Healing from a Pandemic and Building Resilience into Future Clinical Trials

Lessons Learned from a Virtual Town Hall held on June 5, 2020

Halloran’s ninth town hall focused on how sponsors are looking beyond the pandemic to design and plan resilient clinical trials with the ability to withstand future pandemics and mitigate some of the key challenges experienced. Some of these challenges include the inability to treat patients, access to investigational products, missed patient visits and limited data collection. COVID-19 has forced our industry to do to critically examine and make decisions on what specific data we really need to assess the safety and efficacy of products. We must now rethink our design strategies and planning processes before starting studies to find the right ‘fit-for-purpose’ virtual solutions and push the boundaries on our designs to ensure we are collecting what is truly important for research and our patients.

In previous town halls, sponsors have thoroughly discussed both reactive and proactive responses to the pandemic – whether it is switching to remote visits, investing in centralized monitoring platforms, investigating home healthcare options or simply taking a more patient-centric approach to study design. But what has truly changed, in the short-term, is that studies need to start because patients need to be treated and drug development cannot cease altogether. There is little doubt that the pandemic has significantly affected how studies are conducted, but are we seeing new studies now being designed and planned drastically different than those prior to the pandemic?

With 62% of the town hall attendees indicating that they have made changes to their documented processes (due to the pandemic), Halloran focused on understanding exactly what those changes are.

Considerations When Starting a New Trial

Flexibility is the driving force for developing new studies. From decreasing patient burden to diversifying sites to enforcing more rigorous risk management processes, sponsors have creatively enhanced their current processes versus completely re-engineering standard operating procedures (SOPs) that would require significant resource investment. These nimble changes lay the groundwork for future and widespread process changes, when necessary.

Site Selection

• Include a diverse selection of sites – both geographically and by center type. This pandemic has shown that countries and states within the U.S. are affected differently. Center types may be affected differently as well. For example, hospitals have been further taxed than non-hospital centers during the peak of the outbreak due to space and personnel being prioritized for patient treatment.
• Maintaining geographic and center type diversity, when selecting sites, allows you to maintain some level of enrollment. Not all sites will have strict restrictions; some sites were able to stay open during the pandemic due to having the appropriate amount of personal protectice equipment (PPE) and safety measures in place to ensure patient safety.
• For sites that are still open, understanding when the site can continue to contribute in recruiting  (will it be now or in the next 6 months?), will help to plan accordingly and meet recruitment deadlines.
• Since not all visits can be done remotely, adding satellite sites in multiple geographic locations will help reduce travel for patients who require an in-person visit.
• Conduct a site feasibility assessment, using a simple checklist, for sites that are reopening or being newly initiated. Due to COVID-19, some sites may have had to change their infrastructure to accommodate more ICU beds. The site feasibility assessment will be helpful in confirming if the site is still able to conduct the study.

Protocol Flexibility and Simplify Study Design

• Build flexibility into protocols by adding in language not only related to a pandemic, but any other issues, such as weather-related concerns, that may hinder a patient’s ability to attend a visit and to allow more home healthcare and telemedicine options.
• Implement a Protocol Review Committee that will deconstruct your protocol and justify each inclusion criteria, endpoint, assessment, and objective. This will help refine and reduce the number of endpoints you collect, as well as number of visits patients are responsible for attending.
• Combining visits together and limiting non-critical activities are effective ways to simplify study design.
• Map out the patient journey. This will allow you to proactively identify events to execute in parallel and elements to eliminate in order to reduce enrollment time and reduce the number of protocol deviations.
• Get the patient perspective early on when developing the protocol. Industry is seeing a competition for patients across studies and therapeutic areas. Ensuring a patient centric protocol will help with subject recruitment and retainment.

Plan Development, Process Changes, and Committee Development

• Consider risks like future pandemics, natural disasters, and geopolitical issues when developing plans. Cross-functional risk assessment activities are now more important than ever before.
  • Create a Business Continuity Plan that considers issues mentioned above. Ensure that this plan includes a guiding principle on maintaining investigational product supply to patients.
  • Build a Contingency Plan that describes each country’s and site’s regulations regarding onsite visits and restriction expiration dates.
  • Perform a Study Risk Assessment to identify and discuss all the risks, mitigations, and controls with special focus on these new processes and virtual solutions that have not been used before.
• Be aware of new guidance. Develop a spreadsheet or other means to keep track of evolving guidelines.
• Assess SOPs for changes necessary from an inspection readiness perspective.  Thorough SOPs should allow you to continue operations in the current state, while minimizing disruption. There is a possibility that the FDA may want COVID-19-related deviations in the annual report. Ensure you are updating any applicable SOPs/plans regarding protocol deviations.
• Adopt methods from the Oncology Care Model. These methods allow patients to visit different physicians in closer proximity to their homes. These physicians can be included in the study and work with the principal investigator for that patient.
• Leverage a Risk Based Monitoring Program to ensure that key data can be reviewed to meet the study completion deliverables.

