As we begin the new year, there is a lot of talk in the drug development world about Federal Drug Administration (FDA) guidance documents for clinical and decentralized clinical trials (DCTs). This chatter is understandable because we’re likely to see some emphasis put into previous documents that have not been rigidly enforced.
Unfortunately, a lot of trial sponsors aren’t thinking about these guidance documents in a holistic manner; rather, they are treating them in silos. And that’s a mistake because the FDA isn’t treating these guidances as checklists.
Rather, the agency’s goal is to spur a macro shift in clinical trials. The FDA is trying to tell these companies what it wants to be different in trials across the board with regards to digital health endpoints, the use of real-world data (RWD) as regulatory-grade data, and diversity in clinical trial inclusion.
Rather than merely publishing guidance on diversity, for example, the FDA is checking whether companies have put in place a plan to make sure trial sponsors know how many patients of different origins are in their populations and whether they have a strategy to reach them. While we haven’t seen the FDA deny approval based on a lack of diversity in the trial population, officials are calling it out now – and those denials may soon come.
Some new drugs on the market haven’t had to meet those new expectations because the FDA guidance was issued while their corresponding studies were already underway. But if you’re filing a New Drug Application (NDA), the FDA is going to expect you to make and implement a plan and report on how it’s going. Then the FDA will show who was in your trial. (The agency already does this, but it’s going to be more frequent and public.)
What to expect in 2023
There are several interesting events on the horizon for clinical trials. First, we expect FDA guidance on DCTs and how they operate. This guidance, however, likely won’t answer a lot of the questions sites may have, such as what information should be included in FDA Form 1572 (Statement of Investigator) when a sponsor is hiring multiple vendors for a trial but has no say in choosing them.
There will be guidance from the FDA on how it expects physician oversight to be managed, though one distinct possibility is that the agency won’t change anything regarding physician oversight and will offer no guidance on how to define a trial site.
Another item to watch is a Request for Information (RFI), submitted in late October by the White House Office of Science & Technology Policy (OSTP) in coordination with the National Security Council, that seeks input from the public about how a coordinated clinical research infrastructure can be deployed in the event of an emerging disease outbreak. The goals of the Federal Government are to have some mechanism for enabling clinical trials to launch within about 14 days of a decision (which would be fantastic) and to include guidance language about how DCTs would be part of that infrastructure.
On the industry front, the Decentralized Trials and Research Alliance (DTRA) is making great strides in its Priority Initiative project, launched to develop solutions that widen access to decentralized clinical research.
As of today, nine of the project’s 12 specific initiatives are publicly available or close to release. Trial sponsors can now access and contribute to a glossary of terms, review key performance indicators, consult best practices, and tap into educational resources. Coming in early 2023 from DTRA’s Priority Initiative will be a framework that helps sponsors map the patient journey to improve the trial design process.
3 ways to prepare
What can trial sponsors do to best prepare as they plan their clinical trials/DCTs over the next year?
Here are three steps:
- Start early. Begin the design phase 12 months before you expect to enroll a patient and be sure to include the necessary stakeholders – and if you need regulatory approval, start even earlier. Map out exactly what you expect to happen in the trial and then figure out what is achievable and how it can be executed. This allows you to design with the end in mind.
- Do a test run. If it’s possible, trial sponsors should simulate what they’re planning to do in the trial. Create a workflow, recruit end-users, and run through the entire process multiple times. This allows you to figure out what might go wrong, particularly with technology and access to study staff on-site or virtually.
- Don’t strive for perfection. Perfection is the enemy of getting started. Lean into your planning, get input from lots of different stakeholders, and then be ready to iterate. Though you can’t iterate in a way that undermines the rigor of the science, you may be able to iterate on the execution parameters. Remember, the FDA is sending us clear signals; the agency wants DCTs to succeed. You’re not putting your trial at risk if you do the thinking and planning.
The big picture for DCTs
DCTs have attracted a lot of naysayers in the wake of the Covid-19 pandemic. These critics point to the flaws and problems in trial execution as sponsors struggled to retrofit design principles on-the-fly in the face of a global health crisis that made site-based clinical trials virtually impossible in 2020-21. Yet patients showed that they were willing. And while the experience sites and patients had was suboptimal at best, it worked.
It’s important to remember that innovation is a process that never occurs in a linear fashion. It’s a jigsaw pattern – you go up, you fall back, up, and back, over, and over. A Tufts white paper this year found that “the four stages of the innovation adoption process” (Initiation, Evaluation, Adoption Decision, and Full Implementation) take nearly six years on average!
It’s no secret the healthcare and clinical research industries typically adopt new technology and virtual processes much slower than others but that doesn’t mean it isn’t happening. Sure, we’re going to be slower in the world of clinical research; but that doesn’t mean we’re not making progress.
We can expect to see continuing tension and friction in the clinical trial system as the adoption of DCTs grows over the next year. The good news is this may translate into more options for patients, which can only benefit drug development. The reality is that different people want different things at different times in their care and in their trials. DCTs can provide that flexibility while improving the quality of clinical trials for sponsors.
The DCT naysayers may not go away quietly or quickly. Change is hard, a bit scary, and challenges the status quo. But as DCT adoption gains momentum in 2023, we will get closer to the point where the “D” is no longer necessary in “DCT” – because they’re all clinical trials! There may be bumps along the way, but DCTs are well on their way to adoption.
Photo: Warchi, Getty Images