Tim Davis

The role of Real-World Evidence (RWE) in assessing the value of new drugs is increasingly important. RWE typically consists of many types of Real-World Data (RWD) captured by patients directly reporting on their own health outcomes as they take a new drug in their everyday lives.

These patient reported outcomes (PROs) are captured in observational studies, pragmatic trials, and commercial programs. Each of these types of RWD program involves different methods and RWD capture challenges, which are being overcome by novel technological solutions.

In previous blogs we explored this in relation to 

. In the last of this three-part series, we look at how the healthcare industry is starting to harness patient generated RWD as a valuable by-product of commercial programs.

		Pharmaceutical companies are increasingly implementing commercial programs that engage with patients to offer support as they take new treatments in the real world. These patient support programs usually occur after the new drug has been licensed and is available on the market. Commercial programs range from simple apps to more advanced programs that help patients manage their health and maintain their daily routine while taking the treatment.

		By setting up these programs, pharmaceutical companies are aiming to improve patient support and protect the integrity of their brand. An important by-product is the rich source of RWD that they generate.

		How can technology support RWD capture in commercial programs?

		Capturing data in this manner enables companies to engage with patients and support them on a personal level while protecting their brand. One of the by-products of a commercial program that employs electronic data capture is humanistic RWD. This can be used to enhance health outcomes, educate patients, and facilitate discussions between patients and care providers.

		An example of an electronic data capture platform effectively supporting commercial programs and RWD capture is TARGET My Hives, a digital health network set up to support everyone affected by chronic urticaria (hives). 

		The community that uses this digital health network can interact with others suffering from chronic urticaria to reduce feelings of isolation. The network enables patients to set goals for themselves, share their results with each other, and connects them with physicians to help manage their condition. Discussions on digital networks like these can generate valuable information about patients’ specific conditions and treatment journeys that hold the potential to support RWD programs.

		This blog series has outlined how digital platforms are enhancing the efficiency, cost-effectiveness, and reliability of RWD capture in observational studies, pragmatic trials, and commercial programs.

		Such RWD programs improve the quality of RWE, allowing healthcare stakeholders to make more effective and informed decisions that will benefit patients’ lives.

Articles

In this three-part blog series, we look at how electronic platforms can support and enhance data capture in several types of RWD programs: observational studies, pragmatic trials, and commercial programs.

Utilizing Real-World Data Captured During Commercial Programs

A primary focus of the healthcare industry is to generate Real-World Evidence (RWE) to better inform decision making. A key source of RWE comes from patients reporting on their own health outcomes as they participate in Real-World Data (RWD) programs, including observational studies, pragmatic trials, and commercial programs. 

In the first of this three-part blog series, we explored how RWD generated by observational studies can be harnessed effectively. Here we look at pragmatic trials-which have recently re-emerged to generate valuable RWD-and assess how technological solutions are ideally placed to support RWD capture in this setting. 

	Pragmatic trials are gaining momentum in post-marketing research as they are still interventionalâyet carried out in real-world settings. Designed to evaluate the effectiveness of treatment interventions in routine general practice, pragmatic trials provide data that can be generalized and applied in real-world settings. As such, they are an increasingly valuable source of RWD. 

	What role does technology play in pragmatic trials? 

	In this digital age, patients have expectations for digital tools to be intuitive and user friendly, like those they can download and use in their everyday lives. Electronic data capture methods can support pragmatic trials through enabling patients to use their own devices, known as a ‘Bring Your Own Device’ (BYOD) approach. Digital platform solutions allow sponsors to easily collect patient reported outcomes and health-related quality of life assessments in real-time, in a regulatory compliant manner. 

	Patients benefit from the ease-of-use of a BYOD approach in pragmatic trials. They can also access a broad range of engaging and motivational digital content to further improve their experiences. For example, they can view videos about their condition, ask questions through scripted chat-bots, and even integrate other personal devices, such as activity monitors, into the data capture platform if appropriate. 

	Depending on the requirements of the sponsor, some or all of these capabilities can be implemented using the digital platform. The flexibility of a digital platform means they can be adapted to meet the specific needs of each trial, allowing study teams to balance internal validity versus real-world effectiveness. Electronic capture solutions help to ensure the collection of high quality RWD supported by a full audit trail to aid future regulatory approval processes. 

