Moe Alsumidaie

Asia’s biopharmaceutical enterprises are seeing massive market penetration opportunities in the West. Their ability to conduct early-phase trials in Asia at a lower cost and then obtain funding to run later-phase trials in the US puts them at an advantage. As a result, they can enter the Western marketplace with lower-priced medical products. In this interview, Dr. Harish Dave, CEO of Singapore-based AUM Biosciences, discusses evolving strategies for Asian biopharmaceutical enterprises.

Moe Alsumidaie: What is AUM’s vision of bringing affordable cancer treatments and more agility in clinical trials and go-to-market strategy?

 The traditional arena for clinical research has been the US, Western Europe, Japan, and other “westernized” countries based on the robust regulatory framework, capable investigators, and strong research facilities. As the number of clinical trials has increased over time, so has the cost of clinical research. The number of patients willing to participate in clinical research has remained flat or even declined, hampering recruitment and timely study completion. Additionally, facilities and researchers are at a saturation point resulting in further delays.

We have seen several countries in the Indo-Pac region develop a more robust health care and research infrastructure, with highly regarded investigators at the helm of affairs. Patients in these regions are more willing to participate in clinical research, while the population size enables speedy recruitment. Labor and cost arbitrage between regions means we can conduct world-class research cheaper and faster than is possible in the US and EU. The critical element, of course, is that there can be no compromise on trial design, execution and data collection to deliver a robust drug development package. These advantages can be used to carry out Phase I rapidly and, to an extent Phase II studies before incorporating US and EU sites into global Phase II and III designs.

This approach led to the rapid conduct of Phase II and II oncology trials at premier centers and at a global standard before involving many sites and countries, including the US and EU. The time savings results in a longer market time before patent expiration, and there is also the direct cost savings from labor and cost arbitrage.

AUM’s executives are an experienced and diverse group of individuals who have spent time in almost every major region of the world and have the experience and knowledge to use the Indo-Pacific region to accelerate drug development. This translates directly into going to market strategies that do not rely on extracting the maximum price the market will bear but, instead, on a realistic price. More patients stand to benefit from this affordable drug development strategy. AUM hopes to do its part in reducing health care inequities that continue to plague the modern world.

The traditional flow of drugs from the West to the East brings “western costs.” AUM’s strategy is to reverse this flow and go from Asia to the West, satisfying the need of the Asian population for innovative and affordable drug development and reducing the cost of health care in Western countries by introducing drugs at an “Asian” price point.

MA: What challenges have you faced in your Oncology trials?

In a sense, this is not dissimilar to other areas of clinical research but is perhaps more of an issue in oncology. The advances of the last 2-3 decades have resulted in a great deal of segmentation within oncology diseases. Many of our newer therapies address small subsets of patients with inclusion criteria requiring documentation of a particular mutation or biomarker and, sometimes, exclusion of other mutations or biomarkers. This segmentation means we are looking to identify relatively rare subsets for study entry which slows the recruitment process. A classic example is Phase I oncology work. The traditional 3+3 design recruiting “all-comers” with solid tumors can quickly recruit. But if only certain tumor types or certain biomarkers are required, that can greatly slow down fulfilling recruitment goals for each dose cohort.

The second issue is compliance, especially as we move to oral therapies self-administered by patients. Even with a potentially terminal diagnosis, patients may not take their medication on time, or in a fasted or fed state as required, or forget to take medicine altogether. As a general rule, the longer someone is on therapy and the greater the adverse events (AEs), the lower the compliance. This leads to gaps in data and impact outcomes, necessitating a larger trial size to overcome this obstacle. Paradoxically, having a good response may also lead the patient to become non-compliant.

Study retention also can be difficult in a cancer population. Many patients are already debilitated from their underlying disease. Adding to that, AEs of our medications, frequent clinic visits, blood draws, imaging, and other invasive procedures make retention challenging.

The COVID pandemic has also resulted in additional challenges–our patients are reluctant to venture out and risk infection in their immunocompromised state. Many clinics and hospitals are not allowing caregivers to enter the facility to minimize the risk of contagion. And several doctors stopped seeing patients or relied heavily on telemedicine which may not be entirely satisfactory to the patient. From the investigator and pharma perspective, clinic visits were disrupted with missing data and delayed imaging, and Clinical Research Associate’s (CRA) inability to get on site (though this has been mitigated by remote access to Electronic Medical Record (EMR) EMRs). As the omicron variant has demonstrated, we will continue to see newer and potentially more infectious variants emerging, making it difficult to go to the status quo.

MA: How is the pandemic posing challenges for your clinical trials?

 AUM Biosciences were fortunate that our Phase I study had completed recruitment just before the pandemic started. However, the dislocation in services from widespread lockdowns resulted in significant delays in data collection and management of research samples. Critical plasma and serum samples were left to languish at research sites for many months with potential degradation of analytes and loss of valuable clinical research information. Even when we could transfer them to appropriate laboratories for analysis, the staff shortages, backlog of samples, and supply chain disruption of critical reagents and parts caused troubling delays in obtaining and analyzing data. From discussions with other, similarly situated biotechs, we know that recruitment on studies ground to a halt and has only barely started to recover. Investment capital dried up rapidly–many investors became gun-shy and preferred to hold on to dry powder rather than invest when the level of uncertainty was high. And what investment dollars remained made a beeline to COVID-related research and mitigation strategies. This was particularly punishing for small biotechs heavily dependent on ongoing capital raises to fund their research burn.

