Moe Alsumidaie

Clinical research is radically changing as more and more trial sponsors embrace a decentralized model to solve two fundamental challenges: addressing barriers to clinical trial accessibility and improving diversity amongst clinical trial participants.

At least half of FDA trials in the US are conducted in only 1-2% of zip codes. Low participation in clinical trials remains an issue across research, with less than 5% of the global population participating. In addition, 

85% of clinical trials fail to meet their enrollment targets

, which is more than three times the number of 

 Of the trials that achieve their enrollment targets, a lack of diversity due to accessibility remains a big issue. If the current clinical research process doesn’t adapt to these changing population demographics, the life sciences industry will continue developing drugs and devices that are only shown to work for a select few, leaving out the rest.

The access to novel clinical trial digital tools creates opportunities for patient diversity in research. As a result, we see a shift from site-centered to patient-centered research, as the industry is proactively engaging with patients in a way that better fits their needs, according to Dr. MaryAnne Rizk, Medable’s Chief Strategy Officer. The goal, says Rizk, is to ensure that we are actively capturing the voice of patients so we create better treatments for everybody. In this interview, Rizk discusses how this shift will manifest in real life.

Should all drug development be patient-centric? What are the biggest challenges in clinical research today hindering patient-centricity?

 I believe decentralized research is the path to all-inclusive medicine for the broader patient population. We get there by creating a more convenient journey for patients that empowers the flexibility of choice for clinical care as an option that is either remote or a hybrid. Medable’s CEO is a practicing physician and brings a fresh perspective with her medical lens to how we reshape patient engagement, affording us a rare opportunity to put technologies in the hands of patients so we can learn what works best for their needs and drive the best results for more all-inclusive treatments.

However, one challenge standing in the way is learning how to evolve the site of the future. We believe sites are fundamental to patient experiences, so we want to enhance their essential role through technology, not replace sites with technology. The future is a hybrid. Some patients will want to engage remotely as much as possible, and others may prefer to do some visits at a local site and some remotely and just one or two at the primary site. In other words, tomorrow’s research site may not look the same as it does today. For instance, it might be a retail pharmacy or community clinic with a central site coordinating care and leveraging advanced technology. Medable is helping to reduce the patient and clinician burden and capture better data by digitizing as much of the research process as sensible.

Data capture is another challenge—and a significant opportunity to capture critical insights from study visits. Thanks to the decentralization of trials, we have a proliferation of data collected earlier and more often from various sources. There are inherent challenges with the sheer quantity and variety of data today. But Medable is driving a radical movement to be closer to patients, modernize sites, and establish a concierge-like service—a consumer-grade experience for patients that makes data insights easier to capture. When we collect patient data before, during, and after a study, we can partner with sponsors on the meaningful use of that data.

MA: How do you aim to increase DCT adoption in the clinical trials industry?

 Medable has engaged over one million patients across a myriad of over 5,000 sites globally, operating in 40 countries across 60 languages—it’s a significant start. With the broad expansion of reaching more patients and sites globally, we are advancing the capabilities to make an impact. A flexibly decentralized model needs to enable greater patient access while providing a flexible and seamless experience across all users that improves trial operations and time to treatment. 

For example, Medable empowered one precision medicine company to develop new therapies for a rare disease screening of age-related macular degeneration that required a deeper understanding of the disease and cost-effectively screening of 11,000 patients. Our decentralized platform model and direct-to-patient shipment workflow drove a 50% reduction in patient enrollment time and a 75% reduction in study sites, resulting in a $20M decrease in trial costs to achieve the study’s endpoints.

Moving forward, the way to continue to expand the DCT adoption is to design technology solutions that are agile, simple, and elegant—employing human-centered design. A good design is visible, but an exceptional design is invisible. As an example, we’re now seeing improved intelligence to optimize the enrollment period and study startup. We’re getting feedback, not just after a trial but throughout the cycles of a clinical setup. This is important as we’re looking to optimize how we approach our sites, creating programs like our Site Network Council that give us valuable insights to optimize the way they work and create the highest value. To do this, we are creating executive leadership teams at Medable that bring together a rich pedigree of scientific, medical, technology, and design backgrounds to advance how research is conducted from a remote setting.

Second, engaging directly with patients is crucial, and Medable is doing this by nurturing collaborative networks with patient advocacy groups and physicians. Consider the consenting process. Medable’s consent tool ensures patients understand what they’re going to be signing up for, which is critical because the most informed patient is the most engaged patient. As a result, we see up to 90% patient satisfaction.

Lastly, it is critical to up-skill the talent needed for the next generation of the resources necessary to modernize clinical trials. What will a digital CRA or a digital analyst, or an architect look like in a few years? What are some of the things they need to think about when using data, digital technologies, and accommodating patient engagement? The industry should be motivated to champion leaders who will help advance the mission because no one can do it alone. We want to create an ecosystem of partners, sites, patients, sponsors, and CROs motivated to expedite faster treatments.



MA: Will DCTs bridge the racial and economic divides in clinical research? Can you tell me why or why not?

 DCTs are changing the future of research. And the two leading critical success factors in terms of the impact of radically advancing clinical research are access and diversity. The convenience of accessing clinical trials within your iOS devices or mobile devices opens us to a world of ubiquitous access—and this is naturally enabling more diverse data sets so that FDA-approved medicines will be as effective to ensure a diverse representation of people from varied economic and racial backgrounds; expanding clinical trial access to many more patients.

Also, today we see a new trend in patient-centered intelligent protocol design, boosted by a digitally focused mindset. The focus on diversity drives industry-wide change that includes widening the net with more access to care.

MA: Why are you passionate about human-centered research?

 Human-centered research is about putting the patients first and creating a consumer-grade experience for trial participants. Today we put the letter “E” in front of everything, right? E-consent, E-visit, etc. And because we’re moving through this digital age, you recognize that the patterns needed to improve and impact require understanding and predictive analytics.

If we’re able to advance the way we bring data and insights together, not only for clinical research but also, so patients have access to better care—that is why I’m wildly passionate about human-centered design. We recognize that the impact and the outcome are rich in terms of the unique advantage of improving health care through technologies and data tools.

You’ve worked on E-clinical systems at a range of established enterprises like Merck, IQVIA, and Oracle. So, what inspired you to join a growing company like Medable?

 Medable is on a mission to modernize clinical research for the benefit of patients. During the pandemic, I was given this opportunity to go where I could make the largest impact. And when I learned Medable’s vision is to redesign the way clinical trials should be conducted to focus on patients, it was in perfect alignment with my view. Medable wants to create the most intuitive patient experience and build on a true, cloud-based SaaS-enabled technology platform, matching my mission. This is the way to create the most significant impact, with ubiquitous access to care through the modernization of clinical trials. And when we think about what it takes to create this impact, it involves understanding the patient, generating a user community that’s going to provide input on their expectations to create predictive insights on what’s needed for clinical trials.

