Since the late 1990s, the number of countries participating in clinical trials has increased by 78%, but this global expansion has not increased the diversity among participating patients. At the same time, clinical trial sponsors face patient enrollment challenges—particularly in oncology research, which is growing rapidly and increasing in complexity of study design and eligibility requirements. As a result, finding and competing for the right patients is a hurdle that needs to be addressed. A solution to this as an industry is in improving clinical trial patient diversification. This includes service providers, including centralized medical imaging providers, who must challenge their processes to support the enrollment of a more diverse patient population.

Prostate cancer affects Black males ~2X more than White males. Thus, the current situation of Black males only constituting 3% of PCa trial enrollment is misaligned with the disease manifestation in the general population. Likewise, while the incidence of breast cancer is relatively equivalent between Black and White Americans, White women make up 78% of breast cancer trial participants and Black women only 2.5%.

The impact of these discrepancies is threefold: it produces data that does not reflect the general population, it increases regulatory risks to product labeling based on a therapy’s safety and efficacy in a specific demographic, and it limits ethnic minorities’ access to potentially impactful experimental treatments.

Among the factors contributing to the diversification gap is investigative site location. Currently, large academic medical centers make up a high concentration of clinical research sites, limiting access to the broader population that may be served at local community hospitals. Additionally, since participating in a clinical trial requires frequent and logistically challenging investigative site visits, many patients choose to not participate due to the need to take time off from work, secure childcare, and incur the cost of travelling.

This begs the question: If we limit site participation based solely on existing relationships, are we limiting our access to patients?

In clinical trials that require medical imaging, every image counts—especially when imaging data is tied to a primary or secondary endpoint, or to safety or exclusionary criteria.

By leveraging an imaging core lab’s site database and by partnering with enterprise image exchange providers, we can expand options for image acquisition beyond the academic medical centers. In fact, one PI could have multiple centers associated with their investigator site to reduce the burden of patient travel. Traditionally, imaging core labs have been open to qualifying multiple imaging facilities within a trial. The next step is to proactively plan the identification of more accessible centers that will support patient diversification.

Another area of improvement is providing access to zero–technology footprint solutions, which will enable ease of site onboarding, simplify electronic image transfers, and support sites with the execution of local clinical research imaging reads. With fast image-upload and onboarding times, and by making imaging guidelines and trainings available online, we can help expand site participation while maintaining quality and consistency.

By identifying more imaging facilities and providing simplified processes, pharmaceutical companies and CROs can create modified feasibility plans and expand their network of sites, ultimately increasing their reach to a more diverse patient population.

Ultimately, we know we have a systemic problem with patient enrollment, and diversification is part of the solution. If we all do our part in tweaking our processes and services, we can overcome this challenge and better achieve our goal of gaining full knowledge in order to develop the safest and most effective treatments.

Vice President, Technology Solutions – Medical Imaging, Calyx

Articles

A Closing Thought

Centralized medical imaging providers must challenge their current processes to improve patient diversity.

Improving Clinical Trial Patient Diversity: Can Central Imaging Play a Role?

Collectively, rare diseases affect around 4%-6% of the global population–about 300 million people, where half are children living with rare genetic disorders. Patient populations for individual diseases are usually small and spread out across many geographies, making it difficult for researchers to find sufficient people to participate in their studies. Unlike more common ailments, historical rare disease data is either not comprehensive or not available at all.

Along with being difficult to research, living with rare diseases is often extremely challenging. Healthcare providers may not have access to relevant information, making diagnosis and ongoing support difficult, with some conditions so rare that doctors may not have encountered them before. Patients usually move from doctor to doctor, trying to get an accurate diagnosis. There have even been accounts of patients waiting nearly three decades for a diagnosis.

It is not that surprising then to see that many of the COVID-19 vaccine trials lacked participants with rare diseases, even though they are one of the patient populations most vulnerable to COVID-19. Unfortunately, rare disease patients are well-versed in dealing with uncertainty–many times, they, along with their caregiver, have to make tough decisions about their health, often with limited guidance from health specialists.

How, then, are rare disease populations navigating the uncertainties around the vaccines and their overall health due to COVID-19?

Rare disease healthtech, Xperiome, and research consultancy Magnolia Innovation, are running a ‘COVID-19 and You’ survey to understand how COVID-19 has impacted the rare disease community. The survey aims to uncover the emotional toll of the pandemic, along with changes in patient and caregiver behavior. It is open to anyone aged 18 or over who has a rare disease or cares for someone with a rare disease. The survey results will be fed back to participants incrementally and shared with orphan drug researchers to help them build a deeper understanding of the needs of rare disease patients, particularly during a global pandemic.

Initial findings from nearly 80 rare disease patients and caregivers that have taken part so far include eye-opening responses that paint a picture of isolation, uncertainty, and an increased sense of urgency to improve symptoms due to fear of hospitalization.

Early finding 1: people affected by rare disease are anxious about COVID-19

When asked about changes in behavior since the pandemic began, 25% of respondents said they were now looking for information about their rare disease more often, and in terms of new behavior, 43% of respondents said they now regularly spend time searching for information on how COVID-19 could affect their rare disease.

