Check out the latest features and columns!

Applied Clinical Trials June 2022

ACT's biennial Salary Survey takes a look at the future of industry following increased adaptation of decentralized technology 

Salary Survey: The Age of COVID

Emerging tools in data analytics, automation, EMR aggregation, and even social media are enabling faster and easier patient recruitment

Patient Recruitment Goes High-Tech

ClinOne Founder and Chief Solutions Officer

Nobody knows what sites need to optimize clinical trial management better than the sites themselves.

When sponsors and CROs provide sites with long lists of products and platforms, they often overlook the unique needs and preferences of individual sites in favor of one-size-fits-all options.

Site teams already are under a tremendous time and labor burden. They need the flexibility to choose the solutions they want without adding new time or labor burdens or unnecessary costs. Clinical trial technology companies must offer sites the power to work the way they want, and help them unlock new efficiencies in trial conduct.

Following are 3 areas where sponsors and CROs can help make sites’ lives easier while improving access to research for more patients, building more robust physician networks, and developing consent solutions that work for all stakeholders.

A growing number of sites are tired of trying to integrate disparate technology offerings from sponsors and CROs, and are purchasing their own eConsent solutions to enable consistency across all their trials.

Sites choose this approach because it lets them conduct consent activities in ways they and their patients prefer, instead of using sponsor-provided options. For example, a site may not want a typical eConsent option, and prefer to use paper consent for patients who are not comfortable with technology. Or, a patient might be unable to visit the site but still want a personal connection, so the site can obtain consent via video.

These options allow sites to tailor their eConsent program in a way that works best for them and their patients. Flexibility to consent patients in person or remotely, either electronically or via paper, is a powerful tool that helps sites ensure accuracy and security, and convey a consistent message to patients about the risks and benefits of trial participation.

Whether sites procure their own eConsent technology or use technology provided by study sponsors, they should have the ability to load all consents—regardless of how they are collected—into a centralized digital system for secure storage.

Approximately half of all clinical trial patients cite a lack of reliable transportation as a barrier to clinical trial participation.

 Further, a recent survey revealed that 95% of responding clinical trial sites reported the ability to provide transportation for patients would improve recruitment efforts.

 Gas prices are at historical highs; perhaps patients can’t afford to spend the out of pocket expense. There can be many added factors keeping patients from making clinical trial visits, including lack of access to a reliable vehicle, or distances from clinical sites that are not served by public transportation. We need to make it easier for patients to make their site visits, particularly as we redouble our efforts to engage underserved communities and build more inclusive clinical trials.

Leveraging ride-share technologies like Uber is a new option that is helping sites remove transportation-related barriers for patients. Modern trial management platforms can even integrate ride-share scheduling to allow sites to easily arrange for and track patient journeys to and from sites. By making it as simple as possible for both sites and patients, we can decrease or eliminate missed visits and keep studies on track.

Patients trust their doctors. Site teams know general health care practitioners are important gatekeepers to reach more—and more diverse—groups of patients. In fact, in an industry survey 81% of patients who had never participated in a clinical trial indicated they would be likely to do so if referred by their doctor.

 However, most general practitioners are not reliably aware of the types of clinical trials available to their patients who could benefit, and sites are too busy with other critical tasks to add the burden of manually seeking out new physician referrers.

The good news is technology exists today that allows study teams to tap into much larger groups of physicians to spread awareness of clinical trials. Automating clinician outreach based on data that finds specific disease populations and physician specialties can save sites time and money, while significantly expanding the number of doctors who are aware of a given clinical trial.

A more informed network of clinicians is better able to identify patients who might benefit from clinical trial participation, and refer them to specific studies. This approach has the potential to greatly enhance patient recruitment efforts, including efforts to increase patient population diversity.

The role of clinical trial sites in the success of any given study cannot be understated. Clinical trial technology companies can improve the site experience by providing solutions that allow them to work the way the want more efficiently and cost-effectively. Sites can use this technology to provide the best possible patient experience.

, ClinOne Founder and Chief Solutions Officer

https://www.mmm-online.com/home/channel/technology/continuum-and-lyft-to-offer-free-rides-to-clinical-trial-patients/

https://www.appliedclinicaltrialsonline.com/view/overcoming-transportation-barriers-trial-participation

https://pharmaintelligence.informa.com/resources/product-content/patients-rate-their-clinical-trial-experience-positively-but-trial-locations-still-pose-barriers-to-enrollment

Articles

Sponsors and CROs can ease the burdens of patients, sites, and physicians by identifying these 3 key areas.

Empowering Sites to Optimize Clinical Trial Performance

Since its inception, the process of informed consent has evolved incredibly. However, many barriers remain, preventing the smooth and efficient processes we would like to see in clinical trials (CTs).

