Head of Industry Leaders, Life Sciences and Healthcare, TCS

Hilde Vanaken, PhD

Diversity, inclusivity, and accessibility are the new buzz words in clinical trials. An equitable access to easily understandable, unbiased, and consistent communication of any study for informed decision making is the first and foremost fundamental step for any clinical trial participant.

Consenting is the process of information sharing, discussion, and agreement between an investigator and participant. It is one of the most critical steps in a clinical trial since without an agreement, there won’t be any participation. And it is widely expected that a better-informed trial participant will demonstrate a lower probability of dropping out at a later stage.

Despite criticality of this process, consenting continues to remain a painful, cumbersome, and inefficient process to date. Sites need to spend an enormous amount of time in helping participants understand and paraphrase the complex, lengthy paper consent document. Likewise, participants are put under immense time-pressure to “understand it quickly” and decide, many a times influenced by the “my physician knows best” effect. Wrong versions, missing dates, behind the fact’s signatures are just a few other inefficiencies of the consenting process that is picked up during inspection findings.

Use of multimedia can improve the consenting process,

 however its broad implementation is still quite limited. Key factors attributed in a recent survey conducted by Transcelerate

 to its low adoption include heavy resource demand to support development, approval and maintenance; regulatory law and privacy constraints and requirements and cost/benefits considerations.

The COVID-19 pandemic significantly increased awareness of eConsent,

 however it also led to several misconceptions of what eConsent is about. In a few scenarios, eConsent was even incorrectly correlated with eSignature, resulting in incorrect statements such as “you cannot do eConsent in country A & B”. It isn’t because one feature is not allowed, that we cannot use eConsent to support sites and participants with information sharing, documenting, and creating transparency in the consenting process.

It is absolutely imperative to understand that eConsent is not a new process. The basic principles of consent always remains the same, regardless of the medium used (paper versus digital) or location (in person versus virtual) it is carried out,

 Basic principles of consenting process, regardless of media used or location.

Unique considerations for eConsent—authentication, electronic Storage and eSignatures

By its very nature, additional precautions are required to be built in a remote setting to ensure that the trial participant is indeed who he/she is saying they are. Various methodologies can be used to ascertain this, ranging from mimicking the in-person process (e.g. displaying identity card via video conference or upload of identity card) to more sophisticated local authentication systems (e.g. itsme in Belgium). The choice of authentication tool that is acceptable might vary depending on the country, trial, site, etc.

Next, participant also needs to provide consent for electronically storing his/her personal identifiers. In a remote setting, this consent needs to be obtained ‘prior’ to sharing any study related information, and methods e.g., website registration or use of activation code can be leveraged. Electronic storage of participant’s personal identifiers might not be allowed in all countries, or additional requirements (e.g. locally hosted data centers) may need to be met. In such countries where electronic storage is not allowed, the documentation of consent signing, would be limited to a checkbox in the eConsent system.

There are as well wide range of different electronic signatures available (e.g. simple, qualified, and advanced).

 The specific type of eSignature allowed can vary on the country, trial, site, etc. Overall guidance provided by multiple stakeholders is to reduce overcomplicating or placing a disproportionate burden on investigator and participant by striving to the most stringent electronic signature highlighted in the Medicines and Healthcare Products Regulatory Agency (MHRA) & Health Research Authority (HRA) eConsent position statement.

The 1st step towards a successful patient-centric trial begins with the right use of eConsent

Use of digital technologies (e.g. apps, wearables, telemedicine) and novel operational model (e.g. virtual coordinating sites, home nurses, couriers) have immense potential to increase diversity, inclusivity, accessibility and embed clinical trials in participants’ personal life.

The new way of conducting clinical trials—also referred to as hybrid or decentralized trials—unfortunately also significantly increase the complexity of clinical trial execution. Thus, the need to support sites to explain what it is all about to their participants has never been more acute. We cannot simply drop “x” additional consent pages covering modern technologies and novel operational models and expect sites to put it in an easy to understand, consistent and non-biased message to participants.

