Moe Alsumidaie

The clinical trial landscape has changed significantly post-pandemic, and many industry experiences and strategies emerged at DIA 2022. in this interview, Barbara Lopez Kunz, president, and global chief executive at DIA, discusses key themes on the current state of the clinical trials industry and its future.

Moe Alsumidaie: Post-pandemic, what are the most significant changes in drug and clinical development?

 We've all seen drug development evolve over the past few years, but the pandemic catalyzed some of the things we've discussed. It turned our talk into action, which we love, and hope will continue.

As the pandemic spread, we all faced the same challenge. As a result, international collaboration increased, and as part of this international exchange, formal work-sharing initiatives and dialogue emerged, and there is a strong desire to use the pandemic response's flexibility and innovation to address unmet needs in other disease areas. This has been DIA's mission for nearly 60 years.

We’ve seen a few emerging trends. First, we see a sharper focus on including diverse patient populations in clinical research and development so that the solutions are effective for those who need them most. Pandemic urgency helped integrate clinical research into communities that may not have felt welcome or understood how to participate. While diversity inclusion has made strides, we still need to improve our outreach and integration of all communities.

Second, there is expanded collaboration; since it doesn't matter how effective therapies are if patients can't access them, DIA has brought in new players. Pharmacy benefits, reimbursement, health technology assessment, and other experts engage earlier in the drug development lifecycle so all perspectives work together.

Last, decentralized clinical trials have emerged quickly and are here to stay. Tufts University's Center for the Study of Drug Development showed that decentralized processes increase drug development efficiency. Our DIA Global Annual Meeting 2022 program included many DCT themes.

MA: What are some companies' DCT implementation challenges?

 DCT adoption is a significant change, requiring the proper methods, tools, and training. DCTs will bring new challenges, such as ensuring appropriate training and delivery across sites and improving data collection and management. Until new approaches are solidified, drug development will use proven methods. As in change processes, some companies will move forward with decentralized trials while others wait for a larger mandate, monitoring understanding, process, training, and regulatory guidance. Clinical trials are the most time-consuming and expensive part of drug development, so process changes should reduce risk.

MA: Post-pandemic, what regulatory changes have you seen?

 Regulators want to keep pandemic-era flexibilities. Regulators are accelerating changes in structures and processes to be more patient-focused. I'm seeing more patient engagement and patient-centric drug development now.

In the US, the FDA published guidance on patient-focused drug development, including collecting patient input, identifying patient priorities, and developing meaningful outcome assessments. In Europe, the EMA endorsed the PREFER initiative's patient preference, integration, and drug development framework. The ICH is working to harmonize data submission requirements for patient experience. Patient-centricity is entering countries' regulatory agendas. Asia, the Middle East, and elsewhere are seeing new patient engagement communities. DIA has long supported these efforts, and we're actively generating new patient engagement knowledge and learning opportunities for our community.

New data collection and analysis pose challenges throughout the drug development pipeline. Patient privacy, data ownership, and data integration will determine how we use these data to drive R&D efficiency now and in the future. The EMA and HMA (Heads of Medicine Agencies across Europe) maintain a collaborative data steering group to easily integrate big data and advanced analytics into their regulatory assessments. Signal detection uses analytics to automate case adjudication and identify false claims, adverse events, and illegal marketing. Darwin-EU enables real-world data analysis and post-market surveillance and decisions. The FDA has seen a rise in AI/ML-related submissions in the US.

MA: Where do you see clinical development headed in an uncertain world?

 We're all in transition. New covid variants are emerging, and we're preparing a response. In addition to the pandemic, geopolitical issues, war, and unusual weather are causing health-related crises. We've made great strides in healthcare, and I'm proud of that, but we must continue collaborating and sharing our findings. We must create clinical trial designs that address our challenges. We must better prepare for collateral challenges, such as supply chain issues. Many companies and regulatory agencies must stabilize their supply chains to meet demand and launch new products. Global crises will persist. As a neutral convener, DIA will continue to address these issues. And we'll keep putting patients first as a healthcare community. DIA's sharing and learning environment fosters ideas and creates momentum and practical ways to implement them. As new knowledge emerges, we revise and refine our learning offerings to ensure they offer the latest regulatory, clinical, and data science content our community needs.

