By Laurie Halloran, CEO and Chairwoman of the Board, Halloran Consulting Group, Inc.
The impact of COVID-19 on clinical trials has been immediate, due to challenges posed by travel bans, hospital/clinic visitation restrictions, and social distancing precautions, just to name a few. These factors have translated into multiple issues that pose challenges related to corporate milestones, budgets, and data integrity. In this article, we will review eight specific concerns identified by Halloran’s COVID-19 task force, and provide recommendations for mitigating your risk related to each of them.
1. Delays in patient enrollment or missed study visits resulting from the inability of patients to travel to onsite visits or limitations on nonessential in-office visits or testing
We recommend provisions of private car services for patients who have relied on public transportation to travel to sites. We also suggest using home health services for study drug administration (e.g., infusions) and/or study assessments, where feasible. Institutional review boards (IRBs) and ethics committees have been highly receptive to well-thought-out plans that ensure patients have access to care and to the clinical options that investigational agents represent.
2. Delays in study initiation activities resulting from the inability to perform site selection/initiation visits and/or clinical vendor qualification visits, and subsequent downstream delays in patient enrollment
We are encouraging a shift from on-site, in-person meetings for vendor audits, vendor/CRO bid defense meetings, and site initiation/training visits to remote-based models using phone and video-conferencing software. This should include plans to allow for risk identification and future on-site visits as needed. While remote meetings and visits require more preparation on the sponsor side, we have optimistically observed sponsors taking extra care to ensure key clinical points, from supporting safety data to procedures ensuring patient safety, are thoroughly communicated. We believe this extra care and attention may translate to better sponsor/site relations over time.
3. Protocol adherence issues arising from an inability to comply with visit schedules, study procedures, drug administration, and monitoring procedures
We recommend modifying the number of protocol-mandated in-person study visits and supplementing them with at-home visits or telemedicine and using remote labs or home health services for routine or standard-with-blood and non-invasive tests. We also suggest revamping monitoring plans to include more robust remote-based data review strategies and tools. There are several third-party options available to support this shift midstream in your studies. Of course, these must be documented in the protocol and plans, and we have seen some accommodations for expedited reviews under these circumstances. In some very limited cases, under FDA regulations, protocol changes may be implemented immediately if they are intended to eliminate an apparent immediate hazard to subjects, provided the sponsor subsequently notifies the FDA and the IRB.
4. Delays in clinical material distribution and import/export delays due to limited manufacturing and operations staff, limited or reprioritized hospitals staff, and travel bans
We recommend considerations be made to determine if study drug shipments may be sent directly to patient homes with support from home health services for drug administrations and accountability. Recent statements have been released from several health authorities on the supply and distribution challenges: EMA on the impact on medicines supply in EU, Medicines for Europe on COVID-19, and the FDA on foreign product importation inspections.
5. Some delays in local IRB reviews and approvals due to limited or reprioritized site staff
We recommend prioritizing the use of central IRBs, when feasible, to alleviate the delays that are likely to continue with some local IRBs. Of course, this would have to be discussed with the site and documented.
6. In some cases, suspension of all patient activities for trials, sites, or studies that do not have active patients being treated
In these cases, we have seen follow-up visits being performed remotely and the use of third parties being utilized for faster ramp-up of remote monitoring activities and tools.
7. Misalignment with sponsors, investigators, and CRO/vendor team members on regional restrictions, updates, and impact
We recommend ongoing risk evaluations and assessment sessions with sponsors, investigators, and CRO/vendor team members to align on local restrictions and impact assessment, and to create contingency plans to bolster already existing site, vendor, and study-specific risk mitigation strategies. Establishment and joint standing review of vendor key performance and quality indicators will provide insight into their performance. Additionally, having clear and defined criteria on what events should be escalated to the sponsor will ensure that, as a sponsor, you are effectively monitoring your studies, especially as changes are made to these operational activities. This should be a continuous and living process as the situation evolves over the coming weeks to months. Routine and standing touchpoints for study teams are already proving to maintain alignment on key timelines, critical risk points, and other study-specific challenges.
8. Cancellation or postponement (indefinitely, in some cases) of major scientific and professional conferences and meetings, and KOL, investigator, and scientific advisory board meetings
Given that much of the education and collaboration across our industry comes from these venues, we recommend virtual meetings wherever possible. Several industry groups are looking at holding simulated virtual events so we can continue to move forward and share our insights.
The FDA recently issued a guidance, Conduct of Clinical Trials of Medicinal Products During COVID-19 Pandemic, which reiterates the themes outlined above, emphasizing mitigation and precautionary strategies based on study-specific circumstances. It also provides recommendations on the management of procedural modifications, protocol amendments, and deviations (e.g., implementation, IRB approvals, FDA consultation), as well as preparedness to describe the tactics and impact in the corresponding clinical study reports. Some of these recommendations are also highlighted in the Association of Clinical Research Organization’s (ACRO’s) Considerations to Support Clinical Trial Monitoring Oversight During COVID-19 and in the UK Medicines and Healthcare products Regulatory Agency’s Advice for Management of Clinical trials in relation to Coronavirus.
Given the complex risk/benefit considerations associated with each specific clinical trial, there is no single solution to manage the risks facing clinical activities due to the novel coronavirus. Each clinical trial is unique with respect to patient population, study drug mechanism of action, concomitant medications, and geographic needs. It is important to continue to engage the network and community to push forward with creative risk mitigation and issue resolution plans during this challenging time.
For more on the challenges life science companies can expect to face during the coronavirus crisis — and how they should respond — read “Assessing The Impact Of COVID-19 On Regulatory Interactions, Inspections, & Audits.”
About The Author:
Laurie Halloran, BSN, MS, founded Halloran Consulting Group in 1998. Her time as a pediatric ICU nurse had inspired her to start a company that helps move new therapies through FDA processes to get them into the hands of patients desperately in need. Halloran has been named 2018 Women’s Business Enterprise Star by the Women's Business Enterprise National Council (WBENC) and has won a 2017 Enterprising Women of the Year Award from Enterprising Women magazine. Halloran Consulting Group was also named an Inc. 5000 Fastest Growing Company for the past three years in a row.