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Applied Clinical Trials September 2022

Experts discuss solving the EHR-compatibility puzzle in point-of-care trials

‘Record’ Gains in Bringing Research Closer to the Patient

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

Lead, Emerging Technology Strategy – Clinical Design, Delivery & Analytics, Eli Lilly and Company

Arthur Combs, MD is a clinician, serial entrepreneur and thought leader in wearable technology and digital biomarkers. He serves as a consultant to numerous companies especially those bringing new noninvasive or digital technology to market.

As early as 100 years ago (see photograph of Radio News cover, April 1924) the concept of “decentralized care” seemed just around the corner. Several key elements had to evolve over the past century to make this a reality: the sensors (remote patient monitoring), the telecommunication infrastructure (the Internet), the science, and perhaps most importantly, the buy-in from the medical and patient communities. The COVID-19 pandemic greatly accelerated the latter—to the point where we need to ask: what’s next? What did we learn, and how do we pragmatically move forward?

Depending on how we define them, decentralized clinical trials (DCT) are not new– the concept and early trials with a decentralized design significantly antedated COVID 19. Craig Lipset, clinical research pioneer, cites an internet feasibility study from 2003 and a Boston University patent for “Trials over the Internet” in 2007. But they still are not a singularly defined entity which has led to some confusion around the nomenclature (virtual? hybrid? combinations? site-less?) and execution.

Recently, the Clinical Trials Transformation Initiative (CTTI) 

 defined DCT as trials “in which some or all study assessments or visits are conducted at locations other than the investigator site.” Here, we specifically focus on a 

 of this broad spectrum: how technology can enable participation, leading to lower participant burden and better data. We believe this aligns well with the efforts to provide broader access to a more diverse population, which is encouraged by the latest 

In part, pharmaceutical companies and CROs can conduct viable decentralized drug development trials because of the advent of remote patient monitoring technology, wearable sensors, and electronically gathered data such as ePROs, but also as a result of a more patient centered, real-world data focus. How those trials are established, conducted, and validated evolved significantly under the pressure of the COVID-19 pandemic.The question now is what happens next? What have we learned (both pre- and post-COVID) and how can we put it to practical use? How do the benefits to participant burden and cohort diversity balance with the hard endpoints required to establish safety and efficacy for new drugs? What study design elements, enabling technology, and next generation data management are required for all stakeholders including patients, investigators, sponsors, society to benefit? 

Starting with the positives on the patient side, many aspects of clinical trials can be performed remotely—which, when done right, increases convenience, accessibility, and diversity. Medical grade remote patient monitoring (RPM) devices and digital technology can facilitate obtaining high-quality data—but transforming this data into clinical trial endpoints is a high bar. Most importantly, the foundation needs to be established first, which is required for regulatory approvals, and ultimately for the pharma industry’s buy-in.

As anyone who has spent hours in digital “customer support loops” for their wireless carrier can attest, decentralized processes have to be simple, effective, and efficient in order to ensure patient adherence. We have heard from subjects who are motivated but unable to participate in drug trials due to the travel burden. DCT capabilities such as RPM devices can allow them to participate. These medical devices—mostly wearables—must be designed for patient comfort, reusability, and self-service. Depending on the trial, the participant pool could be tech-savvy millennials, or it could be an older demographic who is much less comfortable with technology and/or relies on a caregiver. Trial participants can represent a broad range of demographics as we seek to expand the diversity of participants for various studies.

The pandemic forced some populations to rapidly adapt to various forms of digital healthcare, including telemedicine. This is a positive development, but it is not enough. There is an opportunity to further capitalize on this adoption by driving participation in decentralized trials and expanding to previously underserved populations. To do so means acknowledging issues and developing solutions to ensure the progress attained thus far is not transient and expedites more patient-centric drug development.

Instead of just throwing technology at the problem, both digital healthcare companies and pharmaceutical companies must seek a more deliberate application of wearable and digital technologies. There is a tension between patient burden and convenience, and the ability to gather the hard, statistically significant endpoints for safety and efficacy that are ultimately needed for regulatory approvals. Effective DCT requires being able to remotely monitor patients and obtain precise data that meets both clinical endpoints and those required for FDA approval.

