COVID-19 and trial complications

EAST LYME, Conn.—COVID-19 has left few untouched as the world struggles to deal with and contain the pandemic, and its impact is particularly noticeable in the pharmaceutical and life-sciences industry. Beyond the obvious effects of academic and industry members pivoting their focus to answer important questions about the SARS-CoV-2 virus’ infectious nature and possible targets, the pandemic has also hamstrung clinical trials to a significant degree. Phesi, which offers analytical tools and services for the biopharmaceutical industry, shared an analysis recently detailing the extent of these delays—and warning about how the aftershocks will likely continue to be felt.

 

The analysis builds off of other data shared in May. At the time, Phesi reported that of 300,000 global clinical trial sites, trial suspensions had risen 38 percent from the beginning of the year. In its most recent September analysis, the company noted that trial suspensions peaked in early June, and while they dropped temporarily, numbers have spiked again to the point that more than 28,000 sites are currently suspended.

 

The key issue is trial recruitment, which is the leading cause of trial delays even in the best of times. While recruitment picked back up in June, due largely to an increase in recruiting sites, Phesi pointed out that many were likely added “without analyzing via systematical root cause analysis how well their trials were doing in the first place before the pandemic struck.”

 

“The industry responded well by accelerating the implementation of existing technologies to deal with the challenges inflicted by COVID-19. Virtual trials, for example, have been tried here and there for many years. Under the pressure of delivering trials during COVID-19, we are finally seeing more sponsors and CROs embrace this mature technology,” says Dr. Gen Li, president of Phesi. “It is likely various decentralized technologies will take root even when the immediate and current COVID-19 challenges recede somewhat. However, the industry has not prepared well for the medium- and long-term impact of the COVID-19, and even less so in dealing with the historical challenges that have been exposed and exacerbated by the pandemic.”

 

COVID-19’s impact extends into later-stage trials as well. Phesi reports that approximately 125 trials generally complete their enrollment each month. While nearly 200 trials reached their recruitment goals in June, likely catching up from the previous months’ delays, only 70 trials completed enrollment in August.

 

According to Li, for trials and sponsors to have a better chance of success, their approaches need to become “wholly data-driven,” which he says will manifest in a few ways.

 

“Firstly, to go beyond what COVID-19 might be masking to sift out those ‘zombie’ trials that cannot be salvaged, and focusing instead on viable studies. Equally important, we need to prevent trials with no chance of success from starting. There are existing technologies to enable us to do that,” he remarks. “Secondly, by utilizing the huge volume of patient data gathered over many decades. This will include developing accurate Target Therapeutic Profiles (TPP) to maximize development candidates and optimize protocol design, to give a candidate the highest possibility of success.

 

“Thirdly, a patient-centric approach is critical. Companies must identify opportunities to use synthetic arms and reduce the burden on patients. This will reduce the required sample size of comparator and placebo arms, or even replace them completely with synthetic patient data. In summary, companies need to take advantage of the progress made in big data processing technologies, including AI, and apply historical operational and patient data in a structured way.”

 

Li tells DDN that it’s unlikely things will ever return to their pre-pandemic state, adding that “The overall cost is hard to estimate right now, but the impact of COVID-19 on trials—both financially and on patients—will last for many years.”

 

“The key takeaway is there are long-standing issues in clinical development that existed before COVID-19,” he explains. “The pandemic is a turning point, and actually an opportunity to make tangible improvements out of an awful situation, avoiding the common pitfalls that trials experience. It comes down to taking a data-driven approach and having a clearer understanding of the trial landscape. The reality is that even without COVID-19 in the picture, a fifth of trials fail. Undertaking deeper analyses of available data enables sponsors to identify all the variables associated with their study and mitigate the risk of failure”

 

“This will involve a systematic analysis of the clinical trial, protocol, and site space to identify what is most likely to work—including location, existing studies and patient population—allowing a sponsor to build a better protocol with a higher chance of a positive outcome,” he adds. “Real-world data from current and completed studies are key, as is continuing to evaluate and track site performance to make real-time adjustments based on data. Ultimately, analytics has a very strong role to play in improving trials and is an essential part of the toolkit when it comes to overcoming obstacles.”

 

“With increased global economic uncertainty facing all industries, 2021 will be challenging for most clinical development organizations around the world,” Li concluded. “Without data-driven decision-making, already limited financial resources will be further wasted by resurrecting ‘zombie’ projects which would have failed even without COVID-19. Costs may also spiral as change orders issued by CROs increase and additional internal contingency planning is required. If organizations do not adapt to these changes it could, in the worst-case scenario, lead to company meltdown and multiple-year delays in the development of new therapies. Clinical development companies must have predictive scenario modeling capabilities to accurately manage new change orders and associated costs.”