Capstone Project Using Technology in Managing Data Within Clinical Trials

¶ … Technology in Managing Data in Clinical Trials

TECHNOLOGY IN CLINICAL TRIALS

Incorporation of technology (electronic and digital technology that can utilize the internet or mobile devices) into the process of designing and executing studies in Clinical trials has been a slow process. Currently, individuals and various corporations have already incorporated such technology into their day-to-day lives and rely on electronic platforms. The aim of this paper is to provide a general overview of how e-technologies are used in clinical trials research, especially in the last ten years that have seen internet based-tools and mobile devices grow rapidly. The benefits and challenges that are associated with using e-technologies in collecting data, recruitment, and retention, delivering interventions and dissemination have been provided. The use of e-technologies for designing and implementing clinical trials has the ability to reach an extensive audience thus enhancing the efficiency of trials and reducing the cost: researchers should however be cautious in the adoption of these tools considering the numerous challenges that come with the use of new technologies and the threat to the confidentiality/privacy of the participants. Hence a description of how regulatory oversight of the use of e-technologies in clinical trials research is currently being conducted will also be provided. Careful planning, forethought, and useful partnerships can help overcome the challenges of new technologies. Smartphone and web-based applications have the role of expanding and increasing the use of these platforms by the scientists as well as the public thus making them significant tools that cannot be ignored.

Table of Contents

i. Abstract 2

1. Introduction 4

2. Literature review 4

3. Current e-technology trends in clinical trial design, execution and dissemination 6

3.1. Recruitment 7

3.2. Engagement and retention 7

3.3. Data collection 7

3.4. Using electronic platforms for recruitment, retention and data collection 7

3.4.1. Registries 7

3.4.2. Electronic health records 7

3.5. Dissemination of study results 8

4. Current status of regulatory guidelines for e-technology use, challenges and limitations 8

4.1. Institutional Review Board (IRB) review 8

4.2. Consent 8

5. Advantages and limitations of e-technologies in clinical trials research 9

5.1. Advantages 9

5.1.1. Improving efficiency 9

5.1.2. Lowering cost 9

5.1.3. Fostering research and development 9

5.2. Disadvantages 10

5.2.1. Privacy/confidentiality issues 10

5.2.2. Including a non-representative sample 10

5.2.3. Big data/accuracy of data 10

6. Future directions for the use of e-technologies in clinical research 10

7. Conclusion 11

8. References 13

1. Introduction

In the past, clinical trial activities (such as recruitment, delivery of interventions, retention, and collection of data) were conducted using the conventional "face-face" approach. For instance, radio or newspaper advertisements were used in the recruitment of participants; telephone calls or mail used to in conducting follow-up assessments interventions were personally delivered while paper and pencil instruments are used in data collection. Clinical trials have been reluctant to embrace e-technology in the designing and execution of their studies (Baker, Gustafson & Shah, 2014) and (Riley et al., 2013). They faced the challenge of keeping up with the rapid developments in technology. For instance, in the time taken for designing, implementation, and publication of research findings (around 6 years) the world transformed from playing interactive video games (Wii) to the use of voice activated personal assistants such as Siri (Riley et al., 2013). During this timeframe, about a million iPhone applications were added into Apples app store. Apart from the rate of change in digital technology advancement, the other reason that possibly caused the slow adoption of e-technology use include limited evidence based on whether e-technologies enhance or improve clinical trials design as well as the paucity of the regulatory policies and guidance especially where approval by FDA is required (Rosa et al., 2015). The aim of this paper is to provide a general overview of how e-technologies have been incorporated in clinical trials research particularly for past ten years. 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 the use of e-technology, its limitations as well as challenges;

(3) Present a summary of the benefits and limitations of e-technologies in clinical trials studies; and (4) Outline future predictions of e-technology use in clinical trials research.

