Claudia Berrón

Historically, clinical trial research has focused on participants from predominant populations. A 2020 FDA analysis of global clinical trial participation found, out of 292,537 participants, 76% were white, 11% Asian and 7% Black.

 In addition, LGBTQ+ and individuals with disabilities are among other underrepresented populations. The decentralized clinical trial (DCT) model, whether virtual or hybrid, can help reach previously neglected groups. By understanding best practices, sponsors, and contract research organizations (CROs) can overcome key challenges.

Creating diverse and inclusive investigations

 Every partner and individual working in the clinical trials space can become a voice for diversity and inclusion. For example, within a given geography, consider the demographic composition of ethnic communities and gender identities within it. If 50% of the population is female in the geography of a trial appropriate for that gender, then ensure equitable representation by working toward 50% female clinical trial participation. The result is a more diverse data set reflective of a population’s represented groups and further supports a study’s validity.

Establish a transparent, patient-centric experience:

 Underrepresented communities have experienced past abuses during clinical trials and other healthcare settings. While current law and ethics efforts, such as Institutional Review Boards (IRB) and informed consent, help ensure patient safety, these communities may feel mistrust that can linger for decades and impact their interest in volunteering for new studies.

Transparency is the foundation for conducting inclusive clinical trials with diverse populations. Be proactive and acknowledge historical abuse. Encourage clinical trial patients to actively engage with community leadership, ask questions and provide feedback to create valuable dialogue. Leaders able to deliver these messages, show vulnerability themselves and convey humility can create a personal connection that can help overcome apprehension.

An experienced consultant who is a member of the community can help build trust and engage underrepresented patients. Working with or establishing a community engagement board (CEB) comprising local healthcare officials and community leaders, sponsors and CROs can also help bridge potential trust gaps.

Ensure the clinical trial team reflects the population:

 Help underrepresented patients feel more at ease by leveraging a diverse panel of staff and investigators, as patients are more likely to feel comfortable if they see themselves reflected in the staff—including home care nursing teams that are fundamental to some decentralized clinical trials. This can add another layer of trust in terms of understanding that the clinical trial team doing the work has the patient’s best interest in mind. Partnering with community health organizations with a trusted presence in the community can help facilitate diverse staffing. Equally important: hiring a diverse staff advances diversity in the STEM field overall.

 DCTs and the technology used to support them can minimize barriers to participation by eliminating the need for patients to spend time visiting clinical trial sites.

However, not every patient in a diverse population is at the same place in their digital journey. Consider a clinical trial that requires the use of a wearable device in a brand a particular population is not familiar with. One patient may be comfortable using an unfamiliar device, while another may find the technology intimidating since it is not a familiar brand.

With respect to the digital journey, be sure to think about the age of patients in the trial. Some older patients will be uneasy with technology, and some will also prefer face-to-face engagement with a healthcare professional—from the perspective of their generation’s characteristics, or possibly social issues such as loneliness.

The inability to access the internet can present barriers for patients challenged with economic disadvantages, a digital divide that can encompasses those in both urban and rural areas. In addition, persistent connectivity issues in economically disadvantaged areas can interrupt patients’ ability to participate. Provisions, such as securing grant funding, may need to be made to extend reliable internet access to participants.

Ensure the technology enhances the patient experience:

 Technology is fundamental to decentralized clinical trials but ensure it is as simple and intuitive to use as possible. Consider how best to support technology use, whether it is in-person training with a healthcare professional or a step-by-step video guide. Equally, think if equipment can be set up to work out of the box—e.g., a tablet with charge in the battery and the ePRO (electronic Patient Reported Outcome) software already pre-loaded makes for much simpler participation than placing the burden upon the patient to access and download the correct digital platforms and apps.

 When working with populations in emerging regions, existing infrastructure can present unique challenges. For example, a specific region might be prone to frequent power outages, which can impact refrigerated drugs or patient samples. Local experts can help properly prepare a clinical trial for situations that might not be typical in a study conducted in regions with historically majority populations. Help mitigate risk and create confidence in patient populations by leveraging external and international quality assurance practices.

Navigating regulations in emerging regions with often excluded populations can still be a challenge, despite regulatory advances many countries have made in recent years. For example, the regulatory framework can be lengthier or entail more extensive bureaucracy than countries with historically dominant patient populations. To avoid delays that can potentially impact community trust, start working—during protocol development—with investigators who have expertise in working in areas with underrepresented populations.

 Clinical trial participation can present significant barriers for people living with disabilities, yet technologies and processes can support equitable access and inclusion for these populations. Design clinical trial-related content, like patient instructions or reminders, to work with assistive technologies, like screen readers, while options like telehealth or home healthcare professionals can support participants living with mobility challenges.