One key advantage that DCT can deliver using technology is the ability to gather data in the “real world” with a cadence driven by biology. This requires rethinking how we have historically defined endpoints and looking toward more 

l outcomes that are more meaningful than the results of a point-in-time lab or physician assessment. Even the definition of a 

is changing as we better understand individual and circadian variations. Clearly not all endpoints can, or should, be measured at home. As examples, diagnostic imaging or biopsies will not be performed in somebody’s living room. But the key is determining 

 endpoints that can be obtained from a patient performing daily activities that correlate with the scan or biopsy results, and that provide a more granular picture of the disease trend.

Successful DCT trial implementation is not necessarily fully virtual. We believe that hybrid approaches that incorporate remote features, convenient locations, and conventional methods are here to stay for the foreseeable future. Sleep is an illustrative case study. It is said that sleep studies in the clinic are an accurate measure of how nobody sleeps. People tend to sleep better in their own homes, so data derived from a trial conducted with remote technology is less of a burden for the subjects, more representative, and can be performed nightly over time which establishes patterns and derives analyzable data. Having said that, sometimes sleep studies in a local sleep lab can bring valuable insights with technology that is not readily deployable at home. As another example, in considering endpoints for an arthritis study, is the change in range of motion 90 days after the onset of treatment as reflective of efficacy as data on how, and how much, a patient is actually moving—in the real world, when not observed by a physician. That can be the difference between a singular, objective finding and assessing drug efficacy by the subject’s practical function. The ability to record continuous data provides a longitudinal view of a patient instead of snapshots. Researchers can evaluate a patient’s progress wherein each subject is his own control instead of comparing patient A with patient B for real-world analysis of the condition and applicable trends. This new, richer, more objective data will only be beneficial if we have the ability to adequately structure and analyze the various information streams to reap the benefits of a decentralized model.

With a decentralized model, a new approach to trial endpoints is necessary. The recently issued draft 

 regarding digital health technology and RPM for clinical investigations specifically states that novel endpoints should be justified, and the method of assessing a patient’s response should be “well-defined and reliable.” That can present a challenge for RPM and the data streams it produces. Those conducting a study want to ensure the endpoints will meet necessary standards for safety and efficacy, and thus for approvals.

Remote patient monitoring technologies are an important tool in the DCT arsenal. They contribute to the proverbial win-win-win—to have the cake, eat it too, and not put on the extra pounds:

lower burden for patients, which will broaden access,

better and more objective data that links clinical research to the real world; and

faster recruitment, better retention, increased patient diversity, and cheaper trials that allow for more attempts to reach the desired goal.

The pandemic provided a glimpse into what is possible when pharma, (med) tech, CROs, and regulators work together with a sense of urgency against a common threat. To successfully put a dent in the dire unmet medical need, this spirit of cooperation must continue. This is the only way to develop trials that are tailored to the situation, adapt to the patients, and fit into their lives, as opposed to the other way around.

, Lead, Emerging Technology Strategy – Clinical Design, Delivery & Analytics, Eli Lilly and Company

, MD is a clinician, serial entrepreneur and thought leader in wearable technology and digital biomarkers. He serves as a consultant to numerous companies especially those bringing new noninvasive or digital technology to market.

Articles

What is next for DCTs after acceleration from COVID-19? 

How Remote Patient Monitoring Technology Can Impact Decentralized Clinical Trials

Chief Delivery Officer, Data Services at eClinical Solutions

The industry-wide jump in data complexity, digitization initiatives and volume of data sources, propelled further by the pandemic, require new approaches to clinical data management. A 

 found 75% of life sciences organizations still using SASand Excel to integrate and analyze data. Over 80% of respondents reported data management activities as time consuming and labor intensive. The study also reported a 40% increase in last patient, last visit (LPLV) to database lock cycle times for companies with five or more data sources and concluded that contending with disparate data sources was contributing to longer database lock cycle times.

Since 2019, the trends impacting clinical data have only accelerated, due in part to adoption of decentralized clinical trial (DCT) models that enable increased remote data collection and greater utilization of local labs. Amidst this disruption, digital and analytics-based modern data management is now an imperative. Here are three ways clinical development leaders can approach this data management evolution by aligning people, process, and technology.