MA: How is DIA supporting clinical trials' future?

 One DIA board member said years ago that we’d create it if DIA didn’t exist. I couldn’t agree more. In 1964, our founders couldn't have imagined how important a trusted, neutral, global platform would be for therapeutic development today. We knew years ago that we needed to improve access to DIA's knowledge, so we digitized all of our content and created a multi-year archive that we updated with new information. Creating a digital DIA was unrelated to recent crises. This work was done so that life science professionals worldwide could access the latest knowledge of science and policy. All stakeholders developing new therapies should use the latest information.

We've created a digital platform to keep clinical development experts like you informed and educated and to share what you've learned. In the early days of SARS-CoV-2, we launched the DIA Direct series to share China's experiences with healthcare delivery, drug use and repurposing, and clinical trials. This helped us engage thousands of members and stakeholders in knowledge exchange, accelerating the response to covid. Today, we're publishing a new DIA Direct series on clinical trials and the Ukraine war. This series has helped clinical research, and care communities in Ukraine share their experiences so others can learn and support them.

DIA offers regulators and the healthcare community a global, digital, virtual, and in-person neutral platform. We'll keep building strategies to prepare for the next disruption. You may remember that we presented a snapshot of the future of healthcare at DIA 2022. Next year's DIA Global Annual Meeting 2023 (in Boston) will focus on clinical research and healthcare challenges. This meeting's theme, Illuminate, aims to highlight the latest in drug development and our global collaborative network, which can transform individual professional expertise into actionable progress that benefits everyone. The DIA 2023 Call for Abstracts is open until October 6.

Articles

Barbara Lopez Kunz, president, and global chief executive at DIA, discusses key themes on the current state of the clinical trials industry and its future.

Key Clinical Trial Industry Themes Post-COVID

Moe Alsumidaie: Danielle, why did you start Black Women in 

 I started Black Women in Clinical Research after attending an investigator meeting in 2019. In a room of hundreds of people there we only two Black women, including myself. It made me question whether it was a lack of diversity in the room or in the industry. This all stated with a Facebook group. I never imagined that people would join the group or even like the idea.

Initially, spreading the word was difficult. We've partnered with CROs and pharmaceutical companies over time. Big pharma and CROs supported my mission to increase diversity in clinical research because many companies want to increase diversity. The organization has grown to over 12,000 members. People who want to join the clinical research industry are often rejected. I want to be a resource for my members and companies looking to increase workforce diversity.

What's the significance? Why is this important?

 Early in my career, I wanted to go to medical school, but there weren’t a lot of career options for someone who has a bachelor’s degree in biology. I ran into a college classmate who told me about clinical research who said I could work from home and travel. I said sign me up immediately! Unfortunately, I was rejected for every clinical research job I applied for. I used my challenges to assist members with the tools to help them enter and succeed in the clinical research industry. It's my life's work. My passion is assisting Black women, men, and minorities enter the clinical research industry.

Indeed. August is Black Business Month; Black entrepreneurs launch innovative startups, but many lack a strong network, mentors, and advisors who foster growth and create a supportive community. 58% of Black business owners in the US believe a strong network would boost their success. How does BWCR help black women enter clinical trials?

 We offer career services to the members. Some of the services include resume reviews, interview prep, mock interviews, career coaching, and LinkedIn summaries to name a few. We want to help members get into the clinical research industry. So, we equip members with the tools to prepare them to enter the clinical research industry. Applying to positions and getting rejected can be daunting when starting a career in clinical research. Many people are disappointed when they are rejected and think what is wrong with me?I've been there, so I can relate with what some of the members go through. We provide sisterhood, brotherhood, and support. As you said, the industry lacks mentorship. We want to offer that to members because many don't realize they have transferrable skills and experience. People often don't know what positions their transferable skills apply to, and we provide a safe place for people to get into clinical research. We discuss various clinical research careers monthly, as many only know about CRAs. We want to help people realize their potential in clinical research so they can be successful and thrive.

