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Applied Clinical Trials December 2022

Ukraine invasion tests the resiliency and quick action of CROs and sponsors

Mobilizing and Maintaining Clinical Trials in Midst of War

ACT's biennial Salary Survey takes a look at the future of industry following increased adaptation of decentralized technology 

Salary Survey: The Age of COVID

Dr. Sean Bohen, CEO of Olema Oncology, discusses his career and significant contributions to the clinical research and development of numerous oncology drugs that received regulatory approval for various indications. Plus a look at Olema, how they operate, and challenges they face.

Podcasts

The Rewarding Path Of Science

Brian S. McGowan, PhD, FACEhp, is the chief learning officer and co-founder at ArcheMedX, Inc.

If you were to flip through any issue of 

 over the past 15-plus years you would almost certainly land on an article that highlights the unprecedented challenges faced by contemporary clinical trials. These challenges are real and in many cases they appear to be worsening over time. For example, as the complexity of studies continues to grow, protocol procedures have increased 44% since 2009, study endpoints have increased more than 86% since 2005, and we’ve seen a 10-times growth in Phase III data points in the last 10 years.

In response to the complexity challenge, sponsors, chief resource officers (CROs), and sites are increasingly embracing any number of technical, operational, and tactical solutions to compress timelines and reduce costs while improving study performance (i.e., delays and deviations). These reactive solutions are becoming overwhelming (in both rate and volume)–creating mounting stress on the trial teams, sites, and staff. For example, two-thirds of site staff say that stress adversely affects their performance, 70% of site staff believe conducting clinical trials has become much more difficult over the last five years, the average current turnover rate for CRAs is 30%, following typical turnover for clinical support staff of 16%, and staffing is cited as the #1 challenge faced by sites.

And what is the result of these challenges? Evidence suggests that nearly four out of five clinical trials fail to meet enrollment timelines, half of sites fail to enroll even one patient, and nearly nine out of 10 clinical trials are delayed and/or stopped early because of poor performance.

Given this one-two punch of the mounting complexity challenges and the burden created by reactive solutions, one might paint a dire picture of where we are headed, but I’d like to posit that there is an untapped potential to drastically change our course.

What if I told you that nearly all of the challenges that undermine clinical trial success are due–at least in part–to the same root cause? What if I told you that some really, really smart scientists have been working on the solution to this root cause for nearly 50 years? And, what if I told you that applying this fundamental solution to overcome the challenges of contemporary clinical trials will be surprisingly easy and incredibly rewarding?

In reality, contemporary clinical trials, while increasingly complex, are actually just an exercise in change management. For trials to be successful, the stakeholders (sponsors, sites, and teams, etc.) need to change the way they think, behave, and perform in accordance with trial protocol and goals. And these types of change management exercises have emerged as one of the most productive fields of scientific advancement over the past half century. The evidence is robust and numerous Nobel prizes have been awarded to the pioneers in the field and the findings they have uncovered in settings as various as economics, finance, the military and healthcare. And this evidence illustrates what should be seen as a singular root cause for nearly all that ails our contemporary clinical trials. As a community, we continue to underestimate, underdesign, and under resource the requisite pillars of change management.

What are these pillars of effective change management? Mounting experimental and real world evidence suggests effective change requires individuals (and the teams in which they work) to do three things: Change what they know, change how they think, and change how they behave.

This is where the fundamental solution becomes both surprisingly easy and incredibly rewarding. Because of advances in learning science we have uncovered critical best practices in knowledge change. Because of advances in cognitive science we have a clear roadmap to support critical thinking. And because of advances in behavioral science we have definitive strategies to scaffold behavior change.

While an exhaustive exploration of learning, cognitive, and behavioral science is beyond the scope of this initial article, let's briefly highlight three of the most seminal lessons from each field.

 has taught us that learning is rarely episodic, instead learning happens over time. We also know that learning is rarely passive, instead adult learners (i.e., investigators, site teams, patients, etc.) must be mindfully engaged and motivated to learn. We know that feeling familiar with content is often a barrier to truly mastering content. And, we know that the approaches to learning that learners perceive as being most effective, are often least effective.

 has taught us that the act of thinking is predominantly superficial and irrational, what has come to be known as ‘fast thinking.' For example, we know that adult humans (i.e., investigators, site teams, patients, etc.) are prone to natural short cuts and heuristics in thought that are often misleading and at times fundamentally wrong. We know that we overestimate both hindsight accuracy and forward-looking predictions. And, we know that we are at risk of falling prey to self-consistency biases that prevent change.

 has taught us that behavior change is ultimately the outcome of our motivation, our abilities, and the environment (system) in which the desired behavior takes place. If we are highly motivated, we can often change even if our abilities are lacking. If we have expert abilities, we can often change even if the environment is poorly designed for change. If the environment is well designed, we can often change even if we lack motivation. And, if we intentionally model and practice behavior change, almost any change is possible.