Collaborate with partners committed to clinical trial diversity:

 Another step toward building equitable clinical trials is to establish diversity and inclusion benchmarks for clinical trial best practices. Organizations with expertise in the field can provide the support, guidance and resources to clinical trials that are more representative of real-world populations. Look also for industry partners, from CROs to suppliers, who emphasize diversity in their own organizations and reflect that mindset in the work they do.

We often hear of “patient centricity,” in clinical trials being key for patient recruitment and retention; having diversity built into clinical trials works towards these tenets of a successful study.

Additionally, when clinical trials embrace diversity, our critical work better reflects real-world populations, develops a clearer picture of overall health and well-being, and identifies further opportunities for healthcare advancements. Putting diversity into action also helps us understand differences in geography, populations, demographics, etc., as it relates not just to medical research but how that can be applied to advance health equity and move science forward across the globe.

, vice president, diversity, equity, and inclusion, 

, senior vice president, clinical services, and 

, senior director, global customer development, clinical services; all with Avantor

U.S. Food & Drug Administration. 2015–2019 drug trials snapshots summary report. FDA. (Online) Available at: 

https://www.fda.gov/media/143592/download

Articles

Regulatory compliance, collaboration, and effective use of technology among ways CROs can overcome challenges.

Considerations to Reach Underrepresented Groups

From e-health records (EHR) to digital twins, technology continues to evolve in an increasingly complex landscape that starts with study approval and planning and extends to long-term sample storage. Understanding best practices for tech integration can help partners across the clinical trial workflow, like CROs, sponsors and suppliers, create reliable, patient-centric, and compliant trials that get critical treatments to market faster.

The scope of technology that supports clinical trials extends across the full clinical trial workflow. As you design the trial, consider the full range of tools. One example is artificial intelligence (AI). This technology is being evaluated to create a digital twin to help predict how a patient would react if they had received a placebo. By eliminating the need for a placebo cohort, AI can lower recruitment requirements, reduce trial length, and increase patient access to the active drug.

Logistics is also an area ripe for smart technology integration. Modern packaging options provide far more than a shipping box for a clinical trial kit. Consider savvier technology, like packages enabled with near-field communications. Equipped with radio frequency identifiers, these packages can communicate with an app that not only tracks the package during shipment, but also provides updates on when the patient opened the package. If the patient must access the kit at specified intervals, this type of data can indicate whether the patient is adhering to protocol schedule.

Clinical trial partners increasingly rely on a menu of technology suites to support their trials, particularly decentralized elements, like remote monitoring or mobile visits.

 Without reliable data collection that’s accurate and repeatable, clinical trials face potential delays that waste time and money.

One aspect of creating an ecosystem for reliable data involves asking up front: what’s the right data set and data detail required for our protocol? While this has always been a core question, technology has added additional considerations. Wearable and other technology can inundate investigators with an ocean of data, especially with devices that offer continuous monitoring. And while all that data can be attractive and relevant, it must still be managed and analyzed. If it’s not essential to the protocol, the data—and the management it requires—adds complexity, time, and costs.

In contrast, it’s also important to ask the question: can any data we collect now be used for future drug development? Reliable storage of not just the physical but the digital sample can help bring future treatments to market without the time and cost associated with new patient enrollment.

Streamlining processes to reduce the rate of data errors also supports reliability. For example, the Clinical Trials Transformation Initiative (CTTI), an association that aims to create a vision for the future of clinical trials, recommends that clinical trials be fully integrated into existing health systems. Doing so would potentially allow a clinical trial to access—with consent—a patient’s EHR and eliminate the need to collect data already in the existing record.

3. Develop data management for the full workflow

The scope of available technology demands more robust data management systems than ever before. From start-up to closeout, data management must span the lifecycle of the clinical trial.

Data management requires coverage across the full clinical trial workflow—and that includes long-term sample storage, which sometimes isn’t fully considered until the end of the sample’s lifecycle. Long-term sample storage must include considerations around tracking and tracing of samples at the storage unit level globally. In addition to the track-and-trace technologies that support the sample, technology is critical for biorepository temperature monitoring, maintenance, and kick-off, or redundancy systems in any event that could risk sample integrity.

Clear data ownership at every step of the clinical workflow is critical, from patient recruitment to drug supply to sample processing to long-term storage. If there are questions at approval submission, the sponsor will need to have clear guidance regarding ownership of each data piece.

