As the cost of patient recruitment continues to rise, layered with the need for more diverse trial participants representative of the total population, it’s clear that a deeper level of patient experience that transcends the length and depth of a single study is essential to successful enrollment and retention. To fully engage research patients, we must meet them at their point of trusted care, unlike traditional methods of recruitment.

More than 72% of Americans say they would participate in a clinical trial if recommended by their doctor, but only 22% say a provider has ever talked to them about clinical research.

This is one of the driving forces behind the approach of an Integrated Research Organization (IRO) like Javara. Through partnerships with community-based healthcare organizations and the physicians who provide healthcare for patients, credibility and trustworthiness are established. Meeting patients where they are expands access to research, especially in underserved communities.

The IRO model embeds study teams within the physician’s practice, ensuring seamless care and data optimization. Compliant and trusted access to electronic health records (EHR) significantly decreases the time and cost to identify patients who likely meet study criteria and simultaneously ensures far fewer screen failures.

For healthcare organizations and physicians, contributing to population health initiatives is a key driver. As the cost of care escalates and physicians are held accountable for quality outcomes, clinical research can positively impact both. Significant improvements in quality and cost across some of the most expensive chronic conditions have manifested for healthcare organizations in value-based programs.

 In fact, research shows decreased mortality rates and improved adherence to trial related and non-trial related treatments long after trial participation ends.

Conducting research is a market differentiator, adding to the return on investment for healthcare organizations and physicians that conduct research. More than 70% of physicians report that research advances their practice with cutting-edge options and provides patients with options not readily available elsewhere.

Cultivating enough new physician investigators to support the nearly 261% increase in clinical trials over the last decade is no small 

The traditional model that relies heavily on seasoned investigators no longer meets the industry’s increasing needs.

Emerging investigators may be new to research, but as community physicians who have often practiced medicine for many years, they bring a wealth of knowledge and lived experience to the table. With support and mentorship, motivated physicians who desire to participate in research can significantly help bridge the gap created by the influx of new studies and the ever-increasing complexity of trials.

The heightened commitment in recent years to improve the research participant’s journey must continue. A satisfied patient is less likely to leave a trial midway through, an important factor when an average of $19,533 is spent to replace a single patient lost to non-

To gauge satisfaction, many organizations conduct occasional surveys after study participation.

Javara’s approach to patient experience is unique as patients are surveyed digitally at multiple key times throughout their participation. Their responses are immediately provided to site leadership and incorporated into process improvement plans to enhance patient experience.

Fostering repeat participation and advocacy

Meeting patients at the point of care enables them to truly see research as a care option. Patients learn they have more options to help themselves and the power to help others through clinical research. More than 95% of patients said adding clinical research significantly or somewhat improved their overall quality of 

It is through a 360° approach to ensuring the best possible experience for trial participants that our investigators become more gratified, sponsors get what they need in reliable and full data sets, and our own team becomes further empowered that what we do, in fact, makes a difference. All boats rise as we change the tides of patient engagement.

Research!America, 2013, See full resource 

James, Alycia R., and Costello, Mary. “Down with Silos”, Group Practice Journal October 2019 (p.36-40)

Selby, P. and Autier, P., “The impact of clinical research on health service outcomes”, Annals of Oncology, 2011 (22; vii5-vii9)

Hein A.W. van Onzenoort et al., “Participation in a clinical trial enhances adherence and persistence to treatment: A retrospective cohort study”, Hypertension

Nicoli-Carr, Valeria, “The True Cost of Patient Dropouts in Clinical Trials”, MDGroup Blog, October 1, 2020. See full resource 

Shen, Jane et al., “Clinicalresearch participation asacareoption: Driving patient experience and satisfaction”, PMG Research, 2015. See full resource 

Articles

A Closing Thought

Meeting patients at the point of care can increase trust and engagement.

Currency of Patient Engagement: Changing Tides

The National Center for Advancing Translational Sciences (NCATS), part of the National Institutes of Health (NIH), turns 10 this December. NCATS initiatives aim to reduce frustration and failure in the journey from bench to bedside. “From the time you work on a drug in a lab to the time you put it in a patient, how can you do this more efficiently and effectively?” asks Lili Portilla, NCATS director of strategic alliances.

One key goal of Portilla’s work is to ease passage across the so-called “valley of death,” in which an academic researcher develops a promising new molecule as a disease treatment, but then does not know how to test their invention, apply for FDA approval, or bring it to market once approval occurs. This is the kind of expertise that a biopharma might have; NCATS brings academics and pharma companies together.

Portilla notes increasing biopharma interest in treatment for rare diseases since NCATS began. This is research that often begins in academic labs and which pharma has historically overlooked as the patient base for a rare disease drug is usually small. But pharmas have become increasingly interested in the incentives offered by the Orphan Drug Act, Portilla says, which grants seven years of commercial exclusivity for any drug that treats a rare disease. The Orphan Drug Act has been on the books for almost 40 years, and the pace of approvals for rare disease drugs continues to increase.

 While some health policy observers say that in some cases biopharmas are creatively slicing data

 to generate ever more approvals for rare indications, rare disease research is likely to continue.

In response, NCATS has developed a program to spur rare disease research collaborations between pharma and academia. And since its inception, NCATS has helped biopharma and academic researchers investigate whether a drug that had failed in one context could be repurposed to treat another disease.