The use of electronic informed consent could contribute to overcoming some of these inefficiencies, notably by increasing the flexibility of the process, thus allowing the informed consent document to be better adapted to the patient's needs and facilitating document and process management for study teams. However, the eConsent process is still not widely adopted. We see a number of reasons for this. Firstly, patients are not always comfortable with such technologies. Secondly, the first investment often frightens organizations. Thirdly, countries do not always recognize and allow electronic signatures. Finally, the requirements laid down by regulatory authorities still vary from region to region, country to country, and from one ethics committee to another.

On the opposite, under the increasing digitalization of our world and following the current pandemic, experts claim the necessity of such tool. Many trials had to improvise after the lockdown announcement: sites were suddenly closed, no one could access the documents nor the data, and CRAs were stuck at home.

The recruitment rate of clinical studies, which was already a critical point for trial success, has significantly decreased during this health crisis.

 Patients are stuck at home and cannot come on sites to meet the PI and receive the trial’s information. In addition, the COVID-19 pandemic resulted in a huge shift in the priorities of clinical staff members who needed to focus on COVID units and dedicated clinical trials.

 Consequently, the rate of trials’ enrollment at the end of June 2020 had plummeted from 30% compared with October 2019.

In the recent release (9.0) of “The Medidata Perspective” on the impact of COVID-19 on clinical trials (September 21, 2020), trial sites were asked to evaluate the impact of the pandemic on diverse activities within their studies. On a scale from 1 to 5, the biggest impacts were the sites’ ability to recruit patient (3.02) and to enroll patients (3.02). In response, 39.2% of sites decided to stop recruitment for ongoing trials.

 Nevertheless, this kind of decision is followed by important clinical trial delays and massive expenses.

The eConsent, or digital informed consent, thus appears as a promising solution. More and more CTs stakeholders are showing an interest and are turning to these new tools. Times are changing and we need to evolve with it. For some companies, the digital informed consent is now an integral part of the risk mitigation plan.

However, at the same time, the authorities must ensure that they can judiciously supervise the use of electronic tools. In many cases this calls for a complete revision of existing laws and regulations; it has already been done in the past for some technologies, as for the regulation of electronic signatures, but much more important revisions, such as the 3rd revision of ICH GCP, are underway for the complete integration of the various aspects of emerging technologies.

In the scope of this research project entitled “Toward a global implementation of eConsent in clinical trials”, a survey was conducted to understand how eConsent is perceived and experienced by clinical research experts, how it can improve patient comprehension, reduce site burden as well as to identify areas of opportunities and challenges for further adoption. The survey was based on a prospective questionnaire on eConsent, built to target five types of stakeholders: sponsors, contract research organizations (CROs), ethics committees (ECs), investigational sites (ISs), and vendors of eConsent solutions. The questionnaire was sent to clinical research experts in Belgium, Luxembourg and the Netherlands as, although three bordering European countries, they present disparities in the regulation and acceptance of eConsent.

The survey was sent between September 22, 2020 and November 1, 2020. In total, 342 participations were registered. Of them, 129 were complete responses and 213 were partial responses. Results were analyzed between November 5, 2020 and December 8, 2020.

Overall, the experience with eConsent among the targeted countries and the different stakeholders appeared quite different, but still very low for all of them. On average, 28% of the clinical research experts were novices with eConsent and only 3% had experience. Between the three countries, the Netherlands seemed to be the one with most expertise, followed by Luxembourg and Belgium.

Comparing the stakeholders, each seemed to have a different experience, but overall, very few answered being in full operational usage (~7%). Sponsors were the ones who were most in a pilot phase (~50%). However, half of Sponsors in piloting phase is still very low. The current lack of a uniform regulatory framework around eConsent on a European level appeared to be a rational explanation. In fact, when stakeholders were asked what the main barrier limiting the implementation of eConsent at their organization is, many Sponsors explained that the fragmented guidelines and regulations has considerably hindered their use of eConsent.

Another important barrier that stood out for Sponsors, but also CROs and ISs, was the concern about data privacy and security (~42%). Surprisingly, according to Vendors of eConsent solutions, the main concerns of the customers were not about data privacy but more about the implementation on study sites (50%) and the cost (33%) of such a tool. The site implementation was indeed another important barrier mentioned by the “customer-stakeholders”. However, the cost was evaluated as a hurdle by those in only 12% of the cases.

In a following question, the majority of stakeholders explained that the site implementation wasmore difficult than for a paper-based informed consent (IC) (~61%). In fact, it requires staff training and adaptation and, here again, the fragmented or—in some cases—even lack of regulation around eConsent makes it difficult to implement on sites. However, as one respondent commented, “any change to a normal process is causing difficulties in adapting;” we have to make a first effort if we want to embrace the change and evolution.