	BYOD in pragmatic trials is highlighting the importance of digital capture technology in post-approval research. Sponsors can now assess the effectiveness of a treatment in an environment that can be generalized and applied to real-world settings, while operating in a regulatory compliant manner that does not increase burden on patients or compromise the quality of the data. 

	Look out for the third blog in this series ‘Utilizing Real-World Data Captured during Commercial Programs’ next week!

Generating a Rich Source of Real-World Data Through Pragmatic Trials

The capture of patient generated Real-World Data (RWD) is increasing the influence and value of the ‘patient voice’ in RWE and healthcare decision making. The electronic capture of RWD is facilitating this by overcoming the challenges presented by paper-based capture. 

In this three-part blog series, we look at how electronic platforms can support and enhance data capture in several types of RWD programs: observational studies, pragmatic trials and commercial programs. We reveal the challenges of RWD capture in each setting and how technological solutions can overcome them. 

Here, we focus specifically on observational studies, including why they are an important source of RWD, and why electronic data capture platforms are essential to ensuring effective RWD capture in this setting.

	In post-marketing research, observational studies are used to assess health outcomes in a group of patients as they take a new treatment. They are non-interventional by design, recording what happens to patients via patient reported outcomes (PROs). These studies often involve capturing patient data from geographically diverse populations over long periods of time.

	What are the primary challenges of observational studies?

	A substantial burden can be placed on patients to complete regular and timely data entries using paper forms. This burden must be carefully balanced; too little and the integrity of the data will be compromised, while too much will tip the scales and may impact patient outcomes.

	Electronic data capture platforms used on patients’ own devices (smartphone, tablet, etc.) can help to reduce the burden placed on participants in observational studies. Since they are already familiar with their own devices, patients find it easier and quicker to provide accurate data entries. This approach enables studies to offer a light level of support, limiting intervention and the introduction of bias, while being widely accepted by ethics committees. Digital platforms also enable the use of data protection and privacy tools to ensure security and adherence to clinical rigor.

	Electronic data capture platforms overcome the limitations of paper-based data entries. For example, they allow reminders to be sent to participants to complete data entries on time, are globally scalable, and are adaptable to different healthcare systems and languages to ease RWD capture wherever patients are in the world.

	Digital platforms ensure the efficient capture of high quality RWD in observational studies by reducing the burden placed on patients and overcoming the limitations of paper-based data collection, generating a rich source of RWE that represents the voice of the patient and informs meaningful healthcare decisions.

	Check back next week for Part 2 of the series, ‘Generating a Rich Source of Data through Pragmatic Clinical Trials.’ 

In this three-part blog series, we look at how electronic platforms can support and enhance data capture in several types of RWD programs: observational studies, pragmatic trials, and commercial programs. 

Overcoming the Challenges of Real-World Data Capture in Observational Studies

	Electronic data collection has grown rapidly over the course of the last ten years and has already emerged as a common asset in clinical research for the completion of Clinical Outcome Assessments (COA), including the outcomes captured directly from patients, known as patient reported outcomes (PRO). The global growth of mobile technology over recent years has provided a new and efficient method of accessing patients, creating an ideal platform for capturing eCOA assessments.

	At its core, mobile technology is able to support the diaries, scales and questionnaires required for capture of PROs during trials, however the advantage mobile ePRO holds over paper and other types of ePRO devices lies in the provision of a simple intuitive interface for patients, that facilitates the 2-way communication so important to keeping patients engaged including educational and motivational content delivered via messaging and in-app notifications throughout their participation in a clinical trial.

	The use of mobile ePRO is now becoming commonplace, and the barriers to adoption have been broken down through the incorporation of data security measures to protect patient data, the validation of a huge range of instruments from paper entry to mobile, and the reassurance of regulatory acceptability – both through public statements such as comment last year from the FDA that the “BYOD (bring your own device) approach does not contravene 21 CFR Part 11”* and, perhaps more substantially, the use of mobile ePRO to collect primary outcomes data in numerous product approvals in Europe and the USA.

