The future of clinical trials is now
A paradigm shift is underway in the world of clinical trials as more and more CROs and pharma companies investigate some type of decentralized (i.e., siteless, hybrid, virtual) trial. Given the enormous investment that the life sciences industry makes in drug development, and the regulatory complexity of the work, it is not surprising that adoption of novel approaches has been slow. But the COVID-19 pandemic has changed everything.
Rather than transitioning to this model as a broad strategy, in the face of COVID-19, we are likely to see that many pharmas are making the change more out of necessity. “I believe the industry is at an inflection point,” says Mary Varghese Presti, VP, Life Sciences, Watson Health at IBM. “The impact of COVID-19 to the healthcare system at large will serve as an unintended catalyst for change in the pharmaceutical industry. Health systems are at capacity. There are concerns around the safety of the patients and of the healthcare workers. Consequently, any space within hospitals is being saved for emergency situations. So, suddenly you have a situation where if you want to advance your trial, you must now start looking at alternative ways to do it. And the technology is out there to do so.”
Leverage RWD for more efficient trials
Technology, and its use in transforming the clinical trial process, is a key part of The 21st Century Cures Act (Cures Act), which was enacted in December 2016. The real world data (RWD) that the Cures Act encouraged the use of has led to a willingness to include data captured via mobile devices, videoconferencing (i.e., telehealth), web-based tools, and even biosensors. The FDA further emphasized the value of RWD and RWE (real world evidence) when it released its Framework for a Real-World Evidence Program in late 2018.
Bringing the trial closer to the patient, via technologies that many of us use in our daily life, offers the promise of a more efficient trial, and in some instances, a faster one. Synthetic control arms have emerged in recent years driven by RWD. Of course, these unique arms aren’t a fit for every trial, but they may work for those with an abundance of preexisting data regarding the control group’s clinical attributes and where a traditional trial protocol may be prohibitive (much like the current COVID-19 environment). Oncology is an area often cited as a fit for synthetic control arms because randomizing patients into standard of care tends to prolong recruitment. Furthermore, with oncology trials, recruitment can be a challenge because patients know that they could be put on a placebo. “Setting up a synthetic control arm not only can speed up recruitment but can help get the trial open and closed much more quickly than a traditional randomized trial,” says Varghese Presti. “Additionally, since the number of patients required could be cut in half, these synthetic arms can significantly reduce patient burden. At least in terms of oncology trials, this is one of those situations where the industry is progressing and changing because the benefit to the patient and value to the sponsor are clear.”
A rise in virtual visits
There is no doubt that the COVID-19 pandemic is rapidly producing a culture change for companies conducting clinical research. A survey launched on March 26, 2020 by Greenphire, a provider of financial solutions to clinical trials, asked site staff around the globe about how their operations have been affected as a result of the virus. Within 24 hours, more than 1,700 people responded. Among the data collected were statistics reflecting the increased use of technology in trials. For example, roughly 70 percent of respondents indicated that to support patients who are unable to get to a study clinic due to social distancing, they’re leveraging technology to support at-home patient care (virtual visits/telemedicine). Respondents were concerned, though, that not everyone has the systems needed or are comfortable using the technology.
Varghese Presti says that concern doesn’t go away by simply implementing an electronic data capture (EDC) solution or a clinical data management system (CDMS) built for the data sources of yesterday. With data being generated by everything from wearables, to EHRs, to mobile applications, sponsors and CROs are faced with receiving various types of data, finding ways to make sense of it all to turn it into actionable insights, and then applying only the data applicable to the trial’s desired endpoints. To help achieve those goals, she expects the use of artificial intelligence (AI) and machine learning to increase. However, there is one stumbling block she says that can’t be overlooked — interoperability.