Despite all of the best practices that have been generated by learning, cognitive, and behavioral science, sponsors, CROs, and sites have tragically moved in just the opposite direction. Over the past 25 years, study start up processes have failed to evolve. As a strategy to lessen burden on trial teams, more than 90% of trials have minimized study training requirements. As a strategy to accelerate timelines, the majority of sponsors and CROs have reduced or eliminated the necessary planning and development required for successful training and performance change. As a strategy to reduce budget and simplify planning, less than 10% of trials include personnel with training or performance change expertise.

Each of these responses to the one-two punch of the mounting complexity challenges and the burden created by reactive solutions has in fact proven counterproductive and the resulting training and study start up experiences now deliver little-to-no value for sponsors, CROs, and sites; instead they demand more time, more energies, and more resources from the already overburdened teams.

In short, our community would benefit tremendously by embracing the realities of change management and each of its three scientific pillars.

Learning science affords us the opportunity to empower trial stakeholders to gain knowledge, competence, and confidence more efficiently. From PI meetings to site initiation visits to protocol amendments to informed consent–the success of contemporary clinical trials depends on how well we train and learn.

Cognitive science shows us how to structure critical decisions to ensure trial stakeholders choose more rationally. From protocol development to site selection to staffing allocations to patient identification–the success of contemporary clinical trials depends on how well we think, plan, and choose.

Behavioral science illustrates how to scaffold the right actions at the right times and to motivate trial stakeholders to act in accordance with the protocol. From study start up to patient recruitment to the provision of care to on-going compliance/adherence–the success of contemporary clinical trials depends on how well we perform.

In other words, by viewing each trial as a change management exercise; sponsors, CROs, and sites can establish a simplified, structured, and evidence-based approach to catalyze study start up, elevate trial performance, and ultimately, ensure trial success.

While each trial is unique, the lens of change management is a singular solution that ensures adequate and effective planning and support. By leveraging best practices from the three pillars of change management (learning, cognitive, and behavioral science), study start up takes less time, is more efficient, and can more effectively motivate and engage trial teams.

In the end, it’s my hope that this introductory article generated awareness for some readers, led some to contemplate a need for change, and drove some to take action–this is the journey of change!

Over the coming months our intention is to take a deeper dive into both the root cause and the solution through a series of articles and interviews exploring each of the scientific pillars of change management and to provide specific examples of how these best practices are being applied in practice.

https://www.centerwatch.com/articles/25740-trial-sites-taking-a-hard-look-at-cutting-down-study-startup-times

https://www.centerwatch.com/articles/25847-critical-challenges-persist-for-sites-in-staffing-enrollment-and-protocol-complexity

https://trialsjournal.biomedcentral.com/articles/10.1186/s13063-021-05158-z

https://www.bdo.com/insights/tax/2020-2021-cro-insights-report-while-compensation-levels-and-practices-remain-status-quo,-turnover-c

https://www.appliedclinicaltrialsonline.com/view/recruitment-roles

Brown, Roediger, and McDaniel; Make It Stick: The Science of Successful Learning; 2014.

Fogg; Tiny Habits: The Small Changes That Change Everything; 2021.

Milkman; How to Change: The Science of Getting from Where You Are to Where You Want to Be; 2021.

Articles

Researchers face various challenges that cause their clinical trials to fail to meet enrollment timelines, among other issues.

A Singular Root Cause Undermines Clinical Trial Success: Leveraging Best Practice from 50 Years of Applied Research

While the Eagles football team left Philadelphia to compete in Super Bowl LVII, Uplifting Athletes held its Young Investigator Draft. Inspired by the NFL Draft, the event awards $200,000 in research grants to 10 all-star scientists at the beginning of their careers, and was presented by CSL Behring at Lincoln Financial Field, home of the Philadelphia Eagles.