This was a tremendous learning experience for many of us. It showed how critical the global supply chain was for clinical trials, not just for large companies and medium to heavy industries. Established vendor relationships were crucial to helping many of us weather the cash crunch we faced–their tolerance and willingness to extend credit and offer favorable payment terms helped many biotechs stay afloat. The lesson that cash is king was driven home by the shortage of investment capital during much of the pandemic. It served to emphasize the importance of securing enough financing, including debt financing, to survive such a significant global dislocation.

We, at AUM, were undoubtedly fortunate in that regard. As a company built by industry veterans in the clinical trials space, our extensive and deep connection with contract research organizations (CROs) and other vendors at their highest levels allowed us to secure favorable terms when money was hard to find. Despite omicron, there is a sense that we are emerging from this crisis and, to an extent, have learned to live with it allowing business to go on and research to go forward.

MA: Out of all the small-molecule drugs developed by AUM biosciences, can you cite a case study wherein AUM Biosciences managed to overcome challenges in a unique way?

 AUM has a portfolio approach to drug development and has worked hard to build out a pipeline of drugs at various stages of development, from pre-clinical to Phase I (and now Phase II). While all aspects of business activity slowed down and clinical research almost ground to a halt, we were able to reprioritize our work by shifting the focus to earlier stage drugs and testing in cell culture and animal models instead of human subjects. This allowed AUM to retain staff (and even grow) during the pandemic and progress the portfolio to a point where we could rapidly go back to the clinic once the research facilities opened up for business. Such risk mitigation would not have been possible with a single molecule company–not only would that have delayed us significantly, but it likely would have necessitated a reduction in force. Once disrupted, carefully assembled teams can be hard to put together again and lead to the impaired outcome for many months or years after the event.

Most small companies in our space are far too busy managing their day-to-day activities to pay attention to global risk management. However, COVID has taught us that proactive global risk management is critical, perhaps even more so for small than large businesses. The C-suite must contemplate black swan events and strategies to mitigate against them.

MA: Tell us more about your clinical trial pipeline and if you have any specific strategies to ensure success in times of a pandemic that has impacted investments, focus as well as the speed of clinical trials.

 AUM has two advanced candidates entering Phase II trials and additional candidates in late pre-clinical, all backed by an AI-driven drug discovery platform and a biologics platform. Our approach is to drug the undruggable and avoid or overcome resistance through combination therapy approaches. Drugs in our portfolio are selected for their activity against a single cancer type and, ideally, multiple cancer types, thereby giving us various shots on goal. A consequence of this “one drug many targets” approach is the scalability of our research enterprise. This is amply demonstrated with the AUM001 MNK inhibitor. This selective translation inhibitor has activity in several solid tumors, which allows us to scale our research effort to explore one or multiple tumor types as determined by the availability of capital and availability of clinic resources during the COVID pandemic. Newer trial designs like basket trials allow us to efficiently explore multiple disease targets cost-effectively, channeling investment into the successful arms and pruning the unsuccessful arms. Using Indo-Pac countries as our home ground advantage, we can execute our studies more rapidly than many of our West-focused counterparts. Speed is of the essence in drug development as the patent clock is ticking–every week saved in development is an additional week of patent-protected marketing of the drug.

, MBA, MSF, is a thought leader and expert in the application of business analytics toward clinical trials, and Editorial Advisory Board member for and regular contributor to Applied Clinical Trials

Articles

Dr. Harish Dave, CEO of Singapore-based AUM Biosciences, discusses evolving strategies for Asian biopharmaceutical enterprises.

Asian Biotech Clinical Trial Demand Moves to the West

Decentralized Clinical Trials (DCTs) have evolved from concepts into a much more structured approach within the biopharmaceutical industry. The concept has become so significant that collaborations, such as Decentralized Trials and Research Alliance (DTRA), have emerged with strong support from industry leaders to help provide guidance and clarity around DCTs and industry best practices. In this interview, Craig Lipset, Co-Chair of DTRA, will discuss the evolving nature of DCTs and DTRA’s initiatives.

Moe Alsumidaie: What prompted you to found DTRA?

 The genesis for DTRA dates back before the pandemic. At that time we had many conference panels related to decentralized clinical trials where leaders were coming together, sharing some fabulous ideas and opportunities, but then would all head back to their day jobs and leave all those opportunities on the table until we came back together at the next conference to pick up those conversations. DTRA Co-chair Amir Kalali and I believed there was need for a space for those conversations to develop and ultimately create solutions together, which gave rise to DTRA.

MA: Are DCTs clearly defined, or are we in the beginning phases of defining DCTs?

 When you look at existing initiatives like the Clinical Trials Transformation Initiative and IMI Trials@Home, you start to see some consistent themes for DCT definitions. These definitions tend to include the use of technology and/or innovative processes that enable visits outside of a conventional research site. So, this is about technology such as those that can allow self-reporting of data, sensor-derived data, the use of video, and so on. And it's also about process changes, such as the use of home health and visiting nurses, acquiring labs locally, drug distribution to the patient's home, the possibility of administering medicine in the patient's home, or even configuring centralized or “meta” sites. It's not just a tech play; It can also be a heavy process play, and the desired state is to create options for people in how they engage, not necessarily forcing everything in the home because that's not right for every patient.

You tend to see many of those words resonating in terms of how people define this. But when a study team goes into Google and searches for a decentralized trial provider, it still turns into chaos. You wind up with a list of very different solution providers, which becomes extremely hard for study teams to navigate. Who is doing what? What collection of solution providers do I need to support my study today? Many of the large pharma have gone from late last year relying almost exclusively on their CROs to serve as their general contractor and navigate various solutions, to now having sponsors navigating that space and selecting specific partners for different DCT-related capabilities. I think for a lot of small and midsized pharmas, though, it's still a very confusing ecosystem to have to navigate.