Each participant is as well unique and should have the choice to opt in or out of the proposed technologies and operational models. For example, some participants might not want to opt for telemedicine or want couriers and home nursing to visit their home. These agreements should be captured in the informed consent. When using eConsent, these agreements can even be automatically linked to the underlying supporting tools such as televisits, home nursing, etc., enhancing transparency and overall compliance with participant’s personal choices. Ultimately, the entire process is aimed at enhancing the overall understanding of what participants are truly signing up for.

Reducing data privacy breaches by centralizing patient identifiers

Secure and highly restricted electronic systems can offer increased protective storage for personal identifiers and better control and transparency on who can access the data compared with paper document filings. Moreover, in hybrid and decentralized trials, multiple filings of participant’s personal identifiers might be maintained by various stakeholders (e.g., couriers, home nurses, etc.) that increases the risk of data privacy breaches. Using eConsent, we can eliminate these additional filings and have a “single” secure and highly restricted database for participant’s personal identifiers.

Lastly, the same secure environment can be used to capture participant’s additional personal identifiers (e.g. home address, phone number) or to upload participant’s medical records to enable remote source document verification.

eConsent as an integral part of a clinical trial

Real-time integration with randomization systems ensure that no medication assignments can occur if the consenting process has not been finalized. Consent data can be automatically uploaded in EDC systems and enable reconsenting (or avoid for discontinued participants). Various other data flows, e.g. with laboratory samples, couriers or home nurses systems can increase data quality, data integrity and compliance with participant’s personal choices. Some sites might have their own eConsent system where the focus should be on facilitating seamless integration and avoid any duplication of what is already in place.

It is worth pointing out that eConsent should not be limited to a one-time activity but that certain eConsent features can be re-used throughout the trial conduct to re-iterate to participants on what it is all about or to use snippets of certain assessments prior to an upcoming visit. Long term engagement has been highlighted as another major benefit of eConsent in a recent research study, with callouts to easier reconnects for additional research

 or distribution of lay summaries via EMA Clinical Trials Information System (CTIS) that went live in January 2022.

Automation and standardization—key levers to reduce burden and overall cost

Digital technologies require investment—both from a budget and resource perspective. A careful selection of which eConsent feature to include is critical. For example, long-term safety follow-up studies might not require expeStansive video creation, knowledge assessment, etc. compared with more complex studies or studies involving different stakeholders (e.g. assents and parents in pediatric studies).

Also, every participant is different. Some participants prefer detailing, others don’t. Some like reading, others prefer listening (e.g., audio, video). It is strongly advised to involve the target study population and stakeholders upfront in the design and selection of specific eConsent features. Similarly, evidence generation for eConsent is not a one size fits all. Depending on the study, disease, participant population, etc., the suitability and usability of different eConsent features might differ. Key performance indicators—both qualitative and quantitative—need to be included throughout the study execution to generate evidence of what works best for that specific study, population or disease.

Remember that the site-specific consent form in local language remains the final signed and take-home document of the participant. Artificial Intelligence driven data ingestion technologies should also be explored to automatically transform local consent forms in a multimedia format with tiered sections, tabs for site contact details, glossary, stakeholders, etc. Same applies for the reconsenting process. This will also increase compliance and consistency with the take home document as illustrated in Figure 2 below.

 Smart eConsent development can reduce burden and overall cost.

Addition of other digital features (e.g. chat box, mark unfamiliar words/phrases) should become as simple as checking a configuration box. And for incorporating more expensive and time-consuming features (e.g. videos, knowledge assessment), standardization and libraries should be introduced to ensure re-use of certain elements for other studies (e.g. explanation of randomization, right to decline at any time).

Site and participants as torchbearers to drive eConsent

The need for improving the consenting process has been a struggle since the start of clinical trials, and has increased exponentially over the last years with the introduction of various technologies and alternative operational models.

eConsent has inspired communities for several years, resulting in various guidelines of cross-industry consortia, such as Transcelerate eConsent

 Health Authorities, such as US Food Drug Administration

 and Medicines and Healthcare Products Regulatory Agency;

Ethics Committees such as Belgian Association of Research Ethics Committees

 The COVID-19 pandemic also added an additional boost in eConsent awareness (even though it led to several misconceptions of what it is about). Despite all these activities, broad implementation of eConsent falls behind.