Furthermore, this first burden may be worthwhile, as the majority of stakeholders have found that eConsent improves the clinical staff workflow (~70%), facilitates the management of document amendments (~72%), eases the conduct of audits (~80%) and reduces the number of audit findings (~65%). Indeed, the digital aspect of eConsent prevents IC document loss, makes everything available very quickly, facilitates audit trails, and avoids using wrong/old version of the ICF. For the reconsent process, it is also easier to know which patients have not yet consented to the latest version of the ICF. Nevertheless, in order for eConsent to really lighten the workload of sites it needs to be available on multiple devices: vendors’ solutions thus need to be flexible. This will allow the patient to read the information alone and at their own pace, while the staff is busy with other tasks, and to read the information at home, with their family, before deciding whether or not they want to take part in a study.

Another important outcome from the survey was that all stakeholders agreed that eConsent increases the patient understanding of the trial. Indeed, on average, 80% of all stakeholders stated that eConsent allows patients to better understand the trial. Vendor representatives supported this outcome, evaluating the enhanced patient understanding as the most appealing feature of eConsent for customers. This is not surprising as eConsent is first and foremost a patient centric tool. Interactive features and multimedia components like videos and illustrations can be very helpful to simplify and explain difficult information to the patient as shown in the Figure 1 below.

 Clustered bar graph on the impact of each eConsent feature/component on patient comprehension and engagement.

The use of paper-based IC is an important time constraint for the principal investigator (PI) and the site staff who sometimes do not have a lot of time to go properly over the document content with the patient. As one questionnaire respondent noted, with eConsent, “participants will go through the content.”

Among the various eConsent components/features, the ones that apparently have the most impact on this comprehension are the user-friendly interface, visuals, video, and audio. Perhaps these results also indirectly show the reluctance of stakeholders to try new and unknown components and to fully exploit the potential of eConsent.

On the opposite, the components which seems to have the less impact on patient comprehension and engagement are the comment boxes, knowledge assessment and content flags. Indeed, knowledge assessment is considered by many to be too intimidating for study participants. Conversely, according to a Principal Investigator, interviewed for the purpose of this project, asking the participant to answer some questions at the end of the reading/viewing process allows a more pragmatic assessment of the patient's comprehension. The answers to these questions can also be included in a subsequent analysis to identify the overall understanding of the study participants, as well as the IC content section that should be revised to improve understanding. By following the same process, content flags can also be very useful, especially for Sponsors, to identify the "trend" of flags and thus determine which IC section should be modified to provide a better explanation to the participant. Therefore, even though poorly rated, knowledge assessment and content flags can both indirectly help to enhance participant understanding of the study and hence participant engagement in the trial. Those could also constitute proof that all the study participants went through the IC content, understood properly the information, and that all their questions were clarified during their meeting with the clinical staff.

Overall, when asking their opinion on eConsent, all countries were for a broader and global use of this tool, and the majority of stakeholders expressed their growing interest for it following the COVID-19 crisis. On average, 72% of all country representatives were for a broader use of eConsent and 65% of sponsors, CROs, and ISs stated that the recent COVID-19 crisis had increased their interest in this digital tool. They explained that, with the current need for remote visits and speed of starting-up trials, eConsent has become a very attractive solution.

The results from the prospective questionnaire emphasized three important barriers for the implementation of eConsent in clinical trials:

Clinical research experts are missing a dedicated regulatory framework for the implementation and the use eConsent in clinical trials.

People are not educated about the laws and regulations in force and are not educated about the electronic informed consent itself. It appeared in the questionnaire that the inexperienced stakeholders had a less positive opinion towards eConsent, its features, and components.

Indeed, once the people are experienced with eConsent, when it is not an innovation anymore, then the focus is on the processes, the operations and on how to make them as efficient as possible. In the questionnaire, many respondents pointed out the increased difficulty regarding the implementation and day-to-day processes related to the use of eConsent.

Based upon the above findings we can push forward the following recommendations:

The need for a comprehensive, clear and uniform regulation:

A clear legal and regulatory framework for eConsent

Creation of practical and pragmatic guidelines for the implementation of eConsent in clinical trials

Increased continued education and communication:

About the existing and new drafted laws and regulations.

For sites: during the ICH-GCP certification process, an instruction about eConsent and its subtilities might be a good opportunity to educate the sites on this topic.

For ethics committees: training program to educate ECs on eConsent and creation of guidance to standardize the evaluation of eConsent dossier.

Vendors should communicate more about the data protection system and the security of their solution.