 I think this is an exciting time for decentralized research, but it is a crucial time for us to leverage organizational momentum and enthusiasm to create sustaining commitments in these areas, making sure that our organizations are ready to continue to adopt at scale and ensuring we're learning from the experiences that are going on today to help to optimize our processes in the future. Solutions close to the center of the decentralized universe include many that sponsors have been doing for years: ePRO and eCOA. Many have already been doing visiting nurse and home health. Decentralized builds and expands on these competencies. So, organizations don't have to look at this as foreign and intimidating. Incremental counts and every step forward is an important step.

And so, where decentralized is now increasingly accepted as a competency, what innovations continue to grow and expand this core? It's an exciting time in that there is an established ecosystem of solution providers today, but that ecosystem continues to grow with new and creative innovators coming up with novel approaches to wrap around today’s DCT environment. And that's been very exciting to see, and I encourage folks out there to treat this as an opportunity for incremental expansion.

MA: What methodology is recommended to build a DCT infrastructure?

 What you see today are sponsors that have gone through a disciplined process of looking internally at their portfolio and future study needs. Based on those portfolio needs, they are then identifying which decentralized research methods their study teams will need to be able to access, finding new partners if they don't exist in their network, reviewing SOPs and training to make sure that those solutions can fit in their operating environment, reviewing protocol templates and other tools, and making sure that culture-wise the organization is ready to engage. The next step is then to be able to pair each study with the right decentralized research methods.

Some people may say, "we should use a clinical decision support tool.” Ideally a team should be able to input their protocol and have a data-driven process to find the right decentralized tools to make a successful study. Unfortunately, we don't have the body of data and evidence yet to power that. Until that body of data grows we have human processes that look at regulatory intelligence based on the countries in which you're operating, the safety profile of the investigational product and how it's administered, patient input and insights, and a host of other factors to try to infer which solutions are suitable for which study. Some large pharmas have put in place internal subject matter expert-driven teams to help advise study teams on this. More often than not, the rate limiter for those solutions is driven by cultural constraints within the organization. Cultural aspects include whether teams are supported, or do they feel constrained in how much they can do? How much change could they embed at one time? That tends to be the process today, and that works well for large pharma, but it still is hard for small and some mid-sized pharmas, who need to rely much more heavily on their CROs and other partners to help them navigate that landscape and make good decisions on which solutions to include.

 Once upon a time, a lot of the jargon people were hearing was that studies would evolve from brick and mortar to a hybrid middle state to some desired future state of being fully remote and fully decentralized. And in many ways, that's the technologist's view of the world. However, the reality is that when you talk to patients and research participants the sentiment about a research site is exceptionally high. The average site rating on TrialJourney is 4.4 out of five. When we look at data from CISCRP, perception of their experience at sites is overwhelmingly favorable. The challenge in clinical research studies is not that patients don't like their sites; it’s that they can't always get there. And so when we focus on access as being the challenge, we tend to land more often than not on hybrid studies, not as being a fuzzy middle ground, but being the desired end state for many studies.

Today’s desired future state for many is to enable participants to have more choice and flexibility on a visit-by-visit basis, powered by endpoints and measurement approaches that capture high quality data agnostic to location., In this desired future if a patient wants to go to a site, we do not deny that to anybody, but if they can't, we have other options available based on their individual needs. So, given that future state, sites will continue to play an essential role in research conduct and participant experience. Organizations like SCRS were also very thoughtful in ensuring that the sites had a clear role to play and a pathway for them to start engaging with the use of video to support patient visits, even before the pandemic.

The ability for different types of sites to invest in training and tools to support decentralized trials will vary greatly. We may start seeing separation among different in terms of their ability to invest in the state of readiness for DCTs. I suspect that more and more sites, especially more extensive networks, will take greater ownership over many of the tools and approaches in DCT. For example, will some site networks or academic-based sites make home visits for their partiicpants an internal capability? Can sites invest in their own DCT-supporting technology, such as eConsent or video visits? And can sponsors focus less on pushing less unfamiliar study-specific technology to the site, and instead start to focus on minimum quality standards and interoperability? As we see more of that, it may create some differences among different profiles of sites and how much they're able to do there. As these opportunities emerge, we will need to make sure all sites can be supported so that those unable to invest are not left behind.

MA: What are DTRA’s priority initiatives?

 DTRA is a member organization. One of our first tasks in bringing these leaders together was to define a discreet set of priorities for the organization, and our members defined four. The first is toward a clear set of definitions and language. The second is around best practices and our ability to learn from recent experiences. The third is education and using data and evidence to grow this community. And the fourth relates to those remaining barriers to global adoption and how we can start to address those together.

We then defined a collection of initiatives beneath each of those four priorities. And today, there are 12 initiatives across these four priorities supported by DTRA members. For example, some initiatives create pathways for us to aggregate and share evidence of the impact of decentralizing and use that as a foundation for curricula and other types of education and training. TSome are creating platforms that allow us to track regulatory intelligence and additional insights globally to help study teams and operators understand the global landscape related to DCTs. We share details on all 12 initiatives and their progress at DTRA.org, and all of the work product is meant for the public domain to improve the global research environment. So, there's a wide range of initiatives right now that collectively are meant to ease the global implementation of DCTs for our community and the community at large.

, MBA, MSF, is a thought leader and expert in the application of business analytics toward clinical trials, and Editorial Advisory Board member for and regular contributor to Applied Clinical Trials.

