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Applied Clinical Trials October 2021

New support models range from flexible software platforms, IROs, and DROs.

The Evolution of Site Selection

Medical records and interoperability are major issues in countries around the world. Sometimes departments in the same hospital exchange data incorrectly. Sometimes hospitals in the same country exchange data incorrectly. So, expecting international interoperability seems like a dream to many. But that is what we have achieved as a patient-led start up. For the first time, patients using Andaman7 are collecting their health records from both US and EU-based hospitals, at the same time, in the same software and with them in total control. Health data is normalized in their personal health record (PHR) meaning several exchange protocols, formats and interfaces are used to grab the data and store it in a uniform manner inside their smartphones. Storage of the data in a smartphone is key–not only does the patient have instant access to their data but it is more secure than cloud-based systems and under the patient’s total control. For the patients themselves this represents a huge leap forward in health data empowerment.

Andaman7 were encouraged by the patients’ positive feedback: “Navigating the medical system can be a stressful experience over and above the stress related to your own medical condition. It has been a challenge to keep track of accurate and up-to-date health data which has been scattered across several hospitals, and–in the case of my wife and me–across several countries. With the Andaman7 app, my wife and I were able to gather our health data from hospitals in the US and Belgium and manage it in one app in an organized and intuitive way. It feels right to be in charge of our data to ensure a smooth transition of our medical records from the US to Belgium. In addition, we can share our health records with each other and with our doctors if needed. It can only be hoped this becomes a common option.”

The next step, with patient consent, is to send data back to the hospitals–something Andaman7 is ready for. This innovation has far-reaching implications for the collection of real-world data (RWD) and the forming of real-world evidence (RWE). Andaman7 uses FHIR for inbound and outbound health data exchanges (in addition to other, de facto standards). Internally, they also use a very innovative liquid data model and ‘no protocol API,’ and fully support LOINC and SNOMED for high quality structured data. Properly used, RWD could enable us to reach one of the holy grails of medicine–the right treatment, for the right patient, at the right time.

Empowered international patient data access also has implications for tackling global health inequities. Africa bears the world’s greatest disease incidence and has significant healthcare shortages. Yet it has emerged as a new breeding ground for innovative digital health solutions. Our work with African Sustainable Development Advisors (Afrisda, Inc.) leads us to believe Africa can ‘skip one’ in health digitalization. The framework is already in place–large parts of the continent skipped the landline telecommunication stage and went straight to mobile. Now, there is an opportunity to avoid the step of disjointed, physical healthcare and instead embrace teleconsultations, electronic health records (EHRs) and patient empowerment platforms (PEPs). This could benefit local populations and increase RWD and RWE from diverse populations for global therapy developments. However, to truly seize this opportunity patients must be involved in every stage–from development and process to information access and solutions.

The recent controversy in the UK over the GP Data for Planning and Research program shows what happens when patients do not feel informed about how their data will be used. The initial launch was delayed following a public backlash over a lack of patient involvement and awareness. Now, it has been announced the program will not go ahead until key steps are met. Crucially, they include patient ability to opt out and back in and a trusted research environment. However, it is still only focusing on national interoperability.

To truly seize the opportunities of a global health data revolution we must embrace patient empowerment. International interoperability is a huge step forward to achieving that.

Articles

Embracing patient empowerment in data collection can lead to new standard of care.

Interoperability Cracked as Patients Collect Health Records from Hospitals

Today’s headlines in clinical development tout the potential of decentralized trials, with some even going so far as to predict that trials of the future will bypass sites through a combination of centralized review, technology, and just-in-time clinical resources. To the contrary, keeping the site at the center of clinical research, even when taking a decentralized approach, is crucial for success and health outcomes.

Clinical trial designs today span a wide continuum, ranging from 100% site-based trials, where all interactions with study participants occur at the site, to 100% decentralized trials, where all interactions are remote and leverage wearable technologies supplemented by occasional visits by trial nurses to the participants’ homes. The latter are often referred to as “siteless” trials.

However, a large majority are a hybrid of the two. This is true even as decentralization, accelerated by the COVID-19 pandemic, jumped to a 77% CAGR between the second halves of 2019 and 2020, according to data from more than 1,000 trials.