Sponsors need to continue to work on lean processes, lean operations to facilitate the implementation and the day-to-day use of eConsent.

Flexibility of Vendors is important: eConsent should be available in several type of devices, simultaneously. In addition, vendors should be able to provide a system to achieve the same "IC amendments" and start-up time as for a paper version of the IC.

Overall, it seems that every clinical research stakeholder has a role to play to truly move the needle of eConsent and increase the implementation of eConsent in CTs.

The prospective questionnaire on eConsent gave interesting insight on the opinions and experiences of eConsent between the three bordering countries as well as between the various stakeholders of clinical research. However, in order to draw more conclusions about eConsent, additional surveys gathering more answers from the three bordering countries but also from the other European Member States would be of great help for the development of a European consortium on eConsent.

, NBCD A/S, Herlev, Denmark & Paris, France, 

, University of Ghent, Heymans Institute for Pharmacology, Ghent, Belgium and Professor, Medical Consultancy B.V. in Heerhugowaard, The Netherlands, 

, Janssen Pharmaceutica NV - Portfolio Delivery Operations, Beerse, Belgium, and 

, University of Namur, Faculty of Medicine, Department of Biomedical Sciences, Namur, Belgium

Mahnke, A. N., Plasek, J. M., Hoffman, D. G., Partridge, N. S., Foth, W. S., Waudby, C. J., Rasmussen, L. V., Mcmanus, V. D., & Mccarty, C. A. (2014). A rural community’s involvement in the design and usability testing of a computer-based informed consent process for the personalized medicine research project. American Journal of Medical Genetics, Part A. 

Grady, C., Ph, D., Cummings, S. R., Rowbotham, M. C., Mcconnell, M. V, Askley, E. A., Phil, D., Kang, G., & Ph, D. (2017). Informed Consent.

Davidson, A., Erana, B., Henry, R, PPD. (2020) Protecting Clinical Research and Patients through Decentralized Trial Strategies. 29/09/2020.

Alsumidaie, M. (2020). Clinical Trial Quality Management: ICH E6 (R2) Interpretations Deepen. Applied Clinical Trials Online.

Medidata Solutions, Inc., a Dassault Systèmes company. (2020) COVID-19 and Clinical Trials: The Medidata Perspective. Release 9.0. 21/09/2020.

Zamora, A., Bernardo, M. (2020). Presentation:” Exceptional Measures?”. 17/07/2020.PPD.

Final Business Plan, ICH E6(R3): Guideline for Good Clinical Practice. (2019). Retrieved from 

https://database.ich.org/sites/default/files/E6-R3_FinalBusinessPlan_2019_1117.pdf

Guffroy, L. (2021). Master Thesis. Towards a Global Implementation of eConsent in Clinical Trials.

All stakeholders must play part in increasing implementation.

Towards a Global Implementation of eConsent in Clinical Trials

Kuldeep Singh Rajput, CEO and founder of Biofourmis, with over 10 years of experience in the biomedical space continues to work alongside a previous guest of the ACT Podcast, Jyadev Thakkar, on electronic and biosensing research and products, including wearable solutions and biosignal analytics for cardiac health monitoring.

Podcasts

Linking Healthcare and Clinical Trials with Sensors

Jill Wechsler is ACT's Washington Correspondent

Initiatives to learn more about the impact of drugs and medical products on diverse population groups is driving efforts to assess the effect of medicines and vaccines on pregnant and lactating patients. The aim is to expand and clarify methods for obtaining information on medicines used by or needed for this population through clinical trials and postapproval studies, as seen in a number of policy initiatives and expert assessments of ways to obtain reliable information on how drugs affect these patients.

Pregnant women traditionally have been excluded from preapproval studies due to concerns about potential damage to the health of the mother and the fetus. Unfortunately, that has created a serious dearth of useful information on safe treatments for this group, including individuals coping with serious conditions. While FDA has required sponsors to include in labeling available information on drug impact for this population, the agency does not require research sponsors to collect such data in clinical trials.

Yet the ongoing interest in including more pregnant and lactating women in clinical trials continues to generate research and strategies on the subject, as presented at a recent workshop on the issue organized by the Forum on Drug Discovery, Development and Translation at the National Academy of Sciences, Engineering and Medicine (NASEM).

 The program in mid-June examined the ethical issues and gaps in treatment information due to the exclusion of this population from clinical research. Experts reviewed the laws and regulations governing R&D for pregnant and lactating persons, along with opportunities to improve evidence on the risks and benefits of drug products for these patients. A report will be issued on strategies for overcoming barriers to clinical research, for addressing liability concerns, and short- and long-term proposals for moving forward.