 A lot. But most importantly, I want my members to attend clinical research conferences. The cost of clinical research conferences makes it difficult for newcomers to follow. The clinical research conferences have so much helpful information, but it's hard to convince people to go to those conferences because they're so expensive. If we want diverse people at clinical research conferences, we need to help them financially so they can attend. Newcomers to the industry can't afford to attend $1,000+ meetings. Not to mention the additional costs of travel, food, and lodging. People don't attend conferences for many reasons, but it shouldn't be because of financial restrictions voiced constantly by BWICR members. This is my call to action for the clinical research conference organizers, a scholarship for members and diverse clinical research professionals to attend the conferences would be a great start. I am open to planning or finding a way to get newcomers to the industry to hear this information at the meetings.

What can Black women contribute to conferences, and what will they gain from attending?

 Diversity is essential in clinical research and patient care. You want to be heard. We must show up in these spaces to represent people who look like us because people can relate and contribute perspectives from our communities, especially patients. Everyone should be represented in these spaces, regardless. There are also many learning opportunities, creating a level playing ground for blacks and minority clinical research professionals. I always encourage my members to attend conferences. Fall has many meetings. I'm always asking clinical research conference organizers if there's a discount code because I want to see people who look like me and want them to receive the same information.

Our community finds those conferences valuable; I spoke to as many black professionals as possible at DIA conference. One woman thanked me for talking to her. She said, "You're the first person to say hi, stop, and ask how I'm doing." "What you're doing is important and relevant," she said. "I'm glad you're here," she said. I nearly cried. I was moved to tears. You never know how a hello or introduction will affect someone. I value it. I'm passionate about helping people get into the industry and attend conferences.

Is there anything else about BWICR you want to tell the industry?

 Yes, we have talented and skilled members. Many have master's degrees, PhDs, physicians, and nurses with skills transferrable to clinical research. Our group is diverse. The industry should consider people who do not have clinical research experience a chance. It shouldn't be this hard to enter, especially if you have transferable skills.

Danielle Mitchell, Founder of Black Women in Clinical Research, discusses how her foundation bridges the gap between minority professionals and clinical trials.

Breaking the Minorities Gap in Clinical Operations

Decentralized clinical trials (DCTs) are an ambiguous concept. Some sponsors give patients or sites the option to choose DCT in addition to more conventional clinical trial methodologies. Technology firms that had already based their operations on DCT (i.e., ePRO and EDC companies) before the concept of DCT existed are now repurposed as DCT solutions. Decentralized service businesses have prospered, offering services like remote blood draws at the patient's home.

DCTs are here to stay but are unclear to many, according to an interesting industry discussion I had on the subject with a few clinical trial professionals.

The Decentralized Trials and Research Alliance (DTRA) recently released a definition for DCTs as 

“a clinical trial utilizing technology, processes, and/or services that create the opportunity to reduce or eliminate the need for participants to physically visit a traditional research site.”

Word on the street: The definition is muddled

Qualitative feedback on DCTs indicates the definition is muddled*:

The environment is still very muddy. Many sponsors refuse to take even the smallest steps toward simple "DCT" solutions. I've attempted to persuade sponsors to adopt site-side solutions, but they're not interested. Eventually, I'm sure, things will begin to stabilize, but right now, everything seems to be in disarray.

“DCT/Hybrid trials are a fantastic idea, but their execution is subpar because planning ignores trial sites.”

“DCT will remain in place. Cultural obstacles and technical flaws, or let's call them what they are, "technology knowledge gaps," would progressively decrease after adopting comprehensive quality control measures for bridging these gaps, as required by GCPs.”

 “DCTs have not yet delivered on their promise of patient-centered research with less administrative burden.”

“The concept of DCTs is still relatively new in the clinical research world, and meaningful, lasting change is not something that takes root quickly in our industry. I think it is important to have a consensus or general agreement around the term DCT. Time and clarity around meaning will be the benchmarks for more widespread adoption.”

DCT must be more adaptable so that patients may choose the setting they feel most at ease. I am not opposed to DCT, but it must be comprehensive and consider the rising demands of the larger population. DCT must be more adaptable to let people choose the environment where they feel most at ease.”