Uplifting Athletes is a nonprofit organization that connects student-athletes across the country as well as professional athlete ambassadors with their local rare disease community to raise awareness and funds.

The sixth annual Young Investigator Draft includes 10 emerging scientists, each of whom will receive a $20,000 unrestricted grant to support their vital work in rare disease research.

“The members of our 2023 Young Investigator Draft Class represent a group of early-career, diverse researchers who are tremendous assets to the rare disease community,” said Rob Long, executive director of Uplifting Athletes. The 10 scientists that were honored span the research of rare diseases at institutions across the United States.

Read more about the scientists, and the program.

Ten Emerging Rare Disease Scientists Score Research Grants 

Global clinical trial technology company Suvoda unveiled its purpose-built software platform that unifies its eConsent, IRT, and eCOA solutions. The platform brings certain features including single sign-on, consistent interface, low-code/no-code technology to streamlines study start-up and mid-study changes, and allows the data to be centrally collected, managed, analyzed, and stored.

Platform unifies eConsent, IRT, and eCOA solutions

Suvoda Introduces Extensible Software Platform

Kroger Health, the healthcare division of The Kroger Co., has established its clinical trial site network and announces its first trial for colorectal cancer gut and immune health observation.

In collaboration with Persephone Biosciences, Kroger Health is actively recruiting for the 

 to identify microbiome-based biomarkers indicative of colorectal cancer. Beginning in the Toledo, Ohio area, select Kroger pharmacies and its affiliate, The Little Clinic LLC, locations will enroll its initial cohort of 55 people with a variety of colorectal cancer risk levels to advance the understanding of gut and immune health.

According to Kroger Health president Colleen Lindholz, the larger organization features more than 24,000 healthcare professionals, and with its unique position “at the nexus of food and healthcare” believes it can increase accessibility to clinical trial opportunities.

In addition to accessibility and the fact that 51% of Kroger stores are located in socially vulnerable areas, the network also features the grocer's data analytic capabilities, and the ability to use digital tools, virtual care visits and personalized communication to study participants. In addition, its clinics, dietitians, pharmacy services, and relationships with other healthcare organizations enable Kroger Health to offer end-to-end clinical trial management within a variety of preventive and therapeutic areas.

 Kroger Health on the study and its clinical trial capabilities. 

Kroger Health, the healthcare division of The Kroger Co., has established its clinical trial site network in conjunction with Kroger's first trial in active recruitment for colorectal cancer gut and immune health observation.

Kroger Enters Clinical Trials

Jill Wechsler is ACT's Washington Correspondent

In announcing major changes to the agency’s oversight of foods and nutritional products last week, FDA Commissioner Robert Califf cited the need to “transform” the agency’s field inspection operation. The contemplated realignment of the Office of Regulatory Affairs (ORA) would better focus this vast organization on “critical activities” for ensuring the safety of foods and other regulated products, including drugs, biologics, and medical devices.

 And more unified oversight for human foods will aim to clarify lines of authority between FDA centers and the agency’s investigational force of some 5,000 staffers in more than 200 offices and 13 labs around the country.

These changes come in the wake of an outcry over widespread shortages in infant formula supplies last year due to product contamination that led to the shutdown of a major manufacturing facility and product recalls. Field inspectors complained that FDA food center officials failed to respond effectively to warnings of bacterial contamination at Abbott’s formula plant. In response, FDA now proposes to integrate programs that set food safety standards with operations to handle outbreaks and recalls under a new deputy commissioner for human foods, reporting directly to the commissioner. The goal is to unify the various entities involved in oversight of food and nutritional products (including baby formula) into a single program, and to clarify relationships between field inspectors and headquarters in the process. Details were sparse, with FDA promising to provide more specifics on planned changes at the end of February.

The proposed changes will be tricky to accomplish, as Califf and principal Deputy Commissioner Janet Woodcock indicated at a briefing with reporters earlier this week to announce plans for the elevated foods center. Woodcock cited ongoing efforts to modernize the agency’s IT workflow management system to eventually establish a common platform for all regulated product centers to communicate with ORA, moving away from using multiple different systems for such interactions. Other initiatives involve establishing a clear inventory of the 600,000 various sites overseen by FDA inspectors and unifying state and local food safety partnership functions under the new program. But making significant changes in “how that all works,” Woodcock admitted, would be slow to come without additional resources.