Meanwhile, FDA has encouraged pregnant and lactating women to join registries that collect information on exposure to drugs and vaccines during pregnancy and after.

 And more recently, the agency and researchers have explored how broader use of real-world data (RWD) and postapproval studies can enhance understanding on the impact of drugs on pregnant and lactating women. This topic was the focus of a workshop organized by Johns Hopkins in May, where experts examined strategies for leveraging real-world evidence (RWE) to study medication use in pregnancy and lactation.

FDA also seeks to revise draft guidances issued in 2019 on how researchers can obtain information on drug effects on pregnant and lactating women through pharmacovigilance programs, electronic health record data systems, surveillance programs, and the broader use of RWD to inform the safety of drug use for this population.

A related draft guidance describes how drugmakers should conduct clinical lactation studies for drugs likely to be used in women in this situation.

This issue, moreover, has gained international attention as part of efforts to advance research on women in a wider range of health conditions. The International Council on Harmonization (ICH) agreed at its May meeting in Athens to add this topic to its list of issues warranting global standards. A proposal developed by officials at FDA, the European Medicines Agency (EMA), and the UK’s Medicines & Healthcare Products Regulatory Agency (MHRA) calls for developing a new ICH efficacy guideline on a global framework for including pregnant and breastfeeding individuals in clinical trials.

 The aim is to benefit this often ignored population and to better inform providers and the global pharmaceutical industry.

Of note, Japan’s Pharmaceuticals and Medical Devices Agency (PMDA) recently said it was updating its system for providing advice on use of drugs for pregnant and breastfeeding women. This involves expanding its registry and information system to improve data collection and to provide speedy consultations through online systems tracing the effects of medicines on this population.

Many of these initiatives build on the report issued in 2020 by the national Task Force on Research Specific to Pregnant and Lactating Women (PRGLAC), which was initiated by the 21st Century Cures Act of 2016 to address gaps in knowledge and research on this topic. That panel called for broader pregnancy registries, more research on treatments for this group, design of studies for timely collection of relevant data, and linking health records of mothers and children to address these issues.

And biopharma companies agreed in the latest Prescription Drug User Fee Act plan (PDUFA VII) to support efforts to determine what data and post-market safety signals best indicate exposure to medication in pregnancy and how that may help assess the effects of drugs and vaccines in pregnant women. FDA will explore the use of pregnancy registries and electronic health record systems in establishing a standardized process for this purpose at a public workshop that through demonstration projects and issue a proposed framework and guidance by 2027.

https://www.nationalacademies.org/event/06-16-2022/inclusion-of-pregnant-and-lactating-persons-in-clinical-trials-a-workshop

https://www.fda.gov/science-research/womens-health-research/list-pregnancy-exposure-registries

https://www.jhsph.edu/research/centers-and-institutes/center-of-excellence-in-regulatory-science-and-innovation/news-and-events/FDA%20OWH-CERSI-Collaborative-Workshop.html

https://www.fda.gov/media/124746/download

https://www.fda.gov/media/124749/download

https://www.ich.org/pressrelease/press-release-ich-assembly-hybrid-meeting-athens-may-2022

https://www.pmda.go.jp/files/000246799.pdf#page=10

https://www.nichd.nih.gov/sites/default/files/inline-files/PRGLAC_Implement_Plan_083120.pdf

https://www.fda.gov/media/151712/download

Amid push to include this population more in clinical trials, the goal is to uncover improved evidence on the risks/benefits of drugs for these patients.

Regulators Seek More Drug Effects Research Related to Pregnancy, Lactation

Medidata announced technology enhancements that address key issues in clinical trial management and oversight. Enhancements to Medidata Detect and Rave CTMS will improve both data oversight and reporting for sponsors and contract research organizations in two ways: how they comprehensively monitor their trial data, and how they visualize those data to make faster decisions.

Enhancements to Medidata Detect and Rave CTMS will improve both data oversight and reporting for sponsors and CROs.

Medidata Launches New Clinical Operations Technologies

Director, Client Services, Patient Consent Solutions, 

The healthcare system is intimidating for most, and clinical trials, while often a source of hope for patients, can add an extra layer of stress. Even medically savvy patients can get confused when reviewing a typical informed consent form (ICF) filled with medical jargon, statements of risk, and lists of protocol-required activities—it’s not uncommon for people to walk away without fully retaining the details of the ICF, which down the line, can lead to poor engagement and protocol adherence, as well as study drop-out.

Enter electronic informed consent (eConsent). A multi-media eConsent platform can translate even the most complex protocol into patient-friendly language and transform the paper ICF into a dynamic digital experience that appeals to most learning styles. The result? Participants better understand the study and what it means for them, their health, and their daily lives—leading to stronger engagement and retention throughout the trial in addition to better regulatory compliance. The adoption of eConsent skyrocketed during the pandemic—and it’s critical that we don’t lose momentum amid its numerous benefits. Here are five proven steps to help sites across the globe seamlessly adopt eConsent solutions.

