Off Label Doesn’t Mean No Proof
While off-label uses may not have FDA approval or the gold standard of randomized controlled trials, otolaryngologists are careful to ensure there is clinical experience and basic science to balance the risk-reward.
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December 2019Take the use of Botox to reduce saliva production. While its primary indication is as a cosmetic application, some physicians use it to treat sialorrhea, a condition in which people cannot control saliva production and often drool uncontrollably. Botox binds acetylcholine and prevents its release at the neuromuscular junction, which provides significant relief, helps with oral hygiene, and can make life easier on caregivers. It should, however, be administered using ultrasound guidance, as it weakens muscles and needs to be injected directly into the salivary gland.
If the only thing we did was stick to on-label, FDA-approved uses, there would be a great many patients whom we couldn’t treat, and there would be no advances in the field that led to additional on-label uses. —Robert Sataloff, MD
“There has to be some level of evidence,” said M. Boyd Gillespie, MD, MSc, professor and chair of the department of otolaryngology–head and neck surgery at the University of Tennessee-Memphis. “You have to have a certain body of lower-level evidence in the literature that shows the effect, [and] you have to have a certain number of experts in the field agreeing that a procedure is acceptable. If I was in private practice, I would look to some of the academic leaders and some of the research leaders to provide at least a base of evidence that I could confidently act upon. In academia, often we are a little bit more on the leading edge, and if we’re going to be doing off-label things, we really should have it be part of a research protocol.”
But Dr. Gillespie said that otolaryngologists are used to dealing with lower levels of evidence, and then applying common sense. “So, the reason I can use Botox on salivary glands and know that it works is because I know the effect size is profound,” he added. “I will inject a salivary gland, and within three to four days, the drooling of the patient ceases. It’s objective evidence that you can witness. Whenever the effect size is objective and large, it makes weaker levels of evidence acceptable.”
Kara Detwiller, MD, adjunct assistant professor of otolaryngology–head and neck surgery in the division of rhinology and sinus surgery at Oregon Health & Science University in Portland, said safety is a major factor in off-label use. She points to the low-risk and common approach of adding saltwater to the topical steroid budesonide to create a rinse suitable for patients dealing with chronic rhinosinusitis.
“With a patient you can say, ‘Look, we’ve tried standard-of-care types of things, and that hasn’t worked,” Dr. Detwiller said. “So, the next option is starting to be some of these less-commonly used interventions. And some of them I don’t worry too much about … I feel like the side-effect profile from that is pretty low. I’m not worried. We can have a discussion about risks and benefits, but the risks are really pretty small.”
Dr. Sataloff said some off-label procedures are considered safe because they are already approved in other countries, providing otolaryngologists comfort that their use is not unprecedented. He adds that another pathway for off-label treatments is to extrapolate them from medications that have similar on-label uses. “People are always more comfortable using something off label that has a medically approved use for something else on label,” he added. “For example, very few people are uncomfortable using proton pump inhibitors for laryngeal reflux knowing they are approved for gastroesophageal reflux.”
But, to figure that out, otolaryngologists often must make an informed leap of faith. “There is still a place for art amongst the science,” Dr. Rutter said. “There’s still a place for clinical judgment.”