Have Pharmaceutical Conflicts of Interest Unduly Influenced Asthma Guidelines?

The single maintenance and reliever therapy (SMART) treatment approach to patients with asthma, outlined in the article on chronic asthma treatment in the April issue of American Family Physician, has consistent supporting evidence from multiple randomized controlled trials. A practical guide to implementing SMART has been widely disseminated to clinicians. However, an AFP editorial by Dr. Steven Brown cautioned that SMART, which is strongly recommended in the 2022 GINA guidelines, has been “heavily influenced by the pharmaceutical industry,” namely AstraZeneca, which markets budesonide/fomoterol (Symbicort), the combination inhaler primarily studied in the trials:

The GINA board of directors and scientific committee members have substantial financial conflicts of interest. Twelve of 17 members, including both chairs, have received personal fees from AstraZeneca. … A 2018 systematic review of SMART for persistent asthma found 16 RCTs, and 15 of those evaluated SMART as a combination therapy with budesonide and formoterol in a dry-powder inhaler. Fourteen of the 15 studies were funded by AstraZeneca, had an AstraZeneca employee as a coauthor, or had authors who received honoraria or fees from Astra-Zeneca.

Why is it problematic that clinical trial investigators and GINA guideline panelists have numerous industry ties? A 2017 Cochrane review concluded that “sponsorship of drug and device studies by the manufacturing company leads to more favorable efficacy results and conclusions than sponsorship by other sources,” an inherent industry bias that “cannot be explained by standard ‘risk of bias’ assessments.” A 2020 systematic review found that guidelines with panelists with financial conflicts of interest were 26% more likely to favorably recommend a therapy than those without such conflicts.

In comparison to GINA, the less-conflicted panelists of the National Asthma Education and Prevention Program (NAEPP) focused guideline update, discussed in a previous AFP editorial, made a narrower “conditional” recommendation for SMART in patients age 12 years or older with moderate to severe persistent asthma.

Although some think that public disclosure of conflicts of interest can prevent or mitigate bias in clinical recommendations, Dr. Jay Siwek has previously argued regarding clinical review articles and editorials that disclosure of conflicts is not enough. I do not have any conflicts of interest related to the topic of this blog post.