Beyond rising interest in rare diseases, Portilla observes that biopharma companies now prefer to collaborate with academic partners once a molecule is more of a sure bet for eventual FDA approval. “Fifteen or 20 years ago companies would just license things without a lot of data associated with them. That doesn’t happen anymore,” Portilla says.

In discussions with a wide range of industry leaders, 

 found that the current patterns of academic-pharma collaborations began somewhat as a marriage of convenience once NIH support for basic science research began to soften. This transactional foundation has led to continued breakthroughs in cell and gene therapy, along with new breakthroughs in immunotherapy, over the last decade and the use of real-world evidence within clinical trials may be on the horizon. IRB processes have become more centralized across sites too, and smaller biopharmas are increasingly getting into the game. Even so, some observers say that it’s still challenging to enroll in a clinical trial and that managing the inherent conflicts of interest between academic and biopharma missions remains critical.

Academic institutions once shied away from collaborations with researchers in biopharma companies, recalls Paul Nkansah, senior director for corporate partnerships at Johns Hopkins Technology Ventures.

“If you go back and look at academic institutions and their mission, they’re there to educate and provide a service to the community,” says Nkansah, who works to commercialize Johns Hopkins research and previously spent 14 years at Pfizer. “This idea of ‘let’s bring in a partner whose primary mission is actually to make profit’ was a very difficult thing for any academic institution to process,” Nkansah continues.

Eventually a pharma company might come to a university once it needed help in recruitment for a late-stage clinical trial, Nkansah says, but generally there was little interaction between the two parties.

This arms length approach changed after NIH support for basic science research began to flatten

 in the early 2000s, Nkansah says, following an unprecedented period in which the NIH budget doubled in just five years. The NIH budget flattening meant that multiple universities who had beefed up their grant-seeking activities during the budget doubling days were now competing for an ever-more fixed pie to conduct basic research, Nkansah recalls. This spurred a need to seek new funding for basic research from elsewhere.

Enter biopharma; Nkansah says that drug companies stepped in to fund basic science research once the NIH well began to dry up. A 2017 US Government Accountability Office report

 confirms that most of the molecules tested in clinical trials, and which biopharma companies commercialize if approved, originate in academic labs.

Besides the ability to fund research from the preclinical stage, and therefore have first dibs on commercializing any resulting treatments, Nkansah says that pharma leaders increasingly appreciate that much of the research into the biology of rare diseases, or how to address seemingly intractable neurological problems, is happening on campus. And academics who would like to see their work developed into real-world treatments are less wary of direct collaboration with people in pharmaceutical companies, Nkansah observes, perhaps with the exception of an old guard that still believes that never the twain should meet.

Everyone else, Nkanshah says, is interested in a “true partnership” that leverages the strengths that academics and biopharmas bring to the table.

“Academic partnerships are my passion,” says Bayer’s Global Open Innovation Head, Chandra Ramanathan, who also says that the best biopharma-academic partnerships leverage the unique strengths of both parties. When Ramanathan assesses whether to enter a new academic partnership, considerations include whether the partnership is likely to focus on new disease targets, offer a more efficient means of drug discovery using artificial intelligence, or yield new treatment modalities such a biologic, or cell or gene therapy.

Ramanathan points to Bayer’s partnership with the Broad Institute, which began in 2013, as an example of innovation like the kind he described. At first, this partnership focused on finding new treatments for cancer. In 2015, it expanded focus to include cardiogenomics, and in 2018 evolved again to focus on precision cardiology treatments. That step included opening a joint lab

 housed at the Broad, which includes Bayer and Broad scientists working side by side to develop high-resolution maps of single cells as a way to better understand how cardiovascular disease spreads and could potentially be treated.

New possibilities for academic biopharma partnerships

Although the cultural barriers between academia and biopharma that Nkansah describes were real, they weren’t so formidable that the two sectors truly had nothing to do with each other. It’s easy to find calls for collaboration

 between biopharma and academia from a decade ago or longer.

What is different today, says Sandy Smith, RN, MSN, AOCN, senior vice president, clinical solutions and strategic partnerships of clinical trial services provider WCG Clinical, is that much more genetic information to inform personalized treatments is now available.

“A lot of what’s driven this is the Human Genome Project. There are so many things to begin to break open and study,” Smith says, causing biopharmas and academic institutions to partner in a more concerted way to identify and test new treatments and eventually file for FDA approval.

The full advent of personalized genomic medicine may be sometime in the future, but Smith sees direct benefit of pharma-academic partnerships right here and now.

“Just in the last eight years or so, seeing what’s happening in immunotherapy,” Smith finds new fruit in these collaborations. Many new immunotherapies for different types of cancer have been approved in recent years, Smith says, which pharma companies brought to market after partnering with academic researchers who conducted the foundational research. And although the academic work behind cell and gene therapy is now decades old, Smith sees an increasing acceleration within the last decade in bringing such products to market.

Looking forward, Smith hopes that increasingly robust, digitized medical records will enable real-world evidence to be used as a synthetic data arm in clinical trials. Rather than running every new trial as an isolated data gathering event, the idea here is to incorporate real world experience into a trial’s data sources.

Smith says that medical records are finally detailed enough, and interoperable enough, to make incorporating real world evidence into clinical trials possible. So the need to longitudinally follow people for decades to see how they fare on a treatment, an inherently laborious task that Smith was part of in a prior position, may start to decrease.