Additionally, Medable has put together a world-class team of leaders with rich domain expertise, whether you’re in operations, product management, technology, operations, clinical development, patient engagement, science, or compliance. It’s exciting for me to get the chance to work with such brilliant minds for collective drive impact forward.

My role is to find a unique way to develop novel innovation partnerships for a diversified ecosystem. I’m fully committed so that we can intelligently connect patients and sites to advance medical research.

, 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. MaryAnne Rizk, Medable’s Chief Strategy Officer, discusses why sponsors are embracing the decentralized model more often and how it's solving issues like accessibility and diversity. 

On the Precipice of a Shift to Patient-Centricity in Clinical Research: How Will Technology Help?

Clinical trial inclusion in the biopharmaceutical industry had been driven primarily by federal initiatives. However, there seems to be a renewed strategy in big pharma to incorporate diversity inclusion in clinical trials. For example, 

Eli Lilly has discussed its clinical trial diversity inclusion strategies

, which seems to be driven by social injustice. Now, Genentech/Roche is taking on diversity inclusion as a socially responsible strategy. In this interview, Nicole Richie, Global Head Health Equity and Population Science at Genentech/Roche, will discuss her perspectives on the topic.

Moe Alsumidaie: Can you tell me why Genentech formed the Advancing Inclusive Research Site Alliance, and what was the motivation behind this? What sparked this initiative, and why now?

 We started this work several years ago with the appreciation that clinical trials are homogeneous and that the majority of patients included in clinical trials are of one race, and ancestral background—only five to 15% are not Caucasian. A couple of reasons this was front of mind was, for one, the United States demographics are shifting—we are becoming a more diverse and minority-majority nation. The second element that caused more of an increased focus internally was that we thought about personalized healthcare and invested in that as a pharmaceutical company. With that came this burgeoning awareness in the clinical and scientific communities that genetic and clinical data are homogeneous.

All of the information that’s readily available to us is limited. And the implications of that as we try to develop more and more personalized treatments are significant. It undermines our ability to have more personalized care. And so there was just this kind of bolus of publications and literature around this.

That tipped us into having more of a discrete focus on this work back in 2017. As it evolved, we realized that one of the mechanisms to have more representation in research is by having sites in the right location, with the right capabilities and the proper outreach into patient communities. That is where this focus on an Alliance model was born. It was intended to create an infrastructure that will allow for sustainable and durable commitment and a building of partnerships to have more representative patients in our trials and our research environment. We started with four sites, with the aspiration of having a network that ultimately serves these cohort centers of excellence and partners with us to achieve our aspirations for diversity in clinical research.  

MA: How does that fit with Genentech’s overall product development strategy? You mentioned personalized medicine, and of course, Genentech is big on oncology. Does that have something to do with that? Or is it more of a federal or social mandate that you’re following?

 It is to bring more representation into our clinical trials and to bring greater real-world data cohorts, both clinical and omic, into our strategies and planning and our process that informs our personalized healthcare approach. And then to partner strategically across the healthcare ecosystem with the appreciation that this is a big challenge, and we have to come together in different ways to integrate new solutions.

This work, in general, is about having more representation in our research programs. Roche is fully supportive and synergistic with our aspirations for personalized healthcare, as they align with many of Roche’s vision as a pharmaceutical company to impact patients’ lives. By moving into a more comprehensive solutions-based approach, and not a transactional medicine, we we can impact patient care in an end-to-end manner.

Then, we also think about what our impact on society is. So we are asking questions like, “How do we reduce the burden for society?” Healthcare costs are unsustainable, and this is not a new problem, but as institutions and stakeholders continue to move more and more towards value-based care, these types of solutions and integrating the totality of health becomes front and center to what a pharmaceutical company needs to focus on.

So as such, this is a crucial component to broadening the lens on who informs our science and medicine and who benefits from our innovations. And it’s also coupled with our “Bench to Bedside” efforts that are happening across the organization. So it is the research endeavors, but also making sure that we partner holistically with the access pathways to ensure that we’re bringing not just research, but enabling science understanding in under-studied patient populations and ensuring that patients get served in new ways and have access to these innovations.

MA: What does the diversity currently look like with Genentech’s trials, and what milestones do you have to increase the diversity, and what does that mean for clinical trials?

 Currently, you can look at the last new molecular entities that were published on FDA Snapshots. The metrics are getting better, and the most recent NMEs were approved with the caveat that these are global trials and comprised of different countries enrolling at different rates. So what used to be upwards of 90% of all European or white patient demographics has moved to around 75%, and in some cases even less than that.

So that population that’s growing in some cases is through China. We are doing more and more studies in China, and we’re bringing in more Asian patient populations. We still have much work to do, I would say, in bringing in African American and Black patients and Latin and Hispanic patients, both in the US and Latin America, for example.

The demographics of the studies have to be viewed within what recruitment occurs in the US versus outside of the US if we compare to US metrics. So, for example, in our most recent geocentric approval, the representation of US recruitment is very much in alignment with what you would expect for the epidemiology of disease. However, if you look at the whole global population, it gets diluted that the minority of patients come from the US.

It is contextual as we think about benchmarking and baselining. We are using epidemiology as our metric of what we’re trying to drive towards. We are putting together an understanding of where we were before, so looking at that historic recruitment is a first them. Then, our goal will ultimately be to align to the epidemiology of disease and what we would expect based on demographics. Those are the metrics we’re trying to achieve as we think about what “good” looks like. This is a long process because recruitment, depending on what therapeutic area you’re talking about, takes several years of integrating mitigations or implementing new tactics that, over time, move the needle.

We have seen some great examples in our EMPACTA study. The study was conducted during the COVID-19 pandemic, and it included patient populations in the US. Approximately 84% of patients were non-White and from places worldwide, including Latin America and Africa, and in the US like the Navajo nation and New Orleans, where patients were disproportionately affected by the disease.

We had to show with that study that it’s possible, and we can find these patients. If we can do it in a global pandemic, I’m sure we can think about how to do it more holistically. So many learnings have come from that. There have been several proofs of concepts that have shown what we can achieve. Now it is a matter of how we bring it into the whole totality of the lifecycle of development.

I understand you have global partner trial sites. Can you tell me more about those partner trial sites and how they are working successfully to include diversity while also de-risking it as much as possible?

 Absolutely. That is undoubtedly the plan. We launched the first-ever oncology industry study in Kenya this year. So there are sites that have that high rigor and that fidelity that is necessary, but we don’t typically think about them in that way. From the global vantage point, we’ve been thinking about where those patient populations are particularly understudied. So you end up in Latin America, Africa, India, these vast regions. With the appreciation that, to your point, we have to have an infrastructure that serves us.

In a similar manner that we have established the Advancing Inclusive Research Site Alliance model in the US, we are looking at how we can do something that’s probably quite different in the actual tactical planning but has the same intentionality. So that we again create this infrastructure that is a center of excellence and has fidelity, conveys trust, and creates partnerships that can be forged over time and then maintained.

