At the beginning of the new year, there is a lot of talk in the world of drug development about Federal Drug Administration (FDA) guidelines for clinical and decentralized clinical trials (DCT). This chatter is understandable because we are likely to see some emphasis in previous documents that were not strictly enforced.
Unfortunately, many trial sponsors do not think about these guidelines in a holistic way; rather, they are treated in silos. And that’s a mistake because the FDA doesn’t treat these guidelines as checklists.
Rather, the agency’s goal is to drive macro change in clinical trials. The FDA is trying to tell these companies what it wants to be different in trials across the board in terms of digital health endpoints, use of real-world data (RWD) as regulatory data, and diversity in clinical trial enrollment.
Instead of simply publishing diversity guidelines, for example, the FDA is checking to see if companies have a plan in place to make sure trial sponsors know how many patients of diverse backgrounds 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 be coming soon.
Some new drugs on the market did not have to meet these new expectations because the FDA guidelines were issued while their respective studies were already underway. But if you’re submitting a New Drug Application (NDA), the FDA will expect you to make and implement a plan and report back on how it’s going. Then the FDA will show who was involved in your experience. (The agency already does this, but it will be more frequent and public.)
What to expect in 2023
There are several interesting developments on the horizon for clinical trials. First, we await FDA guidance on DCTs and how they work. However, this guide will likely not answer many of the questions that sites may have, such as what information should be included on FDA Form 1572 (Investigator Statement) when the sponsor hires multiple providers for a trial but has no say in selecting them. .
There will be guidance from the FDA on how it expects oversight of physicians to be managed, although a different possibility is that the agency will change nothing about oversight of physicians and offer no guidance on how to determine a trial site.
Another item to watch is a Request for information (RFI) submitted in late October by the White House Office of Science and Technology Policy (OSTP) in coordination with the National Security Council, seeking input from the public on how a coordinated clinical research infrastructure could be deployed in the event of an emerging disease outbreak. The federal government’s goals are to have some mechanism to allow clinical trials to start within about 14 days of a decision (which would be fantastic) and to include guidance on how DCTs will be part of that infrastructure.
On the industry front, the Decentralized Trial and Research Alliance (DTRA) is making great strides in its Priority initiative project launched to develop solutions that expand access to decentralized clinical research.
To date, 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 use educational resources. Expected in early 2023, DTRA’s priority initiative will be a framework that helps sponsors map the patient pathway to improve the trial design process.
3 ways to prepare
What can trial sponsors do to best prepare themselves as they plan their clinical trials/DCTs next year?
Here are three steps:
- Start early. Start the design phase 12 months before you expect to enroll a patient and be sure to involve the necessary stakeholders – and if you need regulatory approval, start even earlier. Map out exactly what you expect to happen in the process, and then figure out what is achievable and how it can be accomplished. This allows you to design with purpose in mind.
- Do a trial run. If possible, trial sponsors should simulate what they plan to do in the trial. Create a workflow, hire end users and go through the whole process multiple times. This allows you to understand what can go wrong, especially with technology and access to on-site or virtual training staff.
- Don’t strive for perfection. Perfection is the enemy of getting started. Lean on your planning, get input from many different stakeholders, and then be ready to iterate. While you may not be able to replicate in a way that undermines the rigor of science, you may be able to replicate the performance parameters. Remember, the FDA is sending us clear signals; the agency wants DCTs to succeed. You don’t put your process at risk if you think and plan.
The big picture for DCT
DCTs have attracted many skeptics since the Covid-19 pandemic. Those critics point to flaws and problems in trial execution as sponsors have struggled to modernize design principles on the fly in the face of a global health crisis that has made on-site clinical trials virtually impossible in 2020-21. Yet patients showed that they have a desire. And while the site and patient experience was suboptimal at best, it worked.
It is important to remember that innovation is a process that never proceeds in a linear fashion. It’s a jigsaw pattern – you go up, you fall back, up and back, over and over. And Tufts White paper this year found that the “four stages of the innovation adoption process” (initiation, evaluation, adoption decision, and full implementation) take an average of nearly six years!
It’s no secret that the healthcare and clinical research industries tend to adopt new technologies and virtual processes much more slowly than others, but that doesn’t mean it’s not happening. Of course, we will be slower in the clinical research world; but that doesn’t mean we’re not making progress.
We can expect to see continued tension and friction in the clinical trial system as DCT adoption grows in the coming year. The good news is that this could lead to 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 this flexibility while improving the quality of clinical trials for sponsors.
DCT skeptics may not go away quietly or quickly. Change is hard, a little scary, and challenges the status quo. But as DCT adoption gathers pace in 2023, we’ll be approaching the point where the ‘D’ in ‘DCT’ is no longer needed – because they are everything clinical trials! There may be bumps in the road, but DCTs are about to be adopted.
Photo: Warchi, Getty Images