Third-party vendors promote clinical trial integrity

Everything touched on so far—rare disease drug development, biopharma funding of basic science/preclinical work, designing immunotherapies, refining gene and cell therapies—will eventually need to be tested in humans to ensure that they are safe and effective. This often means that a potential treatment will need to be tested in multiple locations, each of which might have its own local practices for managing clinical trials. The resulting confluence is challenging for study sponsors to navigate, according to James Riddle of the clinical trial solutions provider Advarra, which has helped coordinate gene and cell therapy trials for roughly a decade.

In 2016, Riddle says, the NIH began to require that all multi-site clinical trials have a single IRB

 as a condition of funding. Gone were the days of wildly disparate informed consent processes, which meant that participants in different trial sites had a different understanding of the trial. The trend toward centralized IRBs began roughly a decade ago, Riddle estimates, but accelerated in the wake of NIH’s action. It’s less likely now that a university will run its ethics reviews in house, he says.

“If you want National Institutes of Health money, and you have a multi-site project, you have to devise a single IRB strategy—which the commercial IRB’s have been doing for decades,” Riddle says. This centralized IRB strategy has overlapped with the period in which biopharma and academic interests have becoming increasingly enmeshed.

The IRB process is meant to ensure that clinical trials begin on a sound ethical footing, in which every participant understands the risks and benefits of participation. Once a clinical trial is underway, oftentimes a Data Safety Monitoring Board (DSMB) will meet to assess emerging evidence about whether the new treatment’s benefits outweigh its risks. In this way, the DSMB must be a truly independent entity that isn’t swayed by either an academic or pharma partner. WCG and Advarra both offer centralized IRB and DSMB management services designed to ensure that these processes.

Perhaps unsurprisingly, established biopharmas like Novartis are well-positioned to partner with academic institutions and to capitalize on the commercial potential that such partnerships might bring. In a statement to 

, Novartis Director of External Science and Partnering, Ann Schlesinger noted that in 2020 Novartis recently launched the NIBR Global Scholars initiative to link Novartis scientists and academic scholars to fund novel science that may lead to new drug development. And large commercial players are also skilled at leveraging government funding to carry out their research efforts, as shown in the Operation Warp Speed effort in which the US government bore the cost for the clinical trials of COVID-19 vaccines.

But it’s not just the big players, notes Paul VanVeldhuisen of the contract research organization Emmes, LLC. “Smaller biopharmas and some of the emerging companies also seek government funding to do their research,” VanVeldhuisen says, pointing to substance use research as an example.

Emmes has long standing relationships with academic leaders in substance use research, such as New York University and Columbia University, and also knows how to access government funding from relevant entities such as the National Institute on Drug Abuse. But the smaller biotech that wants to test a promising new treatment for curbing addictive impulses to an opioid or to alcohol—research that may now incorporate greater use of genome-wide associate studies,

 but does not have this knowledge at its ready disposal—might look outward to a CRO. In a brokering role similar to that of NCATS, Emmes is in a position to bring the relevant parties together. “That’s our sweet spot,” VanVeldhuisen says.

Increasing enrollment in clinical trials: an opportunity

All of the above is well and good, but perhaps that’s only as far as it goes if the vast majority of people do not participate in clinical trials. As Adrian Hernandez, executive director of the Duke Clinical Research Institute, points out, less than 5% of US residents ever participate in a clinical trial. Hernandez says there is no easy way for people to express their interest in joining a clinical trial, or easy ways for them to learn what trials are happening in the first place. This is because our clinical trial infrastructure is separate from the places where patients actually receive care; Hernandez recommends linking the two together. A listing of a patient’s clinical trial interests within their medical record, so they could automatically be alerted of upcoming trials that match these interests, might help to address this.

Recruitment is just one challenge. Once a clinical trial is underway, Hernandez says, “the costs and complexity of clinical trials have increased in a number of ways.” In particular, today’s trials are more data intensive than they once were, Hernandez says, as researchers try to address potential “what-if” scenarios of potential responses to a treatment as ways to reduce unknowns once it reaches the market. This requires more statistical and analytical resources, increasing costs.

Before recruitment begins, and certainly before the trial starts, it has to be designed. What are the endpoints? How will they be measured? What level of enrollment is necessary for statistical confidence in a trial’s results? In any biopharma-academic collaboration, Hernandez says, representatives of both entities must be at the table during the design phase. And ideally there would be multiple people with different types of expertise, a “team science” approach that Hernandez says could probe the blind spots in any emerging study design to make sure it does not have a hidden bias that tilts the study’s results one way or another rather than letting the data tell the tale.

Any such tilting would not necessarily be at the behest of the pharma partner, Hernandez notes: “Sometimes I find intellectual conflicts are stronger than financial conflicts.” Perhaps an academic partner is truly invested in seeing a molecule that they have spent years of their life on be vindicated in a clinical trial–an understandable, yet unacceptable, consideration when designing that trial. In another sign of how times have changed—similar to the raft of approved immunotherapies and possible use of real-world evidence in clinical trials—Hernandez suggests that principles of open science could shine sunlight on conflicts of interest that the trial designers themselves might not be aware of. This could involve posting proposed trial protocols and rationales, online for public comments, a sharp departure from current practice.

