Since 1975, when provisions allowing for the submission of data from foreign clinical trials were codified, the clinical trial landscape has grown increasingly global, with approximately half of all clinical trial sites outside the United States.1
Of the 234,703 trials registered with ClinicalTrials.gov as of January 17, 2017, 47% were outside the US and another 6% were both US and non-US.2 Further, nearly half of all studies registered by the U.S. National Institutes of Health were drug or biologic studies.2 As this global network of trial sites continues to expand, so too does the number of participants in a given study, meaning a simplified informed consent process (ICP) is necessary to properly manage consent according to participant needs, federal regulations and ethics requirements.
Though the pharmaceutical industry still relies heavily on traditional paper forms when communicating trial information to and obtaining consent from trial participants, electronic informed consent (eConsent) can simplify the process while taking a participant-centric approach. Additionally, eConsent presents an opportunity for contract research organizations (CROs) to strengthen their service offerings and enjoy a strategic advantage when pursuing partnerships with sponsors.
A reliable eConsent process, beginning with electronic informed consent documents (ICDs), allows trial sites to clearly communicate required trial information in multiple formats, easily inspect trial protocols throughout the process, and meet all compliance and ethics requirements while monitoring activity in real-time and controlling costs.3 With all consent documents created, reviewed, modified and signed electronically, trial sites can also easily store and access consent information across multiple global locations; however, to ensure a smooth transition to an electronic system that can meet the rapidly changing demands of the global trial market, the system must be designed to be simple, scalable, effective and focused on the variable needs of the participant.
The Clinical Trial Market is Ready for Change
In March of 2015, the FDA released draft guidance (most recently updated in December 2016) for clinical investigators, sponsors, and Institutional Review Boards (IRBs) regarding the use of electronic systems and processes — including video, audio and various additional forms of multimedia — in clinical trials.4 A few months later, Mytrus, Inc., the first company to receive FDA approval for remote eConsent, helped win clearance for the first use of eConsent in the UK.5Though eConsent may not yet be the standard, the possible advantages of electronic solutions have been demonstrated and found acceptable. CROs may wish to embrace these new options.
According to the 2017 Nice Insight Preclinical and Clinical Contract Research Survey, 64% of respondents outsource clinical trial services and, of those respondents, 34% outsource recruiting, 28% outsource data management and 27% outsource project management, all of which stand to benefit from an eConsent process.6 Though engaging a CRO partner for clinical trial expertise is not a new trend, a reliable eConsent system can help both CRO and sponsor by decreasing study startup times, increasing consent, reducing dropouts and simplifying consent management down to the site level.3 With 73% of respondents also reporting operational, methodological and therapeutic exper-ience as at least somewhat important to the initial selection of a CRO, there is clearly value in working to improve the consent process.6 With this value in mind, exploring an electronic ICP should be viewed as required — rather than optional — moving forward. However, there are a few issues to consider when approaching implementation and leveraging the overall process.
A New System Requires a Brand New Approach
The paper consent process has not improved in over three decades.3 Though paper consent forms have worked well and continue to be effective on a surface level, the needs of the clinical trial industry have outpaced the capabilities of the paper form. Looking strictly at the ICD itself, paper is costly, labor intensive and limited in its ability to effectively convey complex information to a diverse audience. From the costs associated with printing and distribution to the proper maintenance and sharing of paper records between global trial sites, paper ICDs require myriad manual processes. As consent forms grow longer due to more complicated trials, these processes will also grow more cumbersome, further increasing costs and the likelihood of errors that could lead to regulatory issues.
Simultaneously, the length of these documents and the perceived availability of new technology will likely contribute to an increase in participant confusion and potential frustration with the consent process. According to a literature review by The Clinical Trials Transformation Initiative (CTTI) as part of a larger ICP study, many participants already find the information on ICDs to be confusing, lengthy, and complexly worded.7 A separate study published in PLOS One, however, found that participants spent more time reviewing content presented electronically.8
When deciding to transition to an eConsent system, the first inclination may be to simply turn paper forms into digital documents, but this can become costly and ineffective. To best embrace the new medium, rethinking the development process is critical.3 Collaboration - often easier when producing electronic documents due to simplified version control and the ability to trace content development - can reduce development times if embraced early in the process.3 When the document is complete, health literacy, reading level and usability assessments should then be conducted on a demographic similar to that targeted by the study.7 By studying metrics from these assessments and noting completion times required for each section — a feature made possible in electronic systems by the creation of automatic timestamps — researchers can identify sections in need of clearer language or multimedia elements that may simplify communication.