“You shouldn't restrict patients from feasible options in DCT. Choosing where to get blood drawn that particular day gives patients extra freedom. We must consider that extra options also leads to greater programming complexity, so best to find the right balance. More options make a good patient experience, but they must be high-quality options, with supported processes.”

 DCTs must deliver high-quality options to patients and sites.

 Sponsors must incorporate the site’s perspective when designing DCTs.

 More companies adopting and executing DCTs will yield data, contributing to consistency and clarity.

Clinical trial scalability and quality risks are two critical aspects to consider when incorporating optionality. Although clinical trials have a high degree of consistency (especially in relation to ICH/GCP standards), operating studies always vary unexpectedly. While giving patients and sites more options is beneficial and more patient and site-centric, introducing more study risks has a negative impact. For example, the reconciliation of lab data from a mobile blood draw vendor that processes bloodwork within its lab and bloodwork shipped to a central lab from the site necessitates additional training and effort to maintain data quality from two distinct sources (especially if different vendors are used for DCT and traditional clinical trial methods). Another example is reconciling investigational products from two vendors who ship and track them differently (i.e., either to the patient's home or to the site).

Expecting studies to scale with too many options or without consistency (i.e., using two vendors instead of the same vendor to conduct both DCT and traditional methods) not only introduces risks but also increases workload and resource utilization to run the study. The key will be finding a balance between offering robust and consistent traditional and DCT options to allow for clinical operational quality and scalability.

I recall the early days of risk-based monitoring (RBM) when the FDA issued its first guidance on the method. Many sponsors defined their version of RBM, and many vendors jumped on board. It took years for the industry to standardize and implement the process across the board and for genuine RBM vendors to stand out.

I expect a lot of debate and different models on the topic of DCT at first. However, the concept will evolve into a more standardized construct across the industry as regulators, non-profit organizations, sponsors, and vendors work together to standardize it. It will be an interesting evolution to watch.

* Comments are anonymized and rephrased to protect user privacy.

While DCTs continue to take hold on industry, questions remain.

“Decentralized Clinical Trials” is Muddled

Sponsors are losing ground to study sites: “We will deprioritize your study.” Sponsors expend a tremendous amount of resources identifying and initiating new sites for their studies; however, these investments are wasted when a study site deliberately diverts study resources away from studies that are operational failures—or, in essence, when the site quietly quits your trial.

"There is too much risk to prescreen subjects compared to the amount we receive after they enroll," "the protocol is too strict," and "patients aren't enrolling because their stipend is too low" are common reasons why sites deprioritize studies. In this article, I will share my experience and provide recommendations.

What is study deprioritization, and why do they get deprioritized?

After site initiation, study deprioritization occurs when a site deliberately diverts resources away from your trial. The typical cycle begins with the hope that the clinical trial will enroll patients; once initiated, the site attempts to enroll patients but fails (for a variety of reasons), then realizes that the recruitment effort was not worth the risk, and they refocus their resources on studies that are more likely to enroll patients.

Common causes of deprioritization of clinical trials include the following:

Insufficient or No Patient Recruitment Resources:

 Many sponsors erroneously rely solely on the patient volume at the study site to meet enrollment goals without supplementing recruitment with a recruitment campaign. When sites no longer have patients in their database, they begin to forget about your study. In addition, a lack of prescreening services to sift through hundreds (and sometimes thousands) of patient leads will quickly overwhelm sites, who will realize the effort is too resource-intensive and deprioritize your trial.

We are all aware that protocols have become increasingly complex, requiring sites to screen numerous patients before enrolling a single participant in your trial. A screen fail-to-enrollment ratio is no longer an effective strategy (since it works against the site regarding risk/reward). In addition, once a patient is prequalified, obtaining medical records post-pandemic has proven to be a significant obstacle for study sites, exhausting site resources.

 The most frequent question on a site feasibility questionnaire is whether the study site is conducting clinical trials competing for the same patient populations; however, sponsors and CROs rarely, if ever, inquire about whether the site is conducting clinical trials with high study visit or patient stipend compensation. If your budget per patient or patient stipend is too low, sites will deprioritize your study.