However, collaborations between academic and biopharma partners evolve, it seems clear that the fates of the two parties are inextricably intertwined in ways that were not always the case. Some observers are optimistic about what this will mean. “From my perspective I think academic and industry partnerships continue to flourish, probably even more so,” Smith says.

Miller, K.L., Fermaglich, L.J. & Maynard, J. Using four decades of FDA orphan drug designations to describe trends in rare disease drug development: substantial growth seen in development of drugs for rare oncologic, neurologic, and pediatric-onset diseases. 

https://doi.org/10.1186/s13023-021-01901-6

Sarpatwari, A., Kesselheim, A.S., Reforming the Orphan Drug Act for the 21st century. 

https://www.nejm.org/doi/full/10.1056/NEJMp1902943

Mervis, J. Data check: U.S. government share of basic research funding falls below 50%. 

https://www.science.org/content/article/data-check-us-government-share-basic-research-funding-falls-below-50

U.S. Government Accountability Office, Drug Industry Profits, Research and Development Spending, and Merger and Acquisition Deals Report to Congressional Requesters, November 2017. 

https://www.broadinstitute.org/precision-cardiology-laboratory

Lengauer, C., Diaz, L. & Saha, S. Cancer drug discovery through collaboration. 

https://grants.nih.gov/grants/guide/notice-files/NOT-OD-16-094.html

Hall F, S, Chen Y, Resendiz-Gutierrez F: The Streetlight Effect: Reappraising the Study of Addiction in Light of the Findings of Genome-wide Association Studies. Brain Behav Evol 2020;95:230-246. doi: 10.1159/000516169

Feature Articles

Proactive, pervasive, and strategic planning lead industry into future.

Biopharma-Academic Collaborations in 2021

On October 15, the second day of Veeva R&D and Quality Summit Connect, four industry executives shared insights during the Media and Analyst Roundtable: Digital Trials Speed Path to New Therapies moderated by Veeva’s Vice President, Vault R&D, Jim Reilly. Participants from AbbVie, Labcorp, and GSK discuss the opportunities and challenges digital trials bring to the industry, and the importance of addressing them before fully embracing digital solutions.

Reilly: Digital trials have the potential to bring therapies to patients faster and in a more cost-effective way. Where do you see opportunities for improvement in how trials are run today?

Lorena Gomez, senior director of global study start-up, PRO management, and digital implementation, AbbVie:

 Every company had started to dip their toes into the digital world, but COVID-19 pushed us all into the proverbial pool. We had to come up with solutions really quickly to keep our studies afloat, now it’s forcing us to be a little bit more forward thinking.

We are asking questions like: ‘How can we make our trials more accommodating for our sites and our subjects?’ That’s where I see the biggest opportunity. With that comes the challenge of making our protocols simpler and easier to execute, while also thinking about studies in a way that facilitates digital approaches. To effectively do that, a strategic, enterprise-level plan is needed.

Mark Morais, president, clinical operations and commercial solutions, Labcorp Drug Development:

 What we need to think about now is a robust communication platform where we can start to share these learnings. We rushed into the digital space, and we are in danger of increasing complexity in trials. If we don’t understand the challenges, we cannot draw out consistency. That complexity is going to trickle down to manifest itself in terms of site burden. We need to think about the impact to sites, protocol design, and patients—especially in terms of what we’re capturing and how. We have to let digital drive simplicity as we potentially increase all of the disparate data sources.

It’s going to be important that we collaborate as an industry to understand how that patient journey and site relationship is going to change. Historically as partners, we’ve always brought trials to sites. Now, we’re going to find a way to bring patients to trials. This is going to open a new area for therapy of treatment. It’s going to allow us to look at diversity and inclusion in terms of the patients we’re recruiting and the sites that we’re using.

Digital is going to greatly broaden, not only the therapeutic potential, but the opportunities to reach new patients in a more cost-effective way. But if we’re not careful, complexity will derail the opportunity and that will hurt the industry.

 To that end, there are still many unknowns. It’s the wild west in the digital space and even regulators aren’t necessarily aligned on things such as whether devices need to be labeled or not. There are many different moving parts and a lot of work ahead to pave the path to digital.

Mayank Anand, vice president, and global head, data strategy and management,

 There are two components to this. Data and technology, the latter which is going to play a very pivotal role in this entire strategy. The problem is, we don’t have products that are fully mature. There are good solutions where some parts of it are matured, but not entirely. Every organization is looking for multiple solutions to plug in, increasing risk and creating an even more complex environment.

Now imagine you’re going to increase your data by 10-times or 20-times using decentralized technologies like sensors, are we ready for that instant data cleaning? The industry is already struggling with the data we get from trials today. This adds another level of complexity to it.

Data is going to explode in the next couple of years. Instant data cleaning will become a bigger challenge because the expectation will be that if data ingestion is faster, the output has to be faster too. Thinking about data ingestion, in the present world, there are barriers to getting external data. The sharing of data itself is a challenge. Every study brings its own complexity because you have 10 to 15 different external data providers, and everyone uses a different way to inject data. Now just imagine you are making the leap to maybe 20 or 30 different data sources, how would you standardize that?

With technology and data, we must address how we plug in to bring simplicity and a connected architecture. Otherwise, in the next five years we’ll be doing another transformation to address these issues.

Reilly: What can organizations do to advance to a more holistic way that drives a better trial outcome?

