COVID-19 has imposed some unique challenges to the clinical trial community. The pandemic has altered the way clinical trials are conducted with long-lasting effects. Prioritizing patient safety, recruiting new participants into trials, and data collection and management are some of the burgeoning issues faced by the clinical trial community. 80% of non-COVID trials have been suspended and trial-management groups are now faced with new uncertainties around re-starting clinical trials.
All major pharmaceutical companies such as Eli Lilly, Merck, and Pfizer have announced delays in future clinical trial process enrolments. According to BioPharmaDive, as of May 15, 2020, nearly 100 companies and 240 trials have experienced disruptions. This will push the new drug release for critical diseases such as cancer and Alzheimer by several years impeding medical advancements.
The Clinical trials process by design is a global episode. Patients and trial participants are enrolled based on race, ethnicity, age, gender, and geographical proximity, driven mostly by the key qualifying criteria of a trial plan protocol. Often for a single study, multiple trials are performed by trial investigating offices in several regions or countries in a concurrent manner. The data of such trials, often spanning across years, are collected for analysis, defining efficacy paths, and for reporting and approval purposes.
Some of the trials, which are now paused, were in the process for several years. No one anticipated the intensity and the length of the current pandemic. This resulted in untimely stoppage and closure of studies and some of the clinical sites as well. The CROs, pharmaceutical companies, and the trial sites faced some unprecedented times, primarily driven by:
- Patient recruitment and retention: Patient retention remained the most prominent reason among others for the continuation of any meaningful trials. Almost all trials mandate the participants to come to the trial sites on a periodic basis for vital checks, administering medicine (in some cases), and progress mapping of drug effectiveness. COVID-19 has restricted access to participating candidates in the clinical sites. Even the clinical sites were closed based on individual country government mandates. Pandemic has also impeded the recruitment of new candidates further worsening the clinical trial process.
- Patient safety: Trials are often conducted on vulnerable patients and COVID-19 brings a grave concern on increased fatality in such a concentrated population. Even when the sites can put forward safety measures to bring participants in a controlled manner, patient safety because of pre-conditions prohibits such progress.
- Distribution of drugs: A large part of any successful conduct of clinical trial is dependent on the supply of drugs, first to the sites and later to the participating individuals. Often these drugs are shipped from the participating pharmaceutical companies to the trial sites. With the surge of the pandemic the supply chain worldwide has clamped down. Though drugs are considered an essential commodity, yet the supply has remained restricted. Even if the sites have access, not all drugs could be distributed to the participants, as it requires clinical oversight. The pandemic being ubiquitous, clinical sites access to patients are further cut-off. This resulted in ongoing studies to be halted, most of which may have to be redone because of clinical efficacy reasons.
- Limited site research staff: It is not only the patient or participating clinical trial community that is scarce, but also the site staff. Site staff are skilled nurses, who are further trained on particular studies that they are required to conduct. There are also many roles such as investigating officer, site lead, site nurse, research staff, statisticians, epidemiologists, and data operator who are skilled and difficult to replace. Many research associates working on clinical trials have been pulled in to support the COVID-19 patients in medical care facilities. This has further added to the dearth of skilled staff. COVID-19 has in general caused a scarcity of trained site staff.
CROs who participate in early and late-stage clinical trials have to undergo financial loss. Also, the pandemic has delayed pharmaceutical companies to submit their clinical trial findings to FDA. This has caused potential delay in drug launch or learning early which clinical trials to drop. The companies are carrying cost on their books for trials which may not be worth it. Most importantly, it has impeded the release of some of the critical drugs or treatments, which could have saved human lives.