Why is it important to prevent deprioritization?

Deprioritization of your trial is the worst possible outcome. Not only do you waste capital and resources on initiating the site, but you also miss your target enrollment numbers due to missed expectations and, as a result, delayed study completion timelines, continue to spend capital maintaining the site with regular monitoring visits, and pay closeout visits and fees—all of which result in a negative return on investment.

Tips on preventing clinical trial deprioritization

 To increase the likelihood of successful enrollment, you may want to optimize your protocol using real-world evidence (RWE) data. By comparing your protocol's inclusion/exclusion criteria to RWE, you can modify your inclusion/exclusion criteria to maximize enrollment potential and reduce the likelihood of study deprioritization at sites.

Offer Site Resources for Patient Recruitment and Prescreens:

 Even with RWE-optimized protocols, they will remain complex, and it is essential to remember that site staff spends a substantial amount of time prescreening patients before enrolling the one patient who qualifies for your trial. Launching a patient recruitment campaign and providing prescreening support (i.e., phone screening patients and referring only those who prequalify or providing financial support for study site prescreening activities) would prevent deprioritization of the study.

Patients are becoming more knowledgeable about clinical trials, and many expect compensation and reasonable compensation; giving patients $200 for five study visits totaling 14 hours of their time will cause them to flee. Moreover, cutting costs on research budgets gives sites an advantage. They would sign a contract to earn site startup fees, but they would deprioritize your trial once they realized the amount of risk required to enroll patients about the reward of enrolling them. Utilize coverage analyses and consider covering patient costs for standard-of-care (SOC) (as some health insurance may not always accept SOC procedures determined by you). Consider the cost of inflation, which has increased by approximately 10%.

Clinical trial payment delays are common for sites. Ensure that your sites are paid on time, and if you outsource site payments to a CRO or vendor, implement an oversight process to ensure that they are paid on time. Failure to pay sites on time results in legal issues and will cause sites to deprioritize your trial.

The deprioritization of clinical trials seems to be primarily related to risk-reward tolerance, and study sites are adept at measuring this tolerance, leaving sponsors with underperforming trials. Despite this, sponsors ignore the realities of complex protocol design, poor protocol optimization, substandard recruitment and prescreening support, and limited study budgets. By addressing these issues, sponsors could prevent sites from deprioritizing their trials.

Risk-reward tolerance standing in way of underperforming trials for sponsors.

Sites Are Quietly Quitting Your Studies

Minority patients are not participating in clinical trials because they do not trust the medical community, and FDA has noted the lack of diversity and inclusion of patients in clinical trials. In this interview, Patrice Matchaba, MD, President of Novartis US Foundation, created The Beacon of Hope, the first Clinical Trial Center of Excellence focusing on building bridges between clinical trials and minority communities, will discuss how the biopharmaceutical industry can regain the trust of minorities.

Moe Alsumidaie: What is the Beacon of Hope and the purpose of this initiative? And what does Novartis hope to accomplish with it?

That question probably is the most critical as it relates to this vital initiative. You may recall that during the COVID-19 pandemic, the discussion centered on Black and Brown communities not wanting to participate in vaccine trials—and this became a discussion even among the FDA, which noted the lack of diversity and inclusion of patients.

And then the second thing was the impact of COVID-19 on the hospitalization and death rates of African Americans, Hispanics, and other communities. At the time, many rushed to issue press releases saying they encourage patients and embrace diversity and inclusion, which is the right thing to do because we need to know the natural causes of why these patients are not participating in clinical trials.

And as you know, trust is a big issue. The lack of trust in research and development and the US healthcare system has much to do with communities of color not trusting the medical community, and justifiably so.

First, we decided to consult with the communities we want to help increase diversity and inclusion. We engaged with the deans and presidents of the 26 Historically Black Colleges and Universities (HBCUs), including the Thurgood Marshall College Fund, the National Medical Association, and President Valerie Montgomery Rice of Morehouse School of Medicine. Yes, patients are not participating. Yes, there is a trust issue. And then, as you dig a little deeper, we realize that there are no investigators from the community working on these clinical trials.