 One thing, which is a requirement, is the clinical hub. This concept has been around for some time, but with the creation of more integrations and data in different silos, there is a need for a better approach. I think the future lies in having a single source of ingestion and aggregation. This is difficult to accomplish because at present, we are not able to standardize. It’s very important that standardization is at the core among all of this if we really want to simplify trials.

As an industry, companies should stop customizing tools according to protocols. Don’t customize because you have some specific requirements—adopt and adapt the tool the way it is. I think that will be a more efficient way to bring simplicity to trials. This will not only help you, but I can guarantee investigators and patients will benefit because they actually face the complexity of these customized systems.

 I think the customization of systems creates a big drain in terms of how sites are utilizing the tools. This opens itself up for future issues in how we aggregate data, and the quality of the data itself. I think the one thing we need is not an entirely consistent strategy, but alignment as an industry on an end-to-end strategy for platform management and data aggregation, and the governance around that.

If we’re not careful, too much standardization will stifle innovation. Innovation is allowing us to transform the way that we work right now, but it’s also adding complexity.

We have to find that delicate balance between standardization, while still driving innovation and change. We’ve seen it in the post-COVID world as we all rush to create new strategies of how we were going to drive trial continuity and patient monitoring. We all created bespoke solutions, most of which are working great right now, but you’re starting to see those inconsistencies.

We’re also creating a great amount of learning. We need to take those learnings and share it as part of that end-to-end strategy and allow it to influence what we do next.

Reilly: When you look at regional guidelines and country-specific concerns, could you share your perspectives on how, as an industry, we can help overcome that

There are two pieces to this. First, there’s the upfront strategy around how the digital pieces of your program fit together from a data perspective. Companies need to assess these tools to ensure they can gather the needed information and bring all the data together to use it.

Then there’s how to operationalize and implement the tool. Can this even be done in the countries that you’re going to? Having that intelligence, a well-defined infrastructure, an overarching strategy–both from a data perspective and operational implementation perspective–are of critical importance to drive success.

Even regulators are still working on figuring out this space. I don’t know that it’s possible right now to guarantee success, but as an industry we have to continue communicating with one another. As several of our speakers have underscored already, sharing best practices and setting standards as an industry to eliminate all these obstacles will be critical.

As we start to collect more information and going direct to patients through wearables and real-time access, data privacy practices and regulations have not caught up yet. What we’re going to find is, the digital space is innovating and transforming faster than digital patient’s rights are. We’ll need to understand how that’s going to influence our ability to collect the data—what data we can collect, the timing of that data, and how it’s utilized.

 EU data protection doesn’t allow ease in using data centers outside the EU in relation to EU data protection law. This sometimes creates a bottleneck for organizations adopting technology that don’t have data storage within the EU.

As an industry, we must change our mindset. One side is changing and evolving versus the other side still wearing the old hat. One recent example is where we did some sessions for the FDA to understand how artificial intelligence and machine learning works into the clinical space, the uses, the advantage, and how they can improve their own ways of inspecting data. I think that’s the bigger problem, regulation.



is an Assistant Editor for Applied Clinical Trials. She can be reached at

ACT Roundtable

Four industry executives share insights during the Media and Analyst Roundtable at Veeva's R&D and Quality Summit Connect.

Addressing Digital Trials

In line with the industry’s drastic shift to decentralized trials (DCTs) during the pandemic, companies have been quick to adapt. In this interview, Dave Hanaman, co-founder, president and chief commercial operator at Curavit Clinical Research discusses launching the organization at the start of the pandemic and how it operates with a commitment to designing trials with a fully virtual site.

Curavit is the first virtual contract resource organization (VCRO), which means that like a traditional CRO, we provide a full suite of services to design and execute clinical trials. The virtual piece is what is new; and it refers to our 100% dedication to DCTs. At Curavit, we design virtual clinical trials from first principles using IoT, wearables, remote data capture and other digital technologies to improve the speed, quality, cost, and accessibility of clinical research. We address each trial uniquely and bring in therapeutic area specialists to help inform the right technologies and approach, and partner with an extensive ecosystem of technology partners as required.

Of course, there are some trials or therapeutic areas that today are much harder to decentralize, but increasingly we are seeing advanced technologies being applied partially, making hybrid trials the most prevalent type for the foreseeable future. In the near term, fully virtual trials may be limited to specific use cases, however, in the long term they will be more widespread, especially in certain therapeutic areas, such as rare disease, mental health, central nervous system, neurodegenerative and others that have supporting technologies and require patient populations that might struggle to physically travel or don’t live near a site.

While there are defining patient population characteristics in many therapeutic areas that can make some studies more likely candidates for all-virtual research, ultimately, the target patient population, treatment, indication, and available technologies will determine whether a trial is fully virtual, hybrid, or a traditional site-based trial.

ACT: Your company was founded right at the beginning of the pandemic. What has that experience been like?

 We launched the company in November 2019, right before the pandemic took hold. At that time, the industry was breathlessly predicting that 10% of all trials would be virtual in 10 years. Now the DCT market is exploding with an estimated value of $1.63 billion by 2027, a compounded annual growth rate of 14.8%, according to Precision Reports. No one foresaw the impact of the pandemic and the unprecedented adoption of decentralized trials within months. We found ourselves suddenly accelerating toward our goals with massive tailwinds, but also buffeted by turbulence from the hype. We again learned the lesson that “the first casualty of battle is the plan,” and that you must stay committed to the outcome while adapting to the things you can’t control.