Funding to expand or improve FDA’s food regulatory programs, however, suffers from limited budget appropriations and little support from industry-paid user fees. The Food Safety Modernization Act was adopted in 2011 in response to multiple food contamination outbreaks across the country, but only passed Congress by limiting penalties and fees on farmers and food processors—unlike the hefty fees paid by drug and biotech companies. The food industry provides FDA with a mere $10 million a year for facility reinspections, product recalls, and for certain food import activities. An added complication is that much of FDA’s food safety inspection work involves state and local officials, partnerships that Califf said will continue and will be strengthened.

Further realignment of ORA’s operating structure is not a new idea, as it was already implementing significant changes in how it oversees and enforces standards for drug, biologic, and medical product manufacturers when the agency had to make major adjustments in response to the global COVID-19 pandemic. ORA’s Program Alignment initiative for drugs and biologics aimed to move away from generalist inspectors to cadres of specialists trained to better evaluate the more complex medical products moving through the R&D pipeline. Then, as the spreading pandemic shut down travel and on-site plant visits, FDA shifted to virtual, remote oversight of manufacturers and research sites, limiting field inspections to “mission critical” applications and serious safety situations. Regulatory authorities also adopted more mutual recognition agreements with trusted foreign regulatory partners to share the burden of ensuring compliance of regulated facilities in their regions. FDA officials have indicated that many of these efficiencies may remain in effect even as the pandemic wanes.

Meanwhile, Califf’s announcement of the “key elements of a unified human food program” called for “reimagining” ORA, but provided only a vague outline for changing operations by “improving risk prioritization,” “modernizing core operations,” and “creating operational efficiencies.” As noted above, more details to come. And while Califf noted that agency staffers support plans to update ORA operations, he and others acknowledged that more detailed discussion of any changes with the agency’s vast inspection cadre is necessary before making any changes.

Some policymakers want to split FDA into two entities, one overseeing food and another regulating drugs and medical products. That would require a big boost in federal funding for the two entities and further expansion and overhaul of the field force. And it ignites debate over where to put oversight of animal drugs, dietary supplements, tobacco, and other consumer products. Many safety experts and consumer advocates continue to press for more significant change at FDA, but this latest shuffling of operations may suffice.

https://www.fda.gov/news-events/press-announcements/fda-proposes-redesign-human-foods-program-enhance-coordinated-prevention-and-response-activities

Proposed realignment of the Office of Regulatory Affairs would impact oversight of drugs and medical devices as well.

FDA Food Center Reorganization Puts Field Inspections in Limbo

Oncology is a complex field that requires the participation of a diverse patient population to validate the efficacy and safety of new treatments. However, oncology has been lagging in diversity inclusion in clinical trials. This article will discuss the importance of diversity in oncology clinical trials, the challenges faced, and ways to overcome these challenges to increase diversity inclusion.

There have been advances in clinical trial diversity inclusion—generally speaking

Diversity inclusion has been an important topic in the biopharmaceutical industry this year. Clinical trials have made strides in including diverse patient populations, with 

white patients in trials dropping from 83% to 72%, and Latinx patient populations increasing from 3% to 18%

, which is closer to real-world diversity figures.

Additionally, Pharmacies, such as CVS and Walgreens, have also aimed at increasing diversity in clinical trials. 

CVS, for example, has launched a clinical trial initiative aimed at increasing diversity in clinical trials

 by partnering with organizations that serve diverse communities. Moreover, 

Walgreens has launched similar initiatives as CVS on clinical trial diversity inclusion

. But is this enough for oncology clinical trials?

Oncology clinical trials are lagging in diversity inclusion

According to a study published in the JAMA, only 

5% of clinical trial participants are Black, despite making up 13% of the US population

Hispanic patients only make up 1.3% of clinical trial participants

, despite making up 18% of the US population. On the other hand, 

 of cancer clinical trial participants, although they only make up 60% of the US population. The data reveals a clear disparity in the representation of different ethnicities in oncology clinical trials, highlighting the need for diversity in clinical trial participation.