Barriers to Conducting Decentralized Trials

Sponsors have not seen significant barriers to utilizing decentralized methods and are taking advantage of the current circumstances, as an opportunity to accelerate acceptance of decentralized/virtual trials. However, there are some obstacles preventing complete adoption – these include the following:

• Utilizing telemedicine is challenging because many scales or patient reported outcomes (ePROs) are not validated to use virtually. However, some sponsors have continued reporting using these tools virtually to help collect the critical data that is needed to keep the study moving forward and keep patients safe.

• Utilizing home healthcare is challenging in this current environment due to patients’ reluctance to welcome strangers in their home. Notably, this may be less of a problem when the pandemic is behind us.
• Decentralized trials encourage a new way of thinking and can bring about internal challenges.
  • Cross-functional alignment with this new way of thinking can be challenging. Specifically, when not performing 100% SDV, more planning upfront is needed to identify what will need SDV, why, and how remote monitoring and risk-based monitoring will be executed. Getting input from biometrics early on may help with streamlining the planning.
  • Internal stakeholders need to be aware of all changes, clearly lay out any potential risks and mitigations related to patient safety and data integrity. Conducting a risk assessment is mandatory for most studies.
• Upfront costs may be higher when implementing these technologies, but you will recoup from these benefits in the long term because it gives your trial flexibility, alleviating potential time spent retroactively having to make study changes, reducing monitoring on-site, and accelerated end of study data analysis.
• Some sponsors have cited difficulty getting sites onboard with conducting home healthcare visits. This varies on a case-by-case basis, using a site feasibility assessment when choosing sites will allow you to gauge each sites’ willingness to perform home healthcare visits.
• Due to GDPR requirements, telehealth can be more difficult to implement in European countries so it is vitally important to perform feasibility of specific solutions at each site before assuming it will work across the entire study.

Engaging in Multidisciplinary Teamwork

Site Engagement

• Engage with principal investigators. It is extremely important to get their support of decentralized trial models and change implementation thereby leading to greater acceptance by other site personnel.
• Reach out to study coordinators or internal Medical Science Liaisons to get the latest information on what current and future site environments will look like before you set out to lock down your study design and plans.
• Hold web sessions and open office hours to allow sites to call in and give sponsors feedback on current site activities and operations. This will facilitate open, real-time communication.

Vendors

• Reach out to vendors about anticipated risks. Sponsors have reported that some vendors can be helpful in proactively identifying risks and associated mitigations.
• Ask vendors about current technology solutions for decentralized models as they may already have telehealth/home healthcare services in place which will require you to be conscientious of what they use, how it will work and what controls are in place. In some instances, you may want to assess various options to find the best mix of vendors for your particular studies that will provide the best chance of success. Spending the extra time up front to plan the options and select the best vendors will certainly pay off in the end.

COVID-19 has presented challenges across our industry. We can take lessons learned from this difficult situation and use them to improve trial design and planning by adopting a risk-based approach and utilizing our available resources effectively. For years, FDA guidance has encouraged us take advantage of decentralized trials (finally!). COVID-19 has helped us to accelerate into the future but remember success in this new paradigm is only possible with the right upfront design and planning processes. So take the time to do it right!

Please reach out to us if we can help in any way or would like to be included in any of our upcoming town halls.

CONTACT US

Laurie Halloran, CEO | lhalloran@hallorancg.com
Paola Murphy, Chief Client Officer | pmurphy@hallorancg.com
Katie McCarthy, Chief Development Officer | kmccarthy@hallorancg.com
Sheila Gwizdak, VP, Quality | sgwizdak@hallorancg.com
Kim Raymer, VP, Regulatory Affairs | kraymer@hallorancg.com
Jason Milovanovic, VP, Clinical Development | jmilovanovic@hallorancg.com