Seamless data flow between all partners is equally important. Each partner now has a responsibility to make the investment in front-end and back-end integration that supports data management across the clinical trials workflow. While there is still work to be done in regard to seamless data integration, CROs, suppliers, and other partners are making strides to drive this transformation.

The evolving technology landscape and the COVID-19 pandemic’s impact on clinical trials has enabled and accelerated decentralization of clinical trials, creating an experience that brings the trial to the patient. However, these advances can present a challenge: patient-facing technology is only as powerful as its usability to patients. Devices and other technology that are hard to understand or inconvenient to use can negatively impact patient experience—and that can take a toll on everything from patient enrollment to data reliability.

One aspect of building a patient-centric experience is ensuring patients are comfortable with the digital tools that they will be required to use for the duration of the trial. Patients may require training to use some wearable health devices, so it’s important to consider how they will access effective training. For example, in addition to collecting data, a clinical trial app installed on the medical wearable can offer instructions, such as videos that guide a patient step-by-step through a particular process.

Another, sometimes overlooked, technology challenge is aligning device choice to regional preferences where the clinical trial is being conducted. Consider a clinical trial that will collect data, like cardiovascular rhythm or body temperature, via a smartwatch device. If you choose a wearable brand that patients in that region are not familiar with, you risk reduced enrollment and lower adherence—even if the technology in the unfamiliar brand mirrors the regionally familiar smartwatch.

Using technology to support patient-centric clinical trials also requires consideration of what’s referred to as the digital divide. Depending on the population, factors like age and educational differences can impact technology use and adoption.

Despite the challenges, one of the most exciting aspects of the clinical trial technology evolution is that we could soon conduct trials in which the patient will use just one app to manage their full experience, from participation consent to device management to kit receipt to sample packing and shipment instructions. A scenario like that has the potential to not only increase adherence but also further enhance the patient-centric experience.

5. Understand the regulatory framework around technology

Just as regulations for clinical trials, as a whole, have evolved, regulatory frameworks across the globe now increasingly address the use of clinical trial technology. For example, if the study will rely on a consumer device, like a smartwatch, choose a brand that aligns with relevant regulatory standards of that region. A specific wearable device might monitor functions like heart rate but not provide the level of secure data transmission required in the region where the clinical trial is taking place.

The regulatory consideration extends beyond medical wearable devices to the full clinical trial workflow. Consider data and cybersecurity in logistics. In the traditional clinical trial site setting, partners like suppliers and logistics companies didn’t have access to patients’ personal information. Now, a single decentralized clinical trial can require kits to be shipped to thousands of patients’ homes, exposing a patient’s name, address, and perhaps even the type of equipment they receive and trial they participate in. As a result, all clinical trial partners must be ready to navigate GDPR in Europe and HIPAA in the US, as well as other regional data privacy and security regulations.

Conducting trials in emerging regions can require special consideration. In areas like the BRICS block (Brazil, Russia, India, China, and South Africa) and the Middle East, clinical trial regulations have improved in the last several years, helping better harmonize research standards globally. However, like Western countries, they are now challenged with bringing regulatory framework around factors like data and privacy up to speed.

As these nations continue to build and evolve their regulations, it’s critical for CROs, sponsors, and suppliers to work with local experts familiar with that specific region and any evolving standards. Partnering with a local CRO can help ensure proactive and flexible use of the right clinical trial technology to run a smooth trial that stays on track, on budget, and in good regulatory standing.

6. Consider technology when choosing clinical trial partners

Technology cannot be an afterthought when selecting CROs, suppliers, logistics services, and other partners. As you select partners, ask:

Do I already have a formal integration with this partner? And if so, are we already transmitting data seamlessly back and forth, or do we need an improvement?

Who owns the data at any given stage of the workflow?

If the partner’s technology is already integrated with their own suppliers, how quickly can we react if we have an urgent need for equipment in, for
example, Zimbabwe?

If the clinical trial is held in an emerging region, do we have the right level of local expertise to guide technology integration with that specific population? And do we have compliant tech integration for that region at all levels, from patient recruitment to supply chain?

Are all my suppliers and partners fully integrated in a way that makes technology—and data—easy, seamless,
and reliable?

Technology is a powerful tool that helps clinical trial teams get life-changing treatments to market faster, but all partners must work together to create tech integration that’s reliable, patient-centric, and compliant.