The challenge involves limited access to clinical trials for minority populations. Many minority populations face barriers such as lack of transportation, lack of insurance coverage, and limited access to clinical trials due to a lack of knowledge about the trials. Additionally, protocols may not necessarily be optimized to include diverse patients. These barriers can prevent minority populations from participating in clinical trials, limiting the participant population's diversity.

The Importance of diversity in oncology clinical trials

Oncology is a field that is constantly evolving, with new treatments and therapeutics being developed to treat various forms of cancer. However, clinical trials that lack diversity in their participant population may not accurately represent the general population and thus may not represent the treatments’ true impact.

One of the main reasons for the importance of diversity in oncology clinical trials is the prevalence of cancer in different racial and ethnic populations. Cancer incidence and mortality rates vary among different racial and ethnic populations, and this disparity highlights the need for a diverse patient population in clinical trials. For example, the incidence of lung cancer is higher in African American men than in white men, while breast cancer incidence is higher in white women than African American women (SEER Cancer Statistics Review, 1975-2017).

However, an important factor to consider is the genetic diversity among different populations, which can create limitations to diversity inclusion. To elaborate, cancer is a complex disease with a strong genetic component, and the genetic variations among different populations may impact diversity inclusion figures. For example, 

African Americans have a higher frequency of inherited BRCA2 mutations

, which are associated with a higher risk of developing breast and ovarian cancer. Hence, a targeted therapeutic may focus solely on that particular ethnic population, and exclude whites. But, for many cancers, the knowledge obtained from genetic biomarkers and using treatments while maximizing ethnic diversity is crucial for developing effective treatments.

It would be prudent to conduct real-world evidence analyses to evaluate cancer rates amongst existing patient populations and devise trial participation to match ethnic groups in real-world settings.

Strategies for increasing diversity in oncology clinical trials

Several strategies can be implemented to increase diversity in oncology clinical trials. One of the most important strategies is to increase awareness and education about clinical trials among minority populations. A common and well-known approach to engaging minorities can be made through community outreach programs like health fairs and benefit from the momentum that other sponsors and pharmacies have made with certain ethnic groups.

Another strategy is to increase the accessibility of clinical trials for minority populations. This can be done by partnering with community organizations and health clinics that serve minority populations. These organizations can facilitate the sponsor’s transportation offerings, non-standard of care coverage for study-related procedures, and other support services (i.e., insurance coverage) to help minority populations qualify and participate in clinical trials. Additionally, another consideration involves offering coverage for standard-of-care procedures to compensate for lacking coverage amongst ethnic groups.

Furthermore, clinical trial protocols should consider factors such as race, ethnicity, gender, age, and medical history to ensure that the trial results represent the broader population. Optimizing clinical trial protocols to include diversity can also help identify potential disparities in treatment response and ensure that new treatments are accessible to all patient populations. This can be achieved by proactively recruiting diverse participants, addressing potential barriers to participation, and carefully considering demographic data when designing and analyzing the trial results.

One less-known but effective approach is building clinical trial websites, and recruitment campaigns run online through social media or Google ads while combining AI-based technologies, such as engaging videos containing avatars representing ethnic communities who speak and engage minorities.

In conclusion, diversity inclusion in oncology clinical trials is crucial for developing effective treatments and improving understanding of diseases and their treatments. Despite some advances in clinical trial diversity inclusion, oncology is lagging in this aspect, with limited access to clinical trials for minority populations and a lack of diversity in participant populations. To increase diversity in oncology clinical trials, strategies such as increasing awareness and education, increasing accessibility, optimizing clinical trial protocols to include diversity, and using online recruitment campaigns and AI-based technologies can be implemented. Addressing the disparity in the representation of different ethnicities in clinical trials is important for ensuring that new treatments are accessible to all patient populations and accurately represent the impact of treatments on the general population.

, 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.

Challenges and strategies for improving representation.

Boosting Diversity in Oncology Clinical Trials

AARDEX Group and Cambridge Cognition have teamed up to improve adherence monitoring during hybrid and DCTs. AARDEX Group’s MEMS® dosing capture and analytics system will be intergrated with Cambridge Cognition’s Clinpal DCT platform providing sponsors and CROs with a new adherence management tool.

AARDEX Group’s MEMS® dosing capture and analytics system will be integrated with Cambridge Cognition’s Clinpal DCT platform.