The other thing we’re looking at is how Europe and the UK are rapidly diversifying, in certain regions more than others. So really, it takes much global strategy with local implementation and information, which is typically how we do things. So it fits right into our current operating model.

MA: Can you tell me about the disparities in clinical trials? What can the pharmaceutical industry essentially do to bridge that gap? Or at least try to bring that gap together through bringing those innovative and breakthrough medical products to those patients?

 I think there are a couple of elements. As a pharmaceutical company, we can intervene in many ways from a research and data generation perspective. We are moving into real-world data and other forms of information that we can use to supplement and facilitate our understanding of populations that have almost entirely been understudied and left behind by science and medicine.

There is a commitment to leveraging more considerable data assets to generate insights and contribute to scientific discourse in a new way. We’re trying to achieve population-specific medical elements based on the appreciation that disease affects populations differently. For example, there are well-known variations in clinical course and even response to therapy due to therapeutics attributed to race, ethnicity, and genetic ancestry.

As a science company, we have to get the science right. But, we also have to think about health equity, access, and the totality of health. I think that’s deeply at our intersection of how we think about personalized healthcare.

Because research is just one piece of the broader health continuum, there is a leadership element to showing and setting industry standards on addressing health equity.

We must partner in new ways across the ecosystem, which we currently do in many different avenues through charitable giving, for example. We also do so through our External Council on inclusive research and health equity, which includes key opinion leaders that are very established in the health equity space representing healthcare professionals and patient advocacy groups and organizations.

Our role as a biotechnology company is twofold. Firstly, it is to get the research and the science right, increasing the clinical utility and results generation. Secondly, we need to make sure that we address access deprivation and the channels needed to ensure that patients are getting access to our medicines.

We also have to put a line in the sand with public declarations of our intention, hoping that we will instill that in other companies. Because it will take all of us coming into this space to achieve more remarkable health outcomes for more patients. Ultimately it’s also to mobilize the industry and enterprise at large.

MA: The Advancing Inclusive Research Site Alliance is one of the many examples of what Genentech is doing as a trailblazer in the industry. How do you anticipate that the biopharmaceutical industry will also change to address diversity?

 Hopefully, this is setting the standards. We are very active in pharma trade organizations and other cross-industry collaborations, and we are even publishing our approach and methodology. For example, the Advancing Inclusive Research Site Alliance announcement shared how we’re thinking and what infrastructure and foundational elements we’re putting in place are serving us well.

One of the things I like about our approach is that it is very much in Genentech fashion to partner with experts. So this is where again the External Council comes in. We have these incredible minds who have been in this space for decades and can help challenge us and inform our process. So there are tangible outcomes from that.

For example, on the council, we have an incredible multiple sclerosis (MS) clinician who has observed that the clinical course and outcomes look different in Hispanic and Black patients. So, as a result, we now have a study called CHIMES to address this specific hypothesis in Black and Hispanic patients. It goes to show that in pure Genentech fashion, we’re harnessing the best and the brightest because we know that this is bigger than just one company. We understand that this is a substantial multifaceted challenge, and we have the humility to say that that is the case.

There is no magic bullet. This takes much learning and much iteration, and it’s probably different across disease areas, as we’ve come to appreciate as well.

I think the leadership element of this also comes in the fact that we resource it. I have a team of people that focus on this that serve this work globally. Quita Highsmith, our Chief Diversity Officer, has a strategic pillar concentrated on this. There’s a US medical affairs group focused on health equity and inclusive research. Both of our research institutions in Genentech and Roche have cross-functional teams that have come together around this. So I think it all comes back to giving it time, space, money, and funding.

Nicole Richie, Global Head Health Equity and Population Science at Genentech/Roche, discusses a renewed strategy in big pharma to incorporate diversity inclusion in clinical trials.

Clinical Trial Diversity Inclusion is Becoming a Socially Responsible Initiative

As we enter a post-pandemic era, many of us still contemplate what we’ve been through, and how to move forward. The pandemic shifted the way we operate clinical trials, but now that the world is entering a new normal, what will clinical trials look like? In this interview, Terence Rooney, VP of Clinical Development at Janssen, will take us through a journey of how Janssen changed during the pandemic, and what the future will hold.

Moe Alsumidaie: How did the pandemic impact clinical trials for Janssen immunology?

 As the pandemic broke in March, we assembled an Immunology COVID-19 Operations Task Force, with representation from early and late phase clinical development, medical safety, medical affairs, clinical operations, regulatory, Quality, quantitative sciences (biostats), project management, and other functions. This group drove and coordinated our approach to our R&D clinical trial activities in the context of the pandemic crisis.

The three biggest challenges that the pandemic created for our clinical trials were in the areas of: patient safety and wellbeing, study integrity, and study recruitment. To ensure patient safety and wellbeing we created processes to stay abreast of everchanging local safety and quarantine guidance and to adjust to protect patient wellbeing first and foremost. As for study integrity, we recognized that the systems and processes for data capture, correction, maintenance, transmission, and retention could be impacted by the pandemic and required that we be nimble with regard to adjustments or postponement. Finally, the pandemic hindered recruitment for our clinical trials impacting both patient and staff participation. In the interim, we developed supportive content and activated online communication mechanisms to stay in close communication with our patients, study sites, administrators, and sponsors to manage questions and concerns remotely as well as support data collection.

MA: When the pandemic hit, what did Janssen do to stay its course and continue to advance its studies?

 As a priority, the COVID-19 Operations Task Force established foundational guiding principles and communicated them to study teams and investigative site partners—these principles included following up-to-date guidance about the pandemic from local/regional authorities, following approved study protocols, keeping communications open between Janssen and investigators and their staffs, and specifying that final decisions for individual patient care were at the discretion of investigators, based on their medical judgment. These principles seem apparent, but it was helpful to put them in writing and share them and emphasize that they were developed with patient safety and wellbeing in mind.

MA: Were there any special adjustments to protocols? Study sites? Patient tracking? Patient visits?

 Janssen developed and deployed means to track the pandemic’s impact on our studies. We looked at factors such as the instances of COVID infection reported in study subjects and the operational implications of pandemic disruptions on study conduct – including enrollment and post-enrollment study activities such as dosing and patient visits/data acquisition.

MA: How was patient recruitment impacted?

 With pandemic tracking information, we tailored our approach to our trials—including pausing vs. permitting screening and enrollment based on our evolving assessment of the pandemic’s epidemiology, its impact on our study patients, conduct, and data, as well as what was happening across the industry. Our trials are global, allowing us to adjust trial locations and practices, depending on what was happening in one country or region.

MA: Did Janssen implement any new digital technologies that it may not have used before for monitoring, sampling, communication? What were they? How did it go?