Craig Lipset, Co-Chair of DTRA, discusses the evolving nature of decentralized clinical trials and DTRA’s initiatives.

Defining Decentralized Clinical Trials

Many sites are concerned that Decentralized Clinical Trial (DCT) models will cut the site from research altogether. Terms such as “siteless trials” have been used to describe DCTs; however, some enterprises disagree with that notion. Medable, a DCT company, launched the Site Network Council (SNC) to bridge the gap between DCTs and study sites. In this interview, Mary Costello, Head of Site and Investigator Networks at Medable, and Stephanie Abbott, Clinical Research Director at Western Washington Medical Group, will discuss the changing landscape of DCTs.

Moe: Medable launched its SNC in September of this year, but it is a concept that you have been thinking about for some time.

Describe the ideas that led to the creation of the Council.

 When I joined Medable, part of my responsibility was to bring a site perspective to product development, as historically sites have often been cut out of the development process. We announced the SNC in September, but we really launched it at the beginning of 2021 and have been working together for months. One of our main goals was to identify whether technology slows sites and encumbers their work or helps. Could tech be better designed, and how could we help?

Even with this goal, the SNC didn’t just look at Medable’s platform. Instead, we looked at the entire research process from a site perspective, and a lot of our work has been focused on on-site training, which is a significant pain point for staff.

 Medable’s SNC has had several discussions about sites’ pain points regarding technology. As the research director of a site, I’ve experienced a lot of pain points! There are similarities and differences in that pain depending on where you come from and if you’re a free-standing site, part of a network, or are an academic institution. Even so, we’ve uncovered a lot of common themes

 One other important element of the SNC is our focus on inclusivity to learn from many points of view. We have eight inaugural members that represent a wide range of different clinical sites. We have traditional standalone sites that only do research, such as Rochester Clinical Research. We have an academic medical center and several blended healthcare practices. We have a member that is responsible for bringing research into Federally Qualified Health Centers (FQHCs). We have Sun Valley Research Center at the border of Mexico and California, which works with a predominantly Hispanic population. VitaLink Research, now part of Velocity Research, a network of sites in the Southeast, is also a member and, we’re planning to expand into other parts of the U.S. and the EU.

By having access to real-life insights from a range of sites, we can build a flexible solution that can be tailored to all. This group brings different experiences so we can bounce ideas off each other. In addition, they offer a transparent window into all research environments to help Medable create decentralized clinical trial workflows that meet sites’ changing needs and enable greater participation in DCTs.

Moe: Could sites be cut out of the research process altogether with DCTs?

 This is one of those times when words matter—and anyone referring to decentralized trials as siteless trials hasn’t considered the vital role that the site team plays in supporting research. The phrase removes the linchpin of trials, practically excommunicating a whole group of key stakeholders. Why do we want to remove the human connection from clinical research? It makes no sense, especially as the connection between the patient and the study team is the #1 reason why patients stay enrolled in trials.

The site model will undoubtedly evolve as the definition of what comprises a site becomes more dynamic to include pharmacies and other unique settings. All will need to adjust, but good technology should provide greater flexibility to both sites and patients. Sites want easy-to-use technology that allocates high-value resources to clinical needs and focuses more on patients. We don’t believe that research will become completely remote. Instead, Medable wants to design solutions that work for all stakeholders and for every type of research setting, hybrid, virtual, or in-person. I am passionate about this because the site relationship is why patients stay in a trial. They may come for the promise, but they stay for the people.

Medable never wants to take the site out of the research equation. We believe it remains the core of research, and we want to support sites in this evolution and provide more flexibility. Technology disrupts our traditional clinical research model, and we may see some research conducted in local pharmacies soon. We will have to be creative—especially for those in rare disease trials and patients who live hundreds of miles from a traditional site—and work to support a variety of situations. However, sites will still be the cornerstone of research.

 At Western Washington, we had various opportunities to participate in decentralized trials over the past year or so. Similarly, in healthcare, telemedicine wasn’t previously happening, and healthcare payors didn’t support the use of telemedicine at first. But then comes COVID, and we needed to reinvent how we can meet people where they are, regardless of the circumstances.

The silver lining from this horrible pandemic is that we were all forced to get creative and try new research methods. Now we have another layer, more ways to deliver care, and that is huge. If our industry is not able to evolve, then we will not be able to provide the treatments to patients or get them approved in a reasonable timeframe. It’s a balance—leverage modern technology and bringing humanity back to healthcare and clinical research.

Moe: We’re all using so many different eClinical technologies today. How can sites get more proficient at using these technologies?

 I think what’s hard right now is that we have so many different technologies – for instance, EHR systems, CTMS systems, EDC systems (which people are talking about retiring). There are the TransCelerate sponsored single investigator platforms, but then even some of the original founding sponsors aren’t using that platform. Should the site invest in the technology when some of it becomes obsolete? And which solutions should they bet on for their future?

As a bridging strategy, some sites have hired digital natives—staff who don’t have a background in patient care but know modern technology. They may be just out of school, but they’ve never touched paper their whole career. The site brings them in to train patients on using eClinical technologies, support the staff, and troubleshoot, but this is an added cost to the site. At Medable, we are working to develop solutions that fit into sites’ everyday workflows and are easy for them to use and manage.

That is how we will drive and shape the industry because there are a lot of fast followers in the tech space—once you lead, many will follow. Yet, there are very few willing to be the first to cross the chasm.

