With recent National Institute of Health (NIH) and British Society of Haematology (BSH) guidelines recommending the use of hydroxyurea in SCD patients from 9 months of age [35, 36], optimizing adherence across the lifespan is more essential than ever and understanding barriers to adherence may provide valuable and actionable insights. Our study contributes to the emerging literature on hydroxyurea adherence and is the first to examine adherence, HRQOL and attitudes towards technology-based platforms in an Irish context. The number of SCD patients in Ireland has expanded significantly over the past 20 years, reflecting the changing face of the Irish healthcare system. This dynamic patient population therefore represents a unique perspective to inform international SCD research.
Forgetfulness was the most common barrier to hydroxyurea adherence with access barriers being less prevalent, findings which are consistent with other studies [3, 37, 38]. Although knowledge gaps and lack of information have been previously reported as barriers to adherence in SCD [19, 39, 40], these issues were less apparent in our cohort with 92% self-reporting a good understanding of their medication.
Despite this, levels of hydroxyurea- and overall health-related anxiety were high. Importantly, anxiety levels were significantly higher among young adults than adolescents. While elevated anxiety levels have been identified in children and adolescents with other chronic health conditions such as type 1 diabetes and haemophilia [41, 42], few studies have evaluated anxiety in AYA with SCD. Our findings suggest that health and medication-related anxiety is common and healthcare providers should be cognisant of anxiety among adolescents and especially young adults with SCD, which may simultaneously impact upon both quality of life and medication adherence.
Although we did not observe a difference in adherence between adolescents and young adults in this study, increased age and negative perceptions of medication have previously been identified as risk factors for non-adherence and worse HRQOL outcomes in SCD [2, 22]. The finding that young adults were significantly less likely to receive family prompting and are more likely to omit their medication deliberately (not due to forgetting) or due to perceived side effects than adolescents is reflective of patients’ increased independence as they grow older and exert more autonomy over their healthcare decisions. These data highlight the importance of self-management skill-building in AYA with SCD to promote hydroxyurea adherence in adulthood and later life.
Previous studies have shown that patients with higher hydroxyurea adherence rates have better HRQOL [3, 11, 12]. Consistent with these findings, we observed that participants with recall barriers had a significantly reduced hydroxyurea adherence using a VAS. Moreover, respondents with recall barriers were less physically able to do the activities they most enjoy. Due to the cross-sectional nature of this study, directionality of any cause-and-effect relationship between recall barriers and HRQOL outcomes such as physical ability cannot be determined. Additionally, in AYA with SCD, deficits in cognitive and executive functioning may be present which could reflect disease severity and impact HRQOL as well as contributing to recall barriers. Although we did not detect a statistically significant difference for other HRQOL domains (e.g. pain, fatigue and poor concentration), this could be related to our small sample size and relatively low statistical power.
Evidence from a recent systematic review of interventions to improve medication adherence in general including eHealth technologies suggest that smartphone applications have the potential to improve medication adherence in SCD [23, 43]. The majority of our cohort expressed interest in a potential app to improve hydroxyurea adherence. Interestingly, patients with recall barriers were significantly more likely to express an interest in the app, specifically in the daily reminder feature, than those without. This suggests that poor recall does not necessarily indicate a lack of patient engagement or willingness to take medication if appropriate prompting and support systems are available. Discussion forums were significantly more popular among young adults than adolescents, again reflective of the increased independence of the former group.
Our study has some limitations that warrant discussion. Firstly, this was a cross-sectional study using convenience sampling and the relatively small sample size may have constrained our ability to find statistically significant relationships between some hydroxyurea adherence barriers and HRQOL scores. Additionally, patients with poor attendance who did not get an opportunity to complete the survey may have provided further insight. Nevertheless, the fact that the study was carried out at two separate hospitals which are the largest and only tertiary SCD referral centres in Ireland adds strength to the findings and generalisability of the study. Furthermore, although absolute numbers of respondents are relatively low (n = 63), this sample represents over 10% of the Irish SCD population. Secondly, we evaluated hydroxyurea adherence using self-reported measures and this method may over-estimate adherence [16, 17, 44]. Supplementation of self-reported data with objective measures such as pill-counting or surrogate laboratory markers of adherence (e.g. haemoglobin F percentage) has been used in other studies [3, 45, 46]; however, this was not possible here due to the anonymous nature of our survey. Information pertaining to indications for treatment, current and maximum tolerated dose of hydroxyurea were also unavailable for the same reason. Finally, we did not explore details in relation to technology access or socioeconomic factors which may influence both adherence barriers and access to technology. However, studies in the USA indicate that the majority of AYA SCD patients have access to smartphones, findings which are likely generalizable to other developed countries such as Ireland [34, 47].
Future developments of any eHealth interventions including smartphone applications should include patient input from the outset of intervention design to ensure both long and short term engagement. Additional consideration must be given to cost analysis of any eHealth intervention going forward as there is a paucity of economic data to support the use of eHealth interventions to date [48, 49].