 Our COVID-19 Operations Task Force steered adaptations in the conduct of our studies to prioritize patient wellbeing and study integrity while maintaining compliance with regulatory/GCP/other applicable standards. Transformations in clinical trial conduct included remote visits, direct-to-patient provision of study drugs, and exclusion of subjects with recent COVID infection from study enrollment. In terms of communication among the team, we relied on intranet sites, regular meetings with Zoom, and other methods to keep our staff connected to internal and external guidance and additional news flow relevant to trial conduct.

Across Janssen Research and Development we developed and deployed an interactive platform that integrated public data sources on COVID infection (and then vaccination) rates by geography, overlaying our trial sites and including forecasting algorithms. Detailed feedback from our local sources provided texture as to local logistical conditions providing key information regarding the virus, patient, and staff challenges. This allowed us to adapt our global resources appropriately as COVID waxed and waned by region.

MA: Is Janssen doing anything to move to a model of decentralized clinical trials? Or are there any new remote processes or technologies implemented during the pandemic that you found valuable and may continue using post-pandemic?

 As a general direction and where it makes sense, yes. We have had to adapt many ways of working to deal with the demands of the pandemic and are certainly looking to retain the best and most valuable of these innovations in our practices in the future. Offering greater flexibility in how we bring our clinical trials to patients is undoubtedly one of these themes.

Two major innovations in our clinical trial practices will stay post-pandemic: data science approaches to trial recruitment and technologies that enable remote trial conduct. They match trials to the right sites and patients and make those trials attractive and flexible to participate in. We will retain and develop these innovations to help speed our potential medicines to patients, to stay competitive, and to be prepared for future crises like the present one.

, 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

Terence Rooney, VP of Clinical Development at Janssen, talks through the journey of how Janssen changed during the pandemic, and what the future holds.

Post-Pandemic World Forces Change in Big Pharma

After nearly 15 years of studying a novel pathway to treat immune-driven diseases, AstraZeneca surprised the medical community when it announced that the first of its two Phase III trials in systemic lupus erythematosus (SLE) did not meet its primary endpoint. But instead of unrooting years of progress, the company turned its second trial into a success through applied learnings, engagement with the lupus community, and arming trial sites with the right tools.

Moe Alsumidaie: After TULIP-1 missed its primary endpoint, how did the anifrolumab program evolve into a success with TULIP-2?

 Before we dive in, let me set the stage for you by backing up and discussing lupus. Lupus is an incredibly debilitating disease for patients. There has only been one new medicine approved in the last 60 years, and the medicines that these patients often rely on, such as oral corticosteroids or immunosuppressants, also contribute to the comorbidities they experience – so there is a desperate need for alternative treatments.

At AstraZeneca, we spent the last 15 years focused on targeting the interferon pathway, and we’ve been encouraged by our data. I led the team through the Phase II results in SLE, and we were anticipating hitting this first Phase III study out of the park – so the unblinding of TULIP-1 surprised us. Afterward, somebody suggested that we consider delaying the unblinding of TULIP-2, which had not been read out yet. And I’ll be honest, my initial instinct was a concern about staying to our timelines, but then we got the final tables from the Contract Research Organization (CRO), and it became clear that the right decision was to pause, apply learnings from the encouraging results seen in TULIP-1 across other endpoints, and adjust our approach to TULIP-2.

So that’s what we did, and after unblinding TULIP-2 about a year later, we saw that the primary endpoint was met, and the data were highly consistent with the encouraging results from TULIP-1 – that anifrolumab resulted in early sustained response using the British Isles Lupus Assessment Group-Based Composite Lupus Assessment (BICLA; an incredibly stringent disease activity endpoint), sustained steroid reduction and improvements in skin disease manifestations.

MA: What exactly were the issues from TULIP-1 that you uncovered, and how did you address those issues in TULIP-2?

 While we failed the primary endpoint of patient response using the SLE Responder Index-4 (SRI-4), this is one of two endpoints in lupus clinical trials that are typically considered to measure disease activity – the other being BICLA, for which anifrolumab demonstrated compelling results. So, it was thinking through the new data we had on anifrolumab from TULIP-1 and realizing BICLA was the right primary endpoint for TULIP-2. We also pulled in lupus experts to align on the path forward for TULIP-2 to make sure everybody was thinking through the solution.

In TULIP-1, the SRI-4 endpoint was not met; however, we saw a reasonably strong BICLA response with a difference versus placebo of about 16%. That didn’t happen in TULIP-2—we saw pretty consistent results between SRI-4 and BICLA measurements, with about an 18% difference in SRI-4 response and 16% difference in BICLA response.

MA: So, if I understand correctly, it was the assessment of these endpoints that made the difference in TULIP-2?

 We don’t fully understand what drove the difference in TULIP-1 between the SRI-4 and the BICLA responses. We are continuing to explore and hope to release a publication with our findings in due course.

Lupus clinical trials are challenging because lupus impacts any organ system, and the endpoints that we use to measure improvements are looking at every organ in the body and assigning some mathematical algorithm to it, which is complicated.

And as you know, there have been multiple failed new medicines in lupus. So, it’s a graveyard of clinical products. And my opinion is that it’s mainly due to these endpoints that are trying to mimic what’s going on in the body, which is almost impossible to do. Lupus presents differently in every single person, so you can’t use the same measure to show real-life improvements in these patients. It’s not like rheumatoid arthritis, where you’re always looking at joints. You can’t do that here.

MA: So, would you say this unpredictable way of measurement is due to the nature of the disease rather than sites that aren’t trained on these measurements?

 I think that’s a fair assessment. Of course, it is essential to train sites and ensure there are site investigators who are well-trained in lupus and lupus endpoints. The endpoints used in clinical trials are not typically used in practice, so the investigators must know the nuances of using these measurements.

MA: Compared to your experiences with TULIP-1, what sorts of operational challenges did you experience when running the TULIP-2 trial?

 We started the TULIP-1 and TULIP-2 trials almost concurrently, and I think many of the operational challenges we faced stemmed from the transition from Phase II to Phase III, as in any clinical trial program. This meant increasing our participation and global footprint, and then also working with a CRO required an extra layer of communication.

The AstraZeneca team attended site initiation visits to present the Phase II data and was involved in the oversight of the study, so our approach was hands-on from the beginning. In addition, we worked to ensure strong relationships with our investigators and the CRO, so we worked as one anifrolumab team to help prevent communication or operational challenges.

MA: Can you tell us about any patient-centric initiatives you carried out when designing the trials, such as work with advocacy groups or dry runs with patients?

 We did align ourselves with advocacy groups and conducted small patient focus groups, even a separate almost “pilot trial” where they did some screening visits with patients. Patient centricity is a critical component of study design in our portfolio—it’s one of AstraZeneca’s core values. My team meetings often include discussions about patients and how central they are in our profession. It’s vital to me.

In particular, in the TULIP program, we sought patient feedback on the study design to ensure their voice was included in the process. Again, we can see this by only performing assessments vital to the study’s objectives through our attempt to alleviate the burden on patients.