AARDEX and Cambridge Cognition Partner to Improve Adherence in DCTs

Boehringer Ingelheim will remotely monitor patients using Strados Labs’ FDA-cleared pulmonary wearable device in an upcoming idiopathic pulmonary fibrosis (IPF) 

 Biosensor will be used to monitor cough frequency, severity, and type along with wheezing and other abnormal sounds, such as crackles, IPF patients at home.

Research has suggested that cough may be associated with worse outcomes in pulmonary fibrosis. Boehringer Ingelheim will assess how monitoring cough and crackles with the RESP Biosensor can be used to monitor the status of patients with this disease.

Strados Labs Remote Wearable in BI IPF Trial

Encouraged by regulators and health authorities worldwide, the industry is making efforts to promote patient-centric clinical research. These efforts take many different forms and shapes with a shared aim of putting patients at the center of clinical trial design and execution. In this article, we touch upon the current state of patient-centric clinical research, focusing on the areas of convenience, empowerment, and privacy. We then take a leap forward by examining how Self-Sovereign Identity (SSI), a novel decentralized approach to identity and access management, will help advance patient-centric research by enabling patient data ownership.

Patient-centric initiatives in clinical research often entail promoting convenience with the help of decentralized trial tools, such as eConsent, ePRO, and virtual visit solutions. These tools have become increasingly sophisticated over the years, allowing patients to participate from the comfort of their own home by enabling remote patient onboarding, data capture, and doctor-patient interaction.

However, according to a recent industry-wide survey, only 56% of sponsors and CROs think decentralized trials actually improved the patient experience.

 The main argument is that decentralized trials often use multiple different and disconnected patient-facing applications, thereby adding complexity for patients, especially for those that might not be tech-savvy.

Patient empowerment: a two-way interaction

Next to convenience, patient-centric clinical research centers around empowerment.In the age of growing health literacy and health consumerism, patients have become increasingly autonomous in their healthcare-related decisions. Sponsors can take advantage of this transition by incorporating patient feedback in clinical trial design and execution with the help of tools such as the Patient Protocol Engagement Toolkit and the Study Participant Feedback Questionnaire developed by TransCelerate BioPharma.

 This can be an effective measure, as demonstrated by a study conducted by the DIA, Tufts Center for the Study of Drug Development, and 17 other stakeholder organizations, who evaluated 30 patient-centric clinical research initiatives.

 The study concluded that low-cost initiatives such as patient advocacy groups, patient advisory panels, and focus groups generated the highest return compared to some of the more costly initiatives such as gamifying ePRO.

However, sponsors should not forget empowering patients is a two-way interaction, meaning it’s not only about gathering feedback, but also about informing the patient in the best ways possible. While the informed consent process mandates what information needs to be communicated pre-study, information requirements during and post-study are much less rigid.To illustrate, patients are often left in the dark about clinical trial results or what happens with their data after study completion. This is a missed opportunity, since patients will have a natural interest in knowing the trial results and their performance in a study. Therefore, informing patients on how they contributed to the study results and how their data benefits future research endeavors may offer a most-welcome way to boost patient recruitment and retention.

Thirdly, patient-centric clinical research involves protectingprivacy. As clinical research gets increasingly digital and decentralized, there are growing concerns about privacy and cybersecurity threats. Since healthcare data is often centrally stored, many healthcare institutions have a target on their back and, not surprisingly, ransomware attacks on hospitals have become increasingly common.

 Clinical trial stakeholders should therefore consider what additional security measures can be taken to protect patient data and prevent data breaches, in and outside of the clinic.

Privacy is however not only about data security, but also about control. In Europe, GDPR set the stage for providing users with more control over their personal data and thereby enabling a harmonized level of personal data protection. Sponsors that process patient data within the EU and EEA need to comply with the GDPR’s core principles, such as clearly defining the purpose of data collection and limiting data collection to the scope of that specific purpose only. Paradoxically, this incentivizes sponsors to include broad consent clauses in their ICF to ensure their full control over patient data in and outside the context of the study. By including a “wide enough” research purpose for processing patient data, sponsors are not required to ask patients to re-consent in the case of data reuse since the purpose for doing so was covered in the initial ICF. This is a double-edged sword—it provides the sponsor with freedom to reuse and repurpose clinical trial data without involving the patient, but significantly lowers patient autonomy, ownership, and control. Moreover, it begs the question: should the sponsor be the only one to decide what happens with patient data once it’s collected?