To be successful and move clinical trials out of the privilege of a select group of people; sites and participants should be put in the driving seat for the development of eConsent. The European Forum for Good Clinical Practice (EFGCP) recently discussed problems around informed consent

 and is currently exploring to drive broader adoption in eConsent with the right stakeholders as key drivers.

Flexibility, interoperability, automation, and standardization should become fundamental cornerstones if we intend to make eConsent successful. There is no one size fit all. Each participant, each site, each study is different.

We hope everyone joins this journey to make it work, successfully!

, PhD, Head of Industry Leaders, Life Sciences and Healthcare, 

Classification and analysis of the GCP inspection findings. Retrieve from 

https://www.ema.europa.eu/en/documents/other/classification-analysis-good-clinical-practice-gcp-inspection-findings-gcp-inspections-conducted_en.pdf

Awareness and collaboration across stakeholder groups import for eConsent achieving value-driven adoption. Therapeutic Innovative Regulatory Science, 2019, Hilde Vanaken et al.

Maturity Survey Results of Transcelerate Modernizing Clinical Trial Conduct (MCTC) initiative, data from 2021. Retrieved from 

https://www.transceleratebiopharmainc.com/assets/modernizing-clinical-trial-conduct-solutions/

No place like home? Stepping up the decentralization of clinical trials. 2021, McKinsey. 

https://www.mckinsey.com/industries/life-sciences/our-insights/no-place-like-home-stepping-up-the-decentralization-of-clinical-trials

Guideline on computerised systems and electronic data in 5 clinical trials


https://www.ema.europa.eu/en/documents/regulatory-procedural-guideline/draft-guideline-computerised-systems-electronic-data-clinical-trials_en.pdf

eIDAS Regulaltion: Electronic identification and trust services for electronic transactions in the internal market, July 2014. 

https://digital-strategy.ec.europa.eu/en/policies/eidas-regulation

Medicines and Healthcare Products Regulatory Agency (MHRA) & Health Research Authority (HRA) eConsent position statement, 2018. 

https://www.hra.nhs.uk/about-us/news-updates/hra-and-mhra-publish-joint-statement-seeking-and-documenting-consent-using-electronic-methods-econsent/

Personalized and long-term electronic informed consent in clinical research: stakeholder view. BMC Medical Ethics, 2021. De Sutter et al. 

https://bmcmedethics.biomedcentral.com/articles/10.1186/s12910-021-00675-7

Clinical Trials Information System reaches major milestone towards go-live and application of the Clinical Trial Regulation


https://www.ema.europa.eu/en/news/clinical-trials-information-system-reaches-major-milestone-towards-go-live-application-clinical

Transcelerate guideline, toolkit and landscape assessment, 2017. 

https://www.transceleratebiopharmainc.com/assets/econsent-solutions/

Guidelines for tailoring the informed consent process in clinical trials, 2021, Horizon 2020 funded initiative 

https://www.fda.gov/regulatory-information/search-fda-guidance-documents/use-electronic-informed-consent-clinical-investigations-questions-and-answers

Guidance for sponsors on the use of electronic informed consent in interventional clinical trials in Belgium, 2020. 

Experimental programme on new informed consent processes in decentralized clinical trials, 2021. 

Description of VMK's trial scheme for informed consent in decentralized clinical trials

European Forum Good Clinical Practice (EFGCP) annual conference 2021, Modern problems around informed consent (day 3), 

Articles

Understanding differences in studies, sites, and patients are key to making eConsent successful.

eConsent—The First Step to Enable Clinical Trial Access to Anyone, Anytime, Anyplace

The COVID-19 pandemic has affected numerous lives globally, pushing the world to adapt and embrace innovative models to ensure continuity of business operations. As we see many countries slowly progressing with the “New Normal,” pharma industry, researchers, healthcare providers are assessing newer digital, virtual approaches which could reinstate the much impacted, clinical trials.

Informed consent, being the first step and hence one of the most critical processes in the clinical trial journey, has also been affected directly by the pandemic, as typically this process is carried out at the site in-person. The impact is not just seen, for new (to-be enrolled) patients, but also, existing patients, who are required to provide re-consents in accordance with the COVID-19 led changes for the study conduct.

In addition to the restrictions for in-person site visit, due to social distancing norms, COVID-19 also brought out some other challenges in areas such as traveling (e.g. impacted public transport) and reduced availability of investigators and site personnel (e.g. increased workload due to COVID-19 requirements).