	The move away from ePRO device provisioning and towards a BYOD approach (where patients use their own mobile devices) is currently a topic of hot debate. For me, part of the cause of this debate is the mistaken belief that when introducing BYOD into a protocol, enrollment of patients with a specific type of device is the 

 option. That approach would be offering choice in the same way that Henry Ford did to the choice of color for his Model T car – you can bring any device to this study, as long as it’s an android with Ice Cream version12.2 OS – this clearly isn’t practical as it would seriously limit study eligibility criteria.

	As the only vendor with tangible experience in this field, the reality of BYOD in clinical trials is very different. We have been providing ePRO solutions for BYOD trials for many years and almost always introduce an element of provisioning in pre-approval studies. The key is to be able to identify the specifications of the patient’s device and ascertain whether it meets the requirements for the individual study, if not then a suitable device can be provisioned. I like to think of it being a flexible or ‘choice driven’ approach. The provisioning rate for such studies is decreasing year-on-year as the uptake of more advanced mobile technology increases (did you know in the US almost ¾ of adults over 65 now own a mobile phone?**) and in pre-approval studies we see rates anywhere from about 50% provisioned down to as low as 10%, depending on the study population. This provides 2 significant benefits, not only does it enable the patient to use their own device, the one they selected from all available options, but it significantly reduces the cost and logistical complexity of device provisioning for sponsors.

	I set out 10 years ago to simplify the process of collecting patient data during clinical trials through the use of mobile technology. I couldn’t have predicted back then just how far mobile technology would advance and how it would become such an integral part of daily life for people around the world. Now mobile eCOA is proven to be a highly beneficial and versatile option for data capture in clinical trials. It has been shown to significantly improve data quality of PROs and has been used – both through a provisioning and a BYOD approach – to collect primary outcomes data in Europe and US drug approvals. I believe mobile is set for further expansion and growth as the industry escalates the adoption of existing mobile ePRO as the standard approach to self-reported clinical data.

http://www.pewinternet.org/data-trend/mobile/cell-phone-and-smartphone-ownership-demographics/

Electronic data collection has grown rapidly over the course of the last ten years.

The Era of Mobile Data Capture in Clinical Trials

It is estimated that mobile penetration now stands at 96% globally, with significant growth in subscriptions in the developing world in recent years, increasing from 69% of the population in 2011 to 89% in 2013.

 As access to devices expands across the globe, the use of mobile technology in all walks of life has become commonplace. As a result, mobile communication has been leveraged to provide information and access to services across multiple industries, from simple applications such as checking train timetables to mobile banking with secure access to personal information in a highly regulated industry. Clinical research is no exception to this trend and, indeed, the drug industry has seen an increasing movement to leverage mobile technology to engage with patients and collect their data during clinical trials. 

The evolution of mobile in clinical research

	In many ways, the inclusion of mobile phones and other devices in the clinical arena has been an evolution. The first step began almost a decade ago with the use of short message service (SMS) messages to address the retention and compliance issues so commonly faced during research. The scale of the problem was accurately brought home in a recent article in the Drug Information Association's (DIA) journal, 

Therapeutic Innovation & Regulatory Science

, which revealed that as many as 30% of clinical trial participants do not take their study medication correctly.

 The main reasons cited for non-adherence include forgetfulness;

 poor communication with healthcare professionals,

 especially in remote locations; and absence of symptoms.

 An additional challenge is to retain subjects for the duration of the trial and reduce the number of patients lost to follow-up. In its recent "Perceptions and Insights Study," the Center for Information and Study on Clinical Research Participation (CISCRP) found that patients who drop out of clinical studies tend to be less self-motivated, less confident, and less understanding of the process.

	Mobile technology provided a means for researchers to communicate with patients remotely between site visits through a medium that patients carried with them wherever they were. It provided an effective system for sending reminders to ensure timely actions such as clinic visit attendance, fasting, correct drug intake, etc., while also establishing the means to communicate much more broadly with the patient, serving as a two-way open communication channel that allowed patients to respond to prompts as appropriate. This was the first step toward mobile electronic patient-reported outcome (ePRO) collection.