The areas of empowerment and privacy leave significant room for improvement as patients are often left in the dark about what happens to their data. It’s this particular angle that offers a new cornerstone for patient-centricity, a next phase for patient-centric clinical research—patient data ownership.

Patient data ownership moves away from today’s traditional model with the sponsor as the sole owner of clinical trial data. Distributing ownership requires us to rethink how we generate and store study data and redefine how we view the roles of sponsors, sites, and patients in the clinical trial arena. Providing patients with partial (or full) ownership over their data can offer a novel angle to promoting patient engagement and thereby boosting patient recruitment and retention.

Moreover, patient data ownership may also promote the reuse of clinical trial data beyond the context of a single study. Clinical trial data reuse is essential for improving healthcare and reducing drug development costs. Unfortunately, secondary use of patient-level clinical trial is still uncommon, although attitudes surrounding this topic are shifting and the number of industry and policy initiatives in this domain have rapidly increased in recent years.

Building an ecosystem for patient data ownership

To unlock data from its siloed repositories, we need an open, secure, and interoperable ecosystem where sponsors can exchange and discover data.With data being more liquid than ever and with data coming from a growing variety of sources, such an ecosystem is more relevant than ever, but how do we get there?

Several steps have already been taken in the right direction. Industry-wide standardization has been accelerated by organizations such as CDISC, which aims to ensure the interoperability of data across organizational boundaries. The FAIR data principles, introduced by the GO FAIR initiative, take this a step further by advocating for Findable, Accessible, Interoperable, and Reusable data points—thus being mindful of the reuse of data from the moment it is generated.

However, data standardization is only part of the equation. Building an ecosystem that allows for patient data ownership and promotes data reuse will require novel approaches to coordinate identity and access management. Firstly, we need a secure and privacy-preserving way to link each patient to their own corresponding data, regardless of where that data may be stored over time. Secondly, we need an interoperable way to put patients in control of that data, for instance by providing a mobile interface that allows them to selectively disclose data with clinical trial sponsors. Thirdly, we need a tamper-resistant way to keep track of data transactions and underlying terms and conditions across organizational boundaries and systems, so that patients can be informed and, where applicable, be compensated.

A novel approach to digital identity and access management that meets all of the aforementioned criteria is SSI. As the name suggests, SSI puts users in control of their data. It builds on emerging standards for web interoperability and is considered a cornerstone of the next generation internet—often referred to as ‘Web3’. In practice, patients can use an SSI-enabled mobile app to identify themselves, sign digital documents, and selectively disclose data with other entities over the internet. What’s unique about SSI is that it eliminates the need for a third-party intermediary in any of these processes, meaning patients and external stakeholders can interact in a peer-to-peer and decentralized fashion.

From the perspective of patient-centric clinical research, SSI bring several things to the table. Firstly, SSI excels in empowerment since patients are empowered with their self-owned identity, which they can use to navigate across systems and use to selectively disclose data with authorized individuals. Secondly, SSI excels in privacy, since third-party companies are eliminated from data processing activities such as tracking user activity and/or storing user data in a centralized repository that might be prone to hacking. Lastly, SSI excels in convenience, as SSI can offer patients a single-point access solution that leverages the built-in security and privacy protection features of today’s smartphones such as facial recognition, data encryption, and single sign-on.Now that we’ve covered the relevance of SSI for patient-centric clinical research, let’s touch upon some concrete examples and case studies.

As part of a government-supported R&D program, our company Triall is currently building an SSI-enabled mobile app and infrastructure, where we’ve decided to specifically focus on the informed consent process.

 Uniquely, the application allows patients to use their self-owned identity to provide, update, and revoke consent—throughout a study as well as post-study for future research purposes. In this way, we aim to facilitate a more dynamic consent where patients can also decide what happens with their data after study completion.

