The novel coronavirus has swept across the globe, first hitting China and then Italy and Spain, leaving in its wake sickness, sadness, and loss. No industry has been spared the devastating financial, logistical, and personal impacts of COVID-19. Specifically, the life science industry has seen massive disruptions in clinical trial timelines and milestones due to the diverting of resources, spatial challenges, and overall de-prioritization of non-COVID-19 activities in healthcare settings.
As the U.S. outbreak marches toward its peak, our industry must continue to support frontline response efforts. However, it’s also imperative that we begin to plan for our transition out of the response phase and into the recovery phase so that we can get our therapies to patients in need as quickly as possible. Now that China has entered its recovery phase, it’s important to learn as much as possible from their experience – specifically, conducting clinical trials amid the COVID-19 pandemic so that we can apply any relevant tactics on home soil to optimize our outcomes and accelerate our path back to normalcy.
I recently had the opportunity to attend a DIA-organized panel discussion[i] in which Chinese industry experts shared learnings and considerations around business continuity plans (BCPs), operations, site management, and ethics committee activity. My takeaways are detailed below.
Business Continuity Plan (BCP) Considerations
BCPs provide guiding principles, detail ways of working, align disparate parties, and focus on critical data and processes. To be effective, BCPs must include crisis management plans to minimize the impact.
- Most Chinese BCPs don’t cover clinical trials during a pandemic – the effects on sponsors, staff, and subjects are uniquely far-reaching and the affected period’s endpoint is unclear. The impact of a pandemic is dependent on factors such as study type, location of sites, and investigational product (IP) administration methodology. Now is a good time to revisit existing BCPs and update them to directly relate to specific sites and all relevant parties.
- A useful BCP will document trial status including the number of subjects and various locations. It will also include a robust risk assessment to address pandemic-specific impacts such as stopping treatment, missing data, and logistics around delivering IP. BCPs should also include action plans with steps broken down to the trial and subject level including all trial procedures, follow-up visits, IP supply, and lab testing. Finally, the BCP should include a clear, pandemic-specific communication plan. It’s critical to continuously review and revise the BCP to stay current with rapidly changing directives and guidance.
Operational Considerations
To make the soundest clinical conduct decisions, clinical operations professionals must prioritize patient interests but also triage the demands of sites/vendors, the protocol, and proper documentation and processing. Balancing these priorities is particularly important during a pandemic when on-site patient visits are often not feasible.
Patient safety is paramount, especially when treatment will occur outside the normal site. Investigators must thoroughly assess any local clinics, labs, and imaging centers that patients might visit for safety and efficacy.
- Investigators must also navigate the logistics of delivering IP safely to patients remotely – this includes considering packaging quality and inclusion of thorough instructions for at-home administration. If patients do visit hospital sites, their education around self-protection and personal hygiene is paramount.
- Maintaining trial quality during a pandemic is only possible with optimal cross-functional collaboration. This means updating work instructions, SOPs, guidance, and training promptly to reflect the current environment. Communication with sites and site personnel must be frequent and thorough so that gaps are filled, and errors are addressed rapidly. Monitoring activities must be adjusted and may lean more toward risk-based monitoring (RBM) and central monitoring, and on-site site initiation visits (SIVs) will likely not be possible. Increased utilization of electronic data capture (EDC), electronic Trial Master File (eTMF), and clinical trial management systems (CTMS) is paramount for trial quality, and sponsors should consider allowing e-signatures and digital copies where paper is the typical standard. Utilizing the Note-to-File function can also be key in keeping disparate users up to date on activity. Finally, it’s important to consider delayed turnaround times for trial-specific non-IP supplies and the impact that those shortages can have on trial quality.
- Continuous and rigorous assessment of the situation and acting quickly is key to managing clinical operations during a pandemic.
Site Management Considerations
China saw a huge impact on site activity due to COVID-19 caused by strict entrance criteria for all personnel entering sites.
- Over 97% of hospitals issued specific guidance around trial conduct during COVID-19, and over 75% of hospitals stopped accepting new clinical trials. From February to March, Chinese sites allowing the continuation of existing trials dropped from 80% to 50%. Clearly, site start-up and monitoring activities saw a significant impact under these conditions.
- Over 80% of Chinese hospital sites had enacted rigorous entry exams restricting patients who had traveled through or had contact with people in virus epicenters, had under 14 days of quarantine if traveling from epicenters, had any virus symptoms, etc.
- Approximately 50% of cancer patients could not receive their medication on time due to site visit limitations. To combat this, industry experts recommend subject-level planning considering investigational medicinal product (IMP) type, indication, geographic area conditions, and study phase. After collating this information, experts suggest considering the implications of each subject continuing on-site visits, dropping out, or participating in remote visits.
- Monitoring and protecting site employees is paramount – maintain the clinical research center (CRC) site visit log, log CRC staff health conditions, and track personal protective equipment (PPE) burn rates closely.
Ethics Committee (EC) Considerations
As evidenced by Chinese clinical operations during COVID-19, ECs have considerable flexibility in the process, with minor adjustments having a major impact.
- Simplify the document submission process by allowing online submission for all documents and scans for all signatures. The Investigational Review Board (IRB) can also send all decision letters electronically. Importantly, electronic documents must be consistent with paper documents, and communication between EC and submitter must be constant in the adjustment from paper to digital.
- Accelerate the review process by holding online meetings instead of face-to-face. More than 80% of Chinese IRBs canceled in-person meetings. Be sure that remote meeting software solutions are secure and confidential, and always keep original records of attendance and minutes.
- It’s important to make changes official fast – do so by issuing a special policy for ethical review to fill gaps until there’s time to update existing SOPs or create new ones.
Knowledge-sharing is critical in the life science industry, and it’s even more paramount in the midst of such an unprecedented global struggle. Multi-national, cross-industry and cross-functional collaboration will only serve to benefit all of us as we navigate these trying times. It’s my sincere hope that this forced connectivity, innovation, and creativity will produce lasting efficiencies, and reinforce our collective courage to continue our fight against COVID-19.
[i] DIA WEBINAR: COVID-19: Experts from China Speak on Conducting Clinical Trials During the Pandemic