MA: Could you tell me a bit about any challenges you faced with recruitment or enrollment?

 We found that the best source of success is diligent site selection and aligning ourselves with experienced sites. The best sites are those that understand lupus endpoints and have experience in lupus clinical trials and sites that already had relationships with the participants.

We also found some success establishing a site and study coordinator network so that sites with high enrollment could share their best practices and help others.

MA: And lastly, what systems did you implement to reduce data variability and improve the data quality of these disease measurements?

 I recommend routine and diligent training of the investigators—that’s critical. We also utilized an adjudication committee that reviewed patient entry and the core data to ensure responses were internally consistent and watchable. That, I think, was important and carried through from Phase II into both TULIP-1 and TULIP-2.

MA: And what happens if there is a disagreement between the adjudicator and the investigator?

 A process that remediates it involves a lot of back and forth between the adjudicator and the site until they can come to a solution.

Micki Hultquist, Vice President, Global Franchise Head at AstraZeneca, discusses the journey from a missed endpoint in TULIP-1 to a clinical success in TULIP-2

Digging into the TULIP Trials and AstraZeneca’s Blossoming Ambitions in Lupus

Clinical trial diversity inclusion has recently been at the forefront of FDA’s initiatives. Sponsors have adopted diversity in clinical trials through 

more traditional methods, such as engaging advocacy groups.

 However, the pandemic has fueled clinical trial decentralization, and some enterprises have used decentralization methodologies to increase clinical trial diversity inclusion by going deep into diverse communities. In this interview, Thad Wolfram, President, Matrix Clinical Trials at Matrix Medical Network, will discuss his experiences.

The need for more diversity in clinical trial participant populations is long overdue. From your experience, how has

diversity in clinical trials improved over the last year,

and what can we expect in the future moving forward in a post-pandemic world?

 It’s been known for quite some time that there’s a lack of diversity among clinical trial participants, but it really wasn't until COVID-19 shined a light on the lack of equity around healthcare, as well as the lack of diversity in clinical trials, and what that could mean for a potential vaccine and treatment, that regulators finally stepped in. This put additional pressure on sponsors, along with public pressure on diversifying participant populations, and I. In response, several sponsors presented new landing pages around diversity in clinical trials and new recent strategic statements, saying, "“We're only going to partner with those who have their own strategy for addressing this.” We, as a society, and the regulators and the industry, as a society and the regulators, and the industry, we all recognized the problem and knew we needed to solve this moving forward.

Matrix Medical Network brought clinical trials to

underserved communities during the most critical times throughout the pandemic. How did you connect with these communities to encourage enrollment,

pockets that reject clinical trials and reject new medicines, especially vaccines?

 I think first, it ties back to the fact that Matrix has seen some hesitancy amongst the underserved populations because of how they have been treated in past clinical research. We were able to talk to and educate folks on what's happening with COVID-19, since, as an enterprise, we were also part of screening and testing, and eventually become a part of vaccination efforts. Similarly, we were a part of clinical trial efforts. Our ability to run small, compact mobile health clinics allowed us to cover a lot of much ground within urban areas to get to these underserved populations as well as, for instance, large mobile health clinics out on Native American reservations helping reach those communities. So, I think it’s the combination of the reach, the flexibility, the fact that we really value our relationships with the folks in those communities, and our ability to build trust and confidence in what we're helping to bring to them that allowed us to have such a strong impact.

Let’s talk more about that education around clinical trials and the vaccine.

As a decentralized clinical trial healthcare provider, could you talk about some of the initiatives

 One of the challenges, historically, and this goes back to the diversity aspect for trials, is there's a lack of awareness of the availability of a clinical trial. We’re bringing all that information to underserved communities to promote that dialogue. We start with local community leaders to really help them to understand what we’re doing with patient recruitment for a clinical trial, specifically, how we go about that and what value clinical trials bring. One of the examples I like to give is if you take oncology, for example, for a patient who doesn’t have any other treatment options available, a clinical trial can actually become a treatment option for them. We’re helping to look at ways we can bring those treatment options to the underinsured, the uninsured, and to populations that otherwise would not have that option of care. We’re helping to facilitate those local conversations around what a clinical trial really is, how we can help individuals and what it can mean for their livelihood.

Can you tell me about the benefits of using mobile health clinics for recruiting patients and conducting clinical trials? What are the shortcomings?

 From a benefits perspective, the first is that it allows us to meet a patient anywhere, and that which really does help. For these underinsured and uninsured populations that are not going into a physician's office, they don't have a physician who is talking to them about a clinical trial to frame it as something they can take part in. So first and foremost, it's it’s about enabling the conversation to happen, to give them any line of sight into a clinical trial. And the mobile health clinic gives us provides us with that mobility to get into the community and enable conversations that otherwise wouldn’t have happened. That's That’s one of the big significant benefits; just providing the awareness, access, and the opportunity. There are some risks and some downsides. For instance, we are limited to whatever tests, imaging, or screening we can bring along with us. To mitigate for that, one of the things we're we’re working on is to figure out how can we figuring out how we can further diversify the breadth of screening we bring into the community to support the broadest patient population possible.

talking about Matrix initiatives, could you tell me

about how those initiatives and priorities are coming how those initiatives and priorities come

into clinical trial design, particularly in the mobile setting?

 Decentralized trials saw a great tremendous shift in adoption during the last year or so. When a participant is in a clinical trial. Historically, when a participant is in a clinical trial, they’re taking place at a research center. And so, the historical view is really based around this idea of a site, an investigator, and the research taking place. Now, we’re at a pivotal point where we’re shifting the paradigms to recognize that a clinical trial takes place 24 hours a day, seven days a week, wherever the participant is. And so, what we're we’re doing with the decentralization of trials is we're following that patient, whether they’re at a site, whether they're at home, whether we're we’re managing a virtual visit, or whether we're monitoring with wearables, the trial is always happening. What the mobile health clinic does is it offers yet another lever, if you will, that we can pull around the flexibility of the trial to meet the needs of the patient experience. If the participant isn’t comfortable with us going into their home, the mobile health clinic allows us to bring the clinic to them. We can set up a clinic in an area that otherwise wouldn’t have a research site, which allows for allowing several people to participate at once via that clinic. We wouldn’t want COVID-positive patients going into a medical facility, so we operated as a contained extension of that site with strict safety protocols to be able to enable these trials to happen, but in the safety of that environment. It's all about the flexibility of a trial.