To overcome the myriad challenges of COVID-19 on clinical trials, an expedited introduction and onboarding of an electronic Consenting tool could be a solution.

The virtual approach will enable sites to connect with patients without the need for in-person visits. Patients too can access the informed consent information at their own pace, read and review the easy-to-understand, multimedia, and interactive material without any pressure and discuss virtually, using telemedicine, any concerns with the investigator prior to providing their electronic signature. Updates to the consent material based on study changes introduced by COVID-19, can also be shared remotely and electronically, and by this maximizing the trial continuity.

For studies already using electronic Consenting but deployed at the site, the shift towards the at home setting will be relatively easy. However, for majority of the studies, using the traditional paper-based process, this shift will require a significant change in way of working.

For Roche, the current COVID-19 scenario imposed an immediate threat having a detrimental impact on many of its ongoing and critical new clinical trials across different therapeutic areas. As a result, the team had to act fast to find a way to ensure business continuity of the impacted trials across all geographies. Rapidly deploying a remote consenting process both for ongoing and new studies, and in compliance with country regulations, could be a solution.

Roche collaborated with TCS ADD team and implemented the TCS Connected Clinical Trials (CCT)—eConsent solution, to quickly rollout the digital informed consent. A close collaboration between both teams was the key to ensure that the application and onboarding process was aligned with Roche’s processes and end user expectations. The eConsent solution, which typically takes three weeks to implement, was deployed in a simplified way and enabled in just seven days. This fast track eConsent model was accessible at home through any medium—laptop, smartphone or tablets, in the patient’s own language.

For sites, the eConsent solution also reduced the administrative workload—something that was highly appreciated in the COVID-19 times—and focus more on patient’s targeted questions and concerns. For patients, being able to review the consent in an easier to understand multimedia format and at their own pace and be better prepared for the conversation with the investigator, was welcomed. Currently, the eConsent solution has already been successfully rolled out for multiple studies across global sites, and many more are being planned.

“With the eConsent technology, our studies will seamlessly address the current challenges of providing access to patients. The response received from the sites so far, is truly positive and paves the way for efficiently onboarding eConsent technologies and virtual trials,” said Mandy Sodhi, Clinical Operations Leader, Genentech (Roche).

Implementation of eConsent involves multiple factors in a typical clinical trial setting. However, considering the huge impact of COVID-19 on new and ongoing studies, dynamic and expedited working models need to be leveraged for catering to specific needs.

Following considerations are crucial for implementing eConsent for studies that require the quickest turnaround time:

Highly configurable tool able to quickly handle various study templates

Device-agnostic intuitive material such as videos, images, infographics, etc. and text

Leverage email or SMS messaging option to share eConsent link.

Access at home from any device, e.g. smartphone, tablet or laptop

Tool with virtual contact feature for site—patient connect

Tool with electronic signature or uploaded of printed signed forms sent via regular mail

Real time insights and oversight across all sites, for all partners

24x7 local helpdesk available for any queries or difficulties

“The implementation model has been the key to onboarding studies impacted by the pandemic and ensures the consent information reaches patients at home. Faster turnaround time for the study setup is providing the much-needed push to re-instate the trial enrollments,” says Ramachandran Prasad, Technical lead for Genentech (Roche).

While COVID-19 has been a dramatic experience, it has also shown that technology and team collaboration can help in navigating the negative impact on clinical trials. The hope is that post COVID-19 pandemic, pharma companies will continue to leverage eConsent and other digital patient centric technologies and move towards real patient centricity.

is the Senior Industry Advisor, TCS Life Sciences and Healthcare (Former Transcelerate eConsent Workstream Leader.) 

http://www.transceleratebiopharmainc.com/wp-content/uploads/2017/11/eConsent-Implementation-Guidance.pdf

As many countries slowly progress with the “New Normal,” researchers and healthcare providers are assessing digital/virtual approaches that could reinstate clinical trials.

Fast Track Implementation of eConsent: COVID-19 Paves the Way for Virtual Trials

A new SaaS platform for clinical trials, soon available to all pharma companies, aims to automate clinical supply, improve patient compliance and enable better medication adherence.


