Understanding adherence requires pragmatic trials: lessons from pediatric asthma.

Adherence to medications is critical but often suboptimal in asthmaandother chronicdiseases.1 Intervention studies, particularly those that reflect the real world, are essential for understanding and addressing adherence because it is the realworld setting thatdefines the barriers to adherence. However, most studies are observational and those that are interventions are frequently efficacy rather than effectiveness orpragmatic trials.Efficacystudiesareconductedunder tightly controlled conditions that do not reflect how daily medications are taken by patients, which explains why it is not uncommon for their findings to lack significance when attempts aremade to replicate results in effectiveness studies.2 Patient-centered, real-world pragmatic research is so important that thePatient-CenteredOutcomesResearchInstitutewas established to ensure the conduct of such research,3 the National Heart, Lung, and Blood Institute is considering creating a research consortium to promote this research,4 and the National InstitutesofHealthoffer funding indisseminationand implementation for the adoptionof efficacy studies to the real world.5 These are only a few of the ongoing efforts encouraging such research. In this issue of JAMA Pediatrics, Bender et al6 report their BreatheWell study, apragmatic intervention study topromote adherence to inhaled corticosteroid therapy, essentialmedication for all but themildest asthma. Importantly, this study furtherexamines the rapidlyevolving realworldbyusing information technology. It uses features of the electronichealth record tocommunicatewithpatients,thusaddressingthenationalmandate to use the electronic health recordmeaningfully.7 The study, conducted among 1187 children aged 3 to 12 years insured by Kaiser Permanente Colorado, randomized speech recognition telephone calls toparentswhen the child’s inhaled corticosteroid refill was due or overdue. This intervention was compared with usual care, the guideline-based care of Kaiser Permanente clinicians. The speech recognition callswere tailoredusing information fromtheelectronichealth record including the child’s name and sex, the prescribed inhaled corticosteroid, thephysician’s name, season-related reminders, and the capability for parents to request a call from their medical team or speak with pharmacy staff. The primaryoutcomemeasurewasadherence, calculatedas themedication possession ratio of filled divided by prescribed inhaled corticosteroid over 24 months. Such trials are difficult to conduct, and this trial hasmany strengths. In addition to theuse of a tailored, low-cost speech recognition intervention and pragmatic design, the long 24month observation period allows examination of the intervention’s sustainability. Because the intervention consists of telephone calls, it does not rely on patient familiaritywith information technology.The telephonecallmessages are simple and participants are not required to complete diaries or collect information. Another strength is that no incentives were provided to families for participation, adding to the realworld design that was developed with input from parent focus groups. Finally, the use of a closed system in which both prescribingdataandmedication-fillingdataareavailablemakes such an analysis possible. The study is tantalizing for the questions it raises: what other communications could be tested? Could messages be given in other languages? How couldmessages be further tailored for adolescents, adults, or even the children of the ages studied? This study points theway to other needed effectiveness studies: can such a study be recapitulated in the patient groups with highest morbidity from asthma—those who are poor, are otherwise vulnerable, or have comorbidities? The study’s childrenhad tobeenrolled in their health careplan for at least a year and to have filled at least 1 inhaled corticosteroid prescription in the prior 6 months. As noted by the authors, these inclusioncriteria couldhave thusexcludedagroup particularly at risk for poor adherence and asthmamorbidity. It would be interesting to know what percentage of parents opted out of participation and their reasons. Oneof themost thought-provokingquestionsraised iswhy, if adherencewasbetter in the interventiongroup,was thereno differencebetweengroupsinnumbersofemergencydepartment admissions,hospitalizations,andotherurgentcarevisits?Asthe authors suggest, thesmallnumbersof suchevents likely reflect the fairly well-controlled asthma of the participants, suggesting the need for study in high-risk populations with fewer resourcesandmoremorbidity.Could this interventionbedone in low-incomepopulations inwhomasthmaburden ishighest or where telephonecoverage is spotty—especiallyat theendof the monthwhencoveragecannolongerbeafforded?Howcouldthis intervention be adjusted to promote better asthma outcomes using information technology in these populations? A noteworthy findingwas that adherence did not decline over time in the intervention group, contrary to findings in other studies in which inhaled corticosteroid use was monitored.8,9 However, although there was a 25.4% adherencedifference betweengroups, absolute adherencewas still very low (mean, 44.5% in the intervention group vs 35.5% in theusual care group), revealing that as inprevious studies less than half of prescribed medication was taken from the pharmacy. We also know from other studies that not all prescribeddosesof inhaledcorticosteroidareactually taken, even when patients possess the medication,10,11 so the amount of medication actually taken was likely to be lower. In conclusion, the authors are to be congratulated for this pragmatic intervention study; for demonstrating the feasibility, acceptability, and sustainability of such an intervention; and for raising important questions, demonstrating the need for more pragmatic intervention studies to address them. 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