12 June 2020 - Authored by:Zara Sproul
In recent weeks and months, the life sciences sector has been the focal point of efforts to respond to the Covid-19 threat. While these efforts have – justifiably – occupied many of the headlines, this blog post looks at the impact of the pandemic on “non-Covid” focused clinical trials and steps taken to limit disruption to the development of medicines for other medical needs.
Impact of Covid-19 on “non-Covid” clinical trials
Recent events have led to significant renewed investment and interest in vaccine development. There has been much focus on the potential for the development of a vaccine to treat Covid-19 in a timeframe that was considered fantasy only a few years ago. However, not all recent developments have resulted in advancements at such pace. In particular, restrictions on movement and global “lockdowns” that help to limit the spread of the virus are proving to be obstacles to successfully continuing clinical trials, which are so important for finding effective treatments for diseases across the world. In short, while we have recently seen the life sciences community work together in an unprecedented way to overcome the Covid-19 threat, the challenges posed have also necessitated notable innovation and advancement in approaches to ensure that trials for other drugs continue and that those in the R&D pipeline can come to fruition.
Site closures and concerns about supply chain disruptions mean that alternative approaches to supply of medication and monitoring of trials (compliance, conduct, safety, quality etc.) are needed. In the short-term, the trials that will more easily progress in these times are the more innovative “tech-trials”, where as much as possible is carried out “virtually”. The long-term effects global lockdowns will have on supply chain issues and availability of active product ingredients, as well as the subsequent effects on whether trials can continue, remains to be seen.
Artificial intelligence (AI) may have a part to play in supporting and accelerating clinical trials. For example, British start-up Exscientia and Japanese pharmaceutical company Sumitomo Dainippon Pharma announced earlier this year that clinical testing for an OCD treatment drug had gone to trial after only one year of development, rather than the usual five years. The first step in testing a new drug/treatment is finding the chemical compound that has an effect on the biological target (this process is referred to as “drug discovery”). This can be a lengthy and expensive process. Exscientia uses AI to automate drug discovery by using algorithms to decide on the best chemical structure for the new compound, dramatically reducing the time and cost of the drug discovery process. This completely changes the process of pre-clinical development. Looking ahead, Exscientia has teamed up with Diamond Light Source (UK) and Calibr (USA) to test compounds that could be used for treatment of Covid-19.
Since the outbreak, several large pharmaceutical companies (Pfizer and Bristol Myers Squibb) and a number of smaller biotech companies (Aslan, Moderna Therapeutics, Provention Bio) have announced that they are having to change and adapt their R&D plans. For example, Pfizer paused enrollment in many new and ongoing trials, while Bristol Myers Squibb has begun enrolling new subjects in trials only “where appropriate”. Generally speaking, the majority of changes result in some form of delay to trials. Delays are not the only concern; Aveo Pharmaceuticals cited the impact of Covid-19 as a reason for the failure of its study on ficlatuzumad in acute myeloid leukemia.
Thankfully, the news is not all bad. Some companies, such as GSK and Astra Zeneca have been more optimistic about the impact of Covid-19 on their trials. Astra Zeneca indicated that it expected minimal impact on its late-stage trials, most of which are focused on its checkpoint inhibitor cancer drug “Imfinzi”. GSK stated that, while there are expected delays to many of the trials, “most continue to enrol, albeit less robustly” than before. GSK’s primary focus will of course be on its SARS-CoV-2 (the virus responsible for Covid-19) vaccine collaboration with Sanofi; collaborations in the sector are discussed in more detail on the blog here.
Overall, however, the outlook remains sober for clinical trials. For example, clinical trial activity analyses suggest that there has been a significant decrease in the number of new patients entering clinical trials for actively recruiting studies; globally there has been a 65% decrease in new patient enrolment (year-on-year for March). The market with the highest impact was India (84% reduction) and the market with the least impact was Germany (33%). Perhaps unsurprisingly, this impact correlates with the lock down restrictions put in place in each market.
Regulatory response to the impact of Covid-19 on clinical studies
Across Europe, the EU bodies and certain national authorities have quickly released guidance for clinical trials both for Covid-19 and for other indications, but because clinical trials are regulated on a national level and due to the disruption caused by the pandemic, such rules are not fully harmonised and continue to differ from market to market. Regulators have expressly noted that the policies/guidelines are intended to remain in effect only for the duration of the crisis – although it remains to be seen long that might be.
The challenges posed by the crisis have resulted in a faster uptake of the use of technology and a more flexible supervisory approach in an otherwise highly regulated industry. The guidelines cover a broad range of topics but a notable theme throughout is the increased pragmatism shown by regulators. Most regulators have suggested a more centralised approach to monitoring activities and we have seen a trend towards the use of technology and “virtual” methods where possible. For example:
- EMA (EU): While encouraging the continuation of existing trials, the EMA has called for pragmatism in decision-making in relation to new trials while encouraging an assessment of the benefits versus the risks to the trial participants (as well as the integrity of the trial itself). The EMA has argued that there needs to be consideration as to the immediate necessity to start new trials. The EMA has also suggested that remote site visits and video review of medical records should be used where possible.
- MHRA (UK): The MHRA has also taken a practical approach by suggesting alternative methods to allow for clinical trials to continue and to reduce disruption or unnecessary barriers to trials. The MHRA has proposed that investigational medicinal products could be posted to trial subjects to ensure that trials continue and encourages administrators to first obtain trial subject consents by telephone.
- FDA (US): The FDA guidance on Covid-19 challenges mirrors that from the MHRA. It suggests that home deliveries of medicinal products would be appropriate where site visits are no longer practicable, and that e-consent/telephone consents should now be considered. The FDA called for technological tools to be used to support trials as much as possible, and to prevent the need for suspension/termination of trials.
- BfArM (Germany): BfArM also proposed the use of remote monitoring and remote source data verification. BfArM has emphasised the importance of maintaining data protection integrity suggesting that documents or recordings containing personal data of trial suspects should not leave or be stored outside the trial site.
Looking to the future
The Covid-19 pandemic has clearly had a significant impact on clinical trials around the world. In a matter of weeks, focus abruptly turned to the search for a vaccine to prevent the spread of Covid-19. While the life sciences sector has responded with impressive agility – significant funding, equipment and personnel were redirected away from the development and trials for other conditions. We can already see a corresponding impact on the “non-Covid” clinical trials that were in progress or planned.
As well as racing to find the solution to the pandemic, the increased focus on technology, innovation and adaptability in the life sciences sector will no doubt identify areas where efficiencies can be found and advancements made. As with other industries, companies in the life sciences sector will be seeking to save costs and reduce the impact of the crisis; there is a need for continued rapid and innovative solutions, not just in respect of the fight against the Covid-19 virus, to expedite the progress of other unrelated trials to start, continue and reach completion successfully.
After a number of months in lockdown, we have seen governments encouraging innovation, softening guidelines and supporting the use of technology to enable and support clinical trials. It is becoming clear that we are still in the early stage of the pandemic. There remain many unanswered questions and the long term impact of the pandemic on clinical trials, funding and supply chains in the life sciences sector remains to be seen. The increased reliance on technology and more flexible approach adopted by regulators will, we hope, lead to an exciting and innovative future in the life sciences sector.