While COVID-19 impeded the clinical trials progress, it also opened new avenues for innovation. Slowly but surely the clinical trials are rebounding, and in this new resurgence, technology is playing a pivotal role. The recruitment of new patients is paused as new studies are not getting commissioned. But the institution and research units have found new ways and measures to continue progress on existing clinical trial data management. Some of the key innovation that came to play during the pandemic include:
- Providing participating members medication for a longer period of time, hence reducing footfall at clinical sites
- In a usual setup, the clinical sites receive the medicine for the trials, which get distributed to patients upon their visit. During the pandemic, the institutions and clinical sites readjusted their supply chain to get medicine delivered direct-to-patient. The trial medicines are also in some cases administered to participants at home reducing the risk of exposure
- In March and July 2020, the US Food and Drug Administration (FDA) issued guidance for patient safety to be followed during the COVID-19 pandemic. It provided the investigators and sponsors an avenue to rewrite the clinical protocol to support virtual trials. The institutional review board and ethics committees have prioritized reviewing the revised protocol with extreme urgency, particularly for patients who are undergoing clinical trials for life-threatening conditions where wait may not be an option
- Before administering any clinical procedures on patients, the Good Clinical Practice (GCP) governed by ICH regulatory mandates to take patient consent. Electronic consent, which was not quite popular pre-COVID days is witnessing a surge in demand. This has become a good medium to capture the opt-in regulatory requirements without participants and patients making the trip to their respective clinical sites.
- Technology plays a key catalyst to help conduct periodic virtual visits of the participants in key sites. The proliferation of consumer devices (phone working as a class II device) can be used for test data collection in a secure and safe way to help navigate clinical trials during the pandemic.
While these may appear as stop gap measures, they are also shaping up how the clinical trials will evolve in a post-pandemic world. Regardless of the difficulties faced because of staff, patient, or supply chain issues, the collective learnings will make the future clinical trials more agile, nimble, and cost-effective. Some of the core aspects of new ways of doing clinical trials are listed below:
- Centralized to decentralized: Historically most of the clinical trials are conducted in a centralized manner, in an urban location or large institute. COVID-19 has taught us that with decentralized clinical trials, we can widen our net to recruit more patients, and possibly do trials in a faster manner
- Communication and coordination: One of the key aspects research sites learned is effective communication and coordination. When a site is not staffed properly, the load can be shifted to another site. To enable this, the investigator needs to have a clear line of communication with sites and sponsors. The regulations keep altering and there may be confusion in deciphering it. Investment in communication technology and skills acquired to communicate well will immensely bring agility, quick problem solving, and intra-site coordination to expedite future clinical trials
- Mergers and acquisitions: There is a rapid increase of partnership and M&A to further support the virtual trials in the new world. For example, CRT, a clinical trial data management company is merging with Bioclinica to become a leader in clinical trial endpoint technology
- Patient recruitment: Patient recruitment will be more distributed and decentralized across region and geographies to mitigate scarcity in participant’s risk Electronic patient consent: Virtual consultation, and remote monitoring will become an industry norm
- Virtual clinical trials: FDA and other country-specific regulatory bodies will promote the adoption of virtual clinical trials, providing investigators to rewrite protocol and support remote care
- Data as the universal equalizer: In the pandemic and post-pandemic era, the ability to collect upstream data from trial participants directly in a secure and safe manner will be a big focus area
- Virtual training: Traditionally all trial training is done face-to-face. In future, the training will be done remotely in a virtual setup
- Decrease in cost: We will notice a rapid decrease of clinical trial cost because of remote clinical staff, tele meeting, remote monitoring, and decentralized clinical trial support.
The pandemic undoubtedly drew many concerns. The paused clinical trials impeded several medical research advancements. Despite the uncertainties, the pandemic taught many great lessons, which contrary to many beliefs, showed a new way to conduct trials.
The industry quickly adapted to the virtual way of clinical trials. Protocols were redefined, the supply chain realigned to direct-to-patient delivery, drugs got administrated to patients at home, and clinical staff worked remotely. The regulatory bodies provided directional input on new ways of working and acted urgently to review revised protocols.
Despite the headwind, major pharmaceutical players such as Pfizer-BioNTech, Johnson & Johnson, Moderna, have successfully run several trials for the COVID-19 vaccine mostly in a decentralized way. In the history of vaccine development, we have never seen vaccines discovered, tested, and released in such record time. The researchers, government, and community at large came together in an unprecedented time to successfully perform clinical trials with limited resources. We now have living proof that trials can be conducted faster, safer, and cheaper breaking all bureaucratic barriers to the better of mankind. Virtual clinical trials are here to stay.