As you know, the more complex the studies in terms of radioligands or cancers with gene therapy, you find zero investigators of color. So, if you have a trust situation and don't have the proper investigators to conduct the clinical trials, how will you increase the number of participating minority patients?

Second, the impact of hospitalization and death rates became clear to us that we haven't just aggregated the social causes of the increased morbidity and mortality versus the biological factors, and there is an assumption that race is the crucial factor when it's probably more social.

We met with our partners, stakeholders, and community leaders throughout the last year, and after four months of ongoing discussions, we were able to announce the Beacon of Hope, which is a collaboration and the first-ever Clinical Trial Center of Excellence at Morehouse School of Medicine.

Insight was simple: it all centers on STEM education. Even in high school, kids drop out, so very few get into colleges and study STEM. College fees in the US are costly, as you know, so students of color often don't have enough money to study long courses.

The first thing we learned was even the brightest kids from the African American and Hispanic communities—when they finish their pharmacy, nursing, or medical studies –don't stay at the universities and engage in clinical trials because they have to go back home and work and support their families. And that’s very unfortunate because the HBCU medical schools and universities don't have the same endowments as Harvard or MIT. Therefore, they can't do clinical trials in a sustained manner. And that’s why we included the funding of HBCU scholarships as part of this initiative—a total of 360 over ten years.

MA: How does the Beacon of Hope prepare investigators for entering the field of clinical trials?

So, when we looked at the four medical schools, their experience performing clinical trials was quite different. Howard is the only historically black medical school with its hospital, so they do a lot of clinical trials. Morehouse School of Medicine is also more advanced. But when you look at Charles Drew Medical School and Meharry Medical College, they will need more support in the future than Howard and Morehouse.

What we did with Morehouse was we presented our portfolio from proof of concept to the next ten years and said: “choose the disease areas that have the highest impact in your community in Atlanta.” As a result, the first Clinical Trial Center of Excellence at Morehouse is operational. It will initiate its first study on a clinical trial evaluating a cholesterol management pathway in patients who have also experienced a recent acute coronary syndrome event. And they are currently evaluating cardiovascular, breast, and prostate cancer trials and will soon begin to consider Merck and Sanofi clinical trials.

MA: And over time, I'm assuming they would start as sub-investigator or principal investigators to gain that experience?

Because these are primarily new clinical trials, many of them will be sub-investigators, and the goal is that they will learn from more experienced clinical investigators. But the intention is that, over time, we want to see these investigators conducting clinical trials on more prevalent diseases among populations of color. For example, lupus nephritis is a kidney disorder that is a complication of lupus that can be very serious and is almost 30 - 40% more prevalent in females with African origins. There's another condition called hidradenitis, a condition that causes small, painful lumps form under your armpits, particularly under the skin. This condition almost exclusively impacts females and African Americans.

The principal investigators are the ones doing the clinical work based in the community, particularly given the time it takes to carry out these trials, which may be 10 to 15 years or more. Additionally, we want to build a much more diverse database of investigators in the future. And for this, we are enlisting the help of the National Medical Association, representing more than 70,000 African American and Hispanic doctors.

MA: What kinds of clinical trials do you anticipate will be conducted to expose these investigators to the focus areas of the Centers of Excellence, and why is that beneficial to the African American community?

Regarding clinical trials, the more complicated the trial in terms of technology, gene therapies, cell therapies, the innovative RNA messenger vaccines—the more reason for these clinical investigators to be heavily involved in these new technologies as they learn more about the specific conditions that disproportionately impact the African American community. I go back to what I said before regarding trust being a considerable component of this endeavor. You need to integrate those new technology trials into these communities, and it must be with trusted people and investigators who look like them and are embraced by these communities.

MA: What impact do you anticipate this initiative will have on other pharmaceutical companies?

We are thrilled to have these companies bringing their diverse portfolios, different technologies, and added scalability to the Clinical Centers of Excellence while making them more sustainable. I want to be clear that this is not just about Novartis. We’ve already been approached by several other companies leading up to the Beacon of Hope expansion announcement. Big ones and even small companies bring their unique expertise and experiences to this project, making it more diverse.

