Electronic technologies in clinical trial design, recruitment, and data collection

¶ … 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.

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).

5.2.3. Big data/accuracy of data

Identifying which data to collect, how to capture it, and how to analyze it when given the immense quantity of data available, is one of the biggest challenges to researchers. Once this is sorted, the other challenge faced is data quality and consistency when basing on the current absence of standard methodologies such us diseases for use across all data types, physicians and unique identifiers for patients (Szlezak et al., 2014). There are varying expectations within EHRs and general time to collect data complete in all ways.

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

An enormous opportunity for researchers is provided by availability of "Big Data" and new technologies' advent for clinical trials. However, many challenges that exist. The fact that e-technologies are simply additional types of research tools with no intentions of completely supplanting traditional methods should be kept in mind by investigational teams, particularly considering the constant need for more empirical evidence. To overcome challenges, newly released technologies ought to be tested and refined (Rosa et al., 2015). Our knowledge on the design and interpretation of the impact of e-technologies on clinical trial can be expanded by future research. This is with respect to randomization, and validity of results. Aspects one should consider when determining whether or not to integrate e-technologies into clinical trials:

(1) The target population, their preferences, and access to specific e-technologies,

(2) Possible technological change during the time taken to conduct the trial,

(3) The compliance of the method with regulations set on the use of e-technologies,

(4) The available infrastructure capability to process large volumes of data, and

5) Whether the e-technologies introduce unnecessary risks and/or additional risks to subjects' privacy or confidentiality (Rosa et al., 2015).

Investigators and professionals from multidisciplinary knowledge areas should have a partnership (e.g. information/computer science, engineering, business) with patients to address various challenges that are involved in integrating e-technologies in clinical trials. Careful planning will guarantee a successful implementation of the clinical trial and also increase the chances of the sustainability and usability of the studied technology even after the end of grant funding.

There exist practical and theoretical challenges pertaining new e-technologies in clinical research. Majority of the challenges can be overcome with useful partnerships, careful planning, and forethought. The role of smartphone- and web-based applications, including social media, is expanding in every field creating increased platforms used by scientists and the public. this makes them valuable tools that cannot be ignored (Rosa et al., 2015; Marks et al., 2001). Things that were previously impossible to researchers have been enabled by these new mediums through the potential to lower the cost and improve efficiency of clinical trials while radically expanding both the reach and availability of clinical interventions where they are needed the most.

7. Conclusion

The use of the technology for clinical trials in several fundamental ways has changed the processes of clinical research. Monitoring capability, greatly improved security, and accuracy accompanied by timeliness of study conduct can be achieved at a lower cost. Reduced co-coordinating center effort and enhanced data quality. Technology (especially web-based tools) provides a natural environment to link different components of clinical research, achieving new levels of efficiency and simplicity. The opportunities for recruitment of patients and study investigators are enhanced. Other databases and technology tools can offer assistance in this regard. The relationship of the investigator site to the study as well as the site to the coordinating center is changed in the web-based trials. Different roles and responsibilities result in simplified processes and higher quality data. A number of standard coordinating center activities that include, protocol implementation and amending, document tracking, randomization, adverse report generation and data analysis, site monitoring and event reporting are all fundamentally changed in a web-based trial. Enhanced opportunities aid to identify potential investigators and therefore support their study process successfully. Increased attraction of more primary care medical providers to research is possible. Therefore, more typical patients to studies are provided as compared to traditional research methodology, especially patients at academic study sites. Co-coordinating other activities electronically is enabled with the advent of the web. The Institutional Review Board (IRB) can control investigator participation using online tools. This results in improved patient safety and study efficiency. Electronic performance and recording of financial payments to these sites is enabled, or administered based on quality and timeliness of the data. Indications on early experience with technology in clinical trials show tremendous gains in study accuracy and efficiency. This is made possible by restructuring roles, processes, and responsibilities through a clinical trial that is comprehensive, centralized, and technology-aided. A bright future is apparent for technological-integration in clinical trials.