The application leverages open standards for identity and access management (decentralized identifiers and verifiable credentials) to enable an SSI environment that provides patients with more control over their data.Moreover, the underlying infrastructure is integrated with blockchain—a decentralized database that functions as an immutable and system-independent audit trail. This audit trail provides an indisputable record of all consent-related documents, data points, and activities (what’s stored on the blockchain cannot be altered, hence ‘immutable’). It also remains available regardless of where the original data is located (hence ‘system-independent’), which is stored off-chain for privacy purposes. Due to these two features, blockchain-based audit trails offer unique benefits over traditional system audit trails, which tend to become prone to tampering once the eClinical system of choice is retired and data is exported out of the system. They de-risk the changes of data manipulation and promote the reuse of data across organizational boundaries by promoting stakeholder trust.

At Triall, we’ve been implementing blockchain-based audit trails in clinical trials since our successful pilot in 2019 (which marked the world’s first implementation of blockchain in a live and running clinical trial)—a feature that was recently adopted in a multi-center clinical study led by Mayo Clinic.

Looking ahead, an SSI-enabled solution for dynamic consent can also be used in the context of patient recruitment. In this particular use case, patients can use their self-owned identity to manage and maintain a privacy-preserving patient profile with features for selectively disclosing screening data and/or willingness to participate in future studies. Due to the peer-to-peer nature of SSI, patients directly interact with an authorized investigator (or other authorized individual) without involving a third-party intermediary for any type of data processing.

However, the most disruptive potential for SSI lies in enabling novel approaches to clinical trial data management and thereby facilitating patient data ownership. To illustrate, data generated during a study can be directly linked to the patient’s self-owned identity. This could be health or fitness data generated by a wearable, but also data stored in an EDC system. Put simply, SSI enables connecting patient identities to patient-level clinical trial data in a privacy-preserving fashion, even as that data moves across different systems over time. Here, blockchain can serve as an underlying interoperability layer, logging all data transactions in an immutable and system-independent audit trail.

Going forward: moving towards new data ownership models

By combining SSI and blockchain with traditional eClinical technologies, we can thus facilitate new ownership models for clinical trial data. It’s good to underline that this does not by default have to mean that patients have full control over every data point and transaction. We can, for instance, distribute ownership between sponsor, site, and patient, where all stakeholders benefit from future data reuse. This would allow us to work towards a fair power balance between sponsor and patient.

The good news is that we don’t need to completely reinvent the wheel.While we still have a long road ahead towards industry-wide adoption, SSI and blockchain technologies have been in development for over a decade. Many of the enterprise-oriented SSI and blockchain solutions under development today are based on open standards for web interoperability. With interoperability as a cornerstone principle, these solutions are designed to work with traditional systems and infrastructure. Nevertheless, from a process and regulatory perspective, these emerging technologies and standards are likely to have a profound effect on how we conduct and manage clinical research. Success will therefore be determined by buy-in from all relevant stakeholder groups and adoption will require new regulatory frameworks and guidance.

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https://www.transceleratebiopharmainc.com/assets/patientexperience/study-participant-feedback-questionnaire/

Stergiopoulos, S., Michaels, D. L., Kunz, B. L., & Getz, K. A. (2020). Measuring the impact of patient engagement and patient centricity in clinical research and development. Therapeutic innovation & regulatory science, 54, 103-116.

Nir, S. M., Otterman, S., &amp; Goldstein, J. (2022, December 12). Cyberattack Hits Brooklyn Hospitals That Serve Poor New Yorkers. Retrieved January 27, 2023, from 

https://www.nytimes.com/2022/12/12/nyregion/brooklyn-hospital-cyberattack.html?utm_content=161913562&amp;utm_medium=social&amp;utm_source=linkedin&amp;hss_channel=lcp-33200710

Terry, S. F., & Terry, P. F. (2011). Power to the people: participant ownership of clinical trial data. Science Translational Medicine, 3(69), 69cm3-69cm3.

Ohmann, C., Banzi, R., Canham, S., Battaglia, S., Matei, M., Ariyo, C., ... & Demotes-Mainard, J. (2017). Sharing and reuse of individual participant data from clinical trials: principles and recommendations. BMJ open, 7(12), e018647.

Triall (2022, February 3). Triall awarded R&D grant for blockchain-based eConsent. Retrieved February 1, 2023, from 

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Shapiro, L. (2022, September 2). Mayo Clinic to Use Blockchain Technology to Protect Data in Trial. Retrieved January 27, 2023, from 

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Buy-in from industry stakeholders pivotal to ensure bright future for the decentralized approach.

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