The race for a safe and effective COVID-19 vaccine is on. As the pandemic continues to spread across the country, Americans look to pharmaceutical companies to deliver them from the crisis. Currently, multiple COVID-19 vaccines are in clinical trials, and the world anxiously awaits the results. Prior to COVID-19, the mumps vaccine held the lead for the fastest vaccine to hit the market after four years in development. The new Pfzier and BioNTech vaccine took nine months.
Public figures have spoken up on concerns about the politicization of the development of a COVID-19 vaccine.
“Let me be clear: I trust vaccines, I trust scientists, but I don’t trust Donald Trump,” then-presidential candidate and now President-elect Joe Biden said in September 2020. This followed months of efforts by President Donald Trump to pressure and squeeze pharmaceutical companies and the FDA for a vaccine to boost his chances before the November 3 election.
In October 2020, former FDA Commissioner Robert Califf addressed these concerns in a discussion titled The Future of Clinical Trials at STAT, a news organization that reports on health and medicine.
“The core of the FDA is unperturbed by this,” Califf said. “FDA employees are used to seeing political appointees come and go. So there’s a solid, scientific public-health basis for the FDA that continues on. I don’t see that being changed or affected much.”
Califf added that we’ve discovered ways to speed up clinical trials without sacrificing scientific rigor. “We’ve realized that you don’t need to take two months to negotiate a CDA or to get a contract signed to do a basic piece of research,” he said. “We don’t have to fight for a year over a budget. These things actually can be done, if there’s a willingness to do it on all sides.”
Aside from eliminating bureaucratic inefficiencies, Califf outlined the coming and present technological acceleration of clinical trials. The age of the Internet, Moore’s law increases in computing, and the artificial intelligence revolution are dramatically altering the face of clinical trials, and the pharmaceutical and healthcare industries are feeling it already.
“Computational capability is no longer the limiting factor,” Califf stated. “It’s all about the human interactions and the rules by which we interact with each other.”
He acknowledges the importance of privacy and the complexity of the healthcare stakeholder landscape, and maintains that those concerns, rather than computational concerns, are the real roadblocks. However, technology also has a large role to play in resolving these issues.
In the past, clinical data were collected via fax and processed by hand. However, even now with the Internet, data collection is slow and inefficient. Despite having electronic health records (EHRs) for patient records, which could provide researchers with easier access to clinical data, the information is often non-standardized and separated across many separate institutions or even departments.
“One of the things we’re working on at Google … is the automation of curation of electronic health records to produce the kind of data that you really want,” Califf remarked.
While the current paradigm isn’t quite at the stage of automated curation, rapidly occurring changes in the industry promise to deliver enormous benefits.
“Most of what we do is a waste of time and money,” Califf claims. “If we focus on what we needed to do, we could reduce the cost by more than an order of magnitude.”
He points to the widely hailed Randomised Evaluation of COVID-19 Therapy (RECOVERY) trial, as an example of a well-executed clinical trial, which successfully leveraged technology to implement a solid, adaptive data collection strategy with good trial design.
RECOVERY is a platform trial, aimed at evaluating many different drugs as treatments for COVID-19, and in hallmark studies proved the inefficacy of hydroxychloroquine and the exciting efficacy of dexamethasone — the steroid notably given to President Trump upon his COVID-19 diagnosis in October 2020. The trial is highly praised for its staggering size and efficiency, enrolling tens of thousands of patients across 176 hospitals and involving around three thousand doctors, nurses, and consultants. They conducted enrollment, randomization, and treatment assignment all over the internet. And, in contrast to the conventional paradigm, RECOVERY leverages modern data availability by using electronic health record (EHR) data for long term follow-up studies. By using EHR data, the RECOVERY trial is able to simplify and focus on the immediate effects of COVID-19 treatment.
“Now, it’s a different world,” Califf said. “Everyone has an electronic health record. And that’s really [what] the future is, and it’s what that RECOVERY trial did … Let’s focus on limited data collection of what really matters [and] get that right, and then all that other stuff that people may be interested in. Let’s make the EHR and claims data better and better, so that we can collect it and harvest it electronically and radically reduce the cost of that additional information.”
However, above all this is a guiding principle — transparency and purposefulness. Califf urges regulators and companies to be open to criticism as a form of accountability, to make sure that clinical trials are being done deliberately, with the needs of patients in mind and with a foundational understanding of the underlying clinical question.
“I’m quite proud that in my time, as Commissioner, we push through the final rule that says, you not only have to register your trial and register the results, but you have to submit the protocol and the SAP and the consent form,” Califf reflects. “I’m hoping that the transparency will help us get rid of the trials that are not useful, and focus everyone’s attention on the trials that really matter.”