By Annahita Ghassemi, PhD, Director, Global Product Safety & Clinical Affairs, Church & Dwight Co. Inc., (and Chair of CRN’s Senior Scientific Advisory Council) & Luke Huber, ND, MBA, Vice President, Scientific & Regulatory Affairs, Council for Responsible Nutrition (CRN)

Research will continue to play a key role in developing innovative ingredients and finished products, as top research organizations adapt to the changes required by COVID-19—underscoring the importance of a culture of agility with rapid implementation of new processes.
 
A CRN-convened webinar included insights from the following experts who discussed their experiences conducting clinical trials in the midst of the pandemic: John Marshall, MBA, general manager, Biofortis Clinical and Sensory Research; Andrew Gregg, director, Clinical Research, dicentra; Joshua Baisley, vice president, Clinical Design & Delivery, Nutrasource Pharmaceutical & Nutraceutical Services; and Catherine Kwik-Uribe, PhD, Global Scientific & Regulatory Affairs director, Mars Edge.
 
In the U.S., the Food and Drug Administration (FDA) addresses challenges with conducting research while under a shelter-in-place order in its guidance for industry sponsors, investigators, and institutional review boards (IRBs)—a document that research administrators should familiarize themselves with, especially with a resurgence of COVID-19 predicted, Marshall advised.
 
Marshall described one of Biofortis’ multi-site study’s shift to a mix of three different scenarios: one site shut down completely; another site stayed open and conducted the visits with little interruption; and the third site modified visits to capture only primary endpoints. “There were unavoidable protocol deviations,” he observed. FDA recognizes that changes to protocols are inevitable in these times and emphasizes that these modifications should be well documented.
 
Sponsors, investigators, and IRBs should make every effort to maintain the safety of trial participants and study integrity. Clear documentation is indispensable to ensuring all parties are aligned, Marshall counseled. For example, Biofortis implemented enhanced preparation procedures, checking in with participants the day prior to their site visit and clearly communicating the new measures in place to keep them safe, including outdoor check-in prior to entry into the building, required facial coverings, and use of hand sanitizer and gloves. In addition, tightened controls over participant movement in the facility, with staff rotating through the trial visit one at a time, allows for better participant traceability and a complete wipe-down of the areas occupied by participants—all noted in updates to protocol documentation.
 
Enhanced communication among staff as well as with trial participants and sponsors is another key factor driving success, Marshall observed. He noted that while this can require technology and training investments, these costs are often offset by the savings from fewer in-clinic visits. “The effort Biofortis put into adjusting operations and communicating with trial candidates has paid off,” he stated. “We’ve actually seen an increase in study participant interest.”
 
Gregg echoed Marshall’s comments regarding the ease with which his firm, dicentra, is retaining study participants even during the pandemic. He noted Canada’s regulatory body Health Canada emerged following the last comparable pandemic, The Spanish Flu of 1918, with further regulatory reform for dietary supplement research—an expedited pathway—arising from the COVID-19 pandemic. He noted Canada’s regulatory framework for the clinical research of dietary supplements (Natural Health Products, or NHPs) encompasses the International Conference on Harmonisation (IHC) Good Clinical Practice (GCP) Guidelines. These global quality standards, while the primary foundation of the clinical research industry, are meant to complement additional inputs, Gregg advised. “Now more than ever it’s important to remember that GCP guidelines include not only the ICH guidelines themselves but local regulation and law as well as best practices.” These include safety management and exposure reduction efforts in accordance with local and global guidelines, and enhanced, protocol-specific participant safety considerations.
 
Industry sponsors are looking to re-establish research operations as soon as possible—many in Q3 and Q4 2020 after project re-evaluation and site re-selection, Gregg noted. He advised that global disruption of trials slated to begin in Europe and the U.S. has led to considerable site re-selection by industry sponsors. “Canadian sites accommodated many of these projects due to a lesser degree of industry disruption compared to other jurisdictions,” he stated.
 
Baisley, whose firm, Nutrasource Pharmaceutical & Nutraceutical Services, also headquartered in Canada, provided a global perspective on how regulatory guidance unfolded as COVID-19 spread in early 2019. Similarities across most global regulatory guidance include prioritization of subject safety, which should always be the case in any clinical trial, Baisley noted. Minimizing the risk to data integrity and maintaining compliance with GCPs are also common goals among the guidances. “They’re looking to ensure sponsors and [contract research organizations (CROs)] are conducting risk assessments on the programs that they’re either currently undertaking or looking to undertake,” he explained. Other key similarities include calls for thorough documentation of protocol deviations. Similarities notwithstanding, he noted the importance of maintaining awareness of updates to guidances, especially when conducting multicenter, multi-jurisdictional trials, observing significant differences among various EU countries.
 
The panelists emphasized that preparing for the possibility of ongoing shutdowns and resurgence of the virus is critical. Agencies around the world are expecting this, they agreed, and contract reviews—who’s responsible for what—and additions of contingency plans are must-dos. “We should be looking for business continuity plans and seeing what processes and contingencies are in place if this comes up again with wave two or three,” Baisley advised.
The panelists acknowledged that delays will likely result in extended overall program timelines that can also delay measurements if there are differences among analytical labs. Further, they noted the importance of amending outpatient assessments, optimizing remote reporting procedures and following up on adverse events—especially those related to COVID-19.
 
Some sponsors are finding new opportunities in studies already underway, such as with the COSMOS trial examining multivitamin and cocoa flavanol effects on various health endpoints. Kwik-Uribe discussed how Mars Edge has proactively added to its data collection based on the impact of COVID-19 among its 22,000 participants. “Because of the fact that there’s such comprehensive data being collected on the study participants, we do expect that if there is an impact on COVID-19 or anything related to the study outcomes we’ll be able to capture this information, as well,” she noted. COSMOS will now also explore how risk factors and a subject’s diet and lifestyle habits play into susceptibility and severity of outcomes. The researchers are leveraging the biospecimen collection to learn more about the mechanism of action of SARS CoV-2, the virus that causes COVID-19.
 
The fundamental importance of ensuring studies are well-designed has been magnified by challenges brought about by COVID-19. The pandemic has also shown that attentive, engaged, and communicative partnerships among research organizations and their sponsors is critical.
 
Hear more from these expert panelists via CRN’s webinar on demand. Get details here:www.crnusa.org/CRO.