McKinsey & Company. No place like home? Stepping up the decentralization of clinical trials. (Online) Available at: 

https://www.mckinsey.com/industries/life-sciences/our-insights/no-place-like-home-stepping-up-the-decentralization-of-clinical-trials 

Clinical Trials Transformation Initiative. Transforming Trials 2030. (Online) Available at: 

https://ctti-clinicaltrials.org/who_we_are/strategic-vision/ 

Marquis-Gravel, G. Technology-Enabled Clinical Trials. Circulation. (Online) Available at: 

https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.119.040798 

Six best practices and three key mistakes to avoid in new technology space.

Tech Integration for Clinical Trials 

From Prague to Minneapolis to Dubai, clinical trials are increasingly global—and that makes logistics, now more than ever, a mission-critical factor for conducting a successful clinical trial. However, if there are delays during the clinical trial phase, the financial impact can be staggering.

While any number of factors might cause delays, from strategic challenges to commercial barriers, logistics can play a key role. Every delay, from equipment not arriving at a clinical site on time to patients unable to arrive for an onsite visit, creates an avalanche of effects, from decreased patient retention to increased time
to market.

As with other aspects of clinical trials, the COVID-19 pandemic severely impacted the logistics that fuel the supply chain. By July 2020, almost 200 companies had stopped or delayed their clinical trials because of the pandemic,

 and it’s estimated that about 80% of non-COVID-19 clinical trials were interrupted or stopped.

 As the pandemic continued, with delays continuing for months, trials that were in progress were hampered as any inventory redundancies built into their supply chain eroded.

The pandemic—and the upheaval that came with it—underscored gaps in clinical trial logistics. It also created opportunities for organizations to reimagine the process for creating more efficient, reliable, patient-centric clinical trials.

Before the COVID-19 pandemic, many sponsors and CROs had already begun to leverage digitalization to operate more efficiently and prevent costly downtime. As the need to quickly and safely develop COVID-19 vaccines and treatments emerged, organizations needed visibility into their processes as well as the full supply chain. Sponsors and CROs already using digital solutions were better positioned to make that pivot quickly because they already had real-time transparency to make strategic logistics decisions.

In COVID-19’s wake, sponsors, CROs and their logistics partners will need to continue and even expand visibility into every logistics touch point, ensuring supply chain integrity. Along with making sure shipments meet regulatory guidelines, the “Amazon effect” has also increased visibility expectations. Everyone along the supply chain, including clinical staff and patients, want to know not only where their supplies and equipment are, but precisely when they will arrive.

In addition to the expectation for increased visibility, there’s a growing need for flexibility. Traditionally, sponsors and CROs have relied on recruiting parameters based on numerous factors, from regional patient populations to a disease’s prevalence in the population. Predictions help organizations ensure that they are sending the right kits to the right clinical trial sites. Miscalculations can lead to oversupply at one site and shortages at another.

Digitalization tools can provide the transparency needed to overcome these challenges. For example, a kit with a scannable label can be tracked across the entire supply chain, from the moment it leaves the kit assembly line to the patient’s home and finally to the biorepository. Machine learning tools can take the process a step further by considering various factors, like capacity or hours of service, across multiple supply chains. Radio-frequency identification can also help manage shipments needed to service these clinical trials.

These capabilities provide dynamic, multi-mode estimated time of arrival information, whether a package is delayed at a border crossing or five blocks away from a patient’s home. End-to-end visibility enhances the patient experience but can also create the tracking and traceability needed to meet regulatory demands.

Maintaining regulatory compliance in emerging regions

As the COVID-19 pandemic created the need to fast-track vaccines and treatments, emerging geographies, like the BRICS block (Brazil, Russia, India, China and South Africa) and the Middle East, became important locations for related clinical trials. While their large, diverse populations are ideal for conducting multiple, large-scale trials in parallel, the regulatory process in these nations is still evolving. This creates a challenging regulatory landscape for logistics.

From clinical trial approvals to transporting clinical supplies and medical equipment, regulations can vary greatly from country to country. Regulations for transporting clinical trial products and medical equipment can be inconsistent, making it more difficult to plan and coordinate across jurisdictions, especially if they are governed by different regulatory organizations. For example, different transportation modes within an area might require specific types of paperwork to be secured. In addition, the timelines in emerging markets can run much longer than what might be considered standard when conducting trials in many Western nations. Even in well established markets, regulations change and the supply chain needs to adjust to new regulatory standards, such as EU MDR regulation in Europe that came into effect May 2021.

As clinical trials move forward, CROs and sponsors need to fully understand clinical trial regulations in every jurisdiction in which they operate. Working with local trial coordinators or partners who understand each region’s unique logistics challenges can help organizations understand regulations within all relevant jurisdictions to avoid the inadvertent violations and help trials stay on track.