Despite our extensive involvement in decentralized clinical trials (DCTs), we agree that “siteless” trials are not optimal. The term itself is counterintuitive. The principal investigator’s site, together with trial coordinators, should remain a key part of the trial ecosystem, whether the trial leverages a single site or a network of coordinated sites, local pharmacies, community clinics, and home health aides supported by wearable devices and platform solutions. Technology simply cannot replace people.

Recent industry experience offers a relevant analogy. Between 2005 and 2015, many pharmaceutical companies rapidly adopted salesforce automation tools for their sales representatives while cutting sales jobs at the same time. From its height at 101,000 sales reps in 2005, the number of reps in the US market dipped to 76,000 by 2010 and hit its lowest level of just 66,000 in 2012. Accenture research showed that one in four pharmaceutical sales rep interactions was replaced by digital alternatives, but it did not achieve the intended effect of improved profitability. The strategy backfired and sales dipped. Now, there are more than 100,000 pharma sales reps in the US, according to various estimates, and overall revenues have been setting records year over year. The ship has righted itself.

Today, we are on the doorstep of a similar technology revolution, largely accelerated by COVID-19 when clinical researchers had no choice but to leverage innovative digital technologies to continue their work. Now, the excitement around technology’s potential is soaring again. The innovative technologies enabling remote or decentralized trials have the potential to dramatically reduce the burden for patient participation in research and for sites who manage studies. Recent data backs this claim, with at least half of the respondents to a recent Association of Clinical Research Professionals’ (ACRP) survey anticipate ‘strong’ use of eConsent (63%), eSource (56%), remote monitoring (55%), and wearables (50%) post pandemic.

Industrywide, there is confusion over terms like “virtual,” “remote,” and “siteless” trials; hybrid trials; and even the DCT concept itself. On the one hand, the Society for Clinical Research Sites (SCRS), in a December 2020 white paper defined its subject thus: “For the purposes of this survey, ‘decentralized or virtual’ referred to studies that are fully virtual, meaning that all study visits are remote.”

 On the other hand, even a cursory review of current literature on DCTs will demonstrate phrases like “decentralized or hybrid,” blurring the distinction between trials with or without patient site visits.

The DCT concept traces back to the 2018 Clinical Trials Transformation Initiative (CTTI) white paper that specifies that “DCTs can be conducted as 100% decentralized or as a hybrid study in which the DCT offers the additional flexibility of incorporating both in-person visits and virtual visits into the study as appropriate.”

 Although the intent, was to standardize terminologies, this definition proposes that “decentralized” and “hybrid” are synonymous.

There is also some evidence of the impact of the COVID-19 pandemic changing perspectives on “siteless” or fully virtual trials, and hybrid DCTs. A July 2020 SCRS survey found that a mere 3% of clinicians “had participated in a completely virtual trial, where all visits are conducted remotely.”

 But the December 2020 SCRS white paper, based on a May-to-July survey, found that use of “the fully virtual approach” had risen to 15.46%. More recent data found that 22% of respondents conducted “siteless” trials pre-pandemic; 17% had done so during the pandemic “but not because of it,” and an additional 12% had done so “because of COVID-19.”

The clinical trial lexicon will continue to evolve, but “siteless” should not receive a dictionary reference.

Rather than a “siteless” trial, the better approach is to build fit-for-purpose clinical research with a next-generation site at its center. Some trials might be, in fact, wholly decentralized, but even those should incorporate a site whose role may be a different iteration of what a traditional site looks like today. The best-performing trials will continue to have human interactions between physicians and patients. They will not be without sites but, rather, be technology-enabled to reduce burdens and improve efficiency. That is what well-designed technology should do, for both patients and for trial administrators.

Among other benefits, DCTs promise to 1) improve the recruitment and retention of trial participants and 2) increase diversity in trial populations. Given that only seven of 100 enrolled patients complete trials

, ensuring patient retention through all means is vital to trial execution and research efficiency. Interactions with trial physicians, care coordinators, and operational staff are vital to these goals.

People are foundational to clinical research, and the physician/patient relationship is the building block for long-term participation in a trial. It also builds trust, something that is especially critical today as public confidence among minority communities has eroded dramatically since the start of the pandemic. Patients develop close relationships with their study coordinators, who spend time engaging on a very personal level and deliver tender care. Coordinators and site staff give hugs, call patients by their first names, and nurture the relationship. In fact, this is the number one determinant of a patient’s completion of a trial. A “siteless” experience takes this away.

