E-Technologies in Clinical Trials: Benefits and Challenges

Introduction

In the past, clinical trial activities — such as recruitment, delivery of interventions, retention, and collection of data — were conducted using the conventional face-to-face approach. Radio or newspaper advertisements were used to recruit participants; telephone calls or mail were used for follow-up assessments; interventions were personally delivered; and paper-and-pencil instruments were used for data collection. Clinical trials have been reluctant to embrace e-technology in the design and execution of their studies (Baker, Gustafson & Shah, 2014; Riley et al., 2013), and they have faced the challenge of keeping up with rapid developments in technology. For instance, in the time typically taken for designing, implementing, and publishing research findings — approximately six years — the world transformed from playing interactive video games (Wii) to using voice-activated personal assistants such as Siri (Riley et al., 2013). During this timeframe, approximately one million iPhone applications were added to Apple's App Store.

Apart from the rate of change in digital technology, other reasons for the slow adoption of e-technology include limited evidence as to whether e-technologies enhance clinical trial design, as well as a paucity of regulatory policies and guidance — especially where FDA approval is required (Rosa et al., 2015). The aims of this paper are to: (1) present a summary of the current integration of e-technologies into the design, execution, and dissemination of clinical trials; (2) present the status of regulatory guidelines regarding e-technology use, along with its limitations and challenges; (3) present a summary of the benefits and limitations of e-technologies in clinical trial studies; and (4) outline future predictions for e-technology use in clinical trials research.

Some clinical trial researchers adopted e-technology early on by deploying the power of the internet for recruiting study participants and creating internet- or computer-based interventions — at best in a supplementary role. Gradually, however, over the past two decades, researchers used electronic tools for developing protocols, communicating with study personnel, randomizing participants, collecting data, and analyzing results — a more mainstream application. Earlier on, communication with participants was limited, and individuals were only directed to a website where they could find information about the study. For recruitment and retention purposes, contact information was provided (Scholle et al., 2000). Websites were later used to distribute online questionnaires for consent and eligibility. More recently, social media platforms such as Twitter and Facebook have been increasingly used in clinical trials, while blogs and text messages have been incorporated for recruitment, retention, and meeting regulatory requirements for community consultation. Mobile technologies (smartphones and tablets) are now used for data collection — including patient-reported outcomes and surveys — and for monitoring study compliance. Other innovative data-collection approaches such as GPS, wearable devices, and mobile apps are slowly being integrated as investigational tools (Rosa et al., 2015).

Literature Review

In the last two decades, electronic systems have been incorporated into clinical trial implementation procedures — for example, data entry and randomization. Overall technological advancements have been much faster and larger since then. On March 9, 2015, Apple introduced its ResearchKit software, designed for health and medical research. By March 30, 2015, numerous iPhone applications had been created for large-scale research on Parkinson's disease, breast cancer, asthma, diabetes, and cardiovascular disease (Apple Press Info, 2015). Google Inc. also developed a tool intended to function as a medical device capable of assisting clinical trials in the near future (HIT, 2015).

The clinical trials industry has been late to incorporate and improve its technology use, and there is growing pressure for transformation. The FDA has taken leading strides by publishing recommendations on social media use. Several companies have followed. Pfizer and AbbVie are already using their Twitter accounts to engage the clinical community and patients (Marwaha, Patil & Singh, 2007). However, very few companies have managed to transition from simple Twitter feeds to a comprehensive media strategy that effectively engages the target audience.

Over the last decade, pharmaceutical companies have introduced numerous initiatives to make clinical trials more productive. The introduction of Electronic Data Capture (EDC) systems is one such initiative. These systems allow researchers and patients to enter trial-related information directly into online systems or electronic diaries. There are laudable efforts to adopt new scientific approaches — for example, Bayesian techniques that allow companies to refine trial design stage by stage. Additionally, companies have improved technological capabilities, particularly connectivity, enabling trial managers to maintain continuous oversight of patient retention and trial progress. They have expanded their ability to conduct global trials by increasing the pools of patients and researchers, adopted more disciplined trial management procedures, and borrowed "stage gate" techniques from product design to set strict deadlines for data collection and to refine the objectives of subsequent stages (Marwaha et al., 2007; Marks, Conlon & Ruberg, 2001).

The rapid growth of affordable consumer-grade wearable health monitors represents a significant platform for identifying potential patients and collecting large amounts of longitudinal data. The ease of data collection is the key differentiator — data is gathered via wristbands or devices attached to clothing. Many new market entrants have introduced highly functional, fashionable products that are fully integrated with online portals for analysis and reporting. For example, Misfit Wearables produced a small disc attached to the user's clothing, enabling all-day wear and capturing essential data for accurate mapping of exercise and activity. FitBit uses a flexible wristband to track user movement. Both devices offer numerous features in compact, convenient packages (Marwaha et al., 2007).