 I am a healthcare provider by training, and I have worked in research for over 20 years. And, if I have to need to download a big training manual to use new technology, I’m not going to read it. If it doesn’t work intuitively, then it might as well be broken. On the other hand, we are consumer users of technology, so we get the basics—we have iPhones and bank online, and we expect technology to be almost as easy to use in the clinical research environment. I think someday sites will get fed up and not deal with it anymore.

We have turned down studies because they come with unruly technology. We can’t hire enough people with enough skillsets to manage those types of trials. I have one vendor we don’t work with because it takes at least three hours to onboard a patient using their product despite promises that it will streamline that process. On the other hand, initiatives like those of CTTI and Medable with its Site Network Council set higher expectations, and sponsors will either step up or not have many choices but to step out.

Mary Costello, Head of Site and Investigator Networks at Medable, and Stephanie Abbott, Clinical Research Director at Western Washington Medical Group, discuss the changing landscape of decentralized clinical trials.

Amidst DCTs, Will Sites be Cut From Clinical Research?

The clinical trials industry is beginning to reemerge from the pandemic and is taking a new direction in the new post-pandemic reality. The pandemic has forced the clinical trials industry to adapt to new ways of thinking around patient-centricity; politicization seemed to have generated a renewed interest in clinical trial diversity inclusion, surging demand in decentralized technologies is transforming research, and advances in artificial intelligence (AI) and data access are allowing for new opportunities in RWE predictive research and early patient engagement. These were the main themes discussed at Disruptive Innovations to Advance Clinical Trials (DPHARM) 2021.

One of the main topics included recruitment challenges with COVID vaccine development during the pandemic. Diane Montross, Sr. Director of Patient Recruitment and Retention at Moderna, discussed that while the COVE study initially saw many volunteers, enrolling 30,000 patients in a short timeframe and ensuring diversity inclusion was a big challenge. Accordingly, Moderna needed to expand its recruitment vendor access; however, another challenge included vendor onboarding. To elaborate, specific vendor qualification and onboarding stages took time, such as the request for proposal (RFP) process, bid defenses, procurement and contracting, relationship building, vendor management, and governance, and performance tracking analysis. Hence, they partnered with Citeline Connect, which centralized the process, enabling Moderna to rapidly engage and ramp up numerous recruitment vendors. As a result, within two months, Hispanic/Latinx patients increased from 14% to 20% of the entire study population, and African American patients increased from 5% to 10%, helping to achieve its diversity inclusion and recruitment goals.

This year, diversity inclusion has been an essential topic within the biopharmaceutical industry, as evangelized by 

. Lloyd Miller, VP of Immunodermatology Disease at Janssen, discussed his organization’s approaches towards enhancing diversity, equity, and inclusion in clinical trials. Miller indicated that while FDA advises the biopharmaceutical industry to improve diversity by including patients who will use’ medication post-approval, safety and efficacy differences between patient populations are often not explored in datasets because of lacking statistical power. Nevertheless, the industry has made strides in clinical trial diversity inclusion; for example, from 1995-1999, white patient populations represented 83% of trials, whereas, in 2019, they represented 72%. Of particular note, Latinx patient populations increased from 3% to 18% in clinical trials, respectively, which is close to 

diversity representation figures in the US

Miller mentioned several challenges to enrolling diverse patient populations, including socioeconomic factors (i.e., education, culture, age, and race/ethnicity), awareness factors (i.e., health literacy), opportunity (i.e., geography and poor dissemination of information, and various communication methods), and decision factors (i.e., lacking trust in the industry and investigators, and negative preconceived notions about research). Janssen included diversity elements in feasibility assessments and segmented sites into diversity enrollment categories to overcome these challenges. However, selecting sites that can enroll diverse patients is not enough; hence, Janssen implemented educational programs, such as investigator meeting workshops, training materials, and highlighting diversity in study communications.

Moreover, other recruitment initiatives included targeted social media campaigns, local community outreach, and advocacy group outreach. Additional diversity inclusion strategies included easing the socioeconomic burden by offering patients door-to-door car service and meal stipends. These strategies contributed towards improving diversity inclusion in Janssen’s clinical trial programs.

The pandemic has unleashed demand offered by eClinical technologies that support decentralized clinical trial conduct to 

expand diversity inclusion in hard-to-reach communities

. Amidst this unprecedented demand, the clinical trials industry is known to resist novel eClinical technologies and methodologies to innovate. Accordingly, Ken Getz, Professor, and Director of Tufts CSDD, aimed to answer that question by discussing preliminary study results on the innovation process and opportunities to optimize drug development operations. This study aimed to “

characterize and measure primary process and mechanisms that sponsors use in adopting innovations supporting clinical development operations and to identify best practices and shortcomings

.” Preliminary results indicate that economic risk, regulatory risk, lack of trust in solutions, and lack of commitment contributed towards adoption barriers. The study showed a straightforward four-step process towards new technology adoption (mainly by the biopharmaceutical industry and CROs), which includes the initiation phase (i.e., identifying a need, gauging interest and initial planning), the evaluation phase (assessing and piloting), the adoption decision phase (deciding whether to adopt the technology enterprise-wide), and the full implementation phase (i.e., broad rollout, communication, and training).