Looking at the qualitative data, some respondents feel that because their disease is ‘invisible’ their peers aren’t taking pandemic precautions seriously enough around them. Others are struggling to comprehend the effect coronavirus vaccines will have on their disease and their treatment plans. They are seeking more information and reassurance to make an informed decision regarding the benefit-risk
of vaccination.

“We may look fine and healthy, but our lives, and our risk levels, are much different than yours.”

“Be a bit more empathetic towards us–we are at greater risk than ever.”

“It’s made me a bit more anxious. I’m going to take the vaccine but am worried about the side effects.”

“It just brings out fear of how it might affect us since we’re already dealing with a life-threatening illness–COVID just compounds that fear.”

Early finding 2: rare disease patients and caregivers are emphasizing treatments

Initial responses show a heightened treatment concern in rare diseases brought on by the pandemic. 39% of participants said the extent at which a treatment keeps them from being hospitalized was of increasing importance. Meaning less likelihood to seek treatment in a doctor or hospital setting.

27% of participants also said they are now more likely to search for new treatment options. Participants are starting to evaluate their treatment more closely, with some worried about the effects of immunosuppressants and a higher risk of
COVID-19 infection.

“I wish I wasn’t taking an immunosuppressant during a pandemic, but it has helped me with my rare disease.”

“I worry about drugs suppressing my immune system and COVID.”

“As someone who is immunocompromised too, I’m not about to be getting in a Lyft/Uber or an NEMT Medicaid transportation car to go for appointments for my own safety.”

Early finding 3: lockdowns and shielding measures have always been common in rare disease

Some of the survey participants shared that their condition has prepared them for the COVID-19 measures and normalized a lifestyle they already faced. Others have said these extra measures have heightened the isolation they had felt before COVID.

“I was already masking in high-risk situations and avoiding sick people, so COVID was not a big deal to me.”

“This is a taste of what I live normally, isolated from many friends, and activities.”

“I feel like people need to have more empathy for people with rare diseases or disabilities. Many of us have lived with social distancing, masks, fear of getting sick or dying for years. And many of us will continue going through that. I hope it’s been a wakeup call to employers that you can make accommodations for disabled people like we have been asking for years, like working remotely.”

The early findings from the survey show that there have been significant opportunities for the industry to provide greater support. Rare disease patients and caregivers are anxious about getting COVID-19 and its effect on their treatment and health. As a result, they are spending more time than ever before actively searching for information, yet they find their anxieties and uncertainties unanswered.

Inclusion of rare disease populations in large-scale and accelerated clinical trials such as those for the COVID-19 vaccines will always be challenging. However, it is essential that pharma considers rare disease populations in their analyses of real-world data generated through the mass vaccination programs. Similarly, industry must work together to pool data on the impact of COVID-19 disease and the effectiveness of treatments to understand and communicate both the risk of disease and the benefit-risk of treatment options for rare disease populations.

Moving beyond the effectiveness of treatments and vaccines, the pandemic has created an opportunity for pharma to gain insight into the experiences of those affected by rare disease; what life is like for someone with a disease that isn’t heavily researched, how frustrating it is when answers are not available for important questions, or the feeling of isolation that results from shielding to protect the health of
loved ones.

Given that the findings from the survey to date show there have been no significantly strong indicators of built or diminished trust in pharma, pharma has an opportunity to sway that opinion in the right direction.

No doubt COVID-19 has disrupted orphan drug research, with trial site closures, trial delays, and even cancellations. As trial planning builds momentum once again, industry attention has turned towards the potential for decentralized trials to change the way trials are run in the future.

Early findings from this survey–such as the increased fear of going to the hospital–corroborate those from a report conducted last year, which considered the openness of rare disease patients to decentralized approaches to trials. The report found that study designs involving a mix of home and site visits are attractive as travel to sites is a common barrier for rare disease study participation.

Overall, initial data from the COVID-19 and You Survey shows positive signs for researchers. As the early data shows, patients and caregivers are spending more time evaluating their treatments and how effective they are in today’s post-pandemic world. Could this provide new opportunities for research and an increased willingness from patients to take part in studies?

Learn more about this survey by visiting: 

Feature Articles

Survey data shows individuals are not informed on how COVID-19 could affect their conditions.

Rare Disease Patients Overlooked During COVID

As a response to the worldwide shutdown of non-essential businesses and to maintain clinical trial continuity, the industry turned to decentralized clinical trials (DCTs). Digital clinical trial tools–including eConsents, eSource, electronic patient reported outcomes (ePROs), electronic clinical outcomes assessments (eCOAs), telehealth visits, medication adherence apps, and eDiaries–have made it easier for patients to participate, ultimately positively impacting real-world clinical trial outcomes. It’s no surprise that these tools to decentralize research are being used increasingly. Industry Standard Research’s 2020 survey indicated over 40% of sponsors are currently using hybrid trials and another 32% said they had plans to start using hybrid trials in the next two years.

As life sciences companies began transitioning from brick-and-mortar clinical sites to a decentralized “virtual” research model where study procedures can take place remotely, clinical research ostensibly became more accessible to a broader swath of patients. This new approach dramatically reduced the most common burdens inherent to traditional trial participation. While there are many upsides, one of the most dramatic benefits offered by decentralized trials is the potential to engage historically underrepresented communities.