2. Literature review

Some researchers of clinical trials adopted e-technology early-on, by deploying the power of internet in recruitment of study participants and creation of internet or computer-based interventions -- at best, a supplementary role. Gradually, however, in the past two decades, researchers used Electronic tools in the development of protocols, communication with personnel involved in the study, randomization of participants, data collection and result analysis -- as a more mainstream application. Earlier on, there was limited communication with participants, and individuals were only directed to a website where they could find information concerning the study. For purposes of recruitment and retention, contact information was provided (Scholle et al., 2000). Websites were later used to distribute online questionnaires to collect data for purposes of consent and eligibility. In the recent past, social media (Twitter, Facebook) has been increasingly used for clinical trials. Blogs and text messages have also been incorporated for recruitment and enhancement of participant retention as well as meeting regulatory requirements of consulting the community. Mobile technologies (smartphones and tablets) are used for data collection (outcomes reported by patients, surveys) and monitoring study compliance. Other innovative approaches of collecting data such as the use of GPS (global positioning system), wearable gadgets, and apps are slowly being integrated as tools of investigation (Rosa et al., 2015).

In the last two decades, electronic systems have been incorporated for implementation procedures in clinical trials for example data entry and randomization. However, overall advancements in technology have been much faster and larger since then. On 9th March 2015, Apple's ResearchKit software, which was designed for health and medical research was introduced. By 30th March 2015, numerous iPhone applications had been created to be used in large-scale research of Parkinson's disease, breast cancer, asthma, diabetes and cardiovascular diseases (Apple Press Info, 2015). Google Inc. has also developed a tool that is intended to be a medical device that can be of assistance in clinical trials in the near future (HIT, 2015).

The industry of clinical trials is very late in incorporating and thereby improving its technology use and a there is pressure for transformation in the near future. The FDA has already taken leading strides by publishing social media use recommendations. Several companies have joined the movement. Pfizer and Abbvie are already using their Twitter accounts to engage the clinical community as well as the patients (Marwaha, Patil & Singh, 2007). However, only very few companies have managed to take the steps for transition from simple Twitter feeds into a media strategy that is comprehensive and engages the targeted audience.

Over the last ten years, pharmaceutical companies have introduced numerous initiatives to make clinical trials more productive. The introduction of Electronic Data Capture (EDC) systems is one of these initiatives. These systems allow researchers and patients to enter information regarding their trials directly, either in online systems or in electronic diaries. There are laudable efforts in adopting new scientific approaches, for example, the Bayesian techniques that allow pharmaceutical companies to refine the design of their trials stage by stage. Additionally, technological capabilities of companies, particularly connectivity, have been improved thus enabling trial managers to keep continuous tabs on patient retention and the progress of their trials. They have also increased their ability to conduct trials globally by extensively increasing their patients and researchers. They have also adopted more disciplined trial management procedures by borrowing techniques in some stages (including "stage gates," which allow strict deadlines to be set for data collection and refining the objectives of the next stages) from product design (Marwaha et al., 2007; Marks, Conlon & Ruberg, 2001).

For clinical trials, the fast growth of economic wearable health monitors meant for the consumers is a great platform where potential patients can be identified and large amounts of data collected throughout the patient's life. The ease of collecting data is the game changer- data is collected through wearables such as a wristband on or tagging onto clothing. Numerous new entrants have brought into the market, products that are highly functional, fashionable, and integrated fully with online portals for analysis and reporting. For example, Misfit Wearables delivered a tiny wearable disc attached on the user's clothing thus allowing the user to wear the device throughout the day. All the essential data required to create accurate mapping of exercise and activity are therefore captured. On the other hand, FitBit uses a very flexible wristband that is used to track the user's movements. Both gadgets offer numerous features in very small and convenient packages (Marwaha et al., 2007).

Mobile Health Monitoring is also an aspect of health-related explosion of data that could assist clinical research organizations to collect data without paying for the expensive cost of monitoring systems. For instance, recently, Apple was awarded a patent for the manufacturing of 'earbuds' that will have the ability of monitoring vital signs in the wearer. This will allow users to gather detailed data about their heart rate and other vital signs while working out and listening to their favorite music. Patients are buying these gadgets and applications, thus helping catalogue a lot of data points every year that can be collected and analyzed by clinical researchers and biostatisticians. There are a variety of devices and applications in the market that keep track of heart rate, temperature, sleep patterns, blood pressure and even snoring while sleeping (Marwaha et al., 2007; Marks et al., 2001).