	The introduction of these "retention and compliance" services enabled sponsors to monitor safety, manage compliance, and ensure patient retention throughout the study. For example, in a cardiovascular outcome event monitoring trial, a mobile communication service was included to help maintain contact with patients between subject visits, with a view to increasing the likelihood of the patient reporting if and when an event occurred. The use of this mobile service resulted in a 5% increase in visit compliance and a 4.5% reduction in early patient withdrawal compared to those not using the service. Moreover, in a study of 13,000 patients, it was estimated that if used across the entire study, this would have equated to a four-month earlier finish, resulting in the pharmaceutical sponsor saving more than $14 million in costs.

	The rise of mobile ePRO tools has transformed the way patients engage in clinical trials. The ability to provide familiar technology to patient populations facilitates the collection of time-stamped data, and as mobile technology has propagated across the globe, it serves as an ideal mechanism for communicating and collecting data from hard-to-reach patients in developing markets such as Eastern Europe, Asia Pacific, and Latin America.

	With patient compliance rates typically as low as 55%,

 it is important to ensure the simplicity of the data collection interface. ePRO solutions can provide a simple, familiar, and effective modality to communicate and collect data and information from patients. As users are already familiar with the technology, they can navigate familiarly through the different steps of the data-collection process. As a result, these tools facilitate simple, real-time, and reliable collection of data from study participants, regardless of age or demographic.

	Mobile ePRO solutions can be customized to suit the specific requirements of each trial. The assessment could be a series of text messages sent intermittently to a patient's mobile phone to deliver online questionnaires, which can then be answered instantly via the mobile device. Alternatively, assessments can be delivered via an app-a route which is particularly useful when patients are in regions likely to have limited connectivity; data can be stored within the app and transmitted when connection is available. The use of an app also enables automated connection to medical devices such as blood glucose meters and spirometers via Bluetooth connections.

	Mobile also allows for the inclusion of validated instruments in PRO. To achieve this, the author must approve the use of the scale in question; this is typically achieved through a usability study to ensure patients can interact with the electronic version and a validation study to assess equivalence compared to existing modes of delivery. An example of such a study is the m-WOMAC Osteoarthritis Index, which was found to be valid and reliable using a simple mobile phone Internet connection, showing no difference between mobile and paper scores.

	The traditional model for collecting ePRO measures has been to provision devices, seeking the assurance of fixed parameters for data viewing and validation. Until recently, this option has been fairly restrictive, providing a single device to all populations across each trial, regardless of their familiarity with the technology. However, advances in technology have enabled the onset of a "bring your own device" (BYOD) approach through the ability to recognize device parameters and optimize the configuration of data according to the device in use (e.g., laptop, tablet, mobile phone). The growth of digital and mobile technology means that many patients already own a device that can be used during the study. Device analysis can easily be integrated into patient enrollment and device provisioning can typically be reduced to as little as 10% or 20% of study participants. In some cases, this approach will remove the need for provisioning altogether such that the patients' own devices are employed throughout the study.

	A BYOD approach delivers a cost-effective strategy to engage patients through sharing information and capturing data on their own devices. The requirement to provide devices is reduced, or even removed altogether, as is the logistical challenge of managing large quantities of devices across the globe. An illustration of the cost savings that can be achieved is shown in Figure 1.


	Figure 1. Cost comparisons between paper and electronic-based reporting tools.

	The first step toward BYOD was taken in late phase trials, where collecting real-world evidence from diverse populations is often especially challenging. Unlike the small populations that are closely managed by clinical trial sites in pre-approval clinical research, late phase studies require management of large, diverse populations by physicians and healthcare professionals (HCPs) over long periods of time with fewer "touchpoints." As a result, providing patients with hardware for electronic data capture (EDC) has historically been cost-prohibitive, so trials began to include online self-reporting as an alternative to paper data capture.

 It is now possible to extend this BYOD opportunity through platforms designed to capture data securely from any connected device. Through recognizing the device being used and optimizing the content accordingly, identifying personally identifiable information (PII), and having internal procedures in place to secure this PII, a BYOD approach can be used with confidence as part of an efficient clinical strategy.