This sharp increase in decentralized research came at a time in the United States when racial inequity and social injustice came into sharp focus. Industrywide, the call for greater diversity has never been louder. Historically, only 17% of study participants at any given time and across all therapeutic specialties are people of color.

 By contrast, the Centers for Disease Control and Prevention (CDC) shows the disproportionate disease burden on the same populations in the same therapeutic areas.

More specifically, Moderna and Pfizer’s COVID-19 vaccine trials faced scrutiny that raised concerns were about inadequate recruitment of minority populations and those most impacted by COVID-19 exposure, infection, morbidity, and mortality. The problem became so concerning that FDA expanded its guidelines for enhancing the diversity of clinical trial populations.

Despite recent and profound medical and technological advances, there is limited evidence of these changes moving the needle toward more equitable clinical trial recruitment or improved health outcomes for racial and ethnic minorities. While decentralized clinical trials (DCTs) have great potential to improve these inequities, relying on them alone without accepting their limitations puts too much pressure on novel technologies when awareness of clinical trials and broad acceptance has not been embraced by communities of color.

One key reason why patient recruitment is so challenging is that traditional clinical trials often require patients to take time off from work, have ready transportation, and navigate a host of other inconveniences. Not surprisingly, these factors make many study opportunities inaccessible to the individuals and communities that need them the most. DCTs hold the promise of removing these burdens. In the last year, DCTs have improved recruitment rates by approximately 80%.

Easier participation equates to improved patient compliance, as well. The “in-the-moment” patient accounts afforded by a decentralized approach offer the advantage of more accurate recollections of their experiences than data captured in-person, but weeks later. Patients offered the opportunity to provide study data in the context of their home environments and day-to-day lives also brings the benefit of allowing ongoing improvement of digital health solutions and clinical care. On their face, DCTs offer patients an easier way to participate in trials by providing technology as the intermediary, potentially making participation not only more acceptable but also attractive. Bringing trials to a patient’s home enables the ultimate patient-centric trial experience, replete with easy access to ongoing, high-quality resources and a care team not otherwise easily accessible.

DCTs also have the power to speed patient recruitment, while reducing drop-out rates, possibly saving millions of dollars per day. As of 2016, 85% of trials failed to finish on time, greatly increasing the financial burden on sponsors. Additionally, the ability to collect high-quality clinical and real-world data provide stronger evidence packages and digital endpoints to generate differentiated label claims.

In addition to DCTs’ potential for increased patient enrollment and retention efficiency, they can also enable trial teams to recruit a more inclusive, representative participant population. Yet, DCTs–still evolving–are just one path to diversity. So, what else can be done to bridge the gaps in diversity, equity, and inclusion in clinical trials? As critical, how can combine the drive for decentralized clinical trials and improved equality to ensure truly effective and meaningful change across the industry?

Here are five ways to start moving that needle.

1. Acknowledge inherent privilege and bias up front

Recognize that privilege permeates the clinical trial landscape so most who work within it see with only a limited lens. Trial teams can no longer dismiss obstacles or diminish their impact upstream. Just because a team member does not clearly see a problem does not mean it does not exist. Want to know what works? Ask someone. And then listen. Go back to the drawing board incorporating invaluable intel from the patient populations you seek to engage, then bring them back something that demonstrates they were heard. Repeat until you get it right. Remember this simple equation: Bias in, bias out.

According to data compiled by Shonda Anderson-Williams, healthcare and life sciences digital transformation leader at Microsoft, diverse companies outperform the competition by 35%. Further, millennials are looking for a more diverse and inclusive workplace with 62% saying they want a career with social impact and purpose, and as many as 72% saying they would leave an organization for a more inclusive one.

 But tangible leadership is demanded for one of the most important issues of our times. This kind of leadership can face injury and assault by people who use defensive diatribes. Leadership, however, means pushing back and then measuring the impact of that response. Leadership always sets something measurable into motion. Take a stand. Otherwise, take a seat.

Global Head of D&I at Astellas Pharma, Eloiza Domingo, says pharmaceutical companies should include diversity leaders in their product lifecycle teams and think about how they look at issues such as supplier diversity, community volunteerism, and corporate social responsibility efforts. It is also important to educate managers around hiring, promoting, and engaging diverse talent. Organizations need to build a clear case for diversity, inclusion, and cultural competence into their mission and values and articulate that from the bottom up and the top down.

3. Develop community communications competence

Organizations must start any new trial effort by building community relationships. All too often, enrollment fails due to a lack of any established relationships. Overcome these enrollment barriers by becoming worthy of trust.

Fostering these relationships begins with dialogue to understand the concerns of marginalized communities. Support local educational initiatives that center around creating better health outcomes. Embrace a continuous feedback loop and take criticism with grace. Operationalize ways to consistently collect input from patients the way Medable is doing today, with its Patient Advisory Council.

Once there is a framework established, then follow through with those recommendations. The key to change is meeting people where they are. Lack of trust is well-rooted in history, perception, and fear of ongoing victimization. Thus, any organization looking to make inroads with new populations must first acknowledge the historical facts that got us where we are, and then work to move past it.

