Rationale
Glaucoma refers to a group of eye conditions that lead to damage to the optic nerve, which carries information from the eye to the brain. If uncontrolled, glaucoma first causes peripheral vision loss and eventually can lead to blindness. Glaucoma affects approximately 60 million people worldwide and is one of the leading causes of irreversible blindness [
1]. In Singapore, glaucoma, affects roughly 3 % of those over age 40 and the total number of cases is growing due to Singapore’s ageing population [
2,
3]. The most important modifiable factors of visual field loss in glaucoma are peak intraocular pressure (IOP), average IOP and fluctuations in IOP [
4‐
7]. The majority of patients with glaucoma or suspected glaucoma are initially managed by IOP-reducing single or multi-drug treatments consisting of topical eye drops. This could be followed by surgical treatment for those whose IOP is not adequately controlled via medications [
8,
9].
Correct use of medicated eye drops reduces IOP, subsequently slowing visual field loss for nearly 90 % of patients [
10‐
13]. Despite the effectiveness of topical medication in controlling disease progression, roughly two-thirds of patients report some level of medication non-adherence to their medication [
14‐
16]. Interventions to enhance medication adherence often focus on one or a combination of four strategies: simplification, education, social support and behaviour modification [
17]. Most simplification interventions focus on reducing the number of doses per day, perhaps through extended-release capsules, or the number of medications [
17]. Simplifying dosage requirements has consistently been shown to improve adherence [
17‐
19]. However, there is evidence of non-adherence amongst glaucoma patients taking only one topical medication [
20]. Education and social support interventions aim to increase adherence through greater knowledge transfer and increased self-efficacy. Education and social support interventions have shown some evidence of effectiveness in the short term, but results are less compelling in the long term [
21,
22]. Behavioural interventions cover a wide range of strategies, such as pill organizers, reminder systems, and tailored regimens [
17]. These studies too have shown mixed results, with both positive and negative results relating to the effectiveness of reminders, and no agreement on which behavioural intervention works best [
23‐
26]. In a review of randomized control trials that seek to improve medication adherence, those that were most effective were multi-faceted, and included combinations of convenience, education, reminders, and reinforcement [
19]. However, even the most effective interventions reviewed did not lead to large improvements in adherence. As a result, other strategies are needed.
Behavioural economics theory suggests that an important factor of non-adherence is that patients do not perceive a clear cause-and-effect relationship between non-adherence and the increased likelihood of disease progression, which may not occur until well into the future [
27,
28]. As a result, many patients do not internalize the consequences of non-adherence until it is too late. One strategy to rectify this problem is to provide a short-term reward for increased adherence. Giuffrida et al. [
29] reviewed 11 randomized incentive trials conducted in the United States where patients were paid either cash, gifts or vouchers for meeting adherence targets to various treatments and health services. These rewards, which ranged in value from USD5 to nearly USD1000, showed improve adherence in 10 out of the 11 studies reviewed. However, none focused on glaucoma patients and results varied widely across studies, suggesting that more research is needed to identify an optimal strategy to cost-effectively improve medication adherence [
30].
In this trial we test a novel approach to improve medication adherence among glaucoma patients. The approach consists of adherence-contingent rebates on medication and check-up costs that are granted only when adherence goals are met as verified by a medication event monitoring system. Given that prescription refills and follow-up clinic visits occur regularly, the rebates provide a tangible and near-term benefit resulting from medication adherence. This strategy, which has been suggested by Loewenstein and colleagues [
31], can be seen as a novel form of value pricing (VP) in the context of value-based insurance designs [
32]. With standard value-based insurance designs, the co-payment for clinically effective treatments is reduced in efforts to increase their utilization. With our intervention design, incentives are allocated to medications that have not only been shown to be clinically effective, but that are also being effectively used by the patient, which represents a better use of resources. Another important feature of our approach is that incentives are provided in the form of rebates on costs already incurred by the patient. By offering a rebate that avoids a loss, as opposed to an equally sized reward, loss aversion theory predicts that this approach is likely to have a greater behavioural response [
33].
This trial will provide evidence on whether adherence-contingent rebates can improve medication adherence among non-adherent glaucoma patients. Secondary objectives are to determine whether IOP and quality of life can also be improved, and whether the intervention represents a promising strategy to cost-effectively improve glaucoma management. Finally, explanatory analysis will aim at uncovering factors that might moderate the intervention effect and explain medication adherence.
Objectives
Primary objective: determine whether complementing usual care (UC) with adherence-contingent rebates according to a VP strategy is superior to UC alone in improving medication adherence between baseline and month 6.
Secondary objective 1: determine whether the IOP of patients in the VP arm improves more (or deteriorates less) than that of patients in the UC arm between baseline and month 6.
Secondary objective 2: determine whether the glaucoma-related (GQL-15) and generic health-related (EQ5D-5 L) quality of life of patients in the VP arm improves more (or deteriorates less) than that of patients in the UC arm between baseline and month 6.
Secondary objective 3: determine whether the incremental cost-effectiveness ratio (ICER) of VP compared to UC will be favourable relative to international benchmarks for cost-effectiveness.