	 
	Equipped with extensive data from its technical pilot study and a newly-forged partnership with global information technology firm Tata Consultancy Services (TCS), Janssen Research & Development, LLC (Janssen) is steadily moving forward with plans to roll out a comprehensive “smart” clinical trial platform in late 2017.

	The platform, known within Janssen as eMeds, includes an array of digital technologies that are brought together by a cohesive software program. It seeks to improve patient engagement while also transforming clinical trial medication supply and data management-with the ultimate goal of enabling more efficient trials that will allow pharmaceutical companies to bring drugs to market faster and cheaper than today.

	The platform currently consists of four modules: eTracking, eLabel, eCommunication and eAdherence. Each addresses a different critical element of the clinical trial process. The platform will be externally branded as Connected Clinical Trials (CCT) and accessible to any pharma company by late 2017 in the form of a software-as-a-service (SaaS) from TCS.

	As a next step, the program will scale up into a larger-scope project, known within Janssen as iSTEP (integrated Smart Trial and Patient Engagement Platform). The next phase will include additional inter-linked features such as eConsent, biometric monitoring, additional means for patient engagement, electronic patient-reported outcomes (ePRO) and electronic clinical outcomes assessment (eCOA).

	In early December, Janssen and TCS are holding an informational cross-pharma meeting for drug development companies at the Janssen offices in Beerse, Belgium; more than 30 people from at least a dozen pharmaceutical companies have confirmed their attendance. The objective of the meeting is to raise overall awareness of CCT, which will begin to roll out next year, and to collect feedback on the ongoing platform development.  
	 
	

	Underlying the platform’s development is an acute understanding of the pharmaceutical industry’s need to transform the clinical supply process on multiple fronts.

	Digital technologies have become more and more embedded in the day-to-day life of patients and investigators, and yet are not currently integrated seamlessly into trials. At the same time, drug sponsors are striving to shorten the timeframe for bringing new drugs to patients; they’re seeking novel ways to facilitate adaptive trial designs and combine multiple studies when appropriate. Another driving factor is the regulatory environment, where regulations are rightfully becoming more stringent in the area of data quality, forcing pharmaceutical companies to rethink today’s largely manual and paper-based processes of managing clinical supplies and tracking patient health data. Not only are these processes time-consuming, but they can result in manual errors.

	Further, poor control over patients’ adherence to medication dosage increases the risk for patient safety during the course of the trial. Yet existing technology tools could be leveraged help monitor adherence and communicate swiftly with patients who may be at risk.

	In addition, pharmaceutical companies need a better system of understanding how clinical supplies are being managed for trials, both at the site and when patients are at home. And they seek to address the challenges of today’s paper-based booklet drug labels. To address these factors, the following four modules are in development:

 is designed to enable registration and verification of all medication kit activities at a clinical site, and help to ensure the right kit is given to the right patient.

 seeks to provide customized, real-time patient notifications via a smartphone, as well as how-to videos and simple tools for adverse event data input. It can also facilitate personalized patient support, providing clarity in medication intake and study procedures.

’s goal is to produce highly readable, patient-specific and all in one electronic drug labels in the patient’s native language. It also enables label flexibility, eliminates booklet printing and decreases waste.

 is designed to ensure registration and improve verification of individual medication intake via sensor-enabled and Near Field Communication (NFC) smart medication packages. The tool is intended to help patients take the right pill at the right time, removing guesswork for medication intake and providing key data for regulatory needs. The data also can serve as an early warning to the company of potential trial drop-outs or safety risk and the opportunity to intervene faster.

All of the modules are designed to connect with one another, and with other databases. Together, they collect participant data and automatically analyze and communicate information to stakeholders, taking the place of paper-based or manual data entries.

	During a trial, the data flows securely from the participant’s smartphone-which collects information from the smart packages and patient entries-to the trial site for review and confirmation. After site reviews the information, certain data fields are uploaded to the clinical database for the sponsor.

	The platform works in various ways to support the patient, providing personalized messages and instructions on what he or she needs to do at specific times throughout the clinical trial. This communication, combined with real-time insight in what the patient is doing at home, offers potential opportunities for adaptive trial design, including real-time dose adjustments or, for adding, changing or dropping a treatment arm based on interim result analysis.
	
