Adherence rates during a randomized controlled trial evaluating the use of blinded acetaminophen and ibuprofen in children with asthma

• Published in: Contemporary clinical trials Vol. 104; p. 106334
• Main Authors: Sheehan, William J., Paul, Ian M., Mauger, David T., Moy, James N., Szefler, Stanley J., Jackson, Daniel J., Fitzpatrick, Anne M., Cabana, Michael D., Covar, Ronina, Robison, Rachel G., Phipatanakul, Wanda
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.05.2021
• Subjects: Acetaminophen; Asthma; Asthma - drug therapy; Child; Children; Double-Blind Method; Humans; Ibuprofen; Randomized controlled trial; RCT; Acetaminophen; Ibuprofen; Children; INFANT; Randomized controlled trial; AVICA; Asthma; OTC
• ISSN: 1551-7144; 1559-2030
• DOI: 10.1016/j.cct.2021.106334

When conducting clinical trials comparing over-the-counter (OTC) medications, the wide availability of these treatments are a potential challenge to maintaining study integrity. We seek to describe adherence to a study protocol involving widely available OTC medications. To prospectively evaluate associations between acetaminophen use and asthma in 300 children aged 1–5 years, we conducted a double blind, randomized, controlled trial where parents administered blinded forms of either acetaminophen or ibuprofen as needed to their children over a 48 week period. Written and verbal instructions encouraged the exclusive use of the blinded study medication and discouraged OTC use. Adherence was determined by evaluating the frequency of use of per-protocol blinded study medication compared to off-protocol use of OTC medications. 4195 doses of acetaminophen or ibuprofen were received by children during the study which included 3664 doses (87.3%) of blinded study medication adhering to the protocol and 531 doses (12.7%) of OTC products deviating from the protocol with better adherence among those randomized to ibuprofen as compared to acetaminophen (89.5% vs. 85.5% of doses, p < 0.01). Individually, 227 participants (75.7%) remained fully adherent by not receiving any OTC medications. Pre-study preference for either acetaminophen or ibuprofen by the participants' families was not associated with differential rates of adherence to the blinded medication. This parallel study demonstrated greater than 85% of acetaminophen or ibuprofen doses were blinded study medications adhering to the protocol while less than 15% were OTC deviations from the protocol. This successfully implemented study design provides a template to comparatively evaluate these and other OTC medications.