ReX is a hand-held, mobile device intended to provide solid oral medication on patient demand according to a preprogrammed treatment protocol. ReX aims to address poor patient adherence by providing personalized medication therapy management.

The system comprises a reusable drug dispensing unit (DDU), a disposable cassette, a cellphone app, and a Dose-E Analytics cloud system. Figure 1 shows the ReX device, comprising reusable DDU (1), disposable cassette containing pills (2), cellphone app (3), and Dose-E Analytics cloud system (4). The DDU manages pill administration and includes a touch screen, which guides the user and presents patient-specific clinical surveys and therapy information. The DDU contains a chargeable battery and indicators demonstrating the device and the battery status, a pill window enabling pills to be viewed, operational sensors, and Bluetooth communication to an app on a cellphone. All therapy data are transferred to a patient-specific domain on a Web-based cloud. The DDU is also used to hold and lock the disposable cassette which contains the pills.

The disposable cassette is a locked, tamper-resistant container. It is supplied preloaded with bulk pills, located 1 in each of 16 separated pill compartments. The cassette is opened only on insertion in the DDU. The cassette includes an integral mouthpiece designed for pill ingestion. The mouthpiece incorporates an antichoke mechanism, which ensures that the pill falls directly onto the tongue. An integral protective cover keeps the mouthpiece is clean and sealed. Once empty, the cassette is automatically released by the device. Cassette exchange is easily performed by the user.

The cellphone app transfers data between the DDU and the Dose-E Analytics cloud. The Dose-E Analytics cloud system is a proprietary browser-based app in which all therapies and patient information are collected and managed. The cloud allows caregivers to set up and track the therapy online and follow the patient’s adherence. When a missed dose is recorded, the cloud sends alerts to a predefined contact person or to the call center.

The adherence rate was calculated as percent of doses taken. In the ReX test, percent doses taken before and after the reminder were calculated and included in the adherence rate. Paired differences were calculated for adherence rate and percent of missed doses between the ReX test and control test for all subjects and by age categories. The paired t test and nonparametric signed-rank test for 2 means (paired observations) were applied to analyze the paired differences. All tests were 2-tailed, and a P value ≤5% was considered statistically significant. The data were analyzed using SAS 9.3 (SAS Institute, Cary North Carolina).

The initial feasibility study aimed to evaluate usability, acceptability, and ease of use of the ReX device for oral medication provision. There were 59 subjects, aged 18-92 years, in the study (Table 1).

Following a short tutorial, all subjects successfully inserted the cassette into the DDU and defined the process as easy. The usability of ReX for pill extraction was measured by the success rate of 2 pill intakes. All subjects managed 2 successful attempts at pill intake as required, and 81% (48/59) of subjects required only 1-2 attempts to extract a pill. A learning effect was evident in taking the pills: subjects were more successful in taking their second pill compared with the first.

All subjects easily grasped the concept and functionality of the screen displays. After 2 successful attempts at pill intake, 100% (59/59) of subjects understood the concept of lockout and overdose prevention, as confirmed by a third attempt at pill intake. The overall impression was very positive, with 97% (57/59) of subjects expressing confidence in using ReX by themselves and without assistance.

Figure 4 demonstrates subjects’ response regarding overall ReX ease of use: 81% (48/59) of all subjects rated the ReX device as easy to use. This rating did not appear to be influenced by years of formal education, as 100% of subjects with 6-10 and >20 years of formal education defined the ReX use as easy, while 4%-8% of subjects with 11-15 and 16-20 years of formal education, respectively, defined it as difficult.

However, analysis by age group demonstrated that ReX usability is influenced by age: 29% (2/7) of subjects >80 years old reported that ReX was difficult to use. Opinions as to ease of use slightly decreased with age. Still, 94% (16/17) of subjects aged 18-40 and 81% (42/52) of subjects aged up to 80 years defined the ReX as easy to use.