ACT: How does the VCRO differ from DCT providers or platforms?

There are a variety of DCT providers that offer a combination of both services and software in this space. As a VCRO, Curavit is traditional in the sense that we provide services for the entire lifecycle of a clinical trial, but what makes us unique is our primary focus on designing and executing digitally-native DCTs through our proprietary DCT platform. Our platform is the digital manifestation of our IP and processes. From operations, through data collection and insight, to patient experience, our platform is uniquely configured for each study and manages every aspect of a clinical trial. It operationalizes our expertise, is built from industry-leading technology, configured for each trial, deployed to each patient, and available in real time to our sponsors.

ACT: How does the organization maintain relationships in a virtual model?

An unintentional benefit of the pandemic was not only the increased acceptance of telemedicine and decentralized research, but also the comfort level of conducting business remotely. Coincidentally, we started Curavit just months before the pandemic closed down everything, but we had always planned on building a virtual company with hubs in key markets, such as Boston, Philadelphia, San Diego, and Salt Lake City. All the client work we do takes place remotely—in the cloud. We leverage digital technologies to maintain relationships with all our stakeholders, including patient participants involved in the virtual clinical trials that we execute. As the pandemic restrictions permit, we are increasingly meeting customers, employees, and prospects face-to-face at industry conferences, customer sites, and the traditional meetings.

ACT: Does a sponsor use all of your services, or pick what they need?

Sponsors can select the services they need through our DCT platform. This is where they have access to whatever functionality they need for each trial, and can scale up, or down, depending on their needs. Each trial is unique and configured by our clinical operations team on our proprietary platform, validated, HIPAA-compliant, and audit-ready. Trial participants also participate through the platform to upload their data. All stakeholders can access it to track and monitor progress.

For each specific trial, sponsors use different layers of the platform, ranging from patient experience, data capture and analysis, to operational services. For example, we recently designed and delivered a fully virtual COVID-19 therapeutic trial that used several layers of our DCT platform. This trial was configured completely differently than one we are currently executing for diabetes research that leverages different components of the platform.

In short, sponsors choose between a full-service solution for complete DCTs or a digital layer–a subset of our offerings–to solve a very specific challenge in a hybrid clinical trial.

In this interview, Dave Hanaman, co-founder, president and chief commercial operator at Curavit Clinical Research discusses launching the organization at the start of the pandemic and how it operates with a commitment to designing trials with a fully virtual site.


Taking DCTs to the Next Level

, we discuss the role of academic research and explore its relationship with pharma and clinical trials. In this article, our contributor interviews the NCATS’ (National Center for Advancing Translational Sciences) director of strategic alliances, who explains their work to ease passage across the so-called “Valley of Death.” Coincidentally, I was privileged to attend an in-person conference and learned much more about NCATS. Please visit their 

 to see all of the programs they offer...it’s truly astounding.

. And this map is a gem...or the “board game from hell,” as one of its authors described. The two maps shown—one for small molecule development and one for biologics development—were designed to “provide a common framework for discussing the therapeutic development process and serve as an education tool for those who are new to it,” as well as offer a common language and collective knowledge base to enable systemwide improvements.

Let’s take a moment and just let this sink in. A group of highly intelligent, motivated and truly curious and passionate people, dug in deep into the clinical research enterprise and literally spent a lot of time to elucidate in the most usable and informed way to present this information, in the public domain, to further efficient research.

Then, think about all the blocks and colored boxes that represent a process or function, then imagine all the details that goes into any one of those functional areas on the daily. Regulatory. Operations. IRB. Enrollment. Data. Review. Mind you, this is after the basic science research, target identification, target pharmacology and lead identification.

Which is to say, this is an area ripe for “systemwide improvements that will benefit patients.” This related 

, is a most eloquently detailed summation of any and all challenges in the current drug development system. In fact, in the future, if anyone sends me an article to review outlining the problems in clinical trials, I’m just going to copy and paste this link, and say “next.”

The author calls for increased support of the academic discipline of translational science, which must remain in academia, to vastly improve the current situation. As he noted: “The ultimate goal of translational science is not to traverse the Valley of Death. It is to eliminate the Valley of Death entirely.”

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

From the Editor

Improvement is needed in clarifying the therapeutic development process.

A New Era for Translational Research

Issue PDF

Click the title above for a link to open the Applied Clinical Trials November 2021 issue in an interactive PDF format.

Applied Clinical Trials November 2021 Issue (PDF)

This column reported in August of a push by the current Slovenian presidency of the European Union to drug repurposing—and now, just weeks before the end of its term in the EU's revolving chair, its ambitions have received a concrete endorsement in the shape of the formal launch of an EU pilot program aimed specifically at testing the concept further. Right at the end of October, the European Commission, the European Medicines Agency and the Heads of Medicines Agencies announced "a 

 for a framework to support not-for-profit organizations and academia in repurposing authorized medicines."

Presented as a way of making new treatment options available to patients, the scheme aims at assisting evidence generation on an established medicine in a new indication, with the goal of create a data package robust enough to support a future market authorization application. It will apply to conditions to candidate medicines that are no longer covered by any intellectual property protection, and that could respond to unmet need with significant potential public health benefits. And eligible beneficiaries might be academic units, charities, patient organizations, learned societies, research funders or payers, explains the EU.

