Clinical Trial Material Supply: The Impact of COVID-19By
What has been the impact of the COVID-19 pandemic on clinical trials and thus supplying materials for these trials? DCAT Value Chain Insights takes an inside look and tracks the latest developments.
COVID-19 and clinical trials
One of the consequences of the novel coronavirus (COVID-19) pandemic has been a decision by certain pharmaceutical companies to delay, or in certain cases, suspend clinical trials due to the COVID-19 pandemic due to difficulty in patient enrollment and recruitment and limited access to clinical or hospital settings to conduct the trials. A recent analysis by Medidata, a Dassault Systèmes company and provider of end-to-end solutions supporting the entire clinical trial process, issued last month (July 13, 2020), shows some improvement and a leveling off of the impact from COVID-19. However, new patient enrollment in clinical trials has not yet resumed to pre-pandemic levels. Globally, as of the end of June (June 2020), the company noted an approximate 30% drop in new subjects entering clinical trials using October 31, 2019 as the pre-COVID-19 baseline. This compares to an approximate 70% drop globally in April (April 2020).
The Medidata analysis points out that there is large variability in the extent and timing of recovery within geographic regions as COVID-19 cases continue to fluctuate and policies are adapted over time. Within Europe, Italy, France, Spain, and Germany started to see an improvement in new patients added to trials in May (May 2020), which continued into June (June 2020). The UK is behind these countries with new patients added to trials just starting to pick up in June (June 2020) after a steep decline over the last few months. The UK faced a COVID-19 case rate for June (June 2020) per 100,000 at approximately 3 to 4.5 x that of Italy, France, and Spain.
The US saw the most significant impact on new subjects entering trials in April (April 2020), with a small recovery in May (May 2020) and continued improvement in June (June 2020) although Medidata noted that based on a re-emergence of the virus in many states in late June (June 2020) and early July (July 2020), it expects to see further impact. In Asia, clinical trials in China began to recover in March (March 2020) while at the same time, India and Japan were starting to face an increasingly negative impact and are just starting to slowly recover as of June (June 2020).
From a therapeutic-area perspective at the global level, peak impact on new patients entering trials occurred in April (April 2020), but cardiovascular and oncology trials have recovered globally with new patients being added to study sites at a rate similar to pre-COVID-19 levels, according to the Medidata analysis. Cardiovascular trials had experienced close to a 90% drop in April (April 2020) versus pre-pandemic levels in October 2019 for new subjects entering trials. Oncology trials have been the least impacted, but during the peak, nonetheless, saw an impact of more than 40% drop in new patients entering trials versus the pre-pandemic October 2019 baseline. Lagging behind are central nervous system, dermatology, and infectious diseases/anti-Infectives trials even with the recent uptick in COVID-19 trials, according to the Medidata analysis.
Impact on CDMOs/CMOs
The downturn in clinical trials impacts not only pharma companies’ drug-development timelines but also affects CDMOs/CMOs providing materials for these trials. COVID-19 impacted second-quarter 2020 performance of many of the large pharmaceutical companies (see related story, “Profits and Pharma: The Impact of COVID-19”), and also impacted drug-development operations. Certain large pharmaceutical companies re-adjusted their clinical-research activities in light of the COVID-19 pandemic earlier this year (2020), and several recently reported a resumption of activity or a plan to resume activities of new enrollments or certain trials later this year (2020).
Pfizer reported in its second-quarter 2020 results released on July 29, 2020 that after a brief pause to the recruitment portion of certain ongoing clinical studies and a delay to most new study starts in late-April 2020, the company has restarted recruitment across its development portfolio, including new study starts. The company says it continues to work closely with clinical trial sites and is performing remote monitoring where appropriate to oversee study conduct. In addition, processes to enable tele-health and home healthcare are being used where appropriate to continue the data-collection process and support patient safety.
Novartis reported in its second-quarter 2020 results released July 19, 2020 that its drug-development operations are continuing with manageable disruptions, with its digital technologies allowing it to manage its clinical trials portfolio and mitigate site-level disruptions. The company says that thus far, these measures have limited COVID-related impacts to its expected submission timelines over the next several years.
Roche reported in its second quarter 2020 earnings released on July 23, 2020 that the company’s planned drug launches, filings, pivotal Phase III trial readouts and pivotal trial starts are largely on track thus far in 2020. “We are making significant efforts to protect all studies with continued support from health authorities, but the ultimate outcome will depend on the length and severity of the pandemic,” said Roche in its earnings release. The company reported that it had completed Phase III trial enrollment for pivotal studies in Alzheimer’s and Huntington’s disease and started four important Phase III studies in oncology.
Sanofi did not specifically report COVID-19-related impact on its drug-development projects in its second-quarter results released on July 29, 2020. The company reported that as of the end of July 2020, the company’s R&D pipeline contained 83 projects, including 33 new molecular entities in clinical development (or that have been submitted to the regulatory authorities). Thirty-four projects are in Phase III or have been submitted to the regulatory authorities for approval.