In these rather early stages, it has become difficult to achieve end-to-end improvements in trial performance. One of the reasons is that several companies are not coordinating numerous trials in their organizations to the best of their capability. When various trials are competing for limited resources, delays can be created by the lack of cross-trial transparency. Secondly, most of the organizations have not yet adopted reusability through streamlined approach to the trial design. Some components of the guidance forms used by researchers in trials can be shared and used repeatedly across several trials. However, this principle has not been fully integrated by several companies. The third reason is that although electronic data capture systems have significantly reduced data collection time to 2 weeks, there are some cases where the twentieth to early twenty-first generation systems lacked the flexibility and reliability that would suit the needs of investigators (Marks et al., 2001; Marwaha et al., 2007;). Additionally, verification of electronic data to ascertain that it is similar to the physical data (such as reports from lab tests) is a process that consumes a lot of time. Finally, the measures implemented by some pharmaceutical companies to increase productivity are not applicable to the entire organization, and therefore not all the benefits are captured.

In the recent past, some of the leading pharmaceutical companies have reviewed their IT systems to further streamline the process thus increasing productivity. Such efforts succeed mostly when a clean sheet approach is adopted to redesign the entire trials program while integrating the systems. Applying this principle has seen a 10% increase or more in the speed of trials in some companies. Additionally, various companies have applied lean manufacturing principles to the flow of information thus reducing waste and improving throughput by redesigning their processes of clinical trials, technology and staff responsibilities (Marwaha et al., 2007). Some companies have improved their quality, costs and speed by ensuring that the right data is obtained the first time, increasing the transparency of data in the whole clinical trial process and managing the flow of work to reduce bottlenecks.

3. Current e-technology trends in clinical trial design, execution and dissemination

3.1. Recruitment

To ensure the validity and generalizability of the study, recruiting clinical trial participants is crucial. Most of the time, this is one of the most challenging factors in clinical research. Several clinical trials do not meet the initial objectives of participant recruitment that the study protocol outlines. In the recent past, there has been an increased use of internet-based approaches to supplement the recruitment strategies that were used traditionally and approaches of this nature seem effective (Frandsen et al., 2014). The e-technology preference by patients may affect the extent of effectiveness of these strategies positively. For recruitment and screening, internet-based personal registry tools are used.

3.2. Engagement and retention

Participant retention is another aspect that commonly challenges researchers, particularly during broad follow-up periods after concluding active intervention. Before the advancement of internet and mobile technologies, keeping participants in contact over months or even years of study required a lot of effort from staff and the retention rates often ended up being less than ideal. The ability to use mobile phones to keep in contact with subjects (through calls, text messages and voicemail), websites, and social media has altered the traditional strategies of retention (Frandsen et al., 2014). However, results from recent studies suggest that the preference that participants have for e-technologies may have an advantageous effect on the success of various strategies for engagement and retention.

3.3. Data collection

Most of the research that has been published about the use of e-technologies in data collection concerns the use of Electronic Data Capture (ECD) systems (Babre, 2011), and Internet-based strategies for the administration of questionnaires and surveys for health and behavioral promotion studies. Ecological Momentary Assessment (EMA) is a novel approach for collecting data facilitated by e-technology. A method designed for real time data collection and was extended recently to deliver interventions for people who are addicted to substance use.

3.4. Using electronic platforms for recruitment, retention and data collection

3.4.1. Registries

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

3.4.2. Electronic health records

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

3.5. Dissemination of study results

In any research study, the dissemination of findings and presentation is a critical component. Print publications or peer-reviewed journals are traditionally believed to carry out this role. Typically, these are accessible only to subscribers, contributors, and conference presentations (which are often accessible to the fellow conference attendees). The impact of this study's results is majorly dependent on the effectiveness put in those results dissemination. Cheaper, faster and more efficient means for dissemination will prove to be a promising tool. These means include Facebook, Twitter, and blogs, which are updated regularly; interactive web sites often feature essay-style posts that provide information or opinions (Allen et al., 2013). These platforms are instrumental in disseminating study results to both the scientists and practitioners. The individuals that participate in the studies together with the public also reap the benefits of these platforms. Journal publishers disseminate their current contents through social media thus increasingly promoting their work to reach the individual researchers and research institutions. Researchers have an increasing number of platforms for a wider dissemination of findings and the same time enable sharing with colleagues. These include ResearchGate, Academia.edu, and PubPeer among others.

4. Current status of regulatory guidelines for e-technology use, challenges and limitations

The use of social media and technology faces the challenge of ubiquity in the general population and there have been increased efforts to integrate technology into research practices. However, little regulatory guidance is in place while using technology in clinical research (Rosa et al., 2015).

