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Mobile phones enable innovative tele-, home-, and health-monitoring solutions for clinical trial subjects.
Patient reported outcomes (PROs) as subject experience measures are gathered in most phases of clinical trials (Phase II through Phase IV). Although we commonly use objective researcher-based measures within clinical trials, many effects can be determined only by asking the subjects. Those subject experience measures vary from self-observation and subjective symptoms to quality of life.
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Modern information and communication technologies enable far more possibilities in assessing subjects' health status via electronic PRO (ePRO) applications in both clinical trials and routine care than pencil and paper.1 The patients' health status includes data relating to a number of areas like quality of life, health economics, efficacy, medication adherence, side effects, and treatment satisfaction. FDA's PRO guidance ensures that the PRO instruments used are reliable, interpretable, and valid—in other words, that they measure what they are intended to measure and that they are backed up by solid, scientific rationale.2 PRO instruments including interactive voice response (IVR), personal digital assistants (PDA), digital pens, and mobile phone based applications are used more and more with interactive Web-based eHealth systems.
Web-based systems in combination with desktop-based terminals are generally considered trustworthy and reliable. However, several subjects are not in favor of using such services for more than a short period. It does not fit into their everyday lives because of the lack of ubiquity.
Mobile phones are part of people's everyday lives and enable active requests for data almost irrespective of time and place. In addition, mobile devices can include study subjects in the trial process with the promising benefits of increased subject compliance and lower efforts for data clearance. Furthermore, outcome data are collected more accurately directly at the point of occurrence, once, or if necessary several times a day. Future trends in mobile phones open up new vistas in ePRO applications—from making health data acquisition a simple intuitive process using Near Field Communication (NFC) technologies to using advanced features of mobile phones like Bluetooth, UMTS or imaging and video.
Figure 1. Electronic Patient Reported Outcome (ePRO) using mobile phones in combination with a study center.
One of the most challenging parts of ePRO applications is still the terminal, which is the ability to offer the user a method to enter measured data into a system as well as to receive feedback in a comfortable way. Every method for entering data implies specific advantages and disadvantages. When designing a mobile phone-based ePRO application, the terminal that best fits into a particular monitoring application has to be chosen on an individual basis, depending on the requirements, the user group, and the medical demand. Software specifically developed for the needs of the respective subject group is required to guide them through the data acquisition process.
Although screen size, computing power, memory capabilities, and usability levels are somehow limited, ordinary mobile phones are becoming increasingly suitable as ePRO devices. Additionally, like other handheld consumer devices, mobile phones are a part of people's everyday lives, are lightweight and portable, and relatively inexpensive. Data can also be immediately transmitted to a secure central server. Immediate feedback can be given and reminders sent to subjects to guide them through the self-managing process and help compliance with the study procedures (See Figure 1).
Figure 2. Study subjects with psoriasis are using a mobile phone with a 3.2 megapixel camera to take high-resolution pictures of their lesions.
The simplest way to deploy mobile phones as ePRO instruments is to access a Web-based service using the Internet browser of the mobile phone (XHTML browser).
We established such a Web-based service within an ongoing trial of obese patients.3 We designed appropriate electronic Case Report Forms (eCRFs) asking for medical history according to body weight, previous diets, suspected cause of obesity, motivation for the intended reduction of weight, as well as prescribed medications including dosage. Subsequently, we provided 56 patients with a preconfigured mobile phone. Pushing a particular key automatically opened the homepage of the Web-based service in the XHTML browser. Subjects who did not transmit their parameters within a period of seven days, received up to four reminder messages. Subjects who successfully transmitted their values received one out of three neutrally expressed feedback messages. On average, 14 data transmissions per patient were performed over an observation period of 70 days. Overall the patients reported 245kg (540 lbs) of weight loss within a period of about one year.
Sometimes subjects (e.g., those with type 1 diabetes mellitus) have to be active participants in their treatment because they are inevitably responsible for their own day-to-day care. Those subjects have to gather data several times a day instead of once a week, so appropriate software running on the mobile phone should simplify both data acquisition and synchronization.
We developed a software application called Diab-Memory (based on Java 2 Micro Edition) to support 10 subjects in entering diabetes-related data with synchronization to the remote database at the study center over a period of three months.4 The system has been evaluated in the course of a clinical before and after pilot trial. On average, subjects transmitted 14 values per day. We expected that more than 75% of prescheduled measurements—at least three blood glucose measurements daily—would be performed and transmitted to the monitoring center. The results indicated a therapy adherence rate of 85%. Most likely as a consequence of improved adherence, we observed a statistically significant improvement in metabolic control (HbA1c 7.9% vs. 7.5%, p < .02).