	

Technical pilot points to key platform benefits

	The eMeds platform concept has been in the works at the Janssen Research and Development Operations Innovation group for more than five years. During this time, the team has consulted extensively with internal and external stakeholders from related disciplines including clinical, regulatory, supplies, privacy and others.

	But to gain real-life insights on how the various modules actually work in a clinical setting, Janssen orchestrated a technical trial at a Phase I site in Antwerp, Belgium, through which it collected extensive feedback from study participants and site personnel via surveys and interviews.

	The technical study included 24 healthy volunteers, both male and female, evenly representing three age groups: 18-40, 40-65 and older than 65. Volunteers included native speakers of Dutch, French and English. At the outset of the trial, participants were instructed to take one morning capsule and one evening capsule. Three dosing changes were communicated via smartphone over a 12-day period, changing both the quantity of medication as well as the time of day at which it needed to be taken (morning, noon and evening). Patients were aware that dosing changes could occur during the trial, but did not have any further details. The last dose change simulated a medication recall, with all activities occurring at home.

Because this was a technical pilot, a placebo was given; participants were not required to ingest the placebo.

	The study had two objectives. First was to rigorously evaluate the various components of Janssen’s eMeds platform in a clinical setting-testing the integration of databases with the devices and modules, and evaluate real-time communications/actions among all stakeholders. Second was to gauge user-friendliness and satisfaction, from the perspectives of participants, investigators and sponsors. These “softer” measures were significant given that improving patient engagement in clinical trials is a priority for Janssen.

	The trial site personnel received a site user manual, a tablet-based medication scanner and daily compliance reports that showed when each subject pushed out a pill from the smartblister package (a traditional blister package, but with an electronic circuit added on top to track when each pill is popped out). At the site, reports automatically recalculated what each participant had completed (for example, what time each pill was popped out) along with a list of actions that participants still needed to accomplish, and the time window for completing the remaining actions.

	Each trial participant was given a smartphone and charger, a kit with three smartblister packs (each smartblister contained six capsules per day for four days), a quick-reference card, a participant user manual, and two satisfaction questionnaires to be completed on day five and day 12. Each participant also was interviewed individually at the conclusion of the trial. All documents were provided in the individual’s native language.

	As in all trials, all participants were assigned an ID code. In addition, the participant’s language was a required field during registration. An app on the participant’s smartphone was activated and linked to the individual ID so all participant-specific material (for example, how-to videos, notifications) would be pushed to the app in the individual’s native language.

	Before the trial began, all participants were trained on site in a group setting, and received hands-on individual training when the smartphone and smartblisters were provided.
	
	

	The technical pilot was effective in meeting its objectives, shedding light on key benefits of the technology and pinpointing areas for improvement-all of which have been addressed in the latest version of the platform and related smart devices. Among the highlights:

 Despite a stringent treatment regimen, allowing only a 30-minute deviation before or after set dosage times, compliance rate was very high at 92%. The rate slightly decreased throughout the day (95% compliance in the morning, 94% at noon and 89% in the evening) and was higher for females and participants older than 40. When asked what the most important advantages were of the technology, 71% of participants said it was being notified of changes in dosing, and 38% said it was reminders for treatment intake. Some participants suggested adding an additional notification just prior to intake, rather than 15 minutes before, and repeating the eLabel update once more before the next intake.
					 	

elabel seen as a valuable resource for drug information.

 Whereas paper-based drug booklets are commonly returned unopened to trial sites, participants reported that the eLabel functions were a valued resource during the trial and 92% said the updates were easy to understand. Seventy-two% of the participants proactively consulted eLabel’s content, in addition to reading eLabel smartphone notifications. Notably, the final eLabel notification was a medication recall, in which the site and sponsor were able to monitor in real-time whether patients understood the recall via information communicated from their smartblisters.

 A full 100% of participants under 40 said the smartphone was easy to use, as well as 75% of those 40-65 years old and 50% of those older than 65. Only one participant, a women older than 65, reported not liking using smartphones. These results were significant, as only a quarter of participants (all from the youngest age group) reported having prior experience with smartphone and tablet technologies. The smartphones were used to consult dosing instructions, how-to videos, receive several types of notifications (visit reminders, for example) and uploading of smartblister data. Satisfaction with the smartphone increased with usage, as reflected in responses at the start of the trial versus at the end.  