DCT technology should assist site administrators in fostering a trusted patient relationship, while at the same time provide improvements in data quality, data collection, study startup speed, informed consent, regulatory compliance, and all the other goals of a well-run trial. In the aforementioned 2021 Avoca survey, respondents report the two most substantial benefits of DCT technologies are: retention of study participants (with a mean score of 4.2 on a 1-5 scale); and diversity of study participants (3.9). Technology along with real-life patient engagement are the one-two punch to overcoming two of our greatest trial obstacles.

Besides the obvious obstacle to better patient recruitment and retention of travel to and from trial sites, patients can also suffer from limitations in handling modern technologies, ranging from lack of familiarity with smartphones to poor WiFi connections in their homes. In these cases, site-driven, hands-on guidance is paramount to the success of a DCT–and is another instance where the personal touch provided by a trial site is important.

Another aspect of patient retention in clinical trials is the health of the patients themselves. Rochester Clinical has had direct experience with assisting trial participants in getting necessary (in some cases, lifesaving) medical attention to patients that was unrelated to the trial itself. Some of this diagnosis was captured in the initial intake of the patient, where gentle probing helped get closer to the root of illness or personal insights on the patient’s health. In other cases, trial managers uncovered new health problems that cropped up during the trial because of close monitoring. Maybe some of these cases would have been recognized even with a “siteless” trial leveraging wearable technology; maybe not.

While technology can make the process of getting patients signed up for a trial easier, thanks to eSource, eConsent, and remote monitoring tools, there’s a misconception that it reduces the need for a site and its people. On the contrary, these new technologies open the door for new expertise, including more technology support but do not change the fact that there needs to be a centralized location for research and the back-end aspects of a well-executed trial.

The life sciences industry is having the wrong conversation about DCTs. Rather than talking about how DCT technology can replace sites, the conversation should shift to how to better support sites with technology. Technology companies and site managers should not be at odds with each other. Instead, they should be collaborators in providing the best patient experience and enabling successful trials.

, “Why Decentralized Trials are the Way of the Future,” by Fan Gao, Maurice Solomon, Arnab Roy, and William Chaplain (April 5, 2021).

Association of Clinical Research Professionals, 

, “Delving into eConsent: An Industry Survey,” (January 14, 2020) by Neetu Pundir; Mika Lindroos; Jenna McDonnell; Bill Byrom; Spencer Egan.

“Patient Centricity and Virtualizing Technologies in a COVID-19 World.”

Clinical Trials Transformation Initiative (CTTI), “CTTI Recommendations: Decentralized Clinical Trials (September 2018).

Society of Clinical Research Sites, “Impact Assessment of Decentralized Clinical Trials (DCT) Awareness in the Clinical Research Industry,” (2018).

WCG Avoca Group, “2020 State of the Industry Report” (June 2021).

Advarra Report, “Retention in Clinical Trials: Keeping Patients on Protocols,” (March 23, 2021).

Has technology taken the industry too far?

Sites Still Necessary for Decentralized Trials

means examining a specimen where it is naturally found, or where an event has occurred. These days, in situ could also define the preferred spot for a clinical trial.

Whether it was recognition, for a very long time pre-pandemic, that industry needed new ways to recruit and retain patients, or the success realized last year during the global SARS-CoV-2 vaccine trials, when pharma said we have no choice but to adopt 

–or both reasons–the clinical trial industry is doing a 180, site-selection speaking.

 is in; it guarantees real world evidence because in situ naturally leads to where patients live, are treated, and immortalized, to whatever extent, via their health system’s EHR and other data sources.

What’s remarkable here is how varied are the business models that have evolved to find sites and patients. The sources are extensive–pharmacies, patients’ homes, community hospitals, physicians’ offices. Further, the attempt to include people who are not white, male or of comfortable means, seems real.

What is not varied, said those interviewed, is the goal–consistently but speedily finding and enrolling the right patients, and retaining them in the trial. However, discovering whether the clinical trial services industry is successful with these strategies so far has yet to show up in a peer-reviewed study. Anecdotally, it appears so.

Labeling the clinical trials support industry as ‘niche’ works. Most rely on other niche businesses to help fill a software or service gap if it lacks what a client wants. Elligo Health Research, an IRO, and Syneos Health, a CRO, have a four-year collaboration. Syneos has the clinical trial networks; Elligo has access to Cerner and other EHR systems, said Maria Fotiu, executive vice president, decentralized solutions, Syneos Health.