Speaking of the flexibility of trials, can you tell me about the challenges that sponsors faced

in the beginning of the pandemic and what was so challenging with implementing decentralization through virtual techniques or through the decentralized techniques that at the beginning of the pandemic and what was so challenging with implementing decentralization through virtual techniques or through the decentralized

 Over the last five to 10 years, there have been many different capabilities and techniques that have been brought into the market that there’s this huge vast, fragmented ecosystem. At the beginning of the pandemic, many trials were flat out halted. Many trials were flat-out halted at the pandemic’s beginning because the participants couldn't couldn’t go into a research site. Other trials that were intended to begin were delayed or halted stopped because recruitment couldn't couldn’t take placeoccur in an in-person environment. I think sponsors see our capability to quickly shift to the best option and adapt a trial design or protocol to take advantage of decentralized capabilities as a huge benefit. Secondly, it’s beneficial to work with regulators, to really understand what the regulators would accept,to understand what the regulators would accept because the downstream risk was always regulatory acceptance. We saw regulators also willing to say, "We’re going to learn through this process. We’re going to actually to understand what does and doesn't work through decentralization.” I think what we're we’re seeing coming out the other side is a lot of adoption willingness. We have sponsors, CROs, and regulators who have learned what we can do and where it does work.

that things are opening up again, of course,

do you see a shift back? Do you see a hybrid? Where do you see decentralization fitting in here?

 I think sponsors, CROs, and regulators learned so much over the last year about what we can do and what we can do differently. What we do on a clinical trial, even from a standard-of-care perspective, even from a standard-of-care perspective, what we do on a clinical trial generally reflects what the standard-of-care in the real world looks like. The other thing that's that’s happened this year is that everyone has gotten much more comfortable with virtual visits and with not needing to necessarily go into the doctor's office go into the doctor’s office necessarily. We’re really at a jumping jumping-off point where we're we’re going to continue to build on this decentralization. And I think that while there will always be gold standards in clinical trials that are tied to traditionally run trials wrapped around clinical research sites, I think at a minimum, hybrid studies between site-based and decentralization is here to stay, and it's it’s only going to grow moving forward.

Thad Wolfram, President, Matrix Clinical Trials at Matrix Medical Network, speaks about his experience utilizing decentralization methodologies to increase clinical trial diversity inclusion by going deep into diverse communities.

How the Pandemic Facilitated Clinical Trial Diversity Inclusion

Regeneron’s monoclonal antibody therapy was one of the first therapies to enter the market to treat COVID-19. The treatment was used early in the pandemic and received 

emergency use authorization by the FDA in November 2020

. Many in the industry have been curious about how Regeneron rapidly and successfully developed a therapy to treat COVID-19. In this interview, Bari Kowal, Senior Vice President, Head Development Operations & Portfolio Management at Regeneron, will discuss her experiences.

Moe Alsumidaie: Among the many obstacles faced when executing clinical trials under such urgent circumstances, what was the most challenging from a clinical development perspective, and how did Regeneron overcome it?

 The sense of urgency required to manage clinical trials amidst a pandemic is something we’re used to at Regeneron. Our response was to ensure we were resourcing appropriately to tackle what lay ahead of us. Early in the pandemic (Q1 2020), we began to think about three things: what kind of antibody cocktail we needed to develop, how we were going to plan in a matter of days—not weeks or months—and finally, how were we going to conduct the studies and execute them efficiently. It was groundbreaking to develop an antibody cocktail that quickly. There was a shared sense of determination across the company to complete the analysis to get it from a concept to an Emergency Use Authorization (EUA) approved therapy.

MA: Regeneron’s monoclonal antibody therapy was pushed through quickly. What was that experience like when it came to getting that therapy through trials and out to patients in such a short time frame?

 Our company commitment to doing the right thing, our decision-making process, and our experience creating innovative technologies enabled the process to happen quickly. Early in the pandemic, we did some work on our IL-6 receptor antibody, sarilumab, which we thought could be a potential COVID-19 treatment. Although we didn’t see efficacy there, we ran those trials swiftly, which gave us a strong foundation for the monoclonal antibody cocktail. We also presented our results from the monoclonal antibody trial to the FDA, other regulatory agencies, and physicians. All parties had the necessary confidence in the safety and efficacy of our therapy and that this would be a viable treatment for patients. It was fascinating to see how we could positively impact the globe with treatment options for COVID-19. 

MA:Tell me about how you upheld Regeneron’s scientific values when the globe was desperate for vaccines and therapies.

 Scientific rigor is at the heart of what we do. Our tagline is “Science to Medicine.” We adapt rapidly, even in a remote environment. Every time I’m asked how we did this so fast, I note we didn’t have to change how we went about doing things. We were already taking thoughtful action when we needed to, and we’ve always adapted rather nimbly to evolving situations and new data. So, while the speed and demand during the pandemic were like nothing we’d ever come across, we were able to pivot based on our demonstrated ability to remain flexible. Of course, one crucial element to our success is that Regeneron has built an unprecedented end-to-end suite of proprietary technologies for drug discovery, development, and manufacturing that has been used to develop transformational medicines over the last three decades for several different diseases, including COVID-19.

I don’t know many other companies that have instituted such a rigorous and robust program for COVID-19. Ultimately, we felt it was essential to have the necessary data to be confident in the therapy we developed.

MA: How did you keep your non COVID-19 pipelines moving forward during the ongoing pandemic?

: Managing our pipeline during the pandemic was undoubtedly not an easy task. Some colleagues and I were reminiscing about our work in January 2020. At that time, my team put together an impact assessment given our early knowledge of COVID-19 appearing in several countries outside the US. We could not have predicted what was coming, but we felt prudent to plan for the best- and worst-case scenarios proactively. We started by looking at our drug depot locations and whether they were affected before COVID-19 impacted the US. We acted on then-current data to plan for additional supplies for our existing trials. 

This ability to assess and direct the situation early was how we limited the effect on our portfolio at large. Some of our studies had to pause at specific sites with some countries on lockdown, but where we could keep going, we kept going. Ultimately, we began employing some of the decentralized tactics that aren’t necessarily new but weren’t utilized on an ongoing and consistent basis. For example, as we look at home health, you can do a fair amount to treat patients remotely with a home nurse—such as drawing blood and virological sampling. We also used telemedicine when patients could not visit our sites and asked patients to record their symptoms using their own electronic devices. I’m grateful to say the impact on our pipeline has been limited during this pandemic, and I indeed attribute that towards the planning that we did to prepare ourselves.

MA: Professionals in clinical operations tend to be very conservative about running their trials and want things to be done the traditional way. And you keep mentioning that Regeneron has an innovative culture, but I’m sure there are always naysayers out there. How has this challenge essentially changed the perspectives around implementing novel decentralized approaches in clinical trials?

: I think this is a turning point for our industry and clinical trials. I have seen the industry as a whole recognize how we have progressed our trials at a speed that we hadn’t in the past. Regeneron intends to take advantage of the lessons learned from this past year. With that being said, I don’t expect us to constantly be moving at the speed of the pandemic in the future. I think that’s unreasonable for a standard trial, but I know we can take away key learnings on how to plan and conduct tests faster and be nimbler as an industry, not just at Regeneron.