4.1. Institutional Review Board (IRB) review

IRBs have determined their own policies that are in line with FDA Title 21 and 45 CFR 46 regulations. This is in the absence of any explicit guidance. IRBs have recognized the increase in the number of research protocols submitted that integrate e-technology, the need to develop standards and policies thus progressing from offering virtually no guidance in that issue. Informed consent and privacy are the primary issues researchers ought to consider while using technology in clinical research (Buschel et al., 2014).

4.2. Consent

Majority of online surveys and interviews require consent. The online consent process includes reading through series of questions and indicating an understanding of procedures, benefits, and risks. It also involves voluntary participation, which is shown by checking a box. Researchers and IRBs see online consent as ensuring greater confidentiality thus making them more comfortable prior to online interviews or surveys. It is preferred to paper surveys or face-to-face interviews, which may fail to collect names and location data (address, phone number) (Rosa et al., 2015). However, the lack of face-to-face contact in the consent process is the major drawback of online consent. This may result to the interviewer failing to ensure understanding of the consent form by the participant, which would be possible with the face-to-face interaction. This is common to online consent as well as for the mailed surveys.

5. Advantages and limitations of e-technologies in clinical trials research

5.1. Advantages

5.1.1. Improving efficiency

The following areas can potentially be affected by Technology to improve the efficiency of clinical trials:

(1) Communication: Technology tools enhance communications not only among the study staff, but also with patients and communities. This could expedite regulatory approvals, protocol development, and training, thus reducing the time from studying the concept to the first randomization.

(2) Recruitment: Using apps, social media, registries, and EHR may increase the number of participants who can be contacted, enrolled into a trial and screened (e.g., Apple's ResearchKit application).

(3) Retention: Mobile phones/devices, social media, and apps create the opportunity for connection with participants often, thus potentially improving their retention and engagement into clinical trials.

(4) Delivery of intervention: E-technology-based interventions are able to reduce resource requirements that relate to ongoing supervision and staff training. This increases the accessibility across space and time, maintains consistency in delivery of an intervention, and has the potential to increase staff time thus focusing on more complex treatment delivery.

(5) Data collection: In order to ensure availability of standard clinical data for the purpose of real-time study outcome and at the same time improve targeted recruitment, use registries and EHRs. Smartphones, wearable body sensors and apps can allow for automatic collection of large quantities of data without necessarily having face-to-face interactions with the researchers (Rosa et al., 2015).

5.1.2. Lowering cost

Using technologies for delivery of intervention, recruitment, and data collection has the ability to reduce the time taken to reach targeted recruitment and also enrolling a large number of patients in a relatively shorter duration. The need for personnel/staff hours required to perform these activities (Data entry, delivery of intervention) may be reduced.. This gives the indication that e-technologies potentially may allow clinical trials to be conducted speedily, while incurring fewer costs per patient.

5.1.3. Fostering research and development

In the past decade, there have been reports of an explosion of health-care data availability (Szlezak et al., 2014). Thus, a great opportunity is offered to the researchers and also other stakeholders in health care, to make big advances. The "Big Data" that has become more accessible and available can be used for safety surveillance, research, & development of pharmaceuticals, marketing, and give ultimate better patient outcomes.

5.2. Disadvantages

5.2.1. Privacy/confidentiality issues

A conflation of confidentiality and privacy issues accompanies E-technologies. Frequently, the complex undeveloped or even under-developed IRBs, stakeholder organizations and funding agencies' regulatory guidelines are making things more confusing. The factors that contribute to institutions being hesitant to approve or even allow the use of this new technologies in clinical research include potential violation of patient privacy & confidentiality and generally ethical standards and professional codes of conduct (Szlezak et al., 2014; Rosa et al., 2015). It is difficult to anticipate confidentiality and/or privacy concerns, which may be further complicated by the risk of cyber-attacks and "hacking," especially in mobile apps. Researchers ought to understand the current state, federal, and local regulations. They should also be cognizant that the issues (hacking and thereby, regulatory) are likely to expand and evolve over time.

5.2.2. Including a non-representative sample

Using technology in research is criticized for having participants recruited from online sites and social media. These are not a representative sample. This may introduce bias for most studies. Despite having conflicting information on the "digital divide," especially in people with disadvantaged populations or substance use disorders, research on mobile phone and Internet use shows that the divide is continuing to shrink by income, age, and race (Szlezak et al., 2014).