Healthcare, said Keith Fern, vice president, corporate development, Elligo, has become a heterogenous business. “Partnering with different companies with access to patients in a variety of healthcare settings is very important to [the Elligo] model.” The sophisticated protocols, the move toward personalized medicine, have made eligible patients harder to find, he said via e-mail. Its patient network, he said, surpasses the 100-million mark.

The pandemic’s effect on ongoing and new studies was unprecedented, said Suzanne Caruso, SVP, clinical solutions, insights and analytics, WCG, in a statement. “It led to an environment unlike any we have seen previously. With the increased competition for patients due to the number of new trials, and the struggle hospitals are having finding the staff and time to run trials, the speed of recruitment has slowed significantly.”

In February, Circuit Clinical and LabCorp announced its collaboration. LabCorp, which is also an investor, said Irfan Khan, Circuit’s CEO and founder, allows Circuit to access LabCorp’s network of healthcare systems and centers.

Almost every company interviewed for this story has received private equity support. Trial-support investment, said a consultant, is a safer bet because no risk is involved.

Other trial-support businesses, like Curebase and Reify Health, have designed cloud-based platforms with the primary intent to speed up the site selection, patient enrollment processes, and if the client desires, help with certain elements of the trial itself, like specimen collection. They are neither CRO nor IRO–Reify’s co-founder Ralph Passarella said Reify isn’t interested in labels, but clearly the company is in the trial-support business with its StudyTeam patient recruitment and enrollment technology platform, and its Care Access decentralized research organization that brings clinical trial infrastructure directly to patients, healthcare providers, and communities.

The speculation as to why this find-your-niche trend developed is multi-pronged.

Craig Lipset, founder, Clinical Innovation Partners, told a story in response to the why question.

He was attending the 2020 Summit for Clinical Ops Executives—pre-COVID—when he saw a friend in a hallway. The friend worked at a top five pharma. What’s going on?, Lipset asked. Well, says the friend, we are pulling back from the CROs; we have assembled 100 trial site pros and data analysts. A few minutes later, Lipset met another friend, who worked at another top five company. He asked the same question and received the same answer.

“Before COVID, most [large pharma] had already pulled back site selection in-house,” Lipset said, including those involved in the COVID-19 vaccine trials. It was not a question of saving money, at least immediately, but the need to show that yes, we can find the right sites and assess our own data.

Will more pharma follow? “They tend to move in packs,” he said. “A good idea tends to move quickly.”

Two questions to ponder: Is this new model sustainable? Or will this model, borne out of pandemic-response necessity, revert due to atrophy? Without a concerted, dedicated commitment, to maintain flexibility in trial site selection and enrollment, Lipset said, atrophy will prevail.

As to the other plausible reasons this find-your-niche industry developed:

In the mid-2010s, various studies found that more than half of new investigators would not partake again.

 But the need for more sites, as more trials were going global, was approaching the critical point.

 The amount of time to run a trial, soup to nuts, was getting longer.

It’s hard to speak to an overall trend, said Passarella, noting that the integrated research industry came to be between 2015 and 2019. While CROs and sponsors partnered for decades for the patient identification and recruitment processes, Passarella said people began to realize that to improve study outcomes they had “to really innovate at the site level.”

The trend of the “last half decade is kind of a push in that direction,” he said.

Lipset also had another suggestion. Asking physicians to become investigators is a tall order, just consider the dropout rate of first-time investigators. Without the proper structure, running a trial while running a practice wasn’t worth the physician’s investment, from every point of view. But to have trained trial professionals drop into a “setting and support doctors as investigators,” that provides that needed structure.

And that is where IROs came into being, Lipset said. IROs offer healthcare sites something more sustainable and scalable. Khan calls it the ecosystem of running a trial—from administrative help to training staff on technology to offering data assessment.

Curebase designed software to make trial participation easier for the patient. “Instead of driving to one site to collect vitals, they can see a PCP in town, they can get a blood draw with a mobile phlebotomist at home, an x-ray at a local imaging center, and complete patient surveys on their phone,” said Tom Lemberg, founder and CEO of Curebase via correspondence. Patients have even gotten swabbed in pop-up drive-through centers.

The tech involved includes mobile provider calendars and workflows, along with the healthcare’s own EHR system. According to the Curebase website, its technology propelled the start of a COVID trial in two weeks. It used drive-through testing centers, where patients gave consent and provided samples. The sponsor used its own technology to do the testing.