This process, however, does not appear to be fast enough for respondents, as 83% believe that their company took ‘somewhat’ or ‘much longer’ to adopt an innovation compared to their peers fully, and 58% believe that their enterprise is ‘late to adopt’ or ‘last to adopt.’ The most significant challenges towards innovation are in the later phases of the process, including the adoption decision and full implementation phases. To elaborate, challenges in the adoption decision phase include insufficient evidence, inability to determine ROI, and vendor/solution uncertainty and volatility; alternatively, contributing factors included quantitative evidence, internal champions, regulatory clarity, and senior management support. In the full implementation phase, major challenges included cross-functional buy-in and support, poor commitment, economic continuity, and lack of senior management support; on the other hand, contributing factors included change management planning, communication and promotion, visible senior management participation, and training and incentive alignment.

Interesting insights that may hinder innovation appeared to be culturally related, as 42% of respondents indicated ‘high’ to ‘moderate’ risk in poor performance reviews when pursuing adoption of new solutions, and 57% mentioned that adoption interferes ‘somewhat’ or ‘greatly’ with their current tasks and project deliverables. Nonetheless, 54% of respondents who rated their enterprise as ‘excellent’ at innovation adoption indicated they were rewarded for taking on innovation initiatives.

Real-world evidence, data analytics and AI in clinical trials

Real-World Evidence (RWE), data analytics, and AI was also a topic of discussion at DPHARM, as these topics go hand-in-hand with patient centricity and engagement. Jessica Scott, Head of R&D Patient Engagement at Takeda, and Wendy Sanhai, Specialist Leader at Deloitte, discussed patient experience data (PED) trends in clinical development. There was discussion on regulatory trends with PED; for example, the ICH in 2020 recommends global harmonization in patient inclusion perspectives, and FDA suggested more consistency in patient and caregiver input to inform regulatory decision-making. Asian agencies are also focusing on patient involvement in drug development. As defined by FDA, PEDs contain information that captures patients’ experiences, perspectives, needs, and priorities, including symptoms, impact, treatment experiences, input on study outcomes, preferences, and relative importance of issues. Patient engagement examples include symptoms, the burden of disease, and treatment, to name a few. Sanhai and Scott emphasized that since many regulators across the globe are mandating the use of PEDs, it is vital to increase awareness for PED use within the biopharmaceutical enterprise, and recommended identifying appropriate programs, inviting collaboration both internally and with regulators and patient organizations, and leverage various types of PEDs (i.e., Clinical Outcomes Assessments (COA), Patient-Reported Outcomes (PROs), and qualitative PEDs, such as interviews with patients and caregivers).

Earl Seltzer, Sr. Director of Global Feasibility at Labcorp, discussed how AI and data analytics play a key role in creating better patient experiences through RWE analysis. Seltzer suggested that billions of lab test results in Labcorp’s databases allow for individual and longitudinal data analysis, which can be done with AI and predictive analytics. For example, Labcorp now can predict NASH and use this predictive model to identify and potentially contact patients or their caregivers for health screenings and introduce them to research.

In summary, diversity inclusion, technology adoption, and RWE research were all topics that were linked to patient-centricity at DPHARM 2021. Diversity inclusion has been a regulatory recommendation for several years, and the biopharmaceutical industry is making strides in enhancing diversity in clinical trials via recruitment and site selection strategies, though data on diverse patient populations collected in clinical research is still not large enough to decipher statistical results. In addition, new insights on technology adoption resistance are emerging, and it appears the biopharmaceutical industry can improve and standardize its approaches towards adopting innovation more rapidly. Finally, RWE data collection and analysis are increasing in interest as regulatory authorities are expecting some form of PDEs in submissions, and the increasing availability of data allows for emerging disease prediction and early patient and caregiver clinical trial engagement opportunities.

The main themes discussed at DPHARM 2021.

Industry Update: Highlights from DPHARM 2021

Decentralized Clinical Trials (DCTs) have taken the main stage in the clinical trials industry, which was significantly facilitated during the pandemic. However, similar to the initiation of risk-based monitoring (RBM), the concept of DCTs is at an infancy stage, and many enterprises are competing to make their mark in the field. This prompted the formation of the 

Decentralized Trials & Research Alliance (DTRA)

 to help better define and advance DCTs. In this article, Dave Hanaman, Co-founder of Curavit, will discuss his perspectives on DCTs.

Moe Alsumidaie: What is a Virtual CRO (VCRO)?

 Co-founder Joel Morse and I conceived the company from our experience at C3i, where we spent 20 years at the intersection of digital technologies and clinical research. We saw this space evolving for years and wanted to disrupt research by positively applying technology in new ways. So we launched Curavit officially in November 2019 and became the first virtual CRO—a contract research organization dedicated exclusively to designing and executing decentralized clinical trials.

As a VCRO, Curavit runs fully decentralized trials from start to finish and acts as a virtual site, managing the decentralized components of a hybrid clinical trial. We leverage industry-leading digital technologies, devices, and our cloud-based DCT platform to centrally capture, aggregate, manage, and analyze trial data for sponsors. Curavit also brings specialized therapeutic expertise for decentralized trials to ensure the most proficient minds and the best technologies are applied to every research study.

What are some of the benefits and the challenges associated with implementing decentralized clinical trials? Long term, will sites still be involved in research at all?

 One of the challenges is standardizing our vocabulary and aligning the industry on a collective understanding and definition of decentralized trials. From the vocabulary standpoint, we need to get on the same page, understand what works and what doesn’t work, and share ideas to work more collaboratively in this new digital world. I think organizations like DTRA help in that respect, and the media can help, but it is an evolution to get the industry to agree on definitions about what this is and what it isn’t.

There is also a lot of hype—often well-founded and well-intentioned. Still, it sometimes results in organizations trying to shoehorn technology into traditional trials and then call them decentralized.