Built-in, high-resolution digital cameras enable the use of mobile phones as medical imaging devices, (e.g., for taking pictures of lesions or suspected signs of melanoma). We developed a mobile-phone based electronic therapy diary for documenting the course of patients with psoriasis during acute episodes as well as during remission phases.5 During 2008, the system will be validated in a clinical pilot study.
Besides detailed acquisition and documentation in the course of clinical examinations at the health care centers, the patients are asked to take up to five high resolution pictures of their lesions using a mobile phone with a 3.2 megapixel camera (See Figure 2). All data will be stored on the mobile phone and securely transmitted to a monitoring center via UMTS. All data transmitted by the subjects can be reviewed by the physicians via a Web interface.
Mobile phones can also be used as data terminals in clinical studies where everyday measurements of several medical devices have to be gathered in real world environments, such as at home. In the course of such a study, 14 subjects with chronic heart failure and six subjects with hypertension were monitored for 90 days.6 Each participant was equipped with a mobile phone, an automatic blood pressure device, and a digital weight scale. Every day, patients measured blood pressure, pulse, and body weight at home and transferred the data to the telemonitoring server using a wireless Internet connection of the mobile phone. The entire process of measurements and data transfer took them approximately two minutes, which was rated as acceptable.
Subjects without previous computer experience or the elderly have been less comfortable using the mobile phone as a terminal due to the relatively small keypads and displays. We are investigating innovative methods using mobile phones and NFC technologies to address the most challenging aspect of the self-management process: the human–computer interface.7 While NFC is based on RFID and contactless smart card technology, it breaks the functional separation of the reader and the transponder unit and allows bidirectional communication between two NFC-enabled devices. This permits each of the two devices to start communication on its own. Data exchange is facilitated by bringing two devices within a certain proximity range and the connection remains firm until data exchange is complete.
We developed NFC-enabled prototypes by embedding an NFC module in an off-the-shelf blood pressure meter, a weight scale, and a blood glucose meter. This allows the porting of measured values by bringing the mobile phone next to the meter's display. Special software running on the mobile phone fetches the information from the medical device, adds a timestamp, and initializes the transmission to the study center automatically. Hence, no cumbersome and error-prone user interaction and configuration is needed.
Several studies have shown that mobile phones can successfully be used for ePRO applications in real world environments. Mobile phones are a part of people's everyday lives enabling them to gather PRO measures directly at the point of occurrence—once a week or, if necessary, several times a day. The studies presented indicate the wide range of applications—from obesity to subjects with diabetes mellitus or psoriasis.
The appropriate usage of certain features of mobile phones—from simple Internet browsers to advanced applications using mobile Java software and Imaging—in combination with immediate feedback and reminders guides the subject through the PRO process, improving adherence. Recent and future developments like NFC will further strengthen the possibility to establish mobile phones in ePRO applications.
Günter Schreier,* PhD, MSc, is head of eHealth systems at Austrian Research Centers GmbH-ARC, Reininghausstrasse 13, Graz, 8020, email: firstname.lastname@example.org. Robert Modre-Osprian, PhD, is senior scientist and project manager, and Peter Kastner, MSc, MBA, is ePRO specialist, business development manager, also at Austrian Research Centers.
*To whom all correspondence should be addressed.
1. S. Shiffman, M. Hufford, J. Paty, "Subject Experience Diaries in Clinical Research, Part 1: The Patient Experience Movement," Applied Clinical Trials, February 2001, 46-56.
2. A.L. Shields, C.J. Gwaltney, B. Tiplady, J. Paty, S. Shiffman, "Grasping the FDA's PRO Guidance," Applied Clinical Trials, August 2006, 69-83.
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4. A. Kollmann, M. Riedl, P. Kastner, G. Schreier, B. Ludvik, "Feasibility of a Mobile Phone-based Data Service for Functional Insulin Treatment of Type 1 Diabetes Mellitus Patients," Journal of Medical Internet Research, 9 (5) e36 (2007).
5. G. Schreier, D. Hayn, P. Kastner, S. Koller, W. Salmhofer, R.H. Wellenhof, "A Mobile-Phone based Teledermatology System to Support Self-Management of Patients suffering from Psoriasis," Proceedings of the IEEE EMBC Conference, Vancouver (August 2008).
6. D. Scherr, R. Zweiker, A. Kollmann, P. Kastner, G. Schreier, F.M. Fruhwald, "Mobile Phone-based Surveillance of Cardiac Patients at Home," Journal of Telemedicine and Telecare, 12 (5) 255-261 (2006).
7. J. Morak, A. Kollmann, G. Schreier, "Feasibility and Usability of a Home Monitoring Concept Based on Mobile Phones and Near Field Communication (NFC) Technology," Medinfo, 12 (Pt 1) 112-116 (2007).