Table 4.
Study details and results from all identified studies of Proteus Discover (ingestible sensors) (adherence, clinical outcomes, and health care resources use)
| Study name | Study objective | Study design | Indication | Sample size | Follow-up period | Key results |
|---|---|---|---|---|---|---|
| Au-Yeung and DiCarlo (2012)43 | To compare costs of direct confirmation of treatment using WOT vs SOC utilizing WHO-recommended 7-day and 3-day DOT | Prospective (economic model) | Tuberculosis | NA | NA | • Health facility cost-to-treat with WOT was 36% of 7-day DOT and 71% of 3-day DOT • Patient cost-to-be-treated with WOT was 4% of 7-day DOT and 8% of 3-day DOT • Public health worker time/subject treated using WOT was 34% of 7-day DOT and 67% of 3-day DOT • Total cost for 7-day DOT was US$3,472 (86% personnel cost; 13.5% retreatment cost) • Total cost for 3-day DOT was US$1,772 (73% personnel cost; 27% retreatment cost) • Total cost for WOT was US$1,273 (38% personnel cost; 61% retreatment cost) |
| Bonacini et al (2017)41 | To evaluate real-world adherence in chronically infected HCV patients treated with SOF/LDV and using the Digital Medicine Offering | Prospective, single-arm | HCV | 28 | 12 weeks | • Patient age (mean) was 59 years • Patients used the Digital Medicine Offering for 92% of expected days; mean ingestion adherence was 94% • Sustained virologic response at 12+ weeks was achieved in 20 of 22 patients (data for six patients were not available) |
| DiCarlo et al (2014)38 | To evaluate the utility of the Proteus® system in patients with uncontrolled hypertension | Prospective | Hypertension | 190 | 14 days | • Patient age was not reported • In patients with complete data (89%), mean medication adherence was 88% • Mean SBP decrease was −7.6 mmHg; mean DBP decrease was −3.8 mmHg • 78% patients had >70% adherence; 53% achieved BP control on prescribed therapy; 25% remained uncontrolled and required treatment modification |
| Frias et al (2017)36 | To assess the impact of digital medicine offerings on BP and glycemic and lipid control | RCT | Hypertension and T2DM | 109 | 4 and 12 weeks | • Patient age (mean ± SE) was 57.8±1.1 years in the Proteus group and 61.6±1.7 years in the usual care group • Medication adherence was ≥80% (calculated for Proteus only) • Hypertension ○ At week 4, the combined Proteus groups had a mean change in SBP from baseline of –21.8 mmHg (SE 1.5) compared with –12.7 mmHg (SE 2.8) for usual care (mean −9.1, SE 2.9, 95% CI 14.8, 3.3 mmHg) ○ A greater proportion of participants in the Proteus group achieved their BP goal (81%, 65/80) compared with usual care (33.3%, 9/27) (95% CI 18.5, 77.3) ○ At week 12, 98% (39/40) of Proteus participants achieved their BP goal compared with 51.7% of usual care participants (95% CI 7.1, 84.5) • Diabetes ○ There was a nonsignificant difference in HbA1c reduction in favor of the Proteus group, compared with usual care (4-week Proteus group mean =−0.32% SE 0.22; 12-week Proteus group mean =−0.08% SE 0.22%; usual care mean =0.28% SE 0.35%) ○ For participants with a baseline HbA1c of ≥8%, the Proteus group experienced a larger HbA1c decrease compared with an increase in HbA1c seen in the usual care group (difference from 4-week Proteus group −0.98%, 95% CI –1.72,–0.24; difference from 12-week Proteus group −0.57%, 95% CI –1.53, 0.39) ○ The differences in change in LDL-C between the Proteus groups and the usual care group were –33.2 mg/dL (95% CI –50.6,–15.8) at week 4 and –19.2 mg/dL (95% CI –36.4, –2.0) at week 12 |
| Godbehere and Wareing (2014)39 | To assess the impact of digital medicine offerings on BP | Prospective | Hypertension | 8 | 2 weeks | • Patient age varied from 49 to 62 years • Taking adherence ranged from 70% to 100% • Timing adherence ranged from 67% to 100% • BP decreased in all patients (−7/+6 mmHg to −54/–24 mmHg) |