In many aspects, the logistical challenges common to traditional, on-site clinical trials are also evident in those that are hybrid or virtual—albeit on an exponential scale. For example, rather than delivering equipment to a dozen sites for a specific trial, a decentralized trial might require thousands of individual shipments to patients’ homes.

Logistical complexity goes beyond simply making sure the right patient gets the right kit at the right time. Other factors might include coordination and pickup of biological samples from patients, or the return of equipment or perhaps materials that are partially used, unused or even expired. And extending beyond logistical complexities, data compliance regulations, such as HIPAA or GDPR, expand further back in the supply chain as partners need to handle patient data that enables home delivery of equipment as well as labeling for sample collections.

Sponsors and CROs may want to consider partnering with specialized companies with the resources and experience to manage direct-to-patient shipments, no matter where the supplies or equipment is being sent. These types of partnerships can help ensure the sponsors or CROs can focus on clinical trial design and outcomes as well as patient experience.

Mobile health (mHealth) is one tool helping facilitate clinical trial logistics. Two-way communication medical wearables, like smartphone apps, patches or other monitoring sensors, can measure essential biometric data. In addition to providing clinical staff with accurate, real-time health data, these devices help to reduce or eliminate the need for in-clinic visits, making it easier for trials to continue even in the face of unexpected macro events. Patients also experience a greater degree of independence because the technology reduces or eliminates the need for clinic visits, which helps increase retention. mHealth devices can reduce costs, too, by decreasing the time and expense related to in-clinic visits.

Wearable medical device usage is perhaps one of the most exciting aspects of the clinical trials of the future. mHealth devices are currently in the first generation of development. As developers continue to refine the technology, it will evolve, much like the apps consumers use on smartphones. CROs able to leverage this new technology by acquiring or partnering with software companies can help move innovation forward to improve the trial’s efficiency and the patient’s experience.

Delivering training in a decentralized clinical trial

Logistics is more than the movement of people and products; it’s also about the movement of information. As COVID-19 led to wider adoption of decentralized clinical trials, sponsors and CROs were prompted to find effective ways to deliver the training patients need to participate in their care. In traditional clinical trials, a recruited staff would receive any relevant training at the team level. However, hybrid and virtual trials require the delivery of that information to each individual patient.

For example, clinical teams can transmit alerts to a patients’ wearable or medical device to remind the patient to conduct a test or provide a sample. An app might also deliver information, like instructions, so if the patient doesn’t understand a process, they can view a step-by-step how-to guide or even contact off-site, 24/7 support.

Data and cybersecurity in logistics is a concern that will become more critical in the near-term. In traditional clinical trial site settings, patients’ private information is blinded from supplier, service and logistics partners. For example, a repository sample might be shipped with a patient information rendered as a code.

Now, hybrid and virtual trials require partners to ship directly to or pick up directly from patients, requiring partners to have access to a range of personal information, from the patient’s name and address to the study type to the serial number of the equipment used. Data that is not properly secured can create cybersecurity risks that potentially expose confidential patient information as well as violate regulatory standards.

In addition to data and cybersecurity compliance with GDPR in Europe and HIPAA in the United States, sponsors, CROs and their logistics partners must navigate emerging regions where the intersection of virtual trials, data and cybersecurity is still in the early stages of development.

No matter how quickly the clinical trial landscape changes or where those changes lead the industry, there is one factor that will not change: expect the unexpected. There is simply no way to predict every unforeseen event. Within the last few years alone, logistics within the pharmaceutical industry, and clinical trials in particular, have been challenged with events ranging from COVID-19 to Brexit to the vessel that temporarily blocked one of the world’s busiest trade routes, the Suez Canal.

The unexpected will continue to challenge organizations to maximize robust, flexible logistics that ensure supply chain integrity—and those in the clinical trials space will rise to meet that challenge and leverage the opportunity it brings. Whether supplies are being shipped to a patient’s home or equipment is being moved from one clinical site to another, reliable logistics is a key factor in creating an efficient and reliable patient-centric clinical trials.

Adams, B. Fierce Biotech. (Online) Available at: 

https://www.fiercebiotech.com/biotech/more-than-two-thirds-trials-hit-by-covid-enrollment-halts-midstage-tests-worst-affected#:~:text=Drilling%20down%20into%20the%20numbers,impacted%20due%20to%20slow%20enrollment

Van Dornb, A. COVID-19 and readjusting clinical trials. Available at 

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31787-6/fulltext 

COVID-19 provides unique opportunity for overhaul of logistics.

Claudia Berrón

Articles

Considerations to Reach Underrepresented Groups

Tech Integration for Clinical Trials

Moving into the Future of Clinical Trials