4. Center the human Factor in decentralized trials

Relying on digital technology to the exclusion of human interaction misses out on the texture of relationships and the very foundation of trust-building—a critical component of effectively engaging communities of color who may often carry justifiable baggage. Relationships matter, particularly when it comes to patient recruitment, and the more the industry humanizes the process, the more humans will feel comfortable taking part in it.

In addition, verify the validity of key performance indicators by making space for real feedback by real people and develop a workflow with an iterative, inclusive process. Use those algorithms to build in checks and balances and that make performance clear based on standards set by the full patient market.

DCTs bring the trial to the patient, removing the burdens of travel and distance, as well as the need to take time off from work. This, in turn, makes trials more accessible across all demographics. At the same time, DCTs require smart devices or computers and a reliable internet connection. The same communities that lack access to traditional trials may also live in areas where there’s immature digital infrastructure. Study sponsors looking to diversify recruitment and democratize access can get an advantage by providing dedicated, reliable, high-speed internet when such situations arise.

While merely setting up a site in a location near a population of color does not translate into study enrollees, DCTs can go a long way to begin to bridge the racial rift. Companies that have leveraged a decentralized model have achieved unprecedented results, including three-times faster patient enrollment and over 90% patient retention rates.

The decentralized model has opened doors to more patients and reduced racial disparity in healthcare to improve overall outcomes. And, with increased trial access across all demographics, study data will grow more all-encompassing for greater insight into developing new treatments that help more people.

Given the road we’ve travelled to get here, infusing decentralized trials with cultural sensitivity and patient-centricity is more important than ever if to diversify study enrollment.

, “Warming Up To Hybrid Trials,” by Rebecca McAvoy (February 3, 2021). See full resource here: 

, Association of Clinical Research Professionals, Representation in Clinical Trials: A Review of Reaching Underrepresented Populations in Research,” by Isabelle Yates, Jennifer Byrne, Susan Donahue, Linda McCarty, and Allison Mathews (August 10, 2020). See the full resource here: 

, “Guidance Document: Enhancing the Diversity of Clinical Trial Populations,” (November 13, 2020). See the full resource here: 

, “What clinical trial statistics tell us about the state of research today,” by Eian Kantor (September 10, 2020) See full resource here: 

, “Bridging the Diversity Gap With Decentralized Trials,” by Kent Thoelke, Tami Klerr, Scott Schliebner. See full resource here: 

 Podcast, “Shonda Anderson-Williams,” by Taren Grom (September 23, 2020) See full resource here: 

, “Medable advisory council works to amplify patient voice, inclusivity,” by Jenni Spinner (March 24, 2021). See full resource here: 

, MPH, is founder and CEO of Clinical Ambassador Inc., founder of iParticipate Inc., Community Engagement Director and Innovation Strategist with EthosExcel. She is also a member of the Medable Patient Advisory Council (PAC). Kalloo can be reached at 

 is a patient advocate with extensive first-hand experience as an advocate in oncology as well as in the industry. She has helped patients navigate their medical journey at the Stanford Cancer Center and at Bay Area Cancer Connections. She currently volunteers with The Second Opinion to help patients connect to services and information about their cancer and is a founding member of the Cancer Patient Advocacy Alliance, serving as an advocate member for grant proposals submitted to the California Breast Cancer Research Program, Department of Defense Breast Cancer Research Program, NCI and the Patient Centered Outcomes Research Institute. Venticinque is also a founding member of the Medable Patient Advisory Council (PAC).

COVID-19 forces life sciences industry to make long overdue changes.

5 Ways DCTs Can Positively Impact Trial Diversity

Early in the 1900s, the medical world began to suspect that different types of people were more prone to specific diseases than their peers. As the century progressed, others outside the medical world began to get suspicious, too.

And when the world lost its semblance of sanity last March, as minority groups were dying from COVID-19 at higher rates than Caucasians, the world reacted; it called for real-world diversity in clinical trials and medical parity in the clinic.

 Studies were published, opinion pieces, too, even ads were aired for clinical trial equality.

 Page after page in Google can provide the details.

No doubt, the historical dominance of the white man as a trial enrollee has thwarted gathering evidence-based knowledge regarding the health and welfare of non-Caucasians. Without the latter’s participation in interventional trials, little can be ascertained as to whether the drug helped, hindered, or even hurt them. This lack of knowledge is acutely felt in the field of oncology. “Certain compounds affect certain populations,” said Diana Foster, PhD, vice president, Strategy and Special Projects, Society for Clinical Research Sites (SCRS). Diverse populations are “critical in drug development.”

To say that pharma has not paid attention to the problem of inclusion prior to the pandemic is inaccurate, those interviewed for this article said. An important point: inclusion can be defined in numerous ways, beyond the color of someone’s skin.

Diversity, said Joan A. Chambers, Senior Director, Marketing & Outreach, Center for Information & Study on Clinical Research Participation, is difficult to define. “It can go down many different paths.”

One such path is pharmacogenomics. The human body has about 30,000 genes, and each one, on average, produces three proteins. That’s a lot of opportunity for therapies to encounter genetic hiccups and disrupted metabolic pathways.

 Add to that how bodies are influenced by prior generations, and the world they are living in now. A 2013 study of 167 new-molecule-based therapies showed that one in five of them acted differently in minority groups, in different races and ethnicities.