Though participant consent is obviously the desired end result, allowing a trial to begin as quickly as possible, the full comprehension of all information contained in the ICD is essential for that consent to hold. Presenting everything clearly and with enough detail for the individual reader/viewer is crucial to minimizing dropouts during the trial that may result from participants feeling ill-informed or poorly supported throughout the process.3 However, a lack of comprehension is, in itself, not solvable with a single solution (e.g. simply transitioning to an electronic ICP). Education, cultural differences, individual health literacy and too much or even too little information can contribute to a lack of understanding. Additionally, the participant’s actions themselves (e.g. skimming a document rather than reading it fully) can lead to confusion.7
Information needs vary widely from one participant to the next, and digital media allows several levels of information to be made available in a single document without overwhelming the reader. This functionality allows researchers to present a brief summary of information — the most important and basic elements as mandated by federal regulations — that can then be expanded though user action to offer additional information. This expansion can be achieved with links to additional pages, drop-down menus, pop-up content, or even expandable content on the page itself and can include more detailed text, videos, graphics, pictographs or additional interactive elements, offering participants an expanded look at the study or clarification on certain words/topics.7 This tiered approached to information allows participants to essentially customize the information they receive, presenting them with the opportunity to access exactly what they need to fully understand the content.
Use and Monitoring in a Digital World
Paper-based ICPs open trial sites to potential compliance and/or ethics issues. Mistakenly omitted information, filing errors, and breaks in the process flow can lead to unnecessary delays or sites working with participants who are not fully consented. Additionally, it can be difficult to track the progress of a document over time or between sites. Even with a central lab, relying on paper forms reduces access to information. A simple, scalable and effective eConsent system alleviates these challenges.
The inherent flexibility of a digital system allows for an improved, trackable process flow and enables trial sites to monitor the effectiveness of an ICD in real-time. This means modifications can even occur during the consent process if comprehension or other issues are detected, and these modifications can occur with minimal expense. The desired process flow can often be built into the system itself, ensuring the document will move smoothly through various stages of review and sign off automatically if requirements are met. Timestamps at every step in the process improve traceability and allow necessary parties to receive system notification (submittal, hold, etc.) via onsite or remote access.3 Additionally, if re-consent becomes necessary during the trial, electronic files remain easily accessible and amendable.3
For an electronic ICP to follow the “simple, scalable and effective” mantra, development of the documents and processes must be thorough and collaborative from the start. And, perhaps most importantly, the flexibility of the document itself should be embraced. Concerns about electronic systems - including document security, the global acceptance of electronic signatures, and a lack of time-tested processes — still linger, but currently the benefits seems to greatly outweigh these reasons for hesitation.7 Ultimately, eConsent can provide a simple review process for the participant, easy tracking and sharing of information amongst trial sites, and simplified compliance with regulations. Best of all, it offers all of these advantages with just a few clicks or keystrokes and that simplicity is something that a sheet of paper can never provide.
- Ayalew, Kassa. “FDA Perspective on International Clinical Trials.” Food and Drug Administration. n.d. Web.http://www.fda.gov/downloads/drugs/newsevents/ucm441250.pdf
- ClinicalTrials.gov. “Trends, Charts, and Maps.” U.S. National Institutes of Health. Feb 2016. Web. https://clinicaltrials.gov/ct2/resources/trends#TypesOfRegisteredStudies
- Sather, Sandra and Lindroos, Mika. “CRF Health - Introduction to Electronic Informed Consent.” Business Review Webinars. 1 Dec 2016. Webinar.
- Shenoy, Premnath. “Electronic informed consenting: A boon to modernize consenting process.” Perspectives in Clinical Research. Vol 6(4). 2015. Web. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4640006/
- Taylor, Nick. “Mytrus makes electronic informed consent breakthrough in U.K.” FierceBiotech. 31 Aug 2015. Web. http://www.fiercebiotech.com/r-d/mytrus-makes-electronic-informed-consent-breakthrough-u-k
- The 2017 Nice Insight Preclinical and Clinical Contract Research Survey
- Lentz, Jennifer, et al. “Paving the way to a more effective informed consent process: Recommendations from the Clinical Trials Transformation Initiative.” Contemporary Clinical Trials. Vol 49. 2016. Web. http://www.contemporaryclinicaltrials.com/article/S1551-7144(16)30085-4/fulltext
- Rowbotham, Michael, et al. “Interactive Informed Consent: Randomized Comparison with Paper Consents.” PLOS One. 6 Mar 2013. Web. http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0058603