When COVID caused many trials to be shelved, there were desperate and courageous efforts to rescue them. Sponsors did some things that made sense and some things that didn’t. I think the challenge is to understand what is realistic now, and soon. At Curavit, we design virtual trials from first principles – meaning, we work with sponsors and investigators upstream. These are professionals who understand IoT, wearables, digital technologies, remote data capture, and how to design digitally native trials. We focus on the elements of a trial that can be done well, using tech and work at the earliest stages to design protocols where innovative technology is integral to success and not an add-on.

Are DCTs at a stage where there is a clear definition of what they are, or are we still in the early stages?

 The simplest definition is: if you’re applying digital technologies to replace traditional face-to-face or bricks-and-mortar interactions, then you’ve designed a decentralized trial. The middle ground is less understood – the so-called hybrid trial that includes a mix of both in-person and virtual components of research.

We talk a lot about trials being entirely virtual or decentralized – and we have done some of these, but overall they still represent a small fraction of all trials – less than 5%. Before COVID, leaders predicted that 10-20% of trials would be fully decentralized in 10 years. I think that’s still a good prediction. COVID forced early adoption and created some premature hype, but significantly increased the acceptance of these processes and technologies. So, I believe DCT adoption will be considerably higher than predicted.

Some therapeutic areas are more challenging to decentralize. Even so, there are aspects of nearly every trial that could benefit from virtual technologies, even oncology. The growing middle of the bell curve for the foreseeable future is going to be hybrid trials. People have been working on this for 20+ years, but I think we’re finally getting to the point where DCTs are accepted, even embraced whenever possible.

It was the right idea at the wrong time then, but now it’s the right idea at the right time?

 Yes, and the technology is catching up to the vision. In 2007, Veeva introduced cloud-based CRM to an industry desperate for lower-cost technology models because so many major brand-name blockbuster drugs were coming off patent. Veeva’s well-touted success is an example of the right solution at the right time. Decentralized trials are similarly destined, supported by developments in IoT, wearables, and big data. People have been working to make DCT a reality for years, but the technology is finally maturing and readily available while the industry is calling for a greater focus on patients and access to trials for all. So once again, we have a case of the right solution at the right time.

Are there concerns around data privacy and what precautions is Curavit taking to protect it, especially now where the U.S. and many Western nations are under attack by foreign hackers. What can be done to address those concerns using a DCT model for research?

 From banking to life sciences, every industry is extremely concerned about protecting data. As in most things, there are tradeoffs. Decentralized trials that do not involve sites can be an advantage in limiting data risk. DCTs can be much more secure in many ways because you can centralize data in very safe, modern cloud systems. That is what Curavit is doing.

Curavit’s platform has been purpose-built for decentralized trials with proven, industry-leading software. HIPAA compliance and validation are built into the individual tools as well as the overall platform. No corners were cut in terms of applying modern cyber defenses.

Part of Curavit’s vision is to make research more accessible across all the demographics. How are you expanding clinical trials to those demographics through DCTs?

 First, DCT technologies and processes are fundamentally more suited to reaching previously underserved or underrepresented patient populations. It’s easier to expose more people to the opportunity to participate in research across social media, digital communities, and websites supporting specific diseases or conditions.

Second, and more specifically, DCTs leverage community-based outreach. For example, we partner with Clinispan out of North Carolina whose purpose is to recruit underserved populations. Par 80 in Boston partners with community health centers serving minority populations. These efforts reach out to minority populations to include those who distrust or have not been previously exposed to research.

Third, we have had ongoing discussions with a global pharmaceutical company interested in Native American populations that embody two distinct underserved groups: indigenous and rural populations.

Where do you see DCTs going in the next ten years?

 Optimistically, in 10 years, we won’t think of DCTs as unusual because the technologies and processes will be commonplace. DCTs won’t be any more novel than computerized businesses are today.

Most data capture will be in the cloud a decade from now, and DCTs will enable a more burdenless patient research experience. To clarify, that doesn’t mean face-to-face interactions with physicians will go away. Even in complex therapeutic areas like oncology, there’s plenty of opportunities to use digital technologies to gather new data and reduce patient burden. We won’t think of DCTs as a distinct subset. In 2031, DCTs will have disrupted clinical research in profound ways that are better for all patients, better for all sponsors, and ultimately better for public health.

Dave Hanaman, Co-founder of Curavit, discusses his perspectives on decentralized clinical trials.

Insights into Definining Decentralized Clinical Trials

Emerging areas in cancer clinical research pose new challenges in the small biotech industry. However, some enterprises are efficiently navigating their clinical trials by incorporating novel strategies, including the incorporation of analytics, to expand clinical trial access to patients who need it. In this interview, Vanessa Tassell, Vice President, Clinical Operations at Mirati Therapeutics, will discuss her experience in this rapidly evolving field.

Moe Alsumidaie: Mirati is progressing to a precision oncology pipeline, focused on hard-to-treat cancers in innovative ways, including targeting KRAS mutations. Considering that KRAS is known for being hard to target with drug treatments, can you talk about the challenges Mirati experienced, how those challenges shaped Mirati’s guiding principles with clinical trial program design, and how you targeted this pathway?

 As you know, Mirati was founded in 2013, and since then, we’ve pursued the most challenging mutations for our trial designs, like KRASG12C. Part of our investigational programs are looking at the most difficult-to-treat cancers, like lung, colon, and others. Our guiding principles are focused on the patients first and foremost. We also are guided by the analytics, the clinical trial design, education for our clinical trial sites/investigators, and partnerships. It is essential to work closely with our partnered molecular labs to assess the feasibility of testing to place our clinical sites in suitable locations. That is critical for understanding how to bring our clinical trials to the locations where patients are being tested. Are they academic centers? Are they community-based centers?