“Diversity certainly has a higher profile now, but pharma began funding [our Diversity Site Assessment Tool project] four years ago,” said Foster. “Diversity is a scientific and conceptual issue that continues to evolve and develop.”

COVID-19 was not the impetus for pharma’s current focus on diversity in its trials, said Marie-Pierre Hellio Le Graverand, MD, DSc, PhD, senior vice president and Pfizer’s Clinical Development & Operations, Global Product Development lead. “We have been working on [minority inclusion] for a number of years. It takes time to move the needle.” Hellio Le Graverand and colleagues recently published Pfizer’s own clinical trial diversity track record for the last 10 years.

 The Pfizer representatives recently called for industry to address equity access to clinical trials.

But the pandemic made it clear that the world wants that needle to move and move fast.

Scientists began noticing differences among various groups, early on, starting in the late 19th century. (Mendel was growing and analyzing his peas around 1865.) In 1932, J.M. Adams wrote about the differences in blood pressure levels between a “group of white and [African American] workmen” in the American Journal of Medical Sciences.

Researchers then started reporting that different types of people react differently to medical therapies. In 1952, Hockwald et al. showed that red blood cells of 10% of African Americans and some Caucasians were fated for destruction if these patients were regularly given the antimalarial primaquine.

 In 1962, Tarlov et al. deemed the problem to be “an intrinsic abnormality of the erythrocyte,” as this “hypersusceptibility to hemolysis by drugs is a genetically transmitted inborn error of metabolism.”

FDA began its decades-long quest for inclusion in 1993, telling trial sponsors that if they wanted financial support for their clinical trials, they had to enroll other people besides young and middle-aged white males. Five years later, FDA got specific: break out the efficacy data according to the participants’ age, race, gender and ethnicity. With the first installment of the Human Genome Project a few years away, maybe the agency was gearing up to review precision-based medicines.

In 2001, J.F. Wilson et al. set out to see how drug response worked in participants from China, New Guinea, Sub-Saharan Africa and Western Eurasia. They were tested for shared genetic regions and then grouped with their genetic kinsman. Ultimately, the participants were put into four groups. Expecting to find the four groups geographically aligned as well, what they found was that geographically, borders don’t exist: Ethiopians joined people of Jewish descent, Afro-Caribbeans were, genetically speaking, neighbors of the West Eurasians. Human demographics are complex, the authors said, with no apparent natural clustering arrangement. The work does provide, they continued, a framework “for assessing the appropriate level of resolution in relating genetic structure to drug response.”

While FDA has approved and continues approving assay tests to ensure that the right medication, primarily for cancer patients, reaches the right genetic target, pharma’s long-running, one-size-fits-all approach was still in use.

In 2015, the CDER approved 45 new drugs with more than 105,000 patients enrolled. White people comprised 79% of that number, African Americans, 5% and Asians,12%.11 By 2019, African American participation had reached 11%, according to FDA figures.

This past February, an overview of 230-U.S.-located vaccine trials with 219,550 patients conducted between 2011 and 2020 showed both ethnic and racial underrepresentation. About 100 of the trial sponsors, or 58%, reported race; 79, or 34%, ethnicity.

In mid-May, another enrollment overview, this time of 207 U.S trials from 2007 to 2020 involving 8,429 pancreatic ductal adenocarcinoma patients showed that rates of enrollment for minority groups weren’t reflective of real-world, higher diagnostic rates.

The rates of somatic and germline mutations in Black patients differ from other racial subgroups, so their response to therapy also differs, said co-author Kelly Herremans.

 Black participants were less likely, at 2.9%, to be included in a Phase III trial than in Phases I and II, with each about 10%.

Just two more studies of note: In 2010 Booske et al. found that social circumstances, environment and genetics affected health by half;

 by 2016, the United Health Foundation found those three drove a person’s health by 60%.

In 2019, a study underwritten by Merck & Co. along with many stakeholders, including the Association of Black Cardiologists, Inc. and SCRS, surveyed cancer centers, looking for those more successful in recruiting racially and ethnically diverse patients than others. In essence, these centers found it takes informed, back-and-forth communication among all involved, while giving enrollees, their family and their referring physician more of a voice in making decisions. These sites also trained their investigators in cultural mores.

 Work on the Diversity Site Assessment Tool, now scientifically validated, began in 2016. Merck wanted help in finding non-Caucasian trial participants. “We consciously decided to approach the work scientifically,” Foster said. “What are the sites lacking, what do they know and what are we going to teach them?” Over the next four years, the group devised self-assessment surveys to get answers to these questions. Its financial supporters include pharma members and CROs.

Some sites don’t know their own communities, she said. “The site could be in an urban location, and three blocks behind the hospital is a huge population of Spanish-speaking people, and they don’t even know it.”

For the last survey, questions were sent to 437 sites located in hospitals, private physician offices that conduct trials and academic institutions and other research companies. Foster said SCRS will make the tool available; no specific training programs have been developed yet.

The targeted improvements pinpointed in the study are similar to findings in the 2019 Merck-funded study: locate minority-based organizations that can help build a network to find minority participants, like community centers, churches, support groups; include different languages on the phone prompt; and help participants get over hurdles, like finding housing should the patient need to visit a site, for himself and family.