Slovenia's principal interest in the concept has been overtly the desire to open an avenue to cheaper medicines. The formal EU approach in this scheme, however, is more nuanced. Ideally, in official EU thinking, it could provide some constructive response to the dilemmas posed by extensive off-label prescribing. "The absence of a bespoke regulatory route for, off-patent, authorized medicines already on the market to be developed for new uses and reach formal regulatory approval sometimes poses problems to physicians, patients and health systems," says the background documentation to the scheme. "Well-established evidence based on off-label use is not converted into on-label use", with possible "negative consequences for patient safety and treatment options." Additionally, "potentially useful new or established non-approved indications will be hampered if the medicine is suddenly withdrawn from the market."

The principal assistance available through the pilot will be in terms of scientific advice. Eligible academic sponsors developing orphan medicines will automatically benefit from a fee waiver. And additional fee waivers will be granted to a subset of selected applications taking into account the extent of the expected public health benefits and the strength of the evidence to substantiate the promise held by the proposal.

As observed in this column in August, there is a long history to this ambition. The concept of support for a repurposing framework features in EMA's Regulatory Science Strategy to 2025 and has been extensively discussed in the European Commission’s expert group on safe and timely access to medicines for patients, STAMP, where representatives of EU member states, EMA and stakeholders from not-for-profit organizations, patients, healthcare professionals, industry, health technology assessment bodies and payers contributed.

But a clearly delineated challenge repeatedly arises whenever attempts are made to turn ambition into reality. As the EU announcement makes clear, any success ultimately depends on the engagement of a pharmaceutical company, and that is far from guaranteed. Non-commercial generation of new evidence "should then be followed by the engagement of the marketing authorization holder/applicant of the concerned medicinal products applying for the new indication through standard regulatory processes." Not "will be followed". Just "should be followed".

The pilot will run until the completion of scientific advice for the selected repurposing candidate projects, says the EU announcement—adding that it will continue "optimally until the filing of an application by a pharmaceutical company for the new indication." It has been immediately and warmly welcomed by non-commercial organizations—notably the Anti-Cancer Fund, a longstanding proponent of repurposing. "We are very glad that EMA and the national medicines agencies are now ready to provide regulatory support, especially scientific advice, to not-for-profit organizations and academia who are willing to investigate existing drugs for new indications," said its managing director, Lydie Meheus. But it has also received a qualified welcome from some industry organizations. The generic industry's Medicines for Europe, which is active in the development of value-added medicines, saw it as "a great first step", but insisted that it "must become a part of a broader sustainable repurposing ecosystem" – by which it means some regulatory simplification, and better pricing and reimbursement policies. 

The pilot may prove that repurposing really can deliver. Or it may indicate the contrary. For European policymakers, the scheme provides a convenient way of deferring any decisions—and maybe making it possible, in the end, to drop the discussion completely, bring to an end what some regard as a futile distraction.

View from Brussels

European authorities have announced a proposal for a framework to support not-for-profit organizations and academia in repurposing authorized medicines.

European Drug Repurposing: An Update

Given everything else patients have going on in their lives, it can be an unsurmountable burden for people living with a chronic illness, such as elderly cardiovascular patients, to comply consistently with self-administered medication protocols.

While most clinical trials spend millions of dollars or more on clinical systems to improve data management, very few provide any meaningful support for patients at home to help them stay active and compliant.

Why aren’t more companies using these cost-effective and easy-to-implement solutions? Let’s take a look at one that did.

The importance of consistent medication adherence for studies with self-dosing requirements cannot be overstated. As has been reported in Applied Clinical Trials, poor compliance has an exponential impact on the number of patients needed to reach the same statistical outcome, shown in Table 1 below.

Research shows 40% of patients become non-compliant at 5 months on study.

 This means an average Phase III trial will require an additional 460 patients at an estimated cost of $12 million.

Costs will be even higher for certain programs such as lengthy cardiovascular studies and complex oncology trials.

Even an incremental improvement can make a significant difference in time and on the study budget. The Phase III trial referenced above would yield $335k in cost savings for each 1% increase in adherence.

As the following case study below shows, a technology-based dosing manager can help patients, even in the challenging elderly patient demographic, achieve compliance rates up to 98% at 18 months on study.

A leading pharmaceutical company sponsored a cardiology trial that required elderly patients to self-administer cardiometabolic medication in tablet form 2x/day in a chronic fashion over multiple years. Published data for average medication adherence in cardiometabolic disease is 56% over 12 months. Twice-daily dosing has even lower adherence.

For this Phase III trial the study team deployed a technology-based dosing mechanism. It helped improve medication adherence by using interactive SMS messages on patients' personal phones. The dosing manager solution sent protocol-specific automated text messages that prompted patients to take their medication at the scheduled time.

The system prompted patients twice daily with an SMS message that enabled them to quickly and easily confirm they had taken their dose—i.e., the patient would hit the Number one to confirm they took their medicine on time. In addition to ensuring compliance, easily access dosing records mitigated the risk of patients over-medicating because they forgot they had already taken a dose.

This simple process removed burden for elderly patients who (counter-intuitively) typically have higher technology compliance than younger people, in part because they have more spare time and stronger relationships with their care teams.

Sites received weekly compliance reports which allowed them to identify patients who would benefit from additional support and follow-up.