The importance of seamless interconnectivity
“If you think about the promise of RWD and the extraordinary opportunity we are now faced with to completely change the drug development paradigm, we are going to need a bold vision where data is seamlessly and consistently flowing,” says Varghese Presti. The healthcare industry experienced such a turning point years ago with the introduction of EHRs, but progress was hampered amid interoperability and integration issues. The result, according to Varghese Presti, was going from paper charts to basically digital paper charts that were not open nor connected to other systems, creating data trapped inside each proprietary system.
We can’t make those same mistakes when we think about enabling decentralized trials. We don’t have time, especially during this coronavirus crisis. Making a process, product, or system “patient-centric” (no matter how you define that term) has never been so imperative. For example, patients using ePRO systems are more likely to participate and comply if they can use their own devices (i.e., a BYOD approach). “The emphasis should not be on just what data we need to collect from patients and through what device. It’s as equally important to understand how a patient interacts with the device and how these data collection tasks fit into their everyday life,” says Varghese Presti.
Such data should be gathered through intuitive and easy-to-use interfaces. Patients expect this technology to have the same look and feel as when they are, for instance, ordering food on their phone or capturing their workout data for the day. And the device they are expected to use should already be provisioned to connect seamlessly with all applications and systems involved in the trial. In fact, it’s imperative that all clinical trial software solutions are built on an open platform that easily integrates with the various applications (e.g., clinical trial management [CTMS], trial master file [eTMF]) used during a trial.
Of course, the value of a streamlined and intuitive design also applies when implementing a clinical data management platform. Consider the case of the CRO Biorasi. Seeking to shorten its drug development life cycle, the company implemented IBM Clinical Development, a unified, cloud-based CDMS platform. Thanks to a design focused on ease of use and efficiency, the Biorasi team was able to reduce its database build time by 25 percent and the full life cycle cost by 50 percent.
The ongoing evolution toward decentralized trials
As more technologies, and the novel trial methods they power, are proven to be effective — and approved — for use in clinical trials, the industry is likely to lessen its dependence on site-based trials and focus more on decentralized models that enable remote procedures and visits. This evolution isn’t new; it’s ongoing. Consider then-FDA Commissioner Scott Gottlieb’s, M.D., comments from a Jan. 2019 speech, where he said, “Pragmatic and hybrid clinical trials, including decentralized trials that are conducted at the point of care — and that incorporate real world evidence (RWE) — can help clinical trials become more agile and efficient by reducing administrative burdens on sponsors and those conducting trials, and can allow patients to receive treatments from community providers without compromising the quality of the trial or the integrity of the data that’s being collected.”
Data, of course, is at the crux of this shift. But simply having more data isn’t the solution. Data is only valuable if you have the technologies, processes, and systems that can leverage it to reduce development time and costs. Just think about what it takes to amend a protocol. By the time you determine that an amendment is necessary, the trial has already been delayed. Then, you have to resubmit to the FDA, retrain your sites, and restart recruitment. “We need a way to design smarter protocols utilizing existing real world data that help in setting meaningful, practical inclusion and exclusion criteria,” Varghese Presti says.
In the FDA Guidance on Conduct of Clinical Trials of Medical Products during COVID-19 Pandemic it says, “… if planned on-site monitoring visits are no longer possible, sponsors should consider optimizing the use of central and remote monitoring programs to maintain oversight of clinical sites.” In the Q&A section of that guidance it also says, “If the technology is available, electronic methods of obtaining informed consent should be considered [i.e., e-consent].” Varghese Presti notes that, currently, those people who have or even think they have COVID-19 are encouraged to use tele-health services, a technology that is a big part of decentralized clinical trials. This is a good example of how a technology’s acceptance in a general healthcare setting can translate to increased adoption in the world of clinical trials. “I know the industry can be slow to adopt new technologies, and emerging trial methods. There’s a lot on the line, and sometimes it feels safer to go with what you know,” she says. “And I understand that there are some unknowns associated with anything new. But the only way we’re going to get through those unknowns is through more experience, and an appetite to try alternatives. I feel very optimistic that we’ll see a move to more decentralized trial methods powered by associated data and technologies in the next 12 to 18 months.”