Lisa Henderson

As of Sept. 1, 2020, ClinicalTrials.gov lists 284 clinical trials as suspended. Not all of those trials are suspended for COVID-19, some are holdovers on financial issues, R&D problems, etc. And while upwards of 1,200 trials were suspended at the peak, 

, 67% of healthcare experts plan to use decentralized clinical trials in the near future due to COVID-19. To address the walk back to clinical trials, 

 is planning a virtual event mid-November that will highlight the successes that clinical trials experienced during this time, and open dialogue for the continued innovation within the industry.

Solutions to enhance patient participation

According to press releases and reports of the time, solutions to ensure that participants could continue to stay in clinical trials safely were on the rise. In 

, we noted that the “newer methods” of patient-centric clinical trials trend toward home study visits, telemedicine, and remote patient monitoring, have been happening over the past few years, but uptake was slow. We know the numbers for low patient enrollment: Tufts Center for the Study of Drug Development found no significant differences in the mean number of patients enrolled per site or by therapeutic area in 2019 versus 2012. The study also showed that late-development studies had a higher average drop-out rate in 2019 (19.1%) than in 2012 (15.3%).

During the pandemic, service providers offering safe patient access and decentralized model enablement, found increased interest in their business. Darcy Forman, vice president of clinical operations for Science 37, a provider of virtual clinical trials, commented at the time, “We have been unbelievably busy with this pandemic as sponsors are wanting to transition to a virtual model. It’s really accelerating, and they are finally pushing through their hesitancy.” 

 to implement their cardiac safety, respiratory, and imaging solutions to capture data from participants in decentralized trials.

, Michelle Longmire, MD, co-founder and CEO of Medable, reported increased business across the board. She said, “…everyone from existing partners to totally new partners were calling us around the clock looking for help. We created a workstream for rapid validation and qualification of individual studies, as well as partners, so that we could deploy technology quickly. What was never thought possible before was suddenly turned around in a matter of days to a week. We literally turned months-long timelines into days—and this was key, as was the ability to deploy technologies with necessary processes around patient data privacy, security, and data quality.”

That sense of urgency and can-do attitude is what our event will highlight. We are currently recruiting speakers to share their experiences in the following topic areas: the patient participation piece; the New Clinical Trial and how sites and sponsors transitioned to address the barriers of COVID; and Ensuring Data Quality and eSource Implementation—again another “old is new again” strategy to gain forward momentum in the clinical trial discourse. We look forward to sharing your ideas during this forum.

Articles

A look into the future based off what we've learned about trials during the pandemic.

Trial Innovation Beyond the COVID-19 Pandemic

 that interruptions of clinical trials due to COVID-19 have been on the decline since June, this 

, also from GlobalData, detailed the reasons behind trial disruption. The primary one, at 67.3%, was suspension of enrollment; delayed initiation of planned trials followed at 18.4%, and slow enrollment at 14.4%. Of the trials affected by the latter, 20.7% were due to the availability of sites and investigators.

The majority of disrupted trials were in Phase II, at 44.8%; Phase I, with 26.1%; Phase III, at 21.7%; and Phase IV, with 7.4%. By therapeutic area, oncology has the highest number of disrupted trials, with 33.3%, followed by CNS, at 16.1%, infectious disease (9.3%), gastrointestinal (9.1%), and respiratory (7.7%).

But, as the data showed, trials are coming back again. And that’s where the cracks in the traditional approach are being exposed. It is why so many articles and observations from experts in clinical trials were calling on the industry to adapt, learn, and change so the fundamental breakdowns in clinical trials can be addressed. You can peruse our online articles and blogs from the past four months for a clearer picture of the calls to action.

 we posted was from Gen Li, PhD, president and founder of clinical development analytical products and services provider Phesi. In this article, Li urges the industry to reexamine its delayed, suspended, or low-enrolling studies on a deeper level. Clearly, sites and investigators were unavailable during the early days of the pandemic in the Northeast and now again in the South. But what other factors existed besides COVID?

Li suggests that many trials are poorly designed from the outset, “so their execution is intrinsically flawed—and would be highly likely to fail or require rescue, even if COVID-19 had never happened.” Specifically, Li says that poorly executed site activation is one of the main drivers of slow patient enrollment. If sponsors now take a data-driven approach, by identifying high-performing sites or finding the most relevant CRO with a performance record in the indication under study, they could potentially avoid a trial destined for failure.

Another area of examination? Competition between studies and sites, which has significant impact on patient enrollment. Li uses the example of the number of recruiting sites in Crohn’s disease that increased in the three years before COVID-19, from under 2,000 to more than 9,000, and without acknowledgment of the limited patient population. This has led to poor country allocation and site selection. It leads to the reality that some of these programs will have to be terminated and reallocated to those with the best chance of succeeding.