Joan Chambers knows all about the hurdles of finding minorities for trials, and the need to use local organizations to find them. CISCRP has been minority focused since its founding in 2003. The goal has always been “how do we share this information about clinical trials in easy-to-understand content that does not sound scientific,” she said. The group disperses the information in the community, but it’s up to the recruitment arm to tailor the message for a specific study.

Local organizations can support gatherings at community centers or churches, and educate about clinical trials. And when they do, the questions that people ask at these gatherings all punch the holes as the studies geared to find
minority patients:

Does a participant have to know English to participate in clinical studies?

Can your primary care doctor refer you to a clinical trial?

What are trials, why are they important, who is involved?

At ZS, helping with minority recruitment is more about getting to the roots of “I won’t participate,” and “I won’t invite this person in.” ZS, a professional problem-solving firm, began its cognitive and behavioral science project six years ago. It has pharma sponsors, as does
Foster’s work.

The point of this project, said Jacob Braude, principal, is to identify the so-called mental shortcuts people take to make decisions, and to dismantle those shortcuts that prevent someone from enrolling in a trial, as well as those shortcuts that site coordinators and referring physicians take to discourage a would-be participant. Braude said academics have identified 100 such shortcuts. An example: A person with osteoporosis in her knee can get site injections four times a year. But this person only comes once, because her physician has told her, “Come back when there is significant pain.” This shortcut is called moral regulation in which the patient is balancing good and bad behavior. “We asked the patients, ‘do you have to earn your injection? and 60% said yes.’”

Expanding inclusion criteria is a front-burner item, supported by FDA and not a few pharma houses.

At IQVIA, researchers are “pressure-testing” inclusion and exclusion criteria, said Mark Brown, head of Global Patient and Site Solutions at IQVIA in a statement. At Phase III, some eligibility criteria have become universally accepted, or used as a template across trials. The impact: certain patient populations have been excluded from participation “without strong clinical or scientific justification.” However, Brown continued, lifting those exclusions and using them to decide if these patients are eligible, and how including these patients would impact the trial—during trial design—could help trial sponsors better determine eligibility requirements.

During the COVID trials, pharma had little choice but to get creative in finding minority participants. Trial sponsors had constant contact with regulators; sponsors monitored trial sites to see who was enrolling, and then compared site numbers to make adjustments; they received FDA feedback and approvals while the trials were ongoing. The risk averse had morphed into the risk be damned.

They relied heavily on technology to find human beings: digital health suites, virtual study coordinators, and mobile phone information to look at traffic patterns that would indicate where people were in lockdown. If a trial site needed help in recruitment or its staff needed help with the technology, the sponsors would send in the Marines, as it were. They took the trial to the patients.

Janssen used mobile units to make sure its satellite services could help screen potentially eligible patients in their communities. Pfizer also monitored traffic. AstraZeneca “chased the virus with interactive speed maps to have a global picture of the affective areas,” said AZ’s Rachele Berria, vice president, U.S. Medical, BioPharmaceuticals in a Prix Galien webinar.

 AZ worked with IQVIA, governments and universities to find sites and used predictive modeling. It also ran systems in parallel (as did the others) and used wearables to monitor vital statistics. “We made ample use of telehealth,” she said.

In a typical trial, sponsors look post-trial to see how well recruitment went, and so on, said Terry Murphy, Janssen’s Global Head of Strategic Operations, Pharmaceutical Development and Manufacturing Sciences, in the webinar. With COVID, “we asked, how are we doing and how can we change things?”

The casual observer will note that these new approaches rely heavily on technology to achieve what ultimately is a person-to-person event. However, it is certainly the improved technologies and processes used during COVID—taking the trial to the patient—that can help change the overall inclusion demographic in clinical trials.

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Laura E. Flores, Walter R. Frontera, Michele P. Andrasik, et al. Assessment of the Inclusion of Racial/Ethnic Minority, Female, and Older Individuals in Vaccine Clinical Trials. 

Bridget C. Booske, Angela M. K. Rohan, David A. Kindig, et al. Grading and Reporting Health and Health Disparities. 2010; 

Margarita Alegría, Kiara Alvarez, Rachel Zack Ishikawa, et al. Removing Obstacles To Eliminate Racial And Ethnic Disparities In Behavioral Health Care. 2016; 

Jeanne M. Regnante, Nicole A. Richie, Lola Fashoyin-Aje, et al. US Cancer Centers of Excellence Strategies for Increased Inclusion of Racial and Ethnic Minorities in Clinical Trials. 

https://ascopubs.org/doi/full/10.1200/JOP.18.00638

Galien DH 2021 / The Impact of Digital Technologies – Lessons from COVID-19

How COVID-19 blazed a new trail for greater patient inclusion.

The Many Paths of Diversity in Clinical Trials

Throughout the pandemic, clinical research stakeholders have been both amazed and immensely proud at the collective effort to adapt and address a monumental global health crisis in record time.

A great deal has been written and said about the factors that have contributed to the delivery of COVID-19 vaccines more than five years faster than typical development timelines and to the more than 1,000 COVID-19 treatments and vaccines now in the pipeline. The top contributing factors include:

The proactive and accommodating way that regulatory agencies and ethical review committees have supported development planning and activity.

The rapid mobilization of internal and external scientific and operating teams with a singular and common focus.