Real-time insight has the potential to bring practical benefits for patient safety.

 The site could immediately interfere when participants missed or took an incorrect dose. This feature could provide immense patient safety benefits as well as pick up early signs of drop out. During the technical pilot, the sponsor was able to monitor the progress of the investigational drug activities, with real-time insight into the site and at home, reducing the need for the sponsor to make in-person visits.  

Immediate insight into patient dosing intake at home may enable adaptive trial design.

 Real-time changes to dosing via eLabel alerts, combined with real-time insight into whether these changes are understood and acted upon as expected, can be an important enabler for supporting patients in complex study designs, as well as adaptive trial design.

Paperless flow achieved, date-entry errors eliminated.

 Databases, devices and stakeholder communications were integrated smoothly, enabling a paperless flow without any data entry during the trial. The process automatically triggered new communications and reminders based on actions, such as when medications were removed from the smart packages.

For participants, uploading data from smartblister to smartphones was a smooth process.

 No one indicated that data upload onto the smartphone took too long, with 54% saying it was very quick and the rest saying it was acceptable. All participants reported it was easy to find the correct location on the smartblister package to upload data. (The location was indicated with an icon that appeared on both the package and smartphone.) Eighty-three% said the whole uploading process was very easy or easy, which is significant given that the majority of participants did not consider themselves experienced with smartphones.     

Sponsor and site personnel feedback was positive.

 The site rated the devices, applications and reports as user friendly, and could achieve 100% remote access to participant’s at-home compliance data. Sponsor had 100% remote access in all activities happening at the site and with the participant, so no in-person visits were needed for reviewing medication-related activities. All stakeholders also said they appreciated the convenience and usability of the apps and quick reference cards.

	Site personnel, sponsor personnel and participants were overall very positive about their experience with the smartphone and smartblister. They noted ease-of-use, clarity and frequency of smartphone notifications, ease of uploading data with smartphone, ease of pushing out capsules, layout of the capsules and on-site training.

	But feedback also brought to light age-related differences. Participants under 65 generally rated all steps of the process as easier and reported a better experience with their smartphones, while older participants were more compliant. Younger participants also commented that the smartphone and smartblister package seemed too large and the hands-on individual training was too long, while the older group said the contrary.

	When participants were asked what they thought was the biggest advantage, they ranked “being notified of changes in dosing” as the most important. This was followed by “reminder for medication intake” and “my doctor has insight into my medication intake.”

	Janssen is now selecting pilots (from among Janssen’s clinical trials) to actively deploy and implement all the different modules of the platform by end-of-year 2017. Once the platform is released, it will be available for other pharmaceutical companies to use.

	Mainstream technology exists today to improve clinical trials in many ways, from tracking adherence data to communicating seamlessly with patients in ways that can help the trial become more flexible and potentially improve patient safety.

	As an industry, we must work to reduce the complexities of clinical trials, from labeling to protocol compliance. The open-format Connected Clinical Trials platform will set us on the path toward this goal, with more engaged trial participants and stronger regulatory data to support innovative new pharmaceutical products. We are on an exciting journey, moving the clinical trial into the digital world, where we will be able to simplify and improve many aspects of the trial while also enhancing important relationships and maximizing the input of patients.  
	
	

, is director of the R&D Operations Innovation Department at Janssen Research & Development, LLC. She also is the TransCelerate eLabel Core Team Member and Transcelerate eConsent Workstream Leader.

Digitally Enhanced: Janssen Drives Effort to Bring Suite of ‘Smart’ Clinical Trials into Practice in 2017

	The drawbacks of today’s paper-based informed consent methods for clinical trials are well understood, but the industry has yet to perfect the process and tools to best ensure human subject protection while at the same time achieving a streamlined electronic consent process. 

	Janssen is working to change that, releasing the findings from the company’s multi-country pilot study of electronic consent technology to guide the development of industrywide practices. The eConsent study was conducted at 13 sites-10 in the U.S. and three in Hungary-in a Phase III clinical trial of INVOKANA™ (canagliflozin) in subjects with type 2 diabetes. 