Jennifer Byrne, CEO of Javara, said its goal is to run trials as a clinical care option. Say a patient learns she has diabetes, Byrne gave as an example. “Her doctor says, ‘here is your treatment regimen. But, if you are interested, we can offer you more. Our healthcare system is running a trial on diabetes that could help you. You can learn more about your disease.’” The patient now becomes a healthcare consumer, and clinical trials become an option with more patient touch points for the patient and trial staff.

“WCG works with all types of investigational sites, including academic centers, integrated health systems, large site networks and independent sites, as well as part-time investigators,” said Jill Johnston, president, WCG Clinical, study planning and site optimization, in a statement. WCG has agreements with over 3,300 institutions, in addition to more than 5,000 biopharma and CRO clients.

With these extensive connections, Caruso observes there’s no one-size-fits-all approach for clinical trial recruitment. “It’s not only that the diseases are so different, so too are the specific patient segments.” She noted that these include people with physical limitations or those struggling with day-to-day issues. If the needs of these patient segments aren’t recognized early and addressed at each site, meeting recruitment goals may not happen.

Very often, said Passarella, recruitment will be hospital dependent. A heat map of a particular disease presence might indicate a heavy concentration in a large city, but it also might pick up a smaller hospital or center that is three hours away that is a better fit for the study. “It matters which hospital or clinic you are talking to.”

Elligo’s Fern described the process for finding patients for a possible migraine trial. The Elligo investigators “searched across disparate data sources, normalizing them for a clinical protocol.” The result: patient level data “that will allow the sponsor to identify highly likely participants for their trial.”

Circuit Clinical, which has a presence in 34 states, approaches mid-size, research-naïve healthcare centers, said Khan. These include the federally qualified health centers, which have large minority patient populations, Khan said. “It is our job to pull as much friction out of the process” as possible for healthcare administrators and physicians.

When it comes to training support, the Circuit ecosystem includes training the investigator’s staff on those technologies that Circuit will use to run the trial.

Oftentimes, said those interviewed, smaller providers do not have the up-to-date tech training needed to run a trial. Staff training is on the menu if staff wants it. “It depends on their appetite for engaging,” said Passarella.

Curebase offers virtual support, especially for research-naïve clinics. Principal investigators get help to oversee the study, while virtual research coordinators help the patients with e-consent, scheduling visits, and so on. The software also automates other processes like payments and data entry, Lemberg said.

 in their own homes; vans take trial personnel to patients’ homes for sample taking, collection, medical checks, and so on. Reify works with research-naïve institutions as well, these healthcare providers might not have the up-to-date software, so staff needs to learn how to use them. “When we go to certain settings that don’t have cutting edge technology, part of what we do is bring it in and make it accessible to staff.”

Byrne addressed another important point. Even though the investigators can unload administrative and clerical tasks, the physician still is responsible for the medical and clinical decisions regarding the patient.

Since 2018, said Byrne, the company has built partnerships with major healthcare organizations, like Atrium Wake Forest Baptist Health, allowing the company a patient base of more than 6 million. Collaboration, she said, is key from a healthcare standpoint.

Khan said Circuit’s diversity numbers are two times higher than the average seen in clinical trials, according to figures gathered between May 2019 through May 2021. “This is not because we targeted certain ethnicities—it is because we operate within healthcare and, therefore, see the populations that represent all of the US.”

Circuit also offers its clients a real-time method to improve if and where it needs to. The Trial Journey platform lets patients go online, discuss their experiences, and rank their treatments and physician encounters, from a scale of 1 to 5. The platform is also open to doctors and the healthcare system itself.

At first, he said, the physicians and healthcare systems were “worried that [patients] will trash them. On Trial Journey, the average rank is 4.2. How do the physicians or health systems react when they see less than a 5? They work to improve it, Khan said.

Many of the IROs use existing health system EMRs, to find patients, but, to be kind, the process is incomplete.

“EMR is the best tool we have, but only 50% of it is useful,” said Khan. “It doesn’t have data that helps determine if a patient is right for a trial. People need to understand how limiting it is.”

There are different approaches to how existing EMR data are used. Elligo, for example, extracts the data needed, then transforms it to become standardized. “We build it as we go,” said Fern.

