In Advarra’s first Fireside Chat, CEO Gadi Saarony met with Deb Tatton, Parexel Senior Vice President of Global Clinical Operations, for a video conversation about the future of clinical trials and site engagement. Almost 600 clinical research professionals joined the virtual event to hear about possible ways sponsors and CROs can work more collaboratively with sites to improve study startup and address the changing clinical trial landscape. In part 2 of this Q&A blog, Deb and Gadi consider ways to improve engagement with sites and with patients. Read part 1 for their thoughts on the evolving role of technology in clinical research.
Q: How early in the protocol design process should you engage with sites?
A: It is important to engage with investigators and site representatives early enough to modify the protocol design based on patient and site feedback. At the latest, this should occur when eligibility criteria and assessments are considered, as this will finally determine if sites are able to enroll and conduct the study. Ideally, feasibility specialists should contact at least 1-2 investigators per region to ensure the protocol is feasible in all regions (not just in the lead investigator or sponsor’s country of origin).
CROs like Parexel provide early protocol design services to help sponsors optimize their protocols. And Advarra, often in partnership with the CRO and sponsor, leverages its expansive access to institutions and sites, protocol knowledge, participant insights, and scientific and regulatory expertise to help inform protocol optimization and site selection activities.
Q: How is the patient recruitment approach evolving in these times?
A: The pandemic and the race for approved COVID-19 therapeutics and vaccines have generally increased clinical trial awareness across patient populations. As a result, more patients are seeking out clinical trials to explore participation.
Additionally, there is a strong focus on patient-centric innovation, and significant business investments enable development of new, exciting participant recruitment and retention approaches, including:
- Decentralized Clinical Trials (DCTs) – DCTs help expand research access for diverse populations and geographies, using telemedicine and mobile healthcare providers to bring research beyond the traditional site location. Parexel DCTs combine in-house expertise and patient/caregiver insights with the latest technologies to create bespoke strategies from study design through execution. Technology experts are available to help identify and manage all technology requirements. Advarra added specific in-house IRB expertise to help ensure DCT protocols account for participant safety concerns and consulting expertise to support sites conducting DCTs.
- Patient Insights – A combination of communication approaches are used to examine the practical implications of study design on patients and explore protocol changes to make participation easier. This can make clinical trials more accessible to those who may otherwise not be able to enroll, thereby positively impacting recruitment.
- eConsent – Some of the best eConsent tools include explanations of key consent elements in a clear, engaging, short animation. The animation is made available in local languages and includes questions to help confirm understanding. Participant dropouts have significantly decreased when eConsent is used, demonstrating that a fully informed participant is more likely to remain enrolled for the duration.
- Physician and Participant Engagement Platforms –The best-in-class ones offer a role-based, web-enabled platform with a range of functionalities designed to make sites’ jobs easier, thereby improving investigator engagement. The platforms are customizable based on study or program needs with streamlined communication tools, easier access to study information and critical operational study systems, virtual training videos and tools, study news and updates, a central repository of study documents, and virtual study visit guides with email reminders to site staff and participants.
- Leveraging Data Sources and Analytics – Electronic medical records (EMR) data, genomic data from healthcare organizations, payer data, and site and investigator performance data are helping to better home in on where the patient is and her/his propensity to participate and remain engaged in a trial. In this case, the analytics capabilities and insights are as important as the data sources. Both Parexel and Advarra use a data-agnostic perspective, with a focus on leveraging the right data and then contextualizing it for the protocol, the sites, and the patients.
Q: Sites have up to 7 different types of software with easily 7 different passwords among lab, radiology, electrocardiogram (EKG), regulatory, EDC, patient electronics, queries, etc. It would be helpful if sponsors could provide a single technology sign-on. Why have sponsors not made more efforts to make this part of trial management easier for sites?
A: We could not agree more; this is certainly the vision of both Parexel and Advarra. The industry has made attempts in this direction, including PI’s MyTrials and Advarra’s OnCore. Platform solutions can reduce the number of site accounts if you implement more than one module, as Parexel does with electronic trial master file (eTMF) and study startup (SSU) or Advarra’s Oncore, eReg, Payments, and other systems. Of course, one can also federate accounts between vendor solutions, as Parexel did with Rave and Longboat recently, so the same account can be used for both. The need to simplify the sign-in process for sites will become critical to reduce the burden for the site personnel.
Q: With the potential requirements needed for patients to participate remotely, do you see that as a potential bias excluding some potential participants (e.g., those is rural areas without internet, or those without devices)? Or is the hybrid model the answer to preventing that bias?
A: Yes, this is one of the reasons why the hybrid (DCTs) approach is recommended, and why we believe sites are critical to research. Of course, part of the effort to bolster DCTs means the device and drug supply chain and logistics must be accounted for. For example, for patients who may not have internet access, Parexel can provide electronic devices that allow them to participate in a trial for which they may not have otherwise been eligible.
Q: Are sites involved in protocol design or early development of documents?
A: Ideally, yes. Designing patient- and site-centric protocols is the recommended approach, but this may not always be feasible. In rare diseases, sponsors tend to reach out to physicians and investigators rather early, but often not early enough, which leads to protocol amendments instead of a feasible version 1.0 of the protocol. This usually involves medical advisors and key opinion leaders; unfortunately, often these scientists are not investigators, so they might have a very different perspective than investigators in clinical practice. Sometimes global or local principal leads are involved early on.
The question might instead be if sites are involved in the drug development program. For example, waiting until the phase 3 trial to involve sites can be challenging, as what was done in phase 2 can limit assessments and eligibility criteria.
Q: Other than the need for virtual trial settings, are there any other learnings from COVID-19 for the future of clinical trials?
A: Some critical learnings speak to the importance of clinical research as a whole. The race to develop a vaccine is a great example of why research and development and clinical trials are so important. Another learning is the need for patient- and site-centric protocol development.
Q: Can you please suggest a solution for east coast/west coast CRA monitoring time difference?
A: This is challenging, as CRA assignments are often done within a region/time zone aligning with the site. However, in the cases where we can do remote monitoring, CROs and sponsors are increasingly more flexible with working hours. Therefore, if a CRA is assigned a site not within their time zone, the potential to alter the CRA’s work schedule to accommodate site availability is certainly an option.
For more of these thought leaders’ perspectives on the changing clinical trial landscape, watch Fireside Chat: The Future of Clinical Trials and Site Engagement.