In addition to a dosing manager, technology solutions which kept patients engaged during this trial included:

Patients consistently demonstrated 2x/daily medication adherence at 70% and above throughout the duration of the trial. Patients treated at several major academic research centers reached as high as 98% adherence at 18 months on study, with an overall average compliance rate of 86.5%. A few of the research centers along with their patient adherence percentages can be found in Table 2 below.

Technology providers should evolve their technology and service delivery best practices to ensure continual improvement in patient compliance.

This trial faced unique challenges and presented lessons learned technology providers can incorporate into future clinical trials, including…

Make site participation mandatory—Keeping it optional means fewer patients will receive benefit from a dosing manager.

Focus on supporting ex-U.S. sites—While most eClinical technology is inherently global, some countries may have specific deliverability issues a technology provider can solve with a telecommunications partner should challenges arise. It is important to monitor compliance at ex-U.S. sites to identify and resolve issues proactively.

Follow up with non-compliant sites—This ensures sites are reviewing reports and discussing the importance of consistent dosing with low-adhering patients. It is especially important for sites with significant staff and study coordinator turnover.

Patients trust us to provide the best possible care and clinical trial experience for them. As an industry, we must shift to prioritize technology and tools that make it easier for patients to participate throughout the study’s duration. Even using a simple interactive SMS dosing manager can significantly increase compliance, improve safety, and reduce cost and risk. So, let’s work together to help patients, their caregivers, and their families succeed in our clinical trial.

Adherence to medications: insights arising from studies on the unreliable link between prescribed and actual drug dosing histories. Blaschke TF1, Osterberg L, Vrijens B, Urquhart J., Annu Rev Pharmacol Toxicol. 2012

Smith, Dorothy PharmD, Patient Nonadherence in Clinical Trials: Could There Be a Link to Post Marketing Patient Safety?, Consumer Health Information Corporation, October 2011

Improving Medication Adherence in Cardiometabolic Disease, Journal of the American College of Cardiology, 2017

Elderly patients achieved up to 98% compliance at 18 months on Phase III study.

Increasing Adherence With Dosing Reminders

Despite broad enthusiasm for wider use of real world data (RWD) and real world evidence (RWE) in developing and assessing the efficacy and safety of new drugs and medical products, this approach presents significant challenges in assuring that the information is valid and germane to the research involved.

FDA has worked to clarify how drug development can gain from tapping into information in health care systems and claims databases, as outlined in our 

 on “advancing reliance on real world data and evidence” for these purposes. That 

 discusses the agency’s September 2021 guidance, which addresses a range of issues involved in sponsor utilization of RWD and RWE in clinical research.

Now, FDA seeks to address the added complexities for incorporating such information into submissions to the agency, while addressing concerns about its relevance and reliability. Such challenges are evident in a more 

 on how sponsors should submit RWD to support research submissions to the agency for drugs and biologics, which acknowledges numerous difficulties that arise from utilizing data from a wide range of information systems with different formats, terminologies, data aggregation methods and overall quality measures.

These issues reflect FDA efforts over the past decade to require electronic submission of data to support market applications based on agreed-on standards. The aim is to make it easier and faster for the agency to receive, review, store and analyze the wide range of research, manufacturing and safety information submitted to in applications. Now, to further support increased use of RWD and RWE in applications, FDA outlines here how sponsors should collect and convert or “map” such data collected outside of clinical trials to fit agency e-standards for submitting information in investigational new drug applications (INDs) and applications for generic drugs (ANDAs) and biotech therapies (BLAs), and new drugs (NDAs.)

The guidance addresses how sponsors should format data elements so that they can be exchanged between computer systems in ways to minimize inconsistencies and increase clarity to facilitate FDA review and archiving of the information. The agency recognizes the importance of sponsors being able to utilize data from electronic health records, medical claims systems, disease registries and mobile digital tools, among other sources. Problems arise, though, because such information systems have diverse standards and policies, such as differing diagnosis codes set by national and international data standardization entities. FDA and sponsors acknowledge considerable challenges in mapping data from source systems to fit FDA standards, noting added difficulties raised by differences in definitions and in key variables, even basics such as sex and diagnosis.

For now, FDA advises sponsors to document data sources and conversion processes and decisions, acknowledging that the field is in flux and faces many adjustments and challenges ahead. Collaborative industry efforts are working to develop data standards and mapping tools for electronic health records, but all parties concede that this will be a lengthy and difficult process. FDA acknowledges that its advice is limited by current uncertainties and that sponsors should anticipate changes in policies for collecting and submitting RWD to support applications.

Some assistance may arise from multiple efforts to advance standards for this field. The Professional Society for Health Economics and Outcomes Research (ISPOR) is launching a real-world evidence registry to provide added transparency into the analysis and reporting of RWE in health research, here through a platform for researchers to register study protocols so other experts may assess the potential for biases, sufficient randomization, and uniform data quality.

Additionally, FDA looks to enhance its use of RWE for more rapid assessment of therapies to treat COVID-19 through its partnership with health tech firm Aetion. The agency is expanding the use of Aetion’s platform-based approach for utilizing data from EHRs and other sources to define key research questions, identify fit data sources, and validate ways to capture data on subgroups outside clinical trials. This builds on 

FDA seeks to address the hurdles for incorporating real world data into submissions, while addressing concerns about relevance and reliability. 

Applied Clinical Trials-11-01-2021