Today, few would deny the importance of a data strategy. The current data environment is too complex not to have one. Most clinical data is generated from sources external to electronic data capture (EDC), and trials routinely average 8 or more data sources; many include 15+. The traditional role of the siloed data manager, focused on cleaning and querying listings of EDC data, is in the past. But in its next iteration, data management has even more value to offer. The data management role has evolved continuously, becoming more technically advanced and growing in responsibility and complexity over the last 20 years. We’ve heard it asked, is the data manager becoming a data scientist? I would argue no. Instead, the data manager has evolved into a data steward, the confident leader who owns and guides the modern data strategy.

This new paradigm demands different skills, too. The data manager as data steward applies a breadth of knowledge across clinical development, from data management to quality and regulatory. They collaborate with clinical operations, programming, and biostatistics with enough professional knowledge of each to enable cross-functional empathy, ensuring all data stakeholders can get what they need from the data. This modern data manager looks at the whole picture the data tells across all data sources, connecting it to their knowledge of the data strategy for the trial. They apply their technical skillset to the many different systems used in development to support evolving protocol requirements and ensure that tech aligns to process improvements in support of accelerated timelines.

Empower data management with the right tools

Variety in acquisition technologies creates flexibility to choose what is best for trials and participants. For clinical data infrastructure and analytics, this means interoperability is critical. Centralized data platforms can increase the quality of data deliverables and reduce manual work positively impacting cycle times. Integrated clinical data platforms ingest and organize all sources and structures of data. They must have the ability to serve all their users, not solely the data manager. Data stewards maximize the use of these types of foundational tools that automate end-to-end data flows and enable greater collaboration and faster time to insights.

Optimize processes around a risk-based approach

It’s one thing to have technologies and another to drive their use, adoption, and utilization. For the data steward, upskilling team members and training in technologies is key. It’s important to consider technology as organization-led and supported from a top-down approach. Involve teams across functions in re-engineering processes around the technology. It's not about bringing technology in, but about maximizing its use for the greatest efficiency gains.

Value is recognized when teams adopt and apply these tech-enabled approaches within the context of their data strategy framework. Self-service analytics focus attention where it’s meaningful and create collaboration opportunities among colleagues from a single source of truth. Teams can identify issues, see what has been reviewed and detect trends and outliers in need of discussion. This approach avoids teams waiting until the end of the trial to integrate data risking rework due to missed insights or outliers.

Data is the final product delivered to FDA—the output of research and currency of the life sciences industry. We have reached an inflection point fueled by breakthrough achievements in science, industry disruption, and intent to accelerate research. The data manager is the steward of this most critical asset through this perfect storm. By evolving their skills and adopting tech-enabled processes, they will guide the way—ensuring modern data strategies produce sustainable efficiencies for the future of data management.

, Chief Delivery Officer, Data Services at eClinical Solutions

Accelerating trends in clinical data are forcing changes in strategy.

What the Future State Really Looks Like for Clinical Data Leaders

Jill Wechsler is ACT's Washington Correspondent

An important component of the White House initiative to speed the development of innovative cancer therapies and other critical treatments for patients is to expand modern biotech manufacturing in the US. The effort also aims to reduce US reliance on foreign sources of bioindustrial materials to avoid supply chain disruptions experienced during the pandemic. President Joe Biden unveiled the National Biotechnology and Biomanufacturing Initiative (NBBI) in a speech on Monday to promote his long-sought Cancer Moonshot, while also announcing a new director for the Advanced Research Projects Agency for Health (ARPA-H).

The plan is to spend some $2 billion on the NBBI program, with half of that coming from the Department of Defense (DOD) to help public and private sector entities expand biotech research and manufacturing capabilities, as spelled out at the White House NBBI Summit, held Wednesday.

 Among its multiple initiatives, NBBI calls on manufacturers to use biotechnology to produce new medicines and specialty chemicals, some as alternatives to petrochemical-based production of plastics, fuels, and other materials.

FDA notably will be “spearheading efforts” to advance regulatory science and to “leverage these emerging technologies” to increase medical supply chain resilience and improve patient access to new medical products. Regulatory reform is a goal, and FDA will work with the US Department of Agriculture (USDA) and the Environmental Protection Agency (EPA) to identify areas of “ambiguity” in federal regulations related to biotechnology and to devise plans for reform and for issuing added guidance. A specific provision supports the Bespoke Gene Therapy Consortium at the National Institutes of Health (NIH) in funding up to six new clinical trials focused on rare diseases that utilize streamlined manufacturing frameworks.