| Kim et al (2014)44 | To assess the impact of a digital health feedback system in uncontrolled hypertensive patients | Prospective study (economic model) | Hypertension | 164 | 1 year | • Patient age was not reported • The system was estimated to result in $7.3–$18.3 million in savings ($328–$717 per BP at goal), and to lead to a 3%–9% reduction in the number of CAD and stroke events in 1 year |
| Kim et al (2015)45 | To assess the impact of digital medicines with a mobile app in patients with comorbid hypertension, diabetes, hypercholesterolemia | Prospective study (economic model) | Hypertension, T2DM, and hypercholesterolemia | NR | 1 year | • Estimated cost offsets of the Proteus service offering were $90–$185/month of use (including reimbursements) • Estimated medical cost savings (reductions in outpatient/inpatient services, monitoring, disease management, medication costs) were $850–$980 (5%–11% reduction in diabetes and CVD complications) • Revenue opportunities presented an additional value equating to $80–$95 PPPY, bringing total value of the Proteus offering to $1,020–$1,260 PPPY |
| Moorhead et al (2017)37 | To study the incremental impact of seeing vs not seeing Proteus medication dose reminders on medication taking; and to assess the safety of the Proteus medication dose reminders for the possible risk of overdosing | Cluster RCT | Hypertension and type 2 diabetes mellitus | 57 | 12 weeks | • Patient age (mean ± SD) was 58.0±10.5 years • Proteus device reminder messages were associated with a 16%±16% increase (75%±18% when seeing vs 59%±24% when not seeing mobile dose reminders) in medication taking (when not taken before dose reminder) • The average daily adherence was 85.9%±11.7% • 79% of subjects (45 of 57) achieved >80% adherence • There were no overdose events related to Proteus medication dose reminders |
| Naik et al (2017)40 | To assess the usability and acceptability of passive electronic monitoring for managing hypertension | Prospective cohort | Hypertension | 167 | 2 weeks | • Patient age (mean ± SD) was 68.0±9.0 years • Taking adherence ranged from 53% to 100%, and timing adherence ranged from 21% to 100% • SBP decreased from 154±13 to 145±18 mmHg (P<0.001) and DBP decreased from 85±11 to 80±12 mmHg (P<0.001) • 32% of registry participants were found to be capable of achieving BP control using their chronically prescribed medications |
| Sullivan et al (2017)42 | To monitor patterns of adherence using ingestible digital transmitter and to assess transplant outcomes | Prospective, single-arm, observational | Liver and renal transplant recipients | 30 | 3 months | • Patient age (mean ± SD) was 14.0±3.6 years • The average patch wear adherence was 78% and average digitized medication adherence was 89.3% • While there was no change in emergency department visit rates in the study period, there was a reduction in hospital admissions |
| Virdi et al (2016)77 | To assess the impact of a digital health feedback system in hypertensive patients | Cluster RCT | Hypertension | 103 | 4 weeks | • Patient age (mean) was 58.4 years • Proportion of patients that achieved the BP target was 83.3% in the Proteus group and 33.3% in the usual care group (95% CI 23.62, 76.38) • Average adherence measured by feedback system was 84% (80%–89%) |
Abbreviations: BP, blood pressure; CAD, coronary artery disease; CVD, cardiovascular disease; DBP, diastolic blood pressure; DOT, directly observed therapy; HCV, hepatitis C virus; HbA1c, glycosylated hemoglobin A1C; LDL-C, low-density lipoprotein cholesterol; LDV, ledipasvir; NA, not applicable; NR, not reported; PPPY, per patient per year; RCT, randomized controlled trial; SBP, systolic blood pressure; SE, standard error; SOC, standard of care; SOF, sofosbuvir; T2DM, type 2 diabetes mellitus; WHO, World Health Organization; WOT, wirelessly observed therapy.