Step 1: Embrace different country strategies for eConsent

Global regulatory environments are complex, with nuanced differences among regions, countries and local communities. It’s important to note that while electronic signatures on an ICF are not accepted by all agencies regulating clinical trials, flexible, feature-rich eConsent products can be customized to meet each site’s local laws and guidelines. For example, a product offering eSignature, offline signature and print-to-sign options are all essential to ensuring trial participants, sites and sponsors gain the full benefits of eConsent.

Furthermore, to ensure long-term success of global eConsent adoption, sponsors must maintain a growing database of eConsent signature modality acceptance, highlighting appropriate practices country by country and region by region. Correspondingly, databases must be constantly updated with regulatory intelligence to prevent risk noncompliance, trial delays and a regression back to paper ICFs

In this step, having an eConsent partner that understands how to navigate regulatory agencies with a deep understanding of the types of questions and information required per country is a major plus.

Step 2: Integrate eConsent in trial planning

Commitment to eConsent success begins at trial planning. For this reason, the matter should be included in site-selection questionnaires, and checklists should be in place to help identify any challenges to eConsent adoption concerning experience, patient population, SOPs, technology, and connectivity. When dealing with potential sites, sponsors should clearly convey that eConsent is the established and expected method for consenting patients, honing into the information to demonstrate how it will benefit them and their patients.

Step 3: Optimize informed consent form digitization timelines

Traditionally, the creation of the electronic informed consent form (eICF) would not take place until approval of the paper ICF per country/site was received. However, in my team’s experience, we have been able to optimize the submission strategy in partnership with IRBs and ethics committees by approaching the ICF digitization in parallel with the paper ICF approval process. This approach enables organizers to be ready to start consenting patients by the site initiation visit (SIV), a critical rung in the ladder to higher eConsent site adoption. When sites are trained and confident to start consenting electronically from the first patient visit, we see them embrace the technology rapidly—bringing on multiple benefits.

Once site selection is complete and site initiation begins, eConsent should be included in all team communication and training. To ensure adequate apprenticeship, leaders should implement modules, guides and videos that prepare staff to oversee processes and best practices. In addition, organizers should be ready to discuss frequently asked questions, including a checklist of items to be covered during the site initiation visit. A robust site adoption escalation pathway will quickly reveal any unidentified challenges that arise throughout site selection and study conduct.

Once a site has been successfully activated, it is important to continue to engage with staff regarding their use of eConsent so that the efficiencies of the system in consenting, reconsenting and remote monitoring are realized. One way to ensure success is by providing organizers with a comprehensive list of consent-related tasks to be included in the clinical operation strategy and site monitoring plans. CRAs are on the “front line” with sites and usually are the first to detect if a site requires extra support. I recommend that you identify and train a team of eConsent subject matter experts who can be advocates for CRAs and ensure that your monitoring teams are aware of all the materials, training and support available to them.

The evolution to digitally enabled clinical trials is well underway, but the status quo bias is strong. I know from experience that upfront planning and training go a long way to improving patient engagement, protocol adherence, and patient retention rates. The time is now for trial sponsors and research sites to fully embrace eConsent platforms as the standard for optimal patient experience. I hope these steps help more of my colleagues in the clinical research industry gain the greatest value of feature-rich eConsent platforms and deliver better care for the patients we all tirelessly work to support each day.

While eConsent has become more widely adopted since COVID-19, work still needs to be done in improving patients’ understanding. 

Better Patient Engagement Begins With Electronic Informed Consent

It’s time to stop asking ‘if’ clinical trials should employ bring-your-own device (BYOD) strategies to collect electronic patient-reported outcome (ePRO) data, and instead develop considered approaches to ‘how’ we do it. This is not to say that BYOD will always be suitable for every given context; rather, let’s stop getting caught up in concerns around whether regulators will accept such data and instead focus on optimizing implementation.

Therapeutic Innovation & Regulatory Science

 highlights the anecdotal nature of the current evidence base for ePRO data collected via BYOD being used in medical product labelling, with only one known example being published to date.

 That article calls for greater transparency around data collection methods and proposes a means to capture this experiential data, and the eCOA Consortium has mobilized to drive this initiative forward.