Many have taken advantage of the processes and technologies to help overcome the limitations of trials compounded by the pandemic. We look forward to showcasing more success stories around these technologies as well as their acceptance by the global regulatory authorities to ensure trial continuation. But for long-term change, it will take a concerted effort by many to keep trials moving in an upward motion toward excellence.

While clinical trials are starting to make a return from COVID-19-related interruptions, cracks in their traditional operation are being exposed.

COVID Exposes the Cracks in Trial Problems

	In the world of clinical trials, many issues and observations have arisen because of COVID-19. At the top of that list, is the increased talk and implementation around decentralized or hybrid approaches for clinical trials. These approaches appear noticeably more conducive in supporting the challenges that the pandemic has brought to sites and patients. Whether it’s actual trial suspensions, or limited accessibility by monitors, plain fear of

 contracting the virus, or some combination of these or other challenges, it’s clear that COVID is fomenting change in the industry. You can read more about these initiatives, as well as results of investigative sites surveys in our June 

 of public and patients in April around their knowledge or experience of clinical trials in regard to COVID-19 that is notable for exactly that-the audience. This may be a time where, conceivably, more people have heard the term clinical trials regularly mentioned in media coverage. But the CISCRP survey found that awareness of clinical trials remains low, with 58% of respondents having not heard of a COVID-19 research study.

	“Interestingly, among the minority that had recently heard of a COVID-19 clinical research study in the recruitment phase, we learned that a higher proportion (40%) of Europeans are aware than Americans (34%),” said Annick de Bruin, director, research services, CISCRP, in a press release. “This contrasts with our larger baseline 2019 Perceptions & Insights Study where we found that North Americans are more likely to be aware of a current clinical trial in general than any other region. This may partially be due to the fact that the crisis evolved earlier in Europe.”

	In addition, the survey noted misconceptions about the clinical research development process persist. Most (60%) think a treatment or vaccine for the virus will be developed in less than one year. Once developed, the 

majority (64%) think it will be less than a year before people can start receiving it.

	What this, and other reports highlight, is the larger issue around health and/or scientific literacy among the general public, which is clearly lacking and at times, blatantly misguided. For example, while most in our industry understand the value of vaccines, our Washington Correspondent Jill Wechsler reports 

 about the growing anti-vax movement and other vaccination concerns inspired by the pandemic. 

 were hopeful that the pharmaceutical industry’s ability to rise to the challenges of the pandemic, showcasing the positives of scientific innovation, could well prove to be industry’s finest hour. But can that overcome the overall lack of health literacy?

Recent surveys of the public and patients concerning COVID-19 highlight the larger issue around health and/or scientific literacy among the general public.

A Crisis of Health and Scientific Literacy

	There’s been quite an overwhelming amount of industry-specific information regarding COVID-19 the last few weeks. It appears there are a number of patient registries from specific medical associations, as well as others such as the LabCorp/Ciox Health patient data registry. There are companies offering de-identified data to support clinical care or clinical research decisions, including Ancestry and Cerner. There are clinical trials

 service providers, including WCG and Bio-Optronics, offering internal benchmarking data on investigative sites, as well as investigative site survey data from Contiuum Clinical and Clinical SCORE. Consortiums have formed such as the COVID-19 Research Database, a secure repository of HIPAA-compliant, de-identified patient-level data sets, and EndPandemic National Data Consortium, with the goal of integrating data from all ongoing and future clinical studies to accelerate analysis on COVID-19 and SARS-CoV-2 research. 

, which as an aside lists even more websites that identify and track research on COVID therapies and vaccines-the many competing resources has led the NIH to form a broad public-private partnership to collaborate on prioritizing and coordinating research on COVID-19 drugs and vaccines. 

	And that’s where we are. When the dust settles we will have a bevy of COVID-19 clinical trials listing trackers, with patient recruitment matching capabilities, with a number of patient registries, and de-identified patient-level health data sets that don’t talk to each other? The industry has that now, it’s just not COVID-specific. On top of that, is the clear need for integrated real-world evidence to help with both clinical care response, as well as informing therapeutic intervention in real-time.

	Our Closing Thought op-ed contributors, Ülo Palm, MD, PhD, senior vice president, digital sciences for 

Allergan, and Iya Khalil, PhD, co-founder and CCO, GNS Healthcare, urge the use of AI to get to those more informed evidence and therapeutic decisions, not only in COVID, but moving forward as a whole in drug development. Co-founder and CEO Michelle Longmire, MD, of Medable, in our Q&A, envisions a way forward in drug development where decentralization of trials will lead to less expensive studies that can capture more long-term outcomes data, as well as increased participation, to boost innovation in therapies. 

	Clearly, we need change. Industry experts and observers have been saying that for years and many calling for disruption. Well, this is disruption. Is industry going to go back to its old ways, or will the pandemic result in lasting positive change?

With the bevy of coronavirus-specific information, databases and trackers, registries, and other tools out there at the moment, the challenge in store is integrating these resources to help in both clinical care response and informing drug intervention in real-time. 

Author | Lisa Henderson