This study aimed to evaluate ReX’s usability during home use and its capability to monitor and enhance patient adherence. The study was designed as self-controlled: pill intake using ReX was compared with intake from a standard pill container as the control. The same dose regimen was used for both methods. We enrolled 40 subjects with an age range of 18-90 years, as described at Table 2.

The usability and ease of use of the ReX system were evaluated by questionnaires completed by the subjects (Multimedia Appendix 1), of whom 87% (35/40) found the ReX system easy to use, and 90% (36/40) mentioned that they felt comfortable using ReX for their medications. Moreover, when comparing between the ReX device and standard package, subjects responded that the ReX device was more effective in reminder provision (36/40, 90%) and in error prevention (38/40, 95%), and the ReX device was preferred to keep an e-dairy during medication therapy (33/40, 82%).

ReX is an innovative system designed to manage oral medication therapy by directly monitoring pill intakes, allowing high confidence in the resulted adherence rate. ReX incorporates a “tracking to the mouth” approach. This is based on a patented technology for the safe ingestion of solid pills into the patient’s mouth and digitally tracking this action to provide accurate, reliable, and real-time adherence data to stakeholders. Electronic monitoring devices have been shown to provide good-quality information on adherence rate [8] and found to hold promise of improving adherence [9-11]. Methods that involve reinforcement interventions have been successful in improving patients’ cooperation and adherence behaviors. Clear and effective communication between caregivers and their patients has been found to be essential in improving patients’ adherence [12].

An initial feasibility study was conducted to evaluate the basic usability parameters of the ReX device and acceptability of the pill extraction concept. Results demonstrated that all subjects could successfully use the device for pill intake. The device was defined as easy to use, and 81% (48/59) of subjects required only 1-2 attempts for successful pill intake. Only mature users (aged >80 years) reported more difficulty, although they all could manage and extract pills using the device. These results demonstrate the feasibility of the ReX novel technology.

Following this, we designed a 4-day home-use study to evaluate ReX safety, efficacy, and usability. The adherence rate by ReX was compared with the standard of care. The adherence rate was tested by subjects’ reports, remaining pill count, and by ReX records (during the ReX test). Although patient self-report and remaining pills counts are common methods to assess patient adherence, there is extensive evidence that such methods greatly overestimate medication adherence when compared with plasma drug levels and electronic device measurements [8,13,14]. These methods may also suffer from intentional nonadherence, including removing and discarding pills from a blister card or bottle, to create false records while reporting good adherence [8]. In contrast, the ReX approach eliminates false measurements since each pill is tracked directly during ingestion. The adherence rate is obtained in an unbiased way, without patient involvement.

The 4-day home-use feasibility study demonstrated that ReX device is safe: no adverse events, overdoses, or pill malformations were encountered. The safety of pill ingestion by sucking was previously confirmed in a clinical study evaluating the same technology for pain analgesic medication provision to postoperative patients in the hospital setting [15].

Functionality analysis revealed that all subjects could successfully use the ReX device for pill intake and that adherence data were available for the study’s principal investigators in real time. Study results showed a statistically significant difference of 21.3% in adherence rate between the ReX test and the control test (97.6% and 76.3%, respectively). It is possible that low adherence rates in the control test occurred because subjects took Tic Tac sweets and not real medication, making it less important to them. However, the same subject group achieved 97.6% adherence rate in the ReX test. Such high adherence was due to stringent monitoring of each dose by the study’s principal investigator and timely reminders to subjects in any case of delayed dose. This created effective communication and reinforcement to take the missed dose.

The adherence rate of the control test varied between the 3 different age groups of 18-40, 41-70, and 71-90 years. Only 8% (1/13) of the young subjects (age 18-40 years) took pills regularly and were, therefore, not used to taking pills. Their adherence in the control test was consequently relatively low (64.9%). However, use of ReX increased their adherence rate to 98.1%. Mature subjects (age 71-90 years) demonstrated higher adherence in the control test (86.2%). This may be because all subjects (9/9, 100%) of this age group take pills on a daily basis. However, using ReX enhanced adherence rate in all age groups. All differences in adherence rate between the ReX test and control test were statistically significant.

