A multidisciplinary research team published an article in the World Medical and Health Policy on whether industry-funded continuing medical education modules (CMEs) contain biased material. Thirty-eight participants, ranging from physicians to research assistants, read a non-industry article or an industry-funded article on pain management with opioids. Twenty-three of these individuals assessed critical messages in the texts. Participants who read the industry-funded article, which never mentioned the word ‘death’ and mentioned ‘breakthrough pain’ 55 times, were more likely to view opioids in a more positive light as compared to those who read the non-industry article.

“[P]articipants who read a non-industry-funded article on opioids for non-cancer pain indicated understanding of the risk of addiction or death associated with opioids and the unproven efficacy of opioids in chronic non-cancer pain,” wrote the researchers. “In contrast, those who read an industry-funded article largely failed to mention addiction or other serious adverse effects, instead focusing on the benefits of opioids and specifics of [breakthrough pain] as a discrete disease state.”

While opioids are useful and appropriate in treating pain in cancer and some acute conditions, there has been a concerted effort to push opioid use on physicians for non-cancer pain; by branding pain as the fifth vital sign and condemning opiophobia, opioid use for non-cancer pain significantly increased in the ’90s. One such branding campaign was ‘breakthrough pain’ (BTP), defined as “a transitory increase in pain to greater than moderate intensity… which occurred on a baseline pain.”

In 2007, Fentanyl, which was approved by the FDA to reduce pain in cancer patients, was promoted in lozenge form to treat non-cancer BTP. Despite the promotion, it did not gain regulatory approval, though this did little to deter manufacturers of the drug. In a Pipeline Insight, they wrote, “A key growth strategy will be to gain initial approval for cancer breakthrough pain and then drive sales in additional indications through off-label use or regulatory approval.”

There was indeed extensive use of the tablet off-label, causing the US Department of Justice to order the manufacturers of the tablet to pay a $425 million fine to resolve claims of marketing the tablet and other similar drugs for an unapproved use.

The manufacturer also funded CME programs to promote off-label use of their drugs. CME is often used to promote drugs for unproven use and is done in a way that does not directly break the law. The current study aimed to assess whether an industry-funded CME module had subtle marketing that promoted opioid use as compared to a non-industry funded article.

To do this, the authors first chose a comprehensive CME on BTP, “Persistent and Breakthrough Pain,” which was funded by the lozenge manufacturer and CME-accredited by Johns Hopkins University. Ostensibly, the goals of this module included learning about BTP, tailoring pain treatment, and identifying risk assessment and management strategies for opioid therapy.

The authors initially aimed to find a non-industry CME module on BTP but were unable to do so after an extensive search, instead finding all CME modules to be funded by opioid manufacturers. Instead, the team chose a clinical practice guideline entitled “Opioids in the Management of Chronic Non-Cancer Pain: An Update of American Society of the Interventional Pain Physicians’ (ASIPP) Guideline.” While not totally parallel in purpose to the CME module, both centered on the use of opioids in treating non-cancer pain.

Thirty-eight participants were then randomized to read one of the two articles and take the test that came with the CME module. Twenty-three of those participants were asked to summarize the main points of the article, and 15 were asked whether they thought they received the industry article. The authors also conducted a basic text analysis on each module.

Unsurprisingly, participants in the industry-funded article improved more on the test, which was designed for their module. However, the summaries of key messages vastly differed by group. 9/12 participants who read the non-industry funded article indicated that the effectiveness of opioids in treating pain was unclear, compared to none of those in the industry-funded group, who viewed opioids more positively.

8/12 individuals in the non-industry group identified opioid abuse or addiction as a critical point, compared to 3/11 in the industry-funded article. 4/7 correctly identified themselves as being in the non-industry group, whole 3/7 correctly identified themselves as being in the industry group, indicating that blinding was preserved. The industry article mentioned BTP 55 times, rapid onset opioids (ROOs) 13 times, fentanyl buccal tablet (FBT) 31 times, and never mentioned death; this is contrasted to the non-industry article mentioning BTP once, never mentioning ROOs, once mentioning FBT, and mentioning death 26 times. The industry-funded module encouraged the off-label use of opioids, as 7/9 case studies addressed off-label uses for non-cancer pain.

“Messages retained by readers of an industry-funded CME module appeared to encourage the use of opioids for noncancer pain, and minimized adverse effects,” write the authors. “Vetting bias should not be left to learners, who underestimate bias and arguably cannot determine whether or not the information they have received is supported by evidence.”

Serious side effects, such as addiction and death, were brought up far more frequently in the non-industry article, while the industry article highlighted minor side effects. The authors concluded that the industry-funded article, even though it didn’t mention brand names, served to market the company who funded the CME.

Furthering this point, the authors cite an anonymous pharmaceutical executive, who wrote, “CME contributions are commercial decisions. Commercial does not equal unethical or lacking in value, but it does represent a focus on a particular business objective. The nature of the return may be subtle, nonbranded, or indirect.”

This study provides further support to the claim that industry-funded CME contains marketing messages for specific drugs; physicians who avoid sponsored CMEs prescribe fewer branded prescriptions and more generic medications.

“Differences in presentation of adverse events between the industry-funded and non-industry-funded modules may make a difference in how harms are perceived by learners,” write the authors. “The industry-funded module may have minimized learners’ perceptions of adverse events, including addiction and death. Misperceptions about the addictive properties and adverse effects of opioids may lead to increased comfort with prescribing or continuing to prescribe opioids to patients for whom the benefits may not outweigh the risks.”

The authors suggest that promotion of off-label opioid use via CME is a form of condition branding, a marketing strategy that creates a disease awareness (such as pseudo-addiction or BTP) of a specific disease state, linking a condition to a particular treatment without directly mentioning the treatment. While illegal to market drugs without regulatory approval or for off-label use, it is within the law to market a disease however manufacturers choose. Social anxiety disorder, for instance, was invented as a marketing campaign for Paxil, impotence rebranded Erectile Dysfunction to market Viagra, and heartburn became Gastroesophageal Reflux Disease to sell Prilosec and Nexium. The industry CME module, the authors purport, may be designed to lead physicians to believe BTP is a separate condition despite it lacking a formal diagnosis.

Commercial funding of CME is not a new phenomenon, but existing tools are not equipped to identify subtle biases that this funding creates. While exhaustive and elaborate, the authors suggest their method of text analysis and key message summary may be necessary to uncover commercial bias further. Alternatively, the authors suggest eliminating commercial funding for CMEs entirely.

“It is vital that CME provides information that is evidence-based, accurate, and balanced,” the researchers conclude. “CME affects physician practice, patient care, and public health. As an anonymous pharmaceutical executive states, ‘CME is diminished by dependence on funds deriving from commercial interests … CME is not compatible with commercial intervention’. The argument that commercial funding is needed for CME is untenable when one understands that commercially-funded CME will always support commercial goals.”

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Infeld, M., Bell, A., Marlin, C., Waterhouse, S., Uliassi, N., & Fugh-Berman, A. (2019). Continuing Medical Education and the Marketing of Fentanyl for Breakthrough Pain: Marketing Messages in an Industry‐Funded CME Module on Breakthrough Pain. World Medical & Health Policy. 11. 43-58. 10.1002/wmh3.290. (Link)