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Randomized Controlled Trial
. 2021 May:104:106334.
doi: 10.1016/j.cct.2021.106334. Epub 2021 Feb 27.

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

William J Sheehan  1 , Ian M Paul  2 , David T Mauger  3 , James N Moy  4 , Stanley J Szefler  5 , Daniel J Jackson  6 , Anne M Fitzpatrick  7 , Michael D Cabana  8 , Ronina Covar  9 , Rachel G Robison  10 , Wanda Phipatanakul  11
Affiliations
Randomized Controlled Trial

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

William J Sheehan et al. Contemp Clin Trials. 2021 May.

Abstract

Background/aims: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: Acetaminophen; Asthma; Children; Ibuprofen; Randomized controlled trial.

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Figures

Figure 1:
Figure 1:
Instruction Sheet Given to Families
Figure 2:
Figure 2:
Doses of Analgesics / Antipyretic Received during the Study
Figure 3:
Figure 3:
Number of Doses of OTC Use of Acetaminophen and Ibuprofen Classified by Symptomatology
See this image and copyright information in PMC

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