Overview

• This project with participants recruited online across the nation utilized a smartphone app-based program to improve hypertension outcomes.
• The objective of this trial was to determine if the Medisafe smartphone app improves self-reported medication adherence and blood pressure control in individuals with uncomplicated essential hypertension across the United States.

Organization Name

Center for Healthcare Delivery Sciences, Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women’s Hospital Center; Evidation Health

Organization Type

• Academic Medical Center
• Business

National/Policy Context

• Hypertension is the leading risk factor for cardiovascular diseases worldwide.
• The rate of hypertension has increased steadily to 20,525 per 100,000 individuals in 2015 from 17,307 per 100,000 individuals in 1990. The current global burden of hypertension exceeds 1.4 billion individuals. 
• Poor adherence to medication is the driver of uncontrolled hypertension in more than half of patients.
• Mobile health apps have been recommended as strategies to assist in self-management of hypertension.
• To date, the effect of smartphone technology on controlling blood pressure has been studied by researchers in clinic-based settings. The studies were focused on improving disease management by using mobile technology to foster communication between patients and their physicians but not on using mobile apps as a stand-alone intervention. 

Patient Population Served and Payor Information

• The participants lived all over the United States in rural, suburban, and urban locations. They were recruited via an online platform rather than at specific sites.
• Participants were aged between 18-75 years with a mean age of 52.0.
• All of them had a systolic BP of 140 mm Hg or greater and were prescribed at least one but not more than 3 first-line antihypertensive medications at the time of the study.
• 60% of the participants were female and 25% were of black ethnicity.

Leadership

• Niteesh K. Choudhry, MD, PhD served as the principal investigator who supervised all aspects of the study including the design of the study concept, data acquisition, analysis, and interpretation of data, manuscript writing, statistical analysis, and funding acquisition.

Funding

• The project was supported by an unrestricted grant from Medisafe Inc.

Research + Planning

• The scientific protocol and all patient facing materials for the study were developed by scientists at Brigham and Women’s Hospital.
• Blood pressure pumps were purchased by Evidation and sent to participants.
• Announcement of the study was done by Evidation Health online via various virtual platforms like online patient communities, social media, and advertisements.

Tools or Products Developed

• Medisafe app: It is a smartphone application that alerts individuals to take their prescribed medication at specified times and allows patients to track their blood pressure.
• Baseline survey: A survey used to collect each patient’s demographics and cardiovascular morbidities.
• Hypertension knowledge questionnaire: A questionnaire used to assess the patient’s current knowledge and attitude toward hypertension.

Training

• The scientific team at Brigham and Women’s Hospital oversaw this study. Study related operations and data collection was overseen by Evidation. The implementation of the project did not require specific training, other than familiarity with the study protocol and procedures. Enrollment began on April 25, 2016 and was completed on September 16, 2016. (The full details of the trial design have been published previously)

Tech Involved

• Remote Patient Monitoring
• Bluetooth Blood Pressure Monitor
• Smartphone App
• Medisafe
• Software Program

Team Members Involved

• Clinical Informatics Specialist
• Data Analyst
• Physicians
• Researcher

Workflow Steps

• Patients were recruited via the internet, using platforms like online patient communities, social media, and mobile apps.
• Potential participants completed a baseline demographic and cardiovascular morbidity survey, MMAS-8, hypertension knowledge questionnaire, and the Consumer Health Activation Index. 
• Potentially eligible individuals were then mailed a Bluetooth-enabled blood pressure monitor with instructions to provide 2 blood pressure measurements 5 minutes apart in accordance with the US Preventive Services Task Force guidelines. Their BP was calculated as an average of these measurements.
• The BP measurements were electronically sent to Evidation Health via an Application Program Interface with the manufacturer of the BP monitor. The patients sent the BP measurements by sending time-stamped photos of their monitor display if they were unable to activate the application associated with the Bluetooth-monitor.
• Patients in the intervention arm were instructed to download the Medisafe app. Those in the control arm were not.
• Their individual medication lists and timing of administration are entered manually or auto populated by linking the app to an existing medical record.
• The app then alerts the user to take their medication according to the timing they specified. 
• Patients who did not have one login to the app within two days of randomization were sent reminders via telephone and email. 
• If patients had not logged in after multiple follow-up attempts, they were not contacted further. Outcomes were analyzed using intention-to-treat principles. 
• Both the control and intervention arm underwent follow-up assessments at 4, 8, and 12 weeks after enrollment. Each follow-up assessment was done virtually and included a BP measurement using the study-provided BP monitor. 
• The 12 week follow-up assessment included an exit survey that assessed adherence to medication, hypertension knowledge, and patient activation. Patient adherence was measured using a self-reported measure and validated assessment tool called the 8-item Morisky medication adherence scale (MMAS-8). Knowledge of hypertension was assessed with the hypertension questionnaire. Patients’ ability to manage their own health was assessed with a patient activation assessment tool called the Consumer Health Activation Index.