There are limitations to our innovation from a regulatory standpoint. There are regulations and guidelines that we must follow. As a leader of our clinical trial execution at Regeneron, I have spent much time this year thinking about how we can make development more innovative. For example, we’ve developed novel digital endpoints using wearables to get information for our trials, which we hadn’t in the past. We’re using insoles to predict gait and falls in some of our skeletal muscle trials. We’re also conducting pulse wave analysis to predict heart failure. These are technologies that we hadn’t been looking at as much in the past that we’re starting to look at now to get more real-time data.Through the pandemic, it’s become apparent there are easier, less costly, and more patient-centric ways to execute a trial.

MA:What will drug development look like in the post-pandemic world?

 We’ve internalized more of our trials and assessed whether our operating model could adapt in ways that will enable speed and cost-efficiency. For example, we developed a role to focus specifically on innovation, which we didn’t have before. While we’ve had pockets of innovation roles in our patient and digital endpoint groups, this role will coordinate across all of global development and look at how we utilize the various aspects of innovation—whether that’s happened in our systems group or even within the Regeneron Genetics Center, to benefit the system as a whole. We’ve also hired those who specialize in operational analytics within clinical development. These data scientists are reviewing operational data, not just our clinical data, to extensively benefit our modernization of clinical trial work.

It’s through that lens that I’ve been thinking about our work. What are the roles, and who are the right people to carry the future of Regeneron? We thought a lot about what the clinical research associate of the future looks like. I believe remote monitoring is taking place, and analyzing data in ways that we haven’t been able to before is within our immediate future. This new, transparent digital data flow hasn’t been perfected yet, but we’re certainly on our way.

Bari Kowal, Senior Vice President, Head Development Operations & Portfolio Management at Regeneron, discusses her experiences about how Regeneron rapidly and successfully developed a therapy to treat COVID-19. 

Inside Regeneron’s Monocolonal Antibody Development

The pandemic has dramatically impacted many aspects of clinical trials, ranging from operations to recruitment/retention to clinical trial public perception and technology. In this interview, Lan Fong, Founder and Principal Consultant at Avery Biopharma Consulting and Venture Partner at Congress Avenue Ventures, discusses her perspective on how the pandemic is shifting the clinical trials industry.

MA: How has the pandemic impacted COVID versus non-COVID trials?

 The impact on non-COVID trials was prominent because they have been deprioritized within the clinical trials industry, and the priority has shifted towards COVID-related trials. For non-COVID-related trials at sites, it has been challenging to execute protocols with traditional methodologies in an environment experiencing many disruptions. For example, sites had to have COVID testing measures and protocols in place, limiting patient visit capacity and volume at sites. Sites have had to re-adjust their staff schedules and face the need to ensure enough social distancing procedures if a patient comes in for less than 30 minutes for a quick blood draw or a short assessment. There also have been impacts on patient retention; for instance, if a trial is being executed in a large city, such as Boston or New York, most patients who commonly use public transit did not want to continue using that mode of transportation, henceforth, missing study visits or dropping out of the study altogether. As a result, there have been many COVID-related protocol deviations. Regulators have also issued new guidance around COVID-related disruptions to clinical trials, and as a result, CROs have defined a new category of COVID-related protocol deviations to capture them as a separate category in the clinical study report.

COVID-trials have been just as challenging to execute during the pandemic. COVID studies are pressed against aggressive timelines and face delays in site activation, manufacturing delays, and supply chain issues. There are also investigational product stability and logistical issues, such as monitoring expirations and ensuring stability at specific time points while operating in a tumultuous and rapidly changing environment, as there were shutdowns and delays in transportation. Even though clinical research centers prioritized COVID-related protocols, there were also site activation and IRB approval delays as much of the work had to shift to being conducted virtually when previously the sites, IRBs, and vendors were not necessarily set up to do so.

MA: How have the disruptions impacted minority group participation in clinical research?

 Recruiting minorities has always been incredibly challenging, even before COVID; reaching out to diverse groups has inherently been difficult because, despite FDA mandates for minority inclusion in clinical trials, there has always been less willingness for minorities to participate. Throwing in pandemic challenges has not only hurt overall study recruitment but, recruitment especially for minorities. For example, in larger cities, patients could quickly attend clinical trial visits via public transit. However, since few patients want to take public transit, they don’t have the means to afford different and less risky transportation options (i.e., Uber, Lyft). There has been a massive increase in recruitment and retention budgets from sponsors to support patient transportation and recruitment. It’s a tough decision for a sponsor because, sometimes, if sponsors have poor recruitment/retention strategies or are trying to learn how to recruit a particular patient population in their trial, they will not yield a good return on their recruitment/retention budget investment (ROI). Then you throw the challenges of being in a pandemic, and that decreases the ROI. So, sponsors have had to take a hard look at their enrollment projections and their statistical analysis plans to see if they can reduce the number of subjects needed to evaluate the study’s endpoints. Sponsors have also conducted early data cuts and interim analyses to see if they can uncover early signals.

MA: How has the pandemic impacted public perception of clinical trials?

 With the pandemic and the development of the COVID vaccines, I believe people have come to appreciate the need for clinical trials, and it has put this clinical research front and center. Before the pandemic, clinical trials were not something many people thought about, so I’m glad that it has raised awareness and emphasized the importance of clinical research and the need for clinical trials. Additionally, people now understand the importance of drug development and how badly we need to increase the speed at which new treatments are developed. Vaccine development has been accelerated, timelines have been shortened to address the critical need, and some traditional drug development barriers have been broken due to emergency protocols used to accelerate COVID vaccine development. It has also been a delicate balance between government and industry to establish trust and rigor in science; to successfully accelerate drug development without compromising subjects’ safety is challenging. Despite that, I believe people now understand what’s so essential about clinical trials and hopefully support those efforts.

MA: How many ways exist to execute decentralized clinical trials?

 The adoption of decentralized strategies has been discussed a lot, and I’ve seen two different ways of approaching it. First, many clinical trials center around major medical institutions that have been doing clinical research for a long time. I’ve seen integrated research organizations (IROs) making naive research sites into clinical trial sites by supplementing them with clinical research staffing, such as traveling CRAs and CRCs. The IROs implement their own SOPs at the sites and provide data entry, quality management, recruitment, and staff support to sites to operate studies and conduct visits at patients’ homes. Second, some companies are working on digital solutions, such as electronic consent, electronic clinical outcomes assessments (eCOAs), and electronic patient-reported outcomes (ePROs). Other solutions are moving away from paper and onto electronic modes of data collection, or eSource. Additionally, there is a sudden shift in patient support solutions for recruitment and retention. For example, some companies are providing transportation services or conducting mobile nursing/ phlebotomy. While these platforms have existed for some time, never has there been more need for more digital solutions that can integrate seamlessly with existing systems and databases. 

