COVID-19 has taken us all by storm, and as a result, much of the world has come to a grinding halt.. As you can imagine, this includes the clinical trial universe, as well. Healthcare resources are being diverted, rightfully so, to combat the pandemic. Suddenly, the world is clamoring for what many in clinical research have aspired to for years - expedited clinical trials leading to treatments to patients faster. Perhaps the coronavirus is gifting us a glimpse into the future of drug development.
Existing Trials: Adapting in Real Time
Globally, there is a pandemic unfolding, rippling across countries and targeting everyone in its path. No one - not Hollywood, athletes, politicians (or their spouses), royalty - is safe, but the eldery and the immunocompromised seem to be particularly vulnerable to the virus causing serious or life-threatening problems. Hospital systems are stressed domestically and on the verge of collapse in other parts of the world. Pharmaceutical companies are beginning to ration their resources, delaying start-up or enrollment to lessen the burden on existing healthcare sites.
For clinical trials that are able to move forward, study teams are scrambling to minimize disruption, both to get existing patients treated and maintaining the trial’s integrity in the face of an unparalleled disruption. Veer too far off course, and current and future patients suffer costly, potentially life-threatening delays. To prevent this, adjustments to standard operating procedures have to be made, whether the slow-to-adopt-change world of clinical research wants to or not.
The FDA has, very quickly, issued guidance on conducting clinical trials during this pandemic. It reads as a sort of wish-list of potential operational advances in clinical research:
- “Since trial participants may not be able to come to the investigational site... sponsors should evaluate whether alternative methods for safety assessments (e.g., phone contact, virtual visit, alternative location for assessment, including local labs or imaging centers) could be implemented”
- “The need to put new processes in place or to modify existing processes will vary by the protocol and local situation.”
- “Sponsors and clinical investigators are encouraged to engage with IRBs/IEC as early as possible when urgent or emergent changes to the protocol or informed consent are anticipated…FDA recommends consultation with the appropriate review division regarding protocol modifications for the collection of efficacy endpoints, such as use of virtual assessments, delays in assessments, and alternative collection of research-specific specimens, if feasible.”
- “The implementation of alternative processes should be consistent with the protocol to the extent possible, and sponsors and clinical investigators should document the reason for any contingency measures implemented.”
- “Changes to policy and procedures could address, but not be limited to, impact on the informed consent process, study visits and procedures, data collection, study monitoring, adverse event reporting…”
Think of ways to bring the study to the patient.
Consider how to be flexible.
Engage early with stakeholders.
Accept variance will happen; proactively address, and then record why.
The notoriously reserved clinical research industry is now faced with a decision: adjust your strategy or drop out of the race altogether. Instead of resisting change, adapt and adjust. This is what the future of clinical research will look like - more agile, less rigid; more adaptable, less authoritarian; more personalization, less one-size-fits-all. Most importantly, more human.
COVID-19 Trials: The Future is Now
While existing trials struggle to find their way through this uncertain time, the barriers to clinical research have come down for COVID-19 studies. As of March 23, 2020, there were already five completed studies for COVID-19, and by the time you read this, there’s likely to be more. Notably, there are 113 studies somewhere between “Not yet recruiting” and “Active, not recruiting”, with 62 in recruiting/enrolling/active status. Considering that the World Health Organization wasn’t notified until the very end of 2019 about this new virus, and the average study start-up time is north of 7 months, the swift response to this global pandemic has been unprecedented.
Why has the COVID-19 reaction been so drastically different from “normal”? Was it the life sciences industry changing their standard operating procedures to adjust for the surge in demand for health care? Was it capitalism - and consumers - pushing for a product that a market was literally dying for? Or was it the world collectively realizing that the typical barriers to innovation were not nearly as important as getting treatments or vaccines to patients as quickly and safely as possible? And, importantly, what are we learning about the pace at which clinical research can be done?
First, the caveats - COVID-19 is unlike anything in the modern medical world, so every stakeholder in the drug development process is likely willing to bend on strict adherence to dogmatic Standard Operating Procedures. Many of the trials are for either existing compounds (eliminating the need for a Phase I study) or for diagnostics, both of which accelerate the startup timeline. Physicians and governments are desperate for ANYTHING that could help.
That being said, this is the same clinical research world that regularly regurgitates the following median numbers - seven years, $750 million+, and a success rate of 1 in 5,000, all to get one drug to market. In Duchenne Muscular Dystrophy, it took 8+ years to get exon skipping from mouse models to the approval of Exondys51, the first treatment approved in the United States for DMD. Approval for new sunscreen ingredients languishes, some for the better part of two decades. Even Merck’s hyper-accelerated timeline for Keytruda approval - less than 5 years, an unheard-of number in oncology treatment - was still glacially, frustratingly slow to those who could not access the drug.
The COVID 19 trials were enrolled and complete stunningly quick because:
- Populations of patients were easily identified - this illness could affect ANY and EVERYONE, and potential cases were being brought forward on a daily basis,
- Time was THE most critical factor; the normal back-and-forth during study start-up was plowed over with compromise,
- Existing compounds already had safety data, thereby allowing researchers to skip time-consuming early-phase trials, and
- Pressure was applied universally - from governments, health care facilities, and most importantly, potential patients - to get treatment.
The catchphrase “we are all patients” has never been more applicable, and every stakeholder in this specific development process worked collaboratively to make these trials happen, and happen quickly. Technologies already exist that facilitate all of the above FDA considerations (and a slew of new ones are appearing to specifically address COVID-19), yet adoption prior to 2020 was slow and deliberate. Now, the leadership team at Medable has been actively promoting and incorporating decentralization of trials for COVID-19, getting a trial mobile app live in Italy in under two weeks. Drive through testing has shown mobile healthcare is deployable on a large scale. Virtual trials are on the horizon. Clearly, we can do better than we were - we are now.
Key Takeaways From COVID-19
There are numerous positive things to take from the response to the current pandemic and push forward as our world slowly comes out of its hibernation.
The US FDA can have flexibility in standards. There remains a shortage of diagnostic tests for the detection of COVID-19. In response, the FDA allowed some labs to begin using validated tests before the regulators had finished their review. We will (hopefully) find out soon if the same acceleration will occur if and when a treatment is found; the FDA continues to work with the public and private entities researching those treatments. It is important to balance the rigorous standards for efficacy and safety with the demands for improved and accelerated healthcare.
Guidance that is well-crafted and useful to both patients and sponsors was able to be published in less than 30 days. Too often, this guidance is delayed. The rare disease community has been waiting over 18 months for the new rare disease drug development guidance. The FDA needs more resources to accelerate the rate of product development.
Embracing digital medicine and digital health tools will continue to drive healthcare modernization and mobilization, while simultaneously working to remove man-made barriers to effective and efficient clinical research practices. The world is now pilot-testing-by-necessity many of the technologies that sound great in presentations, but have been largely kept on the sidelines by risk-averse trial sponsors and sites.
Trial design will continue to evolve, and the use of non-traditional trials - virtual, decentralized, direct-to-patient, whatever they are called - should become more commonplace, as sponsors realize they can reach broader patient populations in more effective ways. Trials will be brought to patients, instead of the other-way-around.
Deadly illness is deadly illness, whether a pandemic or a fatal disease. The urgency with which we develop therapies needs to mimic the response and flexibility shown with COVID-19. Let’s not let this crisis - and the accelerated pace of research it forced - go to waste.