Contributed Comment by Angela De Martini, Dean Lockhead, Leandra Plappert, and Elizabeth Rountree

September 28, 2020 | Almost immediately after news reports confirmed that COVID-19 was spreading beyond the epicenter in Wuhan, China, companies involved in clinical research in locations around the globe started wondering “What if?” In just the past few months, that question has rapidly transformed into “What now?” The harsh reality is that the novel coronavirus has affected protocols and timelines for many companies involved in clinical stage drug development and is likely to affect more clinical research efforts in the months ahead.

In assessing the impact of COVID-19 on clinical research and development, companies are considering a range of factors including the ability of patients to access medicines and travel to trial sites, whether patients might decline to participate in clinical research, potential changes in regulatory guidance, and resource allocation at trial sites. To better understand the fallout of COVID-19 and how these and other factors are affecting clinical programs worldwide, our team at the Life Sciences Practice at CRA, a global consulting firm, recently reached out to industry stakeholders including regulatory and policy experts, venture capitalists, and contract research organizations (CROs) for their perspectives. These industry insiders report that the impact of COVID-19 on clinical development programs is already severe and will be broad and long-lasting.

A rapidly evolving challenge

In addition to the companies and treatment centers involved in clinical research, regulatory agencies including the FDA and EMA have been responding to this issue. In general, agencies have reinforced their commitment to being flexible in working with drug developers to try to consider new protocols and keep clinical programs on track. Despite these commitments, for many companies the only option has been to hit the pause button. Smaller life sciences companies Provention Bio and Iveric Bio, as well as pharma giants Eli Lilly, Bristol-Myers Squibb, and Pfizer, have all previously announced pauses or delays in development programs.

According to the industry insiders we contacted, while all trials may be at risk, some are more vulnerable than others, including:   

• those with higher-risk patients including the elderly and patients who are immunocompromised or have other underlying health conditions (e.g. COPD)
• trials that require in-person visits
• research in indications that are not considered priority public health and safety issues
• those that are still trying to recruit patients or have only advanced to Phase 1
• trials taking place in health centers needed for COVID-19 patient management and treatment
• studies where patients require extended hospitalization (e.g. CAR-T cell and gene therapies)
• research involving smaller patient populations (e.g. rare disease patients) where accrual could be a challenge

Anticipating a new range of challenges

While companies are working to address near term issues, experts agree that many new challenges will emerge in the months ahead:

• For many smaller and even larger companies, cash flow could be a major consideration. Delays in clinical research will increase costs at a time when advantageous financing options may be limited or non-existent. Many companies may be forced to make difficult cuts or prioritize development opportunities. Some with commercially promising products may be acquired for bargain-basement prices.
• Delayed timelines to product approvals and launches can mean shorter periods of patent exclusivity and lower revenue forecasts. Delays can also give competitors more time to get to market.
• While regulators will want to be flexible, new guidelines can mean additional and more onerous reporting and record-keeping requirements for investigators, CROs, and others.
• Travel restrictions and social distancing measures could make protocol updates and deviations inevitable. Sponsors and trial sites will need to coordinate with the appropriate institutional review boards to seek approval for protocol updates to reduce the risk that changes ultimately could be rejected by the FDA or EMA.
• If clinical trial participants become infected with COVID-19, this could impact clinical data and the ability of some trials, including many rare disease trials, to reach statistical significance.  

A period of forced innovation

To continue to address the wide range of challenges presented by COVID-19, all drug developers will need to monitor their risk and continually adapt their approaches in clinical research as effectively as possible. Contingency plans will need to be developed and executed rapidly in many cases, balancing patient safety, trial integrity, and statistical power. Companies will have to plan for needs related to financing early and perhaps consider options that were unthinkable even a few months ago. Within this environment, those companies able to assess risk and adapt their clinical programs most effectively will be most likely to succeed.

Angela De Martini is a Vice President and Leandra Plappert is a Senior Associate in the Life Sciences Practice at CRA, based in Switzerland. Elizabeth Rountree is a Vice President and Dean Lockhead is a Principal in the Life Sciences Practice at CRA, based in San Francisco. Dean can be reached at dlockhead@crai.com.

The views expressed herein are the authors’ and not those of Charles River Associates (CRA) or any of the organizations with which the authors are affiliated.