You may recall that FDA guidance on underrepresented racial and ethnic populations in clinical trials was released in April. Now, suddenly, there's pressure to say we need to find new centers and patients, and the smallest companies will struggle to compete for patients. We, at Beacon of Hope, welcome these small biotech companies and say, you come in and create the operational and intellectual capacity and conduct these clinical trials right here in our Centers of Excellence.

MA: What changes would you like to see for Beacon of Hope in the next five years?

Well, the simple one is what everyone is currently talking about: being more representative of the diversity and increasing diversity in clinical trials. But we also want to improve the number of investigators of color, male and female, from all races and ethnicities. The number one lesson I learned the most was the use of race data in diagnosis and algorithms and the 

 published on that. If you remember, during COVID, the pulse oximeters overestimated Black and Brown patients' oxygenation. Because in the calibration, Black and Brown patients were not included as part of original trials and testing.Now there are another 16 diagnostic areas that include race for treatment, and that's why we've created another Center of Excellence to begin reviewing the use of race and data in medicine over the last 200 years. That will be the most significant impact, and then by creating trust among minority communities, they will begin to trust our healthcare system and embrace innovation.This will prove valuable the next time we face another pandemic.

MA: What advantages does Beacon of Hope offer to the minority community compared to DCT companies?

We will announce a technology company joining the Beacon of Hope as our technology partner. Decentralized trials are essential. But there is no point in having the technology if you don't have the trust factor. Without trust, we will not be allowed to enter these vital communities. That's the COVID lesson, which we cannot forget. The technology exists, as you know. But without the trust, you must involve African American stakeholders and influencers, such as churches, barbershops, and community leaders. Then they will allow you to start collecting data and taking samples at home; trust is the main currency here.

In this interview, Patrice Matchaba, MD, President of Novartis US Foundation discusses how the biopharmaceutical industry can regain the trust of minorities.

Engaging Minorities is All About Trust in Clinical Trials

Decentralized clinical trials (DCTs) was a big topic at DIA this year, as the clinical trials industry started adopting more DCT methodologies. Many questions remain about the value of DCTs, but Ken Getz, executive director and research professor at the Tufts Center for The of Drug Development, shed some light on this new area with breakthrough findings with ROI and eNPV models.

Why was DCTs an important topic, and why now?

 The pandemic necessitated rapid adoption of DCTs, but we've been discussing DCT deployments, experience, use cases, and anticipated impact for quite some time. DCT adoption has occurred without the normal phased adoption process that has time to unfold. Because it's been so rapid, the industry has a lot of questions on how to manage the best DCT moving forward, how to allocate resources, and where to invest. Organizations want to know how they can more intelligently manage DCT use.

Medable's Pam Tenaerts, MD, points out the definition of DCTs, so everyone reading is on the same page. We used CTTI's recently updated definition of DCT as those trials in which some or all study assessments or visits are conducted at locations other than the investigator site via any or all of the following DCT elements:

Mobile, or local healthcare providers, including local labs and imaging centers

Home delivery of investigational products

DCTs can be wholly remote or partially decentralized with hybrid approaches. For example, hybrid trials require some visits to be conducted on-site while other visits or assessments are performed at a participant's home or within their local care community.

Pam, who presented with me at the DIA Annual Meeting in June, and her team at Medable are determined to understand whether DCTs live up to expectations of better research. They are committed to providing metrics that indicate protocol performance improvements compared to brick-and-mortar trials…this is the first step on a journey to understanding the real benefits of DCTs.

Can you tell me more about the purpose of Tufts CSDD's study with Medable on DCTs? Why is this research necessary?

 The Tufts eNPV study of DCTs is the first study quantifying the value of DCTs, specifically their return on investment or ROI. It's such a critical metric that's used to evaluate any investment. It's the most common metric to assess investment in new technology. ROI speaks a vital language, most notably to resource managers, senior management, and strategic and portfolio planners, and it can inform decision-making on DCT investments moving forward.