	While there are existing examples of pre-approval BYOD use, such as the vaccine trial case study highlighted on the next page, the final stage in the evolution of mobile in clinical trials will be the broad use of a BYOD approach in Phase II and III trials. This is currently a hot discussion topic across the industry.

 Existing evidence supports scale equivalence across multiple modalities, such as the PROMIS study using interactive voice response (IVR), paper, personal digital assistant, and computer,

 and the ability to identify exact specifications of devices in use (screen size, operating system) and to block their usage if they fall outside of the validation range.

	Assessing the current landscape of the pharmaceutical industry, it is evident that mobile technology has a large role to play in improving the quality, simplicity, and ease of use of ePRO across the clinical-to-real-world continuum. The opportunities mobile solutions hold for the industry are vast, with the potential to reduce the major financial burdens as a result of increasing pressure to accelerate the path of drug candidates through clinical trials. In late-phase and real-world studies, especially, where adherence is often a major issue, mobile solutions provide an opportunity to incorporate patient engagement features to increase adherence and, as a result, collect more accurate, unbiased data.

	Mobile technology is increasingly being implemented as a means of communicating directly with patients across broad demographics and multiple locations in both clinical studies and healthcare programs. The familiarity and universal nature of mobile devices and the ability to select the right tool according to the type of study that is being conducted, region, and demographic, makes the technology well-placed for integration into global markets.

Case study-BYOD in a vaccine surveillance study

 A Phase III, observer-blind, randomized, multi-country, non-influenza vaccine comparator-controlled study to demonstrate the efficacy of an influenza candidate vaccine administered intramuscularly in 3,150 healthy children six months to 35 months of age across multiple countries in Europe.

	The primary endpoint for the study was the efficacy of vaccine in the prevention of RT-PCR confirmed influenza A and/or B disease for any seasonal influenza strain, when compared to non-influenza control vaccines.

The use of a BYOD approach offered parents the flexibility to use their preferred means of contact for completing diary entries. Eighty-four percent of parents/guardians opted to use their own mobile phone or personal computer, thus vastly reducing provisioning requirements for the study.

The use of EDC provided greater resource efficiency and timelier follow-ups for the research team, as the switch from weekly to daily contact was symptom-driven, and, therefore, management would have been immensely complicated and resource-intensive using paper.

	Given the study's scale and geographic spread, 100% provisioning would have been cost-prohibitive, both in terms of purchase of devices, as well as the associated logistics, maintenance, and support necessary. With 84% of parents/guardians using their own device, the BYOD enabled a data capture method that previously was not possible. Parents/guardians benefitted from a user-friendly interface (with automated decision-making via branching logic in the eDiary) and being able to contribute from the familiarity of their own device (minimizing end-user training). They were able to complete assessments and report outcomes throughout the trial in the simplest possible way. This empowered parents/guardians to steer their participation and ultimately improve their child's health. It also enabled high levels of data entry compliance. Considering that the average provisioning cost per device (including setup, monthly data charge, and monthly lease) was $400, the savings were clear to see-and were expected to total almost $3 million upon study completion.

 is CEO and Co-founder of Exco InTouch; email: 

	1. International Telecommunication Union, "ICT Facts and Figures: The World in 2013," 

http://www.itu.int/en/ITU-D/Statistics/Pages/facts/default.aspx

	2. International Telecommunication Union, "ICT Facts and Figures: The World in 2011," 

http://www.itu.int/ITU-D/ict/facts/2011/material/ICTFactsFigures2011.pdf

	3. D.L. Smith, "Patient Nonadherence in Clinical Trials: Could There Be a Link to Postmarketing Patient Safety?," (2012), 

	4. L.R. Martin, et al., "The Challenge of Patient Adherence,"(2005)

	5. G.A. Hamilton, "Measuring Adherence in a Hypertension Clinical Trial," (2002), 

European Journal of Cardiovascular Nursing

	6. E. Vermeire, et al., "Patient Adherence to Treatment: Three Decades of Research. A Comprehensive Review," (2001), 

Journal of Clinical Pharmacy and Therapeutics

	7. The 2013 CISCRP Perceptions & Insights Study, "Report on Ineligible Participants and Those Who Terminate Participation Early," (2013), 

http://www.ciscrp.org/professional/reports/

	9. H.B. Bosworth, " Patient Treatment Adherence: Concepts, Interventions and Measurement," (2005), Routledge.

	10. N. Bellamy, et al., "Osteoarthritis Index Delivered By Mobile Phone (m-WOMAC) is valid, reliable, and responsive," (2011), 