Byrne said Javara hasn’t come up with a universal language; her team works with the client to standardize its EHR language. “We can pinpoint and ID patients through large data sets.” Which Javara did in a COVID vaccine trial. Of the 100-plus sites, Javara performed in the top 5%. While artificial intelligence can help enhance protocol matching tools, pinpointing the right patient takes a human touch. “It is still not widely appreciated that tech is an enabler.” These tech tools are just that: they supplement the human experience.

Taking into account the in situ trial support options and the IRO/DRO models, is there evidence that the industry is showing demonstrable, trial performance results?

When asked that question, Lipset looked down at his desk, made some rustling noises, and then held up a piece of paper to the Zoom screen: He had drawn a large circle with a line through it. A line of anecdotes, he said, is not evidence. “I haven’t seen this taken on by anybody.

Corneli A, Pierre C, Hinkley T, et al. One and done: Reasons principal investigators conduct only one FDA-regulated drug trial. Cornell Contemporary Clinical Trials Communications. 2017; 6:pp 31

Craig Morgan. 10 Tips for Selecting High Performing Clinical Sites. Oracle Health Sciences. Health Sciences, Study Startup . September 3, 2019.

Clinical stage biopharma InterveXion Therapeutics is developing novel products for the treatment of addiction disorders. In this 

, the outline of how the company used Emergency Medical Services (EMS) data to identify sites for a Phase II clinical trial. In this Q&A, InterveXion CEO Keith Ward and Andrew Schafer, vice president of strategy for Biospatial discuss the details of this study.

Applied Clinical Trials: This is an interesting case study. How did the three

companies—InterveXion, Syneos Health, and Biospatial—come together?

 InterveXion had contracted with Syneos Health to support our Phase II study for acute methamphetamine intoxication (Meth-OD) and we thought site selection might be especially difficult for this trial. Syneos Health was already working with Biospatial, and they suggested the Biospatial data might be a good way to identify sites. We looked into it, and it fit our needs, the data were coming in near real-time and that was important for us because a lot of the epidemiology data we could find were out of date and were not compiled nationally using similar collection methods.

 All three companies working together was a great experience. Biospatial was able to help InterveXion, not only identify high-prevalence sites, but we were able to provide demographic information on potential patient pools to help ensure a diverse patient population for the study.

 has covered the clinical development industry for a long time, and we have never heard of using EMS data. Where does it come from and how is it being used?

 As we continue to talk with pharmaceutical companies, CROs, patient recruitment companies, hospitals, and substance abuse centers, we hear the same thing: “I had no idea these data existed.” Biospatial has spent years signing data use agreements with EMS offices at the state level, which allows us to access EMS ePCR (electronic Patient Care Report) data. Think of our data products as EMR-like for an ambulance transport and it comes to us in near real-time, making it especially valuable for studies where patient consent needs to occur in a short timeframe—for example, with stroke, cardiovascular events or trauma—or where healthcare trends change quickly, such as drug use or overdose, COVID-19 infections or other infectious diseases.

We had the same thoughts as well. In our case, we were doing our first study in an emergency medicine setting, so we were delighted to have such an on-target dataset. After diving into the platform, we found it easy to navigate and could use our inclusion/exclusion criteria to help refine our site selection search. The data elements contained in the data set were quite robust.

ACT: How was the ePCR data used specifically for this clinical study?

 As Keith mentioned, we were able to take the study characteristics and the inclusion/exclusion criteria and develop a search of which hospitals have access to the patient population. After that list of approximately 200 was created, we overlayed patient demographic information to help provide a diverse set of sites for InterveXion to consider.

ACT: What were the results and any next steps?

 We’re still a little early to have hard enrollment results as some of the sites are in the process of being initiated. In our early going, however, the patient flow we are seeing definitely matches our expectations based on the Biospatial data. So far, we are happy with the process and the outcomes as we continue to track potential patient volume at each site. We are also currently considering using Biospatial’s ability to notify the project manager and site coordinators, via text and email, as to when a potential patient has entered the hospital.

InterveXion CEO Keith Ward and Andrew Schafer, vice president of strategy for Biospatial discuss the details of a study which utilizes EMS data to identify sites for a Phase II clinical trial.

Utilization of EMS Data in Site Selection

This month’s phrase to watch: “warm and ready” or “ever-warm.” Clearly lacking in business-speak, I found this term repeated at least three times in the past week, so for me, that speaks to a trend. Two instances were in regard to clinical trials sites, and one in regard to vaccine and therapeutics
production capabilities.