The Tufts center does a lot of expected net present value (eNPV) modeling studies. Medable took a leadership role, requesting that we evaluate the ROI of DCTs. This answers some critical questions that many companies are asking now, so it's very timely. Medable was remarkably perceptive in recognizing that this is something that would provide necessary insight now. Medable executives, including Pam Tenaerts, Mary Costello, Andrew McKinnon, Ingrid Oakley-Girvan, and of course, Michelle Longmire, are some of the people who are committed to gathering data and insights that will help us understand how to best leverage DCT solutions.

Speaking of data, can you discuss the study's methodologies and which KPIs the study focuses on?

 Many eNPV modeling studies use anecdotal data or simply assumptions. It's essential to recognize that for this study, we're using actual data to populate the model.

There's a period before drug approval where the cash flows generated are negative—outflows or expenditures to cover all pre-approval development costs. Post-approval is when a period of inflows as the program enters the market and ramps up to achieve its sales potential. We discount that revenue stream, or cash flows, back to the current net present value. Our eNPV model begins with data on benchmarks from existing development programs.

Our model uses a typical drug development expense profile and commercialization revenue generation profile to develop a standard development program's overall cash flow life cycle.

For a development program supported by DCT, Tufts had data from a sample of nearly 200 protocols, where a subset indicated that they used a DCT solution. So, we could compare those roughly 150 protocols that did not use any DCT to that smaller subset of 33 protocols that used a DCT solution to assess DCT impact on clinical trial performance. Medable provided Tufts CSDD with de-identified contracts from 33 phase two and 22 phase three clinical trials so that we could populate the model with actual data on the cost to deploy a DCT solution. The DCT model was based on existing clinical trial performance and investment data.

When it comes to KPIs, the model looks at value drivers. What's driving a cost reduction? What's going a change in speed? These drivers change the shape of the cash outflows and inflows we are modeling. For example, a faster study will result in a shorter development time. So, the time that development expenses are being incurred is compressed, and there are other things like the quality of the clinical data and execution efficiencies that might also change the height or depth of the curve. All of these drivers modify the model. Then, we compare the expected net present value modeled with and without DCT to assess the financial impact—positive or negative. This is precisely how we develop an ROI for a DCT deployment.

Taking a closer look at that visualization of the eNPV, it seems that the cost of conducting research with DCT is slightly less than a traditional trial, especially in later phases. Could you explain that?

 Technically, the direct or absolute cost may not be less. That's something we haven't determined. It's the time value. A dollar spent today is worth more than a dollar spent tomorrow because it's accruing interest. This curve is capturing 12 years, so we know that when we look at the capitalized cost, there are some savings because we're compressing time.

But the direct cost, I can't answer whether the absolute dollars are lower. They may be higher for a concise duration. There may be higher training costs and costs for the actual tech device or the technology itself. But when you discount the revenue stream, and you've had more time in the market for a drug to generate revenue before it loses its patent protection or exclusivity, that's where the real gain is achieved.

So, what about DCT drive speed and efficiency?

 Our study already shows improvements in patient recruitment and retention. Dropout rates appear to be lower in our comparative assessment. Second, the screen failure rates improved, and that may be because there is greater decentralized access to a trial. More people who may be eligible are willing to inquire about participating in the study, essentially self-selecting because it appears to be a more accessible study to join in, either because it's conducted locally or there will be more opportunities to participate from home.

Third, with improvements in recruitment, there are often fewer protocol amendments. The number one reason we amend protocols is to relax the eligibility criteria. So that's another factor that we picked up here, and amendments add a lot of unbudgeted costs. A lower number of amendments is changing the cost curve measurably on the spending side of our product life cycle.

There are many other areas we haven't measured yet, but we hope to have data that will show the impact that DCT offers in the form of automation at the site execution level. For example, does it provide faster access to data? If so, we'll perhaps also see improvements in data management cycle times and data quality.

Were you able to assess patient diversity?

 Unfortunately, we haven't been able to assess that yet. However, there's a possibility that we'll be doing a project in this area in the future. The Tufts Center is currently applying for a grant from a foundation to study population representation in DCTs.

Ken Getz, executive director and research professor at the Tufts Center for the Study of Drug Development, discusses the value of breakthrough findings with ROI and eNPV models. 