	11. P. Wicks, et al., "Accelerated Clinical Discovery Using Self-Reported Patient Data Collected Online and a Patient-Matching Algorithm," (2011), 

http://www.mct-congress.co.uk/pane/programme/

	13. Can BYOD and Smartphones Move Clinical Trials Forward? 

http://www.cio.com/article/736096/Can_BYOD_and_Smartphones_Move_Clinical_Trials_Forward_

	14. Device Independence is the Future of Clinical Trials. 

http://www.appliedclinicaltrialsonline.com/appliedclinicaltrials/Trial+Design+Articles/Device-Independence-is-the-Future-of-Clinical-Tria/ArticleStandard/Article/detail/828040

	15. "Electronic Clinical Outcome Assessments: Coming to a Device Near You!" DIA Annual Meeting 2014, advertised program at 

http://www.diahome.org/en-GB/Flagship-Meetings/DIA2014/Meeting-Program/Find-Sessions-and-Presentations.aspx

	16. J.B. Bjorner, et al., "Method of Administration of PROMIS Scales Did Not Significantly Impact Score Level, Reliability, or Validity," (2014), 

The drug industry has seen an increasing movement to leverage mobile technology to engage with patients and collect their data during clinical trials.

How Mobile Technology is Evolving in Clinical Trials

It is estimated that mobile penetration now stands at 96% globally (see figure 1), with significant growth in subscriptions in the developing world in recent years, increasing from 69% of the population in 2011 to 89% in 2013.

 As access to devices expands across the globe, the use of mobile technology in all walks of life has become commonplace. As a result, mobile communication has been leveraged to provide information and access to services across multiple industries, from simple applications such as checking train timetables to mobile banking with secure access to personal information in a highly regulated industry. Clinical research is no exception to this trend and indeed the pharmaceutical industry has seen an increasing movement to leverage mobile technology to engage with patients and collect their data during clinical trials. 

In many ways, the inclusion of mobile phones and other devices in the clinical arena has been an evolution. The first step began almost a decade ago with the use of short message service (SMS) messages to address the retention and compliance issues so commonly faced during research.  The scale of the problem was accurately brought home in a recent article in the Drug Information Association’s (DIA) journal, 

 The main reasons cited for non-adherence include forgetfulness,

 especially in remote locations, and absence of symptoms.

 An additional challenge for clinical trials is to retain patients for the duration of the trial and reduce the number of patients lost to follow-up. In its recent “Perceptions and Insights Study,” the Center for Information and Study on Clinical Research Participation (CISCRP) found that patients who drop out of clinical studies tend to be less self-motivated, less confident, less understanding of the process, and less satisfied that their questions have been answered.

Mobile technology provided a means for researchers to communicate with patients remotely between site visits through a medium that patients carried with them wherever they were. It provided an effective system for sending reminders to ensure timely actions such as clinic visit attendance, fasting, correct medication intake etc., while also establishing the means to communicate much more broadly with the patient, serving as a two-way open communication channel that allowed patients to respond to prompts as appropriate. This was the first step towards mobile electronic patient reported outcome (ePRO) collection. 

The introduction of these “retention and compliance” services enabled research sponsors to monitor safety, manage compliance. and ensure patient retention throughout the study period. For example, in a cardiovascular outcome event monitoring study, a mobile communication service was included to help maintain contact with patients between subject visits, with a view to increasing the likelihood of the patient reporting if and when an event occurred. The use of this mobile service resulted in a 5% increase in visit compliance and a 4.5% reduction in early patient withdrawal compared to those not using the service. Moreover, in a study of 13,000 patients, it was estimated that if used across the entire study, this would have equated to a four-month earlier finish, resulting in the pharmaceutical sponsor saving over $14 million in costs.