The fast deployment of remote and virtual technology solutions supported by more open data, information sharing, and advanced analytics.

The execution of parallel clinical trials and the compressed time between clinical trial phases.

The de-risking of development activity through the availability of global funding and resources.

The unusual frequency and extent of global media coverage contributing to unusually high public visibility.

The clinical research enterprise has much to celebrate, especially in light of the fact that most adaptations and changes represent a major departure from normal operating conditions. Many of the approaches and solutions deployed—such as remote monitoring, e-consent, home nursing visits, and integrated data management platforms—faced significant difficulty replacing legacy approaches before the pandemic. Many were stuck in planning or piloting stages for decades.

There is now substantial speculation about how the clinical research enterprise will function when the pandemic is fully behind us. How will the enterprise apply and embrace the experiences and lessons learned during this unprecedented period? Beginning in late 2020, articles, podcasts, webinars, and conference presentations began surfacing, most with both wishful thinking and pledges not to return to pre-pandemic operating conditions.

In recent months, we have learned more about underlying conditions that have supported pandemic response and a clearer picture is emerging of issues and challenges that will contribute to some retrenchment and more conservative application of adaptive and innovative practices as we move into a post-pandemic world. Two recent Tufts Center for the Study of Drug Development (Tufts CSDD) studies help paint that picture: the first study is an in-depth collection of interviews with principal investigators and senior study coordinators from the global community of investigative sites and site networks. The second study is a global survey—conducted in collaboration with the Bill & Melinda Gates Medical Research Institute (Gates MRI).

Tufts CSDD conducted a total of 26 in-depth interviews during March and April 2021, approximately one full year after the international community began locking down and clinical trial activity abruptly shifted to remote monitoring and decentralized support. Investigators and study coordinators noted several positive outcomes. The majority pointed to sponsor company and regulatory agency responsiveness and encouragement of adaptive practices as critical success factors. Site professionals felt that the most positive outcome in the transition to virtual and remote clinical trials has been the increased choice and accessibility offered to patients considering participation and the substantial improvement in study volunteer convenience.

But with few exceptions, the global community of investigators and study coordinators indicated that operating remotely and virtually has greatly increased workload for site personnel. Many noted the inordinate amount of time they have dedicated to learning new technology solutions; providing support to remote monitors and health professionals; training vendors unfamiliar with the clinical research process; and coordinating and integrating disparate and fragmented activities. Most interviewees pointed to significant delays that they have encountered starting up studies, receiving clinical trial supplies and lab kits.

Many conveyed concerns about the delays they experienced in receiving payments to help defray the substantial upfront risk sites assumed in supporting modified and adapted execution models.

In nearly every in-depth interview, investigative site personnel discussed the wide variability in approaches and solutions deployed by sponsors and contract research organizations (CROs) that contributed to high levels of uncertainty and the increased potential for errors and mistakes.

Between mid-January and April 2021, Tufts CSDD and Gates MRI gathered 344 global responses primarily from pharmaceutical, biotechnology companies, and CROs. The purpose of this online survey was to assess the experiences and effectiveness of development teams operating remotely. Two-thirds of respondents are employed by major and mid-sized companies and a similar percentage reports having team management responsibility within clinical, data management, and clinical operations functions.

Overall, respondents reported very high levels of productivity while operating remotely. Nearly all (97%) indicated that they can perform their role as a remote employee “very effectively” or “somewhat effectively.” But more than half of respondents (55%) report feeling burned out and 42% report that connections with their colleagues have deteriorated.

Factors contributing to burnout are intuitive and generally familiar to us all. The top three included the frequency of virtual meetings (by 67%); increased workload and additional responsibilities negatively effecting life balance (65%); and the emotional impact of dealing with uncertainty and isolation (54%). Unaddressed, it is likely that the feelings of burnout and loss of connection will continue to rise.

In open-ended responses, several indicated that the inability to travel and meet face-to-face with colleagues detracted from their collaborative effectiveness. Several also noted the challenges of not having a clear sense of the return on investment (ROI) for various solutions deployed and of the higher relative start-up cost and time investment required to support decentralized clinical trial activity.

Despite these experiences and concerns, the vast majority of respondents want to preserve their ability to operate remotely: 86% want their employer to continue offering “mostly remote” work when the pandemic is over; 6% indicate that they are uncertain about what operating model they want in place; and 8% said that they do not want their organizations remote operating model to continue.

We plan to publish the full results of the Tufts CSDD–Gates MRI study in 

Pandemic experience and response has exposed drug development organizations to numerous possibilities that would not have otherwise been widely adopted. Many observers would argue that this unusual adoption experience is not a reflection of a new standard operating environment but rather a one-time occurrence—a grand pilot program—providing a unique opportunity to consider, integrate, and apply “suitable” new options and choices.

Once the pandemic is behind us, these options and choices will likely be offered simultaneously with other more traditional approaches to balance and best satisfy study volunteer preferences, convenience, and scientific and operating requirements. Ultimately, these more expansive hybrid approaches will increase clinical trial complexity and customization, resulting in well-known outcomes: inefficiency, poorer quality, slower timelines, and higher costs.