The ReX system also demonstrates benefits over technological solutions of adherence assessment and enhancement. An available approach is a memory chip embedded in bottle caps or blister packs that tracks medication adherence electronically. For example, the Medication Event Monitoring System cap [9] (AARADEX Group, SA), which records the date and time of each opening. However, since this system does not track the intake of each pill, a false record of dosing can easily be created [8]. A vast pool of medication adherence cellphone apps is also available to help patients manage their medication regimen [16]. However, these apps add a burden on subjects to record and update each time they take a pill. This action may be missed at the real time of pill intake. Also, usual app alerts may be ignored and missed by subjects while in routine use.

During the 4-day home-use ReX study, personalized reminders were shown to add 18% of doses taken. This explains the major difference in adherence rate between the ReX test and the control test. Notably, adherence rates were almost similar between these tests before any personalized reminder. This highlights the effect of personal reminders provided in real time and only when needed. It also confirms the minimal impact of conventional visual and acoustics alerts that automatically appeared and are often ignored by the user.

The final percent of missed doses in the ReX test (2.4%) was almost 10-fold lower than in the control test (23.7%). This observation clearly demonstrates the benefit of using ReX system to monitor and enhance adherence.

The usability of ReX was evaluated by questionnaires filled out by the subjects participating in both the ReX and control tests. After 4 days of use and 12 pill intakes, 90% (36/40) of subjects reported that they felt comfortable taking their medication via ReX, and 87% (35/40) of subjects mentioned that it was easy to use. Moreover, most subjects believed that ReX provided effective reminders (90%), was highly effective in error prevention (94%), and was most suitable to be used as an e-dairy to record symptoms during therapy (82%). These results are in agreement with the high usability and acceptance of the technology as demonstrated in a previous clinical study [15].

The feasibility studies described here demonstrate the potential of the ReX system for medication management. ReX may provide a considerable benefit in medication therapies such as: high risk drugs, to eliminate errors, overdose, and abuse (eg, opioid treatment [17], anticoagulants, or stimulants for attention-deficit/hyperactivity disorder treatment [18]); high cost drugs (eg, specialty drugs [19]); and clinical trials, in which adherence critically affects outcome reliability and study cost [20].

In summary, ReX is an innovative solution providing reliable, unbiased, and cost-effective adherence monitoring and enhancement, while safeguarding the patient by elimination of medication errors, overdose, and abuse.

Two feasibility studies confirmed the safety, efficacy, and usability of the ReX system. All objectives were achieved. Regarding ReX safety, the ReX system was safe under the study conditions; no adverse events, no pill provision during the lockout interval, no overdose, and no pill malformation were found. Evaluation of ReX efficacy demonstrated that all subjects successfully used ReX to take the pills according to their dose regimen. The data were available to the study’s principal investigator in real time, and personalized reminders were provided in any case of a 1-hour delay in pill intake. The adherence rate in the ReX test was 97.6%, significantly higher compared with the control test (76.3%). The effectiveness of real-time personalized reminders was indicated by 18% of doses in the ReX test being taken after the reminders were received by the study subjects. As for ReX usability, ReX technology was well accepted by subjects participating in the studies. Over 80% of subjects described it as easy to use and mentioned that they felt comfortable to use it for their medications.

The limitations of the study included the heterogeneous small group sizes and the use of candies and not real drugs. Also, Tic Tac sweets are chewable and are not swallowed with water like standard drugs. The adherence rate was based on self-reporting and remaining pill counts in the control test. These are known to be unreliable methods. ReX records are more reliable in the ReX test. The study design ensured that half of the subjects completed the control test before the ReX test and vice versa for the other half.