The rise of mobile ePRO tools, particularly those implemented through everyday mobile technology, has transformed the way patients engage in clinical trials. The ability to provide familiar technology to patient populations facilitates the collection of time-stamped data and as mobile technology has propagated across the globe, it serves as an ideal mechanism for communicating and collecting data from hard-to-reach patients in developing markets such as Eastern Europe, Asia Pacific, and Latin America. 

With patient compliance rates typically as low as 55%,

Mobile ePRO solutions can be customized to suit the specific requirements of each trial. The assessment could be a series of text messages sent intermittently to a patient’s mobile phone to deliver online questionnaires, which can then be answered instantly via the mobile device. Alternatively, assessments can be delivered via an app—a route which is particularly useful when patients are in regions likely to have limited connectivity; Data can be stored within the app and transmitted when connection is available. The use of an app also enables automated connection to medical devices such as blood glucose meters and spirometers via Bluetooth connections. 

Mobile also allows for the inclusion of validated instruments in PRO. To achieve this, the author must approve the use of the scale in question; this is typically achieved through a usability study to ensure patients can interact with the electronic version and a validation study to assess equivalence compared to existing modes of delivery. An example of such a study is the m-WOMAC Osteoarthritis Index, which was found to be valid and reliable using a simple mobile phone internet connection, showing no difference between mobile and paper scores.

The traditional model for collecting ePRO measures has been to provision devices, seeking the assurance of fixed parameters for data viewing and validation. Until recently, this option has been fairly restrictive, providing a single device to all populations across each study, regardless of their familiarity with the technology. However, advances in technology have enabled the onset of a “bring your own device” (BYOD) approach through the ability to recognize device parameters and optimize the configuration of data according to the device in use (e.g., laptop, tablet, mobile phone). 

The growth of digital and mobile technology means that many patients already own a device that can be used during the study. Device analysis can easily be integrated into patient enrollment and device provisioning can typically be reduced to as little as 10% or 20% of study participants (see case study below). In some cases, this approach will remove the need for provisioning altogether such that the participants’ own devices are employed throughout the study. 

A BYOD approach delivers an extremely cost-effective strategy to engage patients through sharing information and capturing data on their own devices. The requirement to provide devices is significantly reduced, or even removed altogether, as is the logistical challenge of managing large quantities of devices across the globe. An illustration of the cost savings that can be achieved is shown in figure 2.

The first step towards BYOD was taken in late phase trials, where collecting real-world evidence from diverse populations is often especially challenging. Unlike the small populations that are closely managed by clinical trial sites in pre-approval clinical research, late phase studies require management of large, diverse populations by physicians and health care professionals (HCPs) over long periods of time with fewer “touchpoints.” As a result, providing patients with hardware for electronic data capture (EDC) has historically been cost-prohibitive, so trials began to include online self-reporting as an alternative to paper data capture.

 It is now possible to extend this BYOD opportunity through platforms designed to capture data securely from any connected device. Through recognizing the device being used and optimizing the content accordingly, identifying personally identifiable information (PII), and having internal procedures in place to secure this PII, a BYOD approach can be used with confidence as part of an efficient clinical strategy. 

While there are existing examples of pre-approval BYOD use, such as the Phase III vaccine study case study below, the final stage in the evolution of mobile in clinical trials will be the broad use of a BYOD approach in Phase II and III studies. This is currently a hot topic for discussion across the industry.

 Existing evidence supports scale equivalence across multiple modalities, such as the PROMIS study using interactive voice response, paper, personal digital assistant, and computer,

 and the ability to identify exact specifications of devices in use (screen size, operating system) and to block their usage if they fall outside of the validation range. It is expected that studies providing evidence to support use of BYOD for validated measures will be published in the near future and increasing numbers of BYOD pre-approval studies are set to be announced during 2014. 

Assessing the current landscape of the pharmaceutical industry, it is evident that mobile technology has a large role to play in improving the quality, simplicity, and ease of use of ePRO across the clinical-to-real-world continuum. The opportunities mobile solutions hold for the industry are vast, with the potential to reduce the major financial burdens as a result of increasing pressure to accelerate the path of drug candidates through clinical trials. In late-phase and real-world studies, especially, where adherence is often a major issue, mobile solutions provide an opportunity to incorporate patient engagement features to increase adherence and, as a result, collect more accurate, unbiased data. 