Mobile health monitoring is another dimension of the health-data explosion that could help clinical research organizations collect data without paying for expensive monitoring systems. Apple, for instance, was awarded a patent for earbuds capable of monitoring the wearer's vital signs, allowing users to gather detailed data about heart rate while exercising. Patients are purchasing these devices and applications, helping to catalogue large numbers of data points each year that clinical researchers and biostatisticians can collect and analyze. A variety of devices and applications on the market track heart rate, temperature, sleep patterns, blood pressure, and even snoring (Marwaha et al., 2007; Marks et al., 2001).

Despite these advances, achieving end-to-end improvements in trial performance remains difficult. Several companies are not coordinating multiple trials within their organizations to the best of their capability, and competition for limited resources can create delays due to lack of cross-trial transparency. Most organizations have not yet fully adopted reusability through a streamlined approach to trial design — certain components of guidance forms used across multiple trials could be shared, but this principle has not been widely implemented. Although EDC systems have significantly reduced data collection time to approximately two weeks, some systems have lacked the flexibility and reliability needed by investigators. Verification of electronic data against physical records (such as lab reports) also consumes substantial time. Finally, productivity measures implemented by some pharmaceutical companies have not been applied organization-wide, limiting the capture of full benefits.

In recent years, leading pharmaceutical companies have reviewed their IT systems to streamline processes and increase productivity. Such efforts are most successful when a clean-sheet approach is adopted to redesign the entire trials program while integrating systems — an approach that has yielded a 10% or greater increase in trial speed for some companies. Various companies have also applied lean manufacturing principles to information flow, reducing waste and improving throughput by redesigning clinical trial processes, technology, and staff responsibilities (Marwaha et al., 2007). Some companies have improved quality, costs, and speed by ensuring that the right data is obtained the first time, increasing data transparency across the clinical trial process, and managing workflow to reduce bottlenecks.

Current E-Technology Trends in Clinical Trial Design, Execution, and Dissemination

Recruiting clinical trial participants is crucial to ensuring the validity and generalizability of a study and is frequently one of the most challenging aspects of clinical research. Many clinical trials fail to meet their initial participant recruitment targets as outlined in the study protocol. In recent years, internet-based approaches have been increasingly used to supplement traditional recruitment strategies, and these approaches appear effective (Frandsen et al., 2014). Patients' preference for e-technology may positively affect the extent of effectiveness of these strategies. Internet-based personal registry tools are used for both recruitment and screening.

Participant retention is another area that commonly challenges researchers, particularly during long follow-up periods after concluding active intervention. Before the advancement of internet and mobile technologies, keeping participants engaged over months or years of study required considerable staff effort, and retention rates often fell below ideal levels. The ability to use mobile phones — through calls, text messages, and voicemail — along with websites and social media has fundamentally altered traditional retention strategies (Frandsen et al., 2014). Results from recent studies suggest that participant preferences for e-technologies may have an advantageous effect on the success of engagement and retention strategies.

Most published research on e-technologies in data collection concerns the use of Electronic Data Capture (EDC) systems (Babre, 2011), as well as internet-based strategies for administering questionnaires and surveys in health and behavioral promotion studies. Ecological Momentary Assessment (EMA) is a novel data-collection approach facilitated by e-technology. Originally designed for real-time data collection, EMA has recently been extended to deliver interventions to people dealing with substance use disorders.

Researchers have been conducting randomized registry-based trials, using existing registries for screening, recruitment, randomization, and data collection.

Electronic Health Records (EHRs) are another increasingly essential tool for data recruitment and collection in clinical trials. As precision medicine and comparative effectiveness research have gained emphasis, studies are planning to use EHRs to facilitate consent, recruitment, and clinical data collection. EHRs can provide an automated electronic approach for: (1) flagging or identifying potential subjects at the point of clinical care; (2) differentiating between research and clinical costs and procedures; (3) extracting clinical data for import into research databases; and (4) collecting clinical study outcomes directly.

The dissemination and presentation of findings is a critical component of any research study. Print publications and peer-reviewed journals have traditionally served this role, yet these are typically accessible only to subscribers, contributors, and conference attendees. The impact of study results is largely dependent on the effectiveness of their dissemination. Faster, cheaper, and more efficient means of dissemination — including Facebook, Twitter, blogs, and interactive websites featuring essay-style informational posts — have proven to be promising tools (Allen et al., 2013). These platforms are instrumental in disseminating results to both scientists and practitioners, as well as to study participants and the general public. Journal publishers increasingly promote their content through social media to reach individual researchers and research institutions. Researchers also have a growing range of platforms for wider dissemination and peer sharing, including ResearchGate, Academia.edu, and PubPeer.

Conclusion

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