We also look at what we need to do to help bring education, especially to the community-based centers, for early-stage trials. Education is essential when it comes to that, and partnering with and understanding the needs of those centers is critical to our success—and again, focusing on the needs of the patients, their families and designing the trials in a way where access is a primary focus.

MA: Please describe your analytics strategy in site selection.

 We partner with several molecular labs to find where these patients are being tested. For our U.S. and our global trials, we need to understand our investigators’ treatment patterns and how we can bring more testing to those centers to give patients access to our clinical trials. So the analytics are based on our close partnerships and getting data to target those locations and specialty community centers to connect patients with our clinical trials. 

MA: What has Mirati done differently with its studies to ensure not only continued advancements in clinical development but also to serve the patients who guide your work?

 The science that we pursue is looking at novel mechanisms and combination strategies that the patients don’t have access to. Again, going back to partnering with key opinion leaders, we look to see where we can optimize our clinical trial design to make it easy for patients to access our clinical trials. It goes back to where the testing is being conducted and how we can train sites to get early testing for early-stage trials. As a biotech, we are nimble, but we also have the internal experience of large pharma in our leadership. It’s the best of both worlds when it comes to trial design, as well as a strategy for our clinical trial programs.

Key opinion leaders bring much experience to the table as part of our think tank-type model, and we have been working with them from the beginning at Mirati. Many of us have had experience with many of these investigators through prior companies as well. Collaborating is very critical for us to understand what’s happening in the field. Our current collaboration with MD Anderson is a good example. We work with several investigators who bring their ideas to the table to look at additional novel combinations that will continuously extend our clinical programs.

MA: Mirati has gone from a single asset company to a company with many assets in its pipeline over the past few years. What sorts of changes are you starting to implement to prepare for scaling clinical research and clinical operations?

 We have had incredible progress with our pipeline. I’ve been with the company for eight years, so I’ve seen it go from a single asset to a multi-asset company. We have two clinical-stage assets that both have registration trials currently. We also have two potential first-in-class preclinical programs: a KRASG12D inhibitor and the synthetic lethal PRMT5 inhibitor. Working with key opinion leaders, who hold a strong belief in our science, has helped us because we can go back to these think tanks to support us with the best design options and understand the capabilities of these novel designs to where we can get patients access.

We’re also very fortunate to have an in-house research group with discovery capabilities working closely with our clinical development colleagues. We have this constant pipeline of candidates to build the infrastructure needed to have a late-stage company and a company that can focus on Investigational New Drugs (INDs). We have built those efficiencies over time, and as we’ve grown, those competencies have grown.

MA: Can you tell me a bit about the differences between an early-phase versus a late-phase type of infrastructure? Are you vertically integrating and bringing some of those tasks internally versus outsourcing?

 We have first-in-human studies to large Phase III programs. We have a variety of vendors that we work with to optimize our internal infrastructure and use different service providers to help us scale to what we need, not only in the U.S. but globally. We’ll continue to work in this fashion to build the infrastructure to support our pipeline.

MA: Could you tell me how headquartering in San Diego helped to advance clinical trial programs and what benefit this location provides to Mirati?

 San Diego is an excellent hub for innovation and key for continuing our collaborations and partnerships with key opinion leaders and community-based centers. We’ve recently moved into a large facility in Torrey Pines, where we have our integrated team, including dedicated scientists who will continue to push forward our pipeline. As a biotech hub, it’s an excellent location for talent and a great place to attract talent from other locations. Being in San Diego has helped continue our collaboration and our innovation.

Among the standard obstacles encountered during clinical trials, Mirati had the added challenge of conducting clinical trials within a pandemic. Can you tell me a bit about how COVID-19 impacted the clinical trials for a smaller biotech company like Mirati, and what strategies have you leveraged to navigate this environment?

 Being a science-based company, it was vital for us to focus on the safety of the patients and the staff who were part of our clinical trial program. We worked very closely with the clinical sites to understand their institutional policies and practices and with our vendors to help support the changing landscape. Part of this was understanding how we could be flexible in our clinical trials, follow industry regulations, and establish new processes to allow for flexibility for our patients. We would work with the clinical sites and provide them with flexibility when it came to scheduling patient visits, ensuring that we were supporting them as much as possible to help them accommodate patients.

We modified our protocols; we gave allowance for flexibility. We supported updated procedures at our core vendors to ensure that we could do a decentralized data review. We didn’t skip a beat to ensure that we reviewed clinical data, specifically safety data, and ensured that our patients could stay on the study. Again, focusing on making sure that we were partnering with clinical sites to understand what they could do to help us limit the negative impact on our trial recruitment and continue to add clinical trial sites, which was critical globally. It was essential to partner with our vendors and clinical sites to ensure that we followed regulations and kept patients’ safety in mind.

MA: So, how do you see things moving forward regarding the pandemic and in this new environment that we operate in?

 I think we need to keep our eyes wide open. We need to continue thinking about how we can optimize our clinical trial designs to ensure flexibility. It will be critical to look for processes and technologies that ensure patients can continue to be seen and that sites can continue to access what is needed for their patients. The industry needs to take this very seriously since this will continue to be part of trial design and strategy moving forward. This continuous flexibility will be required to keep patients safe and give them access to clinical trials.

Vanessa Tassell, Vice President of Clinical Operations at Mirati Therapeutics, will discuss how some enterprises are navigating trials by incorporating strategies to expand clinical trial access to patients who need it.