Mobile technology is increasingly being implemented as a means of communicating directly with patients across broad demographics and multiple locations in both clinical studies and healthcare programs. The familiarity and universal nature of mobile devices and the ability to select the right tool according to the type of study that is being conducted, region, and demographic, makes the technology well-placed for integration into global markets. With a variety of industry reports and figures now advocating the use of digital technology in the healthcare industry, sponsors, CROs, and global health organizations are actively searching for opportunities to incorporate mobile solutions into their health programs. 

Case study – BYOD in a vaccine surveillance study

A Phase III, observer-blind, randomized, multi-country, non-influenza vaccine comparator-controlled study to demonstrate the efficacy of an influenza candidate vaccine administered intramuscularly in 3,150 healthy children 6 months to 35 months of age across multiple countries in Europe.

The primary endpoint for the study was the efficacy of vaccine in the prevention of RT-PCR confirmed influenza A and/or B disease for any seasonal influenza strain, when compared to non-influenza control vaccines.

: The use of a BYOD approach offered parents the flexibility to use their preferred means of contact for completing diary entries. Eighty-five percent of parents opted to use their own mobile phone or personal computer, thus vastly reducing provisioning requirements for the study.

 The use of EDC provided greater resource efficiency and timelier follow-ups for the research team, as the switch from weekly to daily contact was symptom driven, and, therefore, management would have been immensely complicated and resource-intensive using paper. 

Given the scale and geographic spread of the study, 100% provisioning would have been cost-prohibitive, both in terms of purchase of devices, as well as the associated logistics, maintenance, and support necessary. 

With 85% of parents/guardians using their own device (PC, laptop, mobile), the BYOD enabled a data capture method that would not previously have been possible. Parents/guardians benefitted from a user-friendly interface (with automated decision-making via branching logic in the eDiary) and being able to contribute from the familiarity of their own device (minimizing end-user training). They were able to easily complete assessments and report outcomes throughout the study in the simplest possible way. This empowered parents/guardians to steer their participation and ultimately improve their child’s health. It also enabled high levels of data entry compliance. 

Considering that the average provisioning cost per device (including setup, monthly data charge, and monthly lease) was $400, the savings are clear to see. As the study draws to a close following the second flu season, savings are expected to total almost $3 million upon completion. 

Tim Davis is CEO and co-founder of Exco InTouch. 

International Telecommunication Union, “ICT Facts and Figures: The World in 2013,” 

International Telecommunication Union, “ICT Facts and Figures: The World in 2011,”  

D.L. Smith, “Patient Nonadherence in Clinical Trials: Could There Be a Link to Postmarketing Patient Safety?,” (2012), 

, et al., “The Challenge of Patient Adherence,”(2005), 

G.A. Hamilton, “Measuring Adherence in a Hypertension Clinical Trial,” (2002), 

E. Vermeire, et al., “Patient Adherence to Treatment: Three Decades of Research. A Comprehensive Review,” (2001), 

The 2013 CISCRP Perceptions & Insights Study, “Report on Ineligible Participants and Those Who Terminate Participation Early,” (2013), 

H.B. Bosworth, “ Patient Treatment Adherence: Concepts, Interventions and Measurement,” (2005), Routledge. 

N. Bellamy, et al., “Osteoarthritis Index Delivered By Mobile Phone (m-WOMAC) is valid, reliable, and responsive,” (2011), 

P. Wicks, et al., “Accelerated Clinical Discovery Using Self-Reported Patient Data Collected Online and a Patient-Matching Algorithm,” (2011), 

Can BYOD and Smartphones Move Clinical Trials Forward?  

Device Independence is the Future of Clinical Trials. 

“Electronic Clinical Outcome Assessments: Coming to a Device Near You!” DIA  Annual Meeting 2014, advertised program at 

J.B. Bjorner, et al., “Method of Administration of PROMIS Scales Did Not Significantly Impact Score Level, Reliability, or Validity,” (2014), 

It is estimated that mobile penetration now stands at 96% globally.