Another interesting trend I’ve seen includes integration strategies and capabilities into CROs, which have provided exposure and growth opportunities for companies specializing in decentralization. Some of these companies have acquired smaller companies that were building these capabilities and are in the process of integrating with their existing platforms. The goal is to make it a seamless and more familiar platform for sponsors to bring those capabilities onto their trials since the CROs have already vetted and conducted due diligence on these companies. However, the execution and actual integration can be challenging.

MA: What other areas from sponsors have arisen as a result of decentralization?

: Remote monitoring and risk-based monitoring have been hot topics for a long time. In the past few years, there’s been much debate around whether you need to do 100% source data verification or if the monitoring plan can be centered around critical variables. Sponsors and CROs also have to decide between on-site monitoring, remote monitoring, or partial remote monitoring, depending on the ease in which the CROs, vendors, and sites can use a fully secure, Part 11 compliant source data platform. Despite this topic being discussed for many years, many sponsors are hesitant to move away from 100% source data verification, and many vendors are not equipped to perform remote monitoring. While every piece of clinical trial data is essential, the necessity of source data verification on every data entry also depends on whether the case report forms were created thoughtfully and intentionally, without unnecessary data fields. While the industry has been slow to move away from traditional methods, it is now more critical than ever to adopt innovative solutions to execute clinical trials in modern times, especially amid a pandemic.

Lan Fong, Founder and Principal Consultant at Avery Biopharma Consulting and Venture Partner at Congress Avenue Ventures, discusses her perspective on how the pandemic is shifting the clinical trials industry.

Pandemic Impact on Trials, Public Perception, and Decentralization

Clinical operations personnel are known to exercise rigidity in their operating models and are resistant to change. However, the COVID pandemic has forced many to expand their perspectives to operate in this new environment. In this interview, Dr. Peter St. Wecker, Director of Clinical Process Improvement & Innovation at Zogenix, will offer a unique perspective on clinical studies operations challenges and changes that sponsors and sites underwent during the pandemic.

Moe Alsumidaie: I hear that there is a decline in new trials started in 2020. What factors are contributing to that?

 The decline in new trial starts last year came from a multitude of places. COVID has had a significant impact on companies’ decisions about whether it was the right time to start new trials. Sites, for example, experienced limited or decreased staff availability. For us, the challenge of getting in touch with sites and were able or ready, with the demands of COVID, to start a new trial. Additionally, with the changing landscape in regulations, sponsors have been figuring out how to navigate new regulations, which may also be contributing to their readiness to start new trials.

Naturally, we had to deal with the initial shock of being in a pandemic, and adjust to the way we work nowadays, being fully remote. The initial challenge was how to keep studies operational while being completely remote; for example, when we’re not able to visit sites and patients cannot go in for their study visits. The clinical trials industry is understandably resistant to change and embracing new technologies and innovative methods for operating studies until they are well proven and scalable. For instance, even though niche vendors exist and offer remarkable technologies to advance decentralization and remote access to sites, it was not easy to scale across study teams.

When companies boast about their success stories of implementing decentralized clinical trials, I think that’s been the exception to the rule. The reality is that we’ve used our existing systems to deal with patient access, site access, and team access; we had to uproot all of that and change our processes from the ground up. Not to mention the challenges of convincing and training clinical operations personnel to execute studies using those new processes in a brief timeframe. After we restructured our clinical trial operating models to support decentralization, such as conducting telemedicine visits, delivering investigational medications to patients’ homes, and collecting data through electronic means, such as electronic patient-reported outcomes (ePROs), that’s when we started to see progress in trials continuing successfully.

MA: What would you say was the most exciting innovation that you’ve seen emerge from this pandemic?

 The most exciting innovation I’ve seen is how rapidly regulators addressed needed changes in clinical operations during the pandemic and sponsors’ quick response to change how they operate trials during the pandemic. As an industry, these recommendations were valuable, as we could leverage the regulators’ recommendations to allow for studies to go on. That partnership with sponsors and how they’ve made those adjustments quickly, given how slow we’ve seen some changes occur in the past, has been great. I also found that the ability of clinical operations personnel to rise to the challenge and exercise their impressive creativity and brainpower to find novel solutions and operating practices was mind-blowing.

MA: What was it like to transition the organization into a remote working model?

At Zogenix, we were well prepared, as we invested in a robust internal IT infrastructure, which supported an easier transition to remote access for all of our employees. It is essential to trust employees to achieve the study’s deliverables and milestones by the defined timelines, despite the challenges that come with working from home. From what I’ve seen, we’ve been successful in our transition, and we have embraced remote work as a part of our lives and culture.

MA: Have there been any changes in SOPs to support these new changes?

 Before the pandemic, my experience was that many sponsors would never allow CROs to conduct remote monitoring of study sites and would have SOPs specifically prohibiting such practices. Now the SOPs have changed to support remote monitoring, specifying the need for remote access to EMR systems and other source data. Other areas where SOPs have changed involve shipping investigational medication directly to the patients’ homes and allowing for study visits to be conducted remotely.

MA: How have study sites responded to these novel remote procedures?

 Like everyone else, I think sites have been challenged with staff working remotely and figuring out how to address resource challenges. Sites were overwhelmed and put under much pressure by all sponsor companies, suddenly coming up with new processes and changing their procedures for running studies during the pandemic. Not only that, but each sponsor company was also operating their trials differently, so sites have expressed concerns that they were receiving calls from multiple people and companies wanting to do things differently.

Then there were institutional changes that site staff had to deal with, such as resource allocation and creating processes to enable remote access to their EMR and other source data systems while maintaining high patient protection and privacy levels. Despite these challenges, sites have been innovative and have been working fast to give sponsors access to their electronic systems to support remote monitoring while maintaining the protections and the well-being of patients, monitors, and site staff. This was a remarkable feat that sites have achieved to adapt to this new environment.

MA: What has this pandemic done to the clinical trials industry?

 What comes out of all this is a real positive change in the industry, the collaboration between parties, and sharing pre-competitive information to overcome hurdles. There have been many great discussions, webinars, and virtual conferences where sponsors, sites, CROs, and others have shared their ideas for how to best overcome these challenges. And we’ve all, in many ways, come together to help each other. We can still be competitive but can accomplish a lot more as an industry by working together for the good of the patients. We can always be good corporate citizens for our shareholders, our patients, and healthcare while still sharing best practices that we can all use to run studies and get new medicines developed in these challenging times.

Dr. Peter St. Wecker, Director of Clinical Process Improvement & Innovation at Zogenix, offers his unique perspective on challenges and changes that sponsors and sites underwent during the COVID-19 pandemic.

Biopharmaceutical Clinical Studies Operations Changes During Pandemic

It is no surprise that the COVID pandemic severely disrupted operations in many industries, including clinical trials. Some personnel had thought clinical trials were booming during the pandemic era. However, data from 

 shows a 38% drop in new clinical trials started in 2020, as illustrated in 

Figure 1: New Clinical Trials Started by Year

Though the industry was expected to boom with new studies—data shows a significant drop in the amount of new trials started in 2020