Warm and ready is a comforting term. Of course, because its opposite is cold and unprepared, or frigid and inaccessible. In the world of clinical trials, it is coming to the fore in response to future pandemic readiness. That is, in order for sites to be able to pivot quickly to clinical trials in the face of a crisis, those sites would need to be up-to-speed with capabilities and scale. What one person described as a “ready-made pandemic clinical trial network.”

That description came during the Reagan Udall Foundation’s Public 

 titled COVID-19 Lessons Learned: Clinical Evaluation of Therapeutics. There were three panels, all of them interrelated, however, the first recommendation from this panel was stated: Identify and leverage existing clinical trial network infrastructure (incl. NIH-funded networks, nonprofit & industry/CRO sites networks) and public-private partnerships (e.g., ACTIV) to maintain a ‘warm base’ for public health emergencies (PHEs) and that can be deployed against high priority unmet needs.” Out of this need to increase the number of sites, additional recommendations such as engaging more community-based institutions and networks, increasing diverse populations in clinical trials, and best practices for increasing participations from those communities.

These are not new ideas. Warm and ready sites, maybe, but embedding trials in the healthcare setting? Increasing diverse trial participation at the site level? No. The problem is how to keep sites monetized at a warm and ready level. The panel recommended a blend of industry and government monies, but that’s for another day. This day is to review our feature article on page 10 and discover that there are a number of new industry business models that are working to get more diverse populations, closer to the point of care into clinical trials.

 doesn’t use the term warm and ready, but it succinctly outlines what the Reagan Udall workshop brought to light: “the need to to support the development and long-term sustainability of an infrastructure that unites clinical research with clinical care.”

 is Editor-in-Chief of Applied Clinical Trials. She can be reached at 

Industry-wide unity paves path for preparedness.

“Warm and Ready” Clinical Trial Sites

New methods and policies necessitated by the global pandemic are slated to become permanent fixtures in FDA enforcement and regulatory programs. Over the last 18 months, FDA officials have tested and adopted a range of procedures to overcome restrictions on visiting facilities in person to evaluate pharmaceutical production and clinical testing operations. Many of these alternative compliance methods now are being retained even with the end of the current health emergency in sight. FDA has devised ways to monitor industry operations and to collaborate more routinely with foreign regulatory authorities to assess facilities and products, efforts important for ensuring continued patient access to needed therapies, vaccines and medical diagnostics.

With some 8000 site inspections of drug manufacturing facilities postponed during the height of the pandemic in 2020, FDA regulatory officials look to retain key operational changes as they work to catch up on their vast oversight obligations. During the hiatus in facility inspections, FDA’s Office of Regional Affairs (ORA) looked to evaluate the inspection status of a facility largely through the review of historical inspection records from the site plus reports conducted by reliable regulatory authorities. Now, even with the return to more normal inspections for domestic manufacturing facilities, ORA will continue to pre-announce domestic inspections “for the foreseeable future,” explained Alonza Cruse, director of the Office of Pharmaceutical Quality Operations in ORA. The aim is to avoid having inspectors turn up at a facility that is not fully operational, has altered hours, or has limited staff available.

While ORA aims to send inspectors to more facilities in the U.S., the agency will continue to limit foreign inspections to those deemed “mission critical,” Cruse noted at the PDA/FDA joint regulatory conference in September 2021. FDA also will utilize the tools expanded during the pandemic to assess product safety and quality more efficiently. This includes more extensive analytical testing and sampling of drugs, particularly at U.S. borders with an eye to denying entry to products with quality problems. In addition, FDA continues to request documents from facilities to review compliance histories off site and to conduct video livestreaming “visits” to plants. The agency updated information on how it was managing and revising its inspection program, initially in a Q&A guidance issued in August 2020 and expanded extensively through the following months through May 2021.

A main initiative has involved greater use of Remote Interactive Evaluations (RIEs) of drug manufacturing, compounding and bioresearch monitoring facilities, a process that FDA compliance offices plan to continue, as outlined in guidance issued in April 2021.

 Cruse highlighted FDA’s process and policies for how the agency will notify, conduct and conclude RIEs and the impact on regulatory timeframes. And Donald Ashley, director of CDER’s Office of Compliance (OC), reported at the PDA/FDA conference that the agency completed over 50 REIs for BIMO programs and 8 for outsourcing facilities since Oct. 1 2020, as part of its effort to utilize all available oversight tools.