In conjunction with the article, an online poll asked sponsors to indicate their intention (or lack of) to contribute to the proposed BYOD database (the poll remains open and can be accessed 

35% of respondents have collected ePRO data using BYOD and would be willing to contribute to a database

22% of respondents have not collected ePRO data using BYOD but knowledge of others doing so would encourage them to adopt this strategy

33% of respondents support this initiative, but are not part of an organization that collects ePRO data for submission to a regulatory agency

8% of respondents have collected ePRO data using BYOD but would not be willing to contribute to a database

It is incredibly encouraging to see the appetite for such knowledge sharing and that representatives of many organizations are supportive of increasing transparency around data collection methods within medical product development. Nevertheless, it is puzzling why a minority of respondents would not be willing to contribute and it is difficult to ascertain the concerns or perceived risks of sharing such data.

This database will serve as a shared resource where all participating organizations can contribute and benefit alike. The vision includes a simple submission system for sponsors (or their delegates) to enter key information into the database as detailed in the real-world example below:

https://www.fda.gov/media/151707/download

This source of information will build confidence in the BYOD approach to ePRO data collection, removing the hesitation around its utilization—the ‘if’—and instead moving to focus on a considered approach to optimize implementation—the ‘how.’

Some key elements of the ‘how’ include the platform facilitating the same presentation (format and functionality) of ePROs across device types to ensure the same user experience regardless of the device—something clearly identified as key by FDA.

 Ensuring study participant support is key. Trial staff will need to assess device suitability or provide a provisioned device alternative, assist with app download or web-URL access. This will also require helpdesk support along with providing backup options for malfunctioning devices or accommodating participants who prefer not to use their own device. While this may be perceived as requiring additional work, the investment of time and resource is worthwhile—BYOD optionality provides the opportunity to enhance the participant experience, facilitate clinical trial participation, and reduce missing data.

As we look into the future, BYOD goes beyond just PRO data collection. Using the participants own device for wearable data synchronization—thus avoiding a second smartphone in a clinical trial—and performance outcome (PerfO) assessment collection offers further potential to reduce participant burden. We can also think about expanding digital health technology (DHT) data collection beyond participant self-reports with their own wearables for remote capture of, for example, physiological parameters (e.g., heart rate) and activity (e.g., step count).BYOD approaches also allow for clinician-reported outcomes (ClinRO) and observer-reported outcomes (ObsRO) data collection.

BYOD is poised to play a transformative role in clinical trials. Let’s work together to optimize its use and realize its full potential much sooner.

Authored on behalf of Critical Path Institute’s eCOA Consortium by 

, Chief Scientific Officer, Koneksa Health, Inc.

Mowlem, F.D; Tenaerts, P.; Gwaltney, C.; Oakley-Girvan, I. Regulatory Acceptance of Patient-Reported Outcome (PRO) Data from Bring-Your-Own-Device (BYOD) Solutions to Support Medical Product Labeling Claims. Therapeutic Innovation & Regulatory Science 56,

https://doi.org/10.1007/s43441-022-00412-1

Food and Drug Administration. Patient-Focused Drug Development Guidance: Methods to Identify What is Important to Patients and Select, Develop or Modify Fit-for-Purpose Clinical Outcome Assessments. Available at 

https://www.fda.gov/drugs/news-events-human-drugs/patient-focused-drug-development-guidance-methods-identify-what-important-patients-and-select

Moving past the ‘if’ to the ‘how.’

Progressing BYOD Adoption

Peter O'Donnell is a freelance journalist who specializes in European health affairs and is based in Brussels, Belgium.

At a recent major European meeting on health technology assessment (HTA), the head of the French drug agency HAS said she was very much in favor of comparative evidence in drug evaluation. It was an observation that might have passed unremarked in other circumstances, since it is what would normally be a statement of the obvious from the head of a prestigious body whose work is based on evidence. But it was remarked, and it was remarkable. Because invocations of “evidence” have recently acquired a new resonance in Europe among those who are suspicious of what they see as a headlong rush to shortcuts in drug approvals. And the observation was all the more conspicuous because it came from a distinguished European figure who had just chaired the first meeting of the committee of 27 EU member states who will play a decisive role in the operation of the new European HTA system.

The following day, at a Brussels seminar on treatment optimization, the head of European Social Insurance Platform (ESIP), one of Europe’s biggest health insurance organizations said: “We need strong evidence for informed and timely decisions. It is important to strengthen cooperation on data requirements among decision-makers.” That remark came on the heels of ESIP’s publication of its proposals for the upcoming review of European drug rules, which emphasized the healthcare payer’s interest in ensuring “robust and timely evidence-generation” enshrined in the new legislation. ESIP considers “the gold standard” to be randomized controlled trials with an active comparator using clinically meaningful endpoints, and warns against the trend to shifting the assessment of safety, quality, and efficacy from pre- to post-marketing authorization. Conditional approval pathways should be limited, it says, and standards of quality and study design enforced, with increased transparency over their methodology.