Budget Details

The following sources of costs were provided by the authors:

• Compensation of $150 for each study participant
• Cost of Bluetooth blood pressure monitors for each participant.
• Labor costs associated with the app’s  administrative and technical support.

Where We Are

• Date (Month/Year) Project Described Started: April 2016 – January 2017
• Date (Month/Year) Paper Published: April 16, 2018

Outcomes

• Change in self-reported adherence: The mean (SD) adherence to medication, as reported on the MMSA-8 scale, increased by 0.4 (1.5) in the intervention group from a baseline of 6.0 (1.8) and remained unchanged among the controls from the baseline of 5.7 (1.8) at 12 weeks follow-up. 
• Change in SBP: There was no significant difference in blood pressure measurements between both the groups at the end of the 12 week follow-up. The mean (SD) systolic BP decreased by 10.6 (16.0) mm Hg in the intervention group. It decreased by 10.1 (15.4) mm Hg in the control group. 
• Number of participants with blood pressure controlled to under 140/90 mm Hg or less: Good control, defined as BP of 140/80 mm Hg or less, was achieved by 35.8% in the intervention arm vs 37.9% in the control arm.

Benefits

• There was significant improvement in self-reported medication adherence.
• The Medisafe app was useful in engaging the patients in their own care although it didn’t lead to a significant improvement in outcomes.

Unique Challenges

• Medication adherence was measured by self-report, and may overestimate true adherence.

Sources

• This primer was developed by the CareZooming team based on our interpretation and analysis of a paper with consent and permission of the author and/or their representatives. Dr. Niteesh Choudhry and Dr. Roya Ghazinouri and/or their representatives reviewed the contents of this primer before publication, and all requested edits have been incorporated into the primer as presented above.
• Morawski K, Ghazinouri R, Krumme A, Lauffenburger JC, Lu Z, Durfee E, Oley L, Lee J, Mohta N, Haff N, Juusola JL, Choudhry NK. Association of a Smartphone Application With Medication Adherence and Blood Pressure Control: The MedISAFE-BP Randomized Clinical Trial. JAMA Intern Med. 2018 Jun 1;178(6):802-809. doi:10.1001/jamainternmed.2018.0447. Erratum in: JAMA Intern Med. 2018 Jun 1;178(6):876. PubMed PMID: 29710289; PubMed Central PMCID: PMC6145760.
• Morawski K, Ghazinouri R, Krumme A, McDonough J, Durfee E, Oley L, Mohta N, Juusola J, Choudhry NK. Rationale and design of the Medication adherence Improvement Support App For Engagement-Blood Pressure (MedISAFE-BP) trial. Am Heart J. 2017 Apr;186:40-47. doi: 10.1016/j.ahj.2016.11.007. Epub 2016 Dec 9. PubMed PMID: 28454831.
• Rehman H, Kamal AK, Morris PB, Sayani S, Merchant AT, Virani SS. Mobile Health (mHealth) technology for the management of hypertension and hyperlipidemia: slow start but loads of potential. Curr Atheroscler Rep. 2017;19(3):12. [PubMed: 28210974]
• Forouzanfar MH, Liu P, Roth GA, et al. Global Burden of Hypertension and Systolic Blood Pressure of at Least 110 to 115 mm Hg, 1990-2015. JAMA. 2017;317(2):165–182. doi:10.1001/jama.2016.19043
• Huffman MD, Lloyd-Jones DM. Global Burden of Raised Blood Pressure: Coming Into Focus. JAMA. 2017;317(2):142–143. doi:10.1001/jama.2016.19685
• Egan BM, Kjeldsen SE, Grassi G, Esler M, Mancia G. The global burden of hypertension exceeds 1.4 billion people: should a systolic blood pressure target below 130 become the universal standard? J Hypertens. 2019 Jun;37(6):1148-1153. doi: 10.1097/HJH.0000000000002021. PubMed PMID: 30624370.
• Required citation and acknowledgement for the 8-item MMAS are as follows:
  • Morisky DE, Ang A, Krousel-Wood M, Ward H. Predictive Validity of a Medication Adherence Measure for Hypertension Control. Journal of Clinical Hypertension 2008; 10(5):348-354 
  • Krousel-Wood MA, Islam T, Webber LS, Re RS, Morisky DE, Muntner P. New Medication Adherence Scale Versus Pharmacy Fill Rates in Seniors With Hypertension. Am J Manag Care 2009;15(1):59-66
  • Morisky DE, DiMatteo MR. Improving the measurement of self-reported medication nonadherence: Final response. J Clin Epidemio 2011; 64:258-263. PMID:21144706 
  • Use of the ©MMAS is protected by US copyright laws. Permission for use is required. A license agreement is available from: Donald E. Morisky, ScD, ScM, MSPH, Professor, Department of Community Health Sciences, UCLA Fielding School of Public Health, 650 Charles E. Young Drive South, Los Angeles, CA 90095-1772, dmorisky@ucla.edu.