Even with reduced onsite inspections, manufacturers may gain regulatory flexibility in expanding or altering production or updating manufacturing methods by gaining FDA recognition for having high quality operations as described in its Quality Management Maturity (QMM) program. FDA has encouraged biopharma companies to establish QMM systems able to measure outcomes that reflect control of problems that lead to complaints, shortages and adverse events, noted Patrizia Cavazzoni, director of the Center for Drug Evaluation & Research (CDER), at the PDA/FDA conference. Now manufacturers stand to benefit from advancing QMM in gaining greater flexibility in scheduling facility inspections and for making post-approval changes in production and product characteristics.

Although industry has challenged earlier CDER efforts to devise measures and “report cards” on manufacturing operations, the pandemic has magnified the need to focus on risk management and to expand efforts by manufacturers to ensure the operation of more mature quality systems, Cavazzoni explained. A critical issue during the public health emergency has been to overcome shortages in medical products due to supply chain constraints and drug quality problems. To facilitate the development and timely production of new COVID-19 therapeutics, CDER expanded the data and analytics employed by its drug shortages program to assess risks of supply disruptions earlier and more effectively.

In the wake of the pandemic, which has heightened the importance of reliable, quality production of medical products, FDA is looking to further support and encourage QMM initiatives at firms able to demonstrate having consistent, reliable and robust business processes to achieve quality objectives, added Ashley Boam, director of CDER’s Office of Policy for Pharmaceutical Quality. FDA is launching two pilot programs to test how QMM may be implemented by domestic drug product manufacturers and by foreign producers of APIs. The pressures created by the pandemic, Boam observed, have supported alternative approaches for plant inspections, streamlined assessment of proposals to add or change manufacturing facilities and suppliers, and increased global collaboration and harmonization in these areas.

https://www.fda.gov/media/141312/download

https://www.fda.gov/regulatory-information/search-fda-guidance-documents/remote-interactive-evaluations-drug-manufacturing-and-bioresearch-monitoring-facilities-during-covid

New methods and policies necessitated by the global pandemic are slated to become permanent fixtures in FDA enforcement and regulatory programs.

Pandemic Alters FDA Inspections, Quality Oversight

Veeva Systems has announced the Veeva Digital Trials Platform, a solution aiming to advance clinical trial execution by providing a complete and connected technology ecosystem that spans patients, research sites, and trial sponsors. The Veeva Digital Trials Platform is available now for early adopters.

The product offering includes the following core solutions: Veeva Vault Clinical Suite, Veeva SiteVault Free, and MyVeeva for Patients.

More on Veeva’s Digital Trials Platform

Veeva Announces Digital Trials Platform

BEKHealth, a Clinical Research Platform company, announced the introduction of Galileo, a trial and research network level feasibility solution. Galileo enables research networks to evaluate clinical trial protocols in a standardized way across all locations.

Galileo is prebuilt with a clinical trial library of 24 million medical terms relevant to researchers. The platform takes unstructured EMR data and translates it into language and clinical terminology used in protocols, resulting in the capture of a larger pool of eligible patients. The platform also enables researchers to obtain deeper geographic and demographic information about the patient population across all practice groups and satellite locations from a centralized location.

BEKHealth Introduces Galileo

Worldwide Clinical Trials, Inc. has announced a partnership with The Christ Hospital Health Network, Cincinnati, Ohio, through Worldwide’s Site Alliance Collaboration, which will increase access to oncology clinical trials and bring new innovative cancer treatments to patients.

Through this new alliance, Worldwide Clinical Trials and The Christ Hospital will focus on addressing time-limiting hurdles aiming to reduce the activation period to less than three months on average.

Worldwide Clinical Trials and The Christ Hospital Partnership Partner in Oncology Treatments

endpoint Clinical and Berlinger & Co. AG have announced their partnership to provide complete end to end visibility of the entire temperature history of an Investigational Medicinal Product (IMP). 

Our organizations understand the risks of managing temperature-controlled IMP, and therefore, we focused on designing a solution that aims to help reduce risk and eliminate the core issues. Such problems include limited transparency and missing information, the lack of immediate centralized visibility, time-consuming excursion management and slow decision making, time-consuming data consolidation for audits, wastage of drugs, and patient rescheduling or lost.

More on endpoint and Berlinger’s partnership

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