Bristol-Myers Squibb did not specify COVID-19-related impact on its clinical trials in its second-quarter 2020 results but noted later that it was making necessary adjustments in it clinical trials. “We are working with health authorities and investigators to protect our trial participants and personnel at Bristol Myers Squibb and our clinical trial sites while ensuring regulatory compliance and the integrity of our science,” said the company in an August 4, 2020 statement. “We have provided clinical trial investigators with updated guidance regarding the conduct of BMS clinical trials worldwide in light of COVID-19 and are taking into account guidance from health authorities, where applicable.”
Eli Lilly and Company reported clinical trial enrollment in existing studies, as well as initiation of new clinical trials, will resume in the second half of 2020 in its second-quarter earnings release on July 30, 2020, and investment in COVID-19 related research, testing and support will continue throughout 2020. The company reported that its research and development expenses decreased 1% in the second quarter of 2020 year-over-year to $1.390 billion, or 25.3% of revenue, driven primarily by lower development expenses for late-stage assets and the pause in new clinical trial initiations and patient enrollment as a result of the COVID-19 pandemic.
GlaxoSmithKline, Merck & Co, and AbbVie, which reported COVID-19 impact on their financial performance for the second-quarter 2020, did not specifically address COVID-19 impact on clinical research activities in the second quarter. GSK said it has had a continued strengthening of its biopharma pipeline, which now contains 35 medicines and 15 vaccines; over 75% of its pipeline assets are focused on immunology.
AstraZeneca reported in its second-quarter 2020 results reported on July 30, 2020: “As the COVID-19 pandemic develops, the company will evaluate the impact on the initiation of clinical trials, ongoing recruitment and follow-ups. It is prudent to assume that some delays will arise as a consequence of the pandemic.”
Clinical trials in the future: lessons learned from COVID-19
Aside from adjusting the timelines in the drug-development programs as a result of COVID-19, pharmaceutical companies also have adjusted the way in which they have conducted trials, such as the logistics of clinical trial materials supply through direct delivery of medicines to patients, telemedicine, and other digital strategies. These changes have brought into consideration the way in which clinical trials may be conducted in the future, including on data management, the logistics and delivery of clinical trial materials, and potentially on drug-development timelines.
José Baselga, Executive Vice President, Oncology R&D, AstraZeneca, provided insight into this in a recent (August 4, 2020) post on the company’s website. “COVID-19 has impacted us all, but for cancer patients the implications are profound. The prospect of a hospital not being able to accommodate a patient for their treatment, or an immunocompromised patient not being able to get to the clinic has become a reality for many cancer patients at some point during the pandemic.”
Baselga recently participated in a virtual meeting organized by the American Association for Cancer Research as an information-sharing forum to discuss how the industry has responded with respect to clinical trials during the COVID-19 pandemic and future learnings. Baselga served as a panelist for the “Regulatory and Operational Implications of Cancer Clinical Trial Changes During COVID-19” session to discuss the impact of the pandemic on clinical trials for cancer and how the industry is adapting.
“This is an opportunity to rethink trial design and implementation,” he said. “The COVID-19 pandemic has revealed inequalities and inefficiencies across the healthcare continuum, but it also showed what is possible when, out of necessity, we focus on the main challenge in front of us.” He said within AstraZeneca, the company has worked with investigators to flex and adapt for cancer patients: by leveraging telehealth, delivering medications directly to patients’ homes, and fast-tracking the implementation of digital technologies to monitor its oncology trials in real time.
“COVID-19 has forced us to take a hard look at and see where we can simplify clinical trials for cancer to ensure we are efficiently answering the question at hand and collecting the most relevant data,” he said. “How can we re-evaluate our protocols while continuing to collect important data and maintain rigorous safety protocols? Are there ways to obtain information without requiring patients to travel to a hospital every few weeks? Innovations in big data, AI [artificial intelligence] and machine learning have allowed us to take a new approach in designing our oncology clinical trials with patients at the center.”
The need to create access for patients participating in clinical trials during the pandemic may also lead to more direct medication delivery in the future. “Trial access is not equitable across all populations,” said AstraZeneca’s Baselga. “Clinical trials within oncology are not as diverse as they could or should be, and some communities are routinely underrepresented. Physical access to academic medical centers (and transportation options) is just one of the most visible barriers. As we work to ‘decentralize’ care, are we doing everything we can to reduce the burden on patients? The pandemic has forced us to ‘virtualize’ in many ways, and we need to carry this through with telehealth, e-consent options, and medication delivery.”
Another important question for the future is will lessons learned from clinical research during the COVID-19 pandemic potentially result in operational changes, including reduced development timelines. “Collaboration and open communication improve system efficiency,” said Baselga. “Virtual interactions have enabled collaboration at an unprecedented scale. We’ve witnessed first-hand the impact of this increasingly efficient communication: the US FDA drafted guidance in a matter of weeks on the conduct of clinical trials during the pandemic—this process would usually take months. At AstraZeneca, my team, along with Drs. Louis Staudt and Wyndham Wilson at the National Cancer Institute, collaborated closely to develop and implement a trial protocol to assess the efficacy of an existing medicine against COVID-19—all in just a matter of days. There are always opportunities for improvement. Nothing is perfect the first time around, and now is the time to look back and ask questions, to understand what worked well and what still needs to be refined.”