefits of opioids and underestimated their potential adverse effects. These studies did not explicitly state that they used enriched enrollment, but companies used these studies to make broad claims of effectiveness that the FDA later found had violated federal regulations.
We also found evidence that multiple studies indicating that opioids were effective and non-addictive were ghost authored, meaning that although they had purportedly been written by independent researchers, they were in fact written by employees of opioid manufacturers. In 2009, Johnson & Johnson was tracking 12 research projects assessing opioids, and for seven of them the company had designed the study, written the study, or both, before sending them to listed authors for review. Papers supported by other companies also showed evidence of ghost authors; one published paper assessing tapentadol implied that it had a lower risk of addiction than other opioids despite concerns from independent authors that this claim was unsupported by the underlying research.
Finally, we found that companies overstated research findings. Even researchers who had received industry support admitted later than their work had been misrepresented. One stated that, “[M]y teaching and writing at various times emphasized the potential benefits… and deemphasized the risks that are always present when opioids are administered… [D]rug companies used my work to provide content and expert support for a strongly positive message about opioids… The effect was to promote opioid therapy to prescribers.”
The study design, research conduct and promotion issues identified in this research remained undiscovered prior to litigation. The findings suggest that preventing inappropriate marketing of medications may require increased federal regulation of clinical trials and promotional material supplied to prescribers, and increased transparency requirements by journals regarding the identification of authors and design and reporting of findings from clinical trials.
Image credit: Photo by Hal Gatewood on Unsplash
Read the original research in Evidence & Policy:
Gac, B.W. Yakubi, H. and Apollonio, D.E. (2023). Issues arising from the study design, conduct, and promotion of clinical trials funded by opioid manufacturers: a review of internal pharmaceutical industry documents. Evidence & Policy, DOI: 10.1332/174426421X16856230946027.
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