The Clinical Trials Transformation Initiative (CTTI) is comprised of more than 80 organizations united by the mission to develop and drive adoption of practices that will increase the quality and efficiency of clinical trials.
The multi-stakeholder member organizations includes representatives from the FDA, big pharma, smaller biotechs, clinical research organizations (CROs), institutional review boards (IRBs), academic institutions participating in clinical research, patient groups, independent patient representatives, and technology companies.
In June, CTTI released “Developing Novel Endpoints Generated by Mobile Technology for Use in Clinical Trials,” which contains recommendations for integrating mobile technology into clinical trials.
We recently spoke with Jennifer Goldsack, CTTI’s Project Manager, about the status of mobile technology adoption in clinical trials, the process behind CTTI’s recommendations, and future projects aimed at overcoming obstacles in endpoint development.
MC10: How does novel technology like wearables and sensors play into CTTI’s mission?
Goldsack: Our goal at CTTI is to develop and drive the adoption of practices that improve the quality and efficiency of clinical trials. I think wearables and remote sensors have a huge amount of potential to tackle both of those issues very effectively.
In terms of quality, we can now get better quality data—meaning much more than just snapshots we get during clinic visits. We can get much more information about the burden of disease and the efficacy of treatment in patients’ daily lives.
These devices will ultimately reduce the barrier for patient participation in clinical trials. People who live in rural areas, or who rely on caregivers to get them to clinical trials, will now be able to participate. People with rare diseases won’t have to get on a plane and fly across the country in order to participate. We’ll have better quality research because hopefully we’ll have more representative populations.
If you have better, more sensitive measures taken more frequently, as well as quicker enrollment, trials will fail faster. We will have a much earlier understanding of whether a therapy is working or not.
Even outside of Phase III trials, and including earlier trials, we’ll have better signals for Go/No Go decisions. We’ll be more likely to take therapies forward that have great potential and make some more pragmatic business decisions about those that are unlikely to be effective.
MC10: Have you seen a big shift in the adoption of mobile devices in clinical trials since CTTI launched three years ago?
Goldsack: It’s gone from being common for companies to have done one or two pilot studies with mobile technology to it being ubiquitous. Everyone's doing small feasibility studies. I think that’s the reason the work we’ve done is so needed.
What we haven’t seen is the step where folks have the confidence in how to leverage these devices, to take it beyond pilot studies and into larger scale clinical trials. We’re not saying it’s ready for a primary endpoint right now—or even if that’s what the ultimate goal should be.
I hope CTTI can shed light on how to use this technology in a way that would be acceptable to regulators and that would meet unmet patient needs. I hope we can start to tip the balance and go beyond these pilot studies and actually start to include these measures as exploratory endpoints in much larger scale trials. I think that’s the necessary next step.
MC10: Why do you think we haven’t seen that jump from people using novel endpoints and mobile technology in pilot studies to using them in larger-scale clinical trials?
Goldsack: I think there are two reasons. One, there is a lack of clarity around the process. My hope is that we have gone a long way in addressing that. And two, it’s not an insignificant amount of work. I think there are huge benefits to be reaped by developing these measures, but they’re not going to happen over night.
One of our recommendations is to collaborate. Pre-competitive collaboration, both across different stakeholder groups—the patient groups, the sponsors, and technology groups— and within those groups. It can’t just be one sponsor at the table if you want to do this in a timely fashion.
I really think some of the difficulty in taking this from pilot to full blown trial has been the fact that it takes awhile to amass the amount of data you need and to gain the knowledge and the understanding of how each measure works and responds in a given patient population. I hope the recommendations we make for collaboration are heeded because I think collaboration coupled with clarity of the process will really expedite things. I think we’re at a tipping point.
MC10: So you think change is right around the corner? In terms of the regulatory side of things, will these kinds of endpoints be acceptable in the near future?
Goldsack: The FDA is our co-founder and our partner. I believe our FDA colleagues are very open to these measures. They encourage anyone thinking about [the endpoints] to come and talk to them.
[The FDA wants] to learn with us, and they see the promise in these measures, for quality and efficiency, just as well as everyone else. We’ve had four FDA colleagues on our project teams who participated in developing the recommendations every step of the way. They not only gave great input but listened and learned from the multi-stakeholder team.
The impetus from our projects came from the FDA. Another one of our recommendations is to engage the regulators. We strongly encourage it throughout the development process.
MC10: CTTI just released recommendations for generating novel endpoints. What was the process in making these recommendations?
Goldsack: We heard time and again that folks were starting with the technology. But first we needed to understand: Where is the opportunity for these devices to capture a measurement that addresses an unmet need? Where can we actually improve existing measures using these technologies?
That was our first step. Then we took an action oriented approach. We had multi-stakeholder teams of experts write four use cases for developing novel endpoints. We ran four parallel workshops that ran for a day and a half each. The use cases were diabetes, Duchenne muscular dystrophy, heart failure, and Parkinson’s Disease.
We looked across the four use cases once they were written and stepped back to see the common steps. What did all of the teams identify as needing to happen in order to select and develop an endpoint to a point where a sponsor or investigator could comfortably include it in a registrational trial?
In addition to helping us establish a common ground for endpoint development, this process also shed light on particular considerations or nuances that might be associated with different patient populations with different existing endpoints.
MC10: How did you choose the four use cases that were used to develop the standards? Do you view these as the groups who can most immediately benefit from the use of exploratory endpoints?
Goldsack: We did a scan of the existing literature to see where there was already some research—evidence that resources in the field are being devoted to this endpoint, that the technology exists, and that there is a need.
One of the tools we created was a novel endpoint selection tool, which we used to select the use cases. We asked questions like: Is this addressing an unmet need? If you develop this measure in one therapeutic area could it be applied to another? Could this potentially reduce the barrier of participation?
MC10: How do you keep different patient groups involved and top of mind when developing recommendations?
Goldsack: We have project team members and team leaders who are either patients or leaders in patient groups. Every time we meet and have a conversation a patient voice is there. When we wrote our four use cases there was a heavy patient presence in each one of those groups. They were front and center in those conversations.
Internally we have a pretty stringent review process. Drafts get sent out to all of our member organizations that provide great feedback. There’s not a single step in the process where the patient voice is missing, and we are really proud of that. I think that is so important in this work.
MC10: You have a sister project coming up dealing with devices. What can you share on that?
Goldsack: It was very purposeful that we started with the endpoint project because we wanted to underscore the fact that the scientific question comes first: What’s the problem? What’s the unmet need? Is it episodic and therefore better suited to continuous monitoring? Are the current measures inadequate?
Think about the measure first. Think about the unmet need. Think about the patient. Once you’ve decided on a pathway you want to take, you recognize there are still many issues that you have to address.
So for this mobile devices project we’re thinking about issues such as device selection. For example, for a given research question or patient population, how can you ensure the device is validated? Calibrated? Who manages the device if you decide to use it in the field? What about an audit trail? How does that look when you’re not using case report forms and everything is kept in a cloud database? How do you prepare for an inspection or monitoring? How do you prepare datasets for FDA submission? What about security and privacy?
We think a lot around not just the device selection but some of those more operational, protocol type questions you would need to ask if you wanted to use one of these novel endpoints in a trial. We’re working on a number of different toolkits and recommendations to try to cover all of the things a sponsor or an investigator would need to think about if they were writing a protocol that was going to leverage a mobile device for data capture.