	Each participating site received an iPad device loaded with the patient eConsent app, as well as a training app and a training webinar for site staff. 

	The eConsent app first informed patients that their name and all data would be time-stamped and securely stored in a database. After patients provided their approval, the app played an animated video explaining the full study and key aspects of procedures. Next came the actual informed consent e-document, along with an app-based dictionary and the ability to indicate when a word was not understood. Finally, patients took an eight-question multiple-choice quiz that highlighted key aspects of the study. Both the patient and site staff signed the document electronically, using a stylus. The study’s sponsor had real-time access to all eConsent activities per patient via a web portal.

	A total of 76 patients participated, each completing a detailed satisfaction survey immediately after the initial eConsent. Sites responded to a brief survey every two months and then completed a comprehensive survey after the study was completed. 

	Overall, satisfaction levels were extremely high from both patients and sites, indicating a broad willingness to transition to an electronic process for consent. As a whole, the eConsent functionalities and features received a “satisfactory” rating of greater than 85%. (Other possible response options were “neutral,” “unsatisfied,” or “not used.”) 

	Highlights included the video (96% of patients rated it satisfactory), content review quiz (94%) and a feature that allowed patients to mark unfamiliar words (90%). Meanwhile, 77% of sites said eConsent improved the entire consent process. 

	Diving deeper into the survey results, here are some of the key takeaways:  

Older participants adapted well to new technology.

 Of patients 60 or older, only 27% had experience with a tablet device. While that could prompt cause for concern, older users universally reported high satisfaction on each eConsent feature. As a whole, all age groups rated the process “easy” or “very easy” to use and no one with experience using paper forms said they thought the traditional process was better.

More time to focus on what’s important.

 When site staff were asked about the length of time it takes to use eConsent versus paper forms, 46% reported it was about the same. Twenty-three percent said it was faster, and 23% said it was more time-consuming. Sites could more quickly address items patients didn’t understand or missed on the form-which didn’t always result in a workload reduction, but was certainly a process enhancement.      

Improved patient understanding and engagement seen. 

Most (69%) of the sites reported eConsent as a helpful tool for improving subjects’ engagement during the consenting process and in boosting their initial understanding of material (also a key advantage reported by patients). In addition, 38% of sites said that eConsent improved patients’ desire to enroll or stay in the trial. 

Valuable insights into the patient’s mind. 

The sites and sponsor were able to see which app features the patients used and how much time was spent on each section, as well as which words were marked as unfamiliar or looked up in the dictionary. This feedback is a promising feature as the industry seeks to make clinical trials easier for patients to understand.

All of the app’s content must be translated into native languages. In addition, country-specific requirements will have to be incorporated. For example, Hungary requires patients to provide date of birth and place of birth.   

	Janssen is sharing these and other findings while leading TransCelerate’s eConsent work stream. In parallel, Janssen is preparing a new eConsent study with visually impaired patients in the U.S. and Canada. The 15-site study will include five different consent forms and additional audiovisual features. Three more studies will kick off within the next year to broaden the global perspective and assess other eConsent functionalities and patient populations. 

	The benefits of eConsent are clear, but now it’s up to the industry’s many players to come together to share their learnings and remove barriers to implementation. This also requires close collaboration with patients, trial sites, health authorities and ethics committees. 

	 As with many new digital technologies for clinical trials, eConsent is a tool to enhance the site-patient relationship, not replace it. A positive experience at the onset of a trial is a gateway to better engagement throughout the study and afterwards, bringing our industry closer to patients-our most important allies.

Hilde Vanaken, Ph.D., is director of the R&D Operations Innovation Department at Janssen Research & Development and is the Transcelerate eConsent Workstream Leader

Janssen releases key findings from its pilot study evaluating the use of electronic informed consent technology in clinical trials.

Hilde Vanaken, PhD

Articles

eConsent—The First Step to Enable Clinical Trial Access to Anyone, Anytime, Anyplace

Fast Track Implementation of eConsent: COVID-19 Paves the Way for Virtual Trials

Digitally Enhanced: Janssen Drives Effort to Bring Suite of ‘Smart’ Clinical Trials into Practice in 2017

eConsent Study Provides Insights to Shape Industry Adoption