The background to that seminar, according to AIM, another major grouping of healthcare payers, and one of the meeting’s co-organizers, is that “many therapies enter the market without sufficient evidence on their clinical benefit for patients,” creating “a challenge of ensuring sustainable access to efficient therapies.”

Such comments highlight a shift in attitude to innovation among many key healthcare constituencies in Europe. The heady days of a decade ago, when the likes of Hans-Georg Eichler—then the senior medic at the European Medicines Agency (EMA)—were advocating exploration of adaptive approvals, have given way to a more cautious approach. Many national health authorities in Europe harbor concerns that faster approvals on limited data are more of an industry-promoted Trojan horse for cutting corners on the way to the marketplace, rather than a rational method of exploiting new science and new data. The dilemma sits at the heart of the EU’s own thinking on how to update its pharmaceutical legislation. “The main source of evidence for the authorization of innovative medicines should remain robust clinical trials with suitable comparators reflecting the standard of care in the EU,” said the European Commission in its 2020 “pharmaceutical strategy” that launched the legislative process—despite its avowed aim “to revise the pharmaceutical legislation to adapt to cutting-edge products, scientific developments (e.g., genomics or personalized medicine) and technological transformation (e.g., data analytics and digital tools) and provide tailored incentives for innovation.”

Europe still has plenty of vigorous advocates of innovative approaches. The main drug industry lobby in Europe, The European Federation of Pharmaceutical Industries and Associations (EFPIA), told the EU in the latest consultation on the plans for legislation that it “must put in place a framework to accommodate tomorrow’s innovation, with the regulatory flexibility to adapt as and when the technology does.” The European Confederation of Pharmaceutical Entrepreneurs (EUCOPE), a European grouping of drug firms with a heavy involvement in advanced therapy products, says adequate policy focus on drug development “has so far been prevented by unfavorable regulatory conditions.” And addressing specifically the prospects for the new EU HTA system, it says that “evidence generated outside of the strict randomized controlled trial design must be accepted such as real-world evidence (RWE), while post-launch evidence-generation should be routinely implemented.”

EUCOPE points out that orphan drugs and advanced therapies in particular, due to their smaller patient populations, rely on less conventional methodological approaches. The HTA discussions chaired by Dominique Le Guludec, the French official quoted above as a champion of comparative trials, provoked an instant response from supporters of a more liberal approach to evidence-generation. RWE4Decisions, a consortium of organizations with an interest in exploring the potential of RWE more extensively, publicly queried what guidance will emerge for the use of RWE in the upcoming joint HTA system in Europe, “since oncology and advanced therapies are priority areas, and often come with little evidence insofar as randomized controlled trials are not always possible.”

Over the next three years, as the EU puts its HTA system fully into place, and revises its pharmaceutical legislation, some of the current battle lines over acceptable or obligatory evidence may be softened by clearer definitions. But, at the same time, the discussion will become more confused because of the growing overlaps and distinctions between evidence for EU marketing authorizations and evidence for national decisions on pricing and reimbursement—a subject which deserves a separate article.

Battle lines being drawn among key healthcare constituencies, as discussions around new approaches to drug evaluation and decision-making heat up.

Bringing Evidence Back into Fashion in European Drug Rules

The first clinical trial under Novartis’s 10-year, multimillion dollar Beacon of Hope collaboration with 26 Historically Black Colleges is set to launch at Morehouse School of Medicine.

Morehouse is the first institution to establish a clinical trial center of excellence under the Beacon of Hope program, which seeks to address systemic health disparities across the research and medical development ecosystem and increase diversity in clinical trial participants and investigators.

The Morehouse Center’s first clinical trial is in LDL-C management, key to addressing a high coronary heart disease mortality rate among African Americans.

Study launch at Morehouse School of Medicine is part of a major expansion of Beacon of Hope.

First Clinical Trial Under Novartis' Beacon of Hope Set to Launch

ActiGraph is now providing carefully tailored scientific services to its clients. These service offerings help clinical trial sponsors maximize the benefits of digital health technologies (DHTs) throughout the clinical development lifecycle.

ActiGraph’s new end-to-end services, which include endpoint design, algorithm validation, biostatistical analysis, and regulatory engagement, are offered in conjunction with the company’s validated, FDA-cleared wearable technology platform. This fit-for-purpose package of solutions is designed to guide study teams through the process of study planning and implementation.

New end-to-end services include endpoint design, algorithm validation, biostatistical analysis, and regulatory engagement.

Featured Content

Applied Clinical Trials June 2022

Salary Survey: The Age of COVID

Patient Recruitment Goes High-Tech