Given cultures that have historically been risk-averse and resistant to change, many sponsor companies and their CRO partners will step-up efforts to scrutinize capital, personnel, and resource investment in, and double down on challenging, newer innovative practices. For the majority of organizations, it is likely that the pendulum will swing back toward slower, more measured response and more
limited acceptance.

A minority of organizations—those willing to take more risk—are already applying the implications of pandemic experience. Many are evaluating ways to better support teams operating remotely with more variable, agile, and flexible staffing models, infrastructure, and standard operating procedures. Several have shared the intent to consolidate their fixed, physical operating footprint, to continue to reduce study participant burden, and to entertain more open collaboration models.

Clinical research data volume has been rising dramatically for decades as protocol design objectives and scope have increased. The diversity of sources for clinical research data—including specialty labs, mobile and wearable devices, and patient health records—has also intensified. Post-pandemic, the juggling of highly customized clinical trial executional models will drive the collection of more data informing operating performance, efficiency, and quality. This rapid expected growth in rich data volume cannot be managed by traditional means alone and will rely more heavily on sophisticated and augmented analytics, including machine learning, risk-based quality management, and risk-mitigation techniques.

As the pandemic recedes and we gather more robust data on its full impact, we can anticipate wider variation in sponsor, CRO, and investigative site operating strategies and practices.

We will look back at our collective response with not only amazement and pride but also the knowledge that the pandemic did not solve our perennial drug development operating conditions. Rather, it necessitated experiences that affirmed, informed, and elevated enterprise-wide commitment to patient engagement and digital transformation.

Clinical Trial Insights

Affirming and advancing patient engagement and digital transformation.

Contemplating the Full Measure of Pandemic Response

Clinical research sites are modernizing trial operations with site-centric applications to provide a digital patient experience. Crofoot Research Center, a Houston-based practice that has run over 200 clinical studies in rare disease, is one site realizing the benefits of using patient-centric, site-first solutions.

With an eRegulatory system and eConsent from Veeva Systems, Crofoot is shifting from manual and paper-based processes to more streamlined, digital execution. Charles Sydnor, CCRA, ACRP-CP, project manager at Crofoot, discussed how offering a digital patient experience in trials enables the site to provide better patient care.

: What challenges did Crofoot experience with traditional, paper-based informed consent?

 Patient reach and accessibility have always been our biggest barriers in studies. COVID-19 made reaching new patients even harder, as most could not physically come into our practice. Using paper-based consenting wasn’t a feasible option because of the travel, distance, and safety concerns, impacting our reach and preventing many patients from considering research as a treatment option.

Over the years, we have seen how paper complicates execution, reduces efficiency, and provides limited accountability. Using paper, paying for storage, and hiring additional staff to manually check all the consent forms for completion, errors, and appropriate signatures dramatically increased our economic burden.

Lastly, we want to ensure that the potential participant understands the study, especially the risks and benefits. The traditional paper-based model of consenting does not lend to better participant comprehension but rather the exact opposite. Handing a 20-plus page consent document is an intimidating and overwhelming event, and many participants complain that the font can be too small for review.

ACT: How has paper-based consent impacted the patient experience?

 Ideally, we’d want to give patients as much time as possible to consider participation, ask questions, and talk to their support system at home before choosing a trial. But once a patient travels into our practice, they usually feel pressure to make a quick decision to avoid another visit. That pressure takes a toll on patients who want to consult family members before deciding to participate in a study, leading to early opt-outs.

Patients also have to come in for a screening, often not scheduled on the same day as consenting. An appointment to provide consent could be in several days or several weeks, but it almost always ends up in another visit for the patient. Thus, paper consent increases the patient burden of participating in trials, requiring more time and travel.

ACT: How has Crofoot’s shift to digital improved the patient experience?

Since we already had an eRegulatory system in place, it made sense to bring in an eConsent solution that enables seamless exchange of information. Implementing eConsent has given patients the flexibility to review documents on their own time and wherever they feel most comfortable.

As clinical research protocols become more complex, the patient’s complete understanding of a study is paramount. Using eConsent allows us to format study information in a more digestible form. This ensures that each participant fully understands what they are signing up for. It is important to remember that each person has different needs, and removing paper will optimize the patients’ experience.

We’ve noticed a significant improvement in patient understanding of studies with eConsent. Numerous patients have expressed gratitude for the ease at which they can access documents, allowing review with those closest to them.

ACT: What improvements has your research center achieved by using eConsent?

Charles Sydnor, CCRA, ACRP-CP, project manager at Crofoot, discusses how offering a digital patient experience in trials enables the site to provide better patient care.

Applied Clinical Trials-06-01-2021

Improving Clinical Trial Patient Diversity: Can Central Imaging Play a Role?

Rare Disease Patients Overlooked During COVID

5 Ways DCTs Can Positively Impact Trial Diversity

The Many Paths of Diversity in Clinical Trials

Contemplating the Full Measure of Pandemic Response

Shifting from Paper to Digital Patient Consent

The Tangled Web of Large Outsourced Providers

Clinical Trials Diversity and Inclusion

Applied Clinical Trials June 2021 Issue (PDF)

Is COVID A Game-Changer for Wider Drug Development Policy?

FDA Promotes Master Protocols to Modernize Clinical Trials

Steps Toward Diversity in Clinical Trials: Building Authentic Trust