In addition, the Department of Health and Human Services (HHS) issued a long list of NBBI projects that will involve spending $40 million to expand biomanufacturing for active pharmaceutical ingredients, antibiotics, and “key starting materials needed to produce essential medications and respond to pandemics,” according to an HHS fact sheet.

 There is support for advanced education programs, pilots for gene therapy manufacturing methods, expanded cell engineering, and platforms and biosafety programs to reduce risks associated with advances in the field. HHS will bolster FDA research programs for advanced manufacturing technologies and for the Advanced Manufacturing Innovation Hub in FDA’s Office of Counterterrorism and Emerging Threats to encourage platform technologies and collaborations in smart manufacturing and closed loop process controls. HHS also cites the development of guidelines under the International Council for Harmonization (ICH) to advance continuous manufacturing of drugs and to enhance safety evaluation of continuous biotech products derived from human or animal cell lines.

A stated objective for the Biden administration is to reduce US reliance on biomedical products from China and other regions. A BioPreferred Program will require federal agencies to purchase US-made biotech products related to medicine, climate change, and food and agriculture, utilizing massive federal data systems to “drive solutions” for these global issues. Such efforts will prevent future disruptions in biopharma supplies, as experienced during the COVID-19 pandemic, when dependence on imported medical products, protective materials, and test components blocked biomedical production and compromised medical services. The executive order also aims to develop a trained, diverse US workforce capable of creating bio-based products and materials.

https://www.whitehouse.gov/briefing-room/presidential-actions/2022/09/12/executive-order-on-advancing-biotechnology-and-biomanufacturing-innovation-for-a-sustainable-safe-and-secure-american-bioeconomy/

https://www.whitehouse.gov/briefing-room/statements-releases/2022/09/14/fact-sheet-the-united-states-announces-new-investments-and-resources-to-advance-president-bidens-national-biotechnology-and-biomanufacturing-initiative/

https://www.hhs.gov/about/news/2022/09/14/fact-sheet-hhs-takes-action-executive-order-launching-national-biotechnology-biomanufacturing-initiative.html

Administration launches national manufacturing initiative, with aim to reduce US reliance on biomedicine from China and other regions.

Advanced Biopharma Manufacturing Key to White House Cancer Moonshot

 joined HeartcoR Solutions as its director of training. Additionally, 

 has joined the organization as director of ECG analysis and quality control.

MMS Holdings Inc. announced the appointment of 

, who will lead the company’s thought leadership team and efforts to engage sponsors and contract research organizations, and 

, who will lead patient-facing strategies.

Elligo Health Research announced Chief Scientific Officer 

 was recently elected Chair of the Vulcan Advisory Council.

Promontory Therapeutics Inc. announced the appointments of 

, as Vice President of Chemistry, Manufacturing and Controls, and 

 as Vice President of Clinical Operations.

 to the newly created role of Chief Operating and Growth Officer and 

, to Chief Medical Officer and Global Head, Oncology Center of Excellence.

. announced that Sarah Cannon Research Institute (SCRI) has joined the Strata Precision Indications for Approved THerapies (Strata PATH) trial.

 announced it has made Inc. Magazine’s Inc. 5000 list.

LaQuinta Jernigan, Chief Operating Officer for 

, has been recognized as one of 100 most inspiring people in life sciences.

’s Vice President, Patient Advocacy and Clinical Research Diversity, Lori Abrams, has been named a Diversity, Equity, and Inclusion Champion.

The latest business and people happenings from the last month, all in one place.

People and Business News — 9/22

Emerging from the COVID-19 pandemic, pharmaceutical and biotech leaders face acute challenges related to patient recruitment, talent shortages, and the increasing complexity of clinical trials.

, reflects today’s challenges and opportunities in bringing new therapies to market, as disclosed by more than 150 decision-making leaders at pharmaceutical and biotech companies around the world. Conducted by pharmaceutical market research firm Industry Standard Research (ISR), the survey asked respondents to consider the therapies in their pipelines, barriers to drug development, latest innovations in use, and the lingering effects and lessons of the COVID-19 pandemic.

Read more about the report and how to download it 

Industry leaders share insights on drug development challenges and trends
in new survey.

PPD Releases R&D Trends in Pharma and Biotech Report

Suvoda announced its new free-picking capabilities included in its latest Interactive Response System (IRT) release, used for patient randomization and supply chain management.

Suvoda’s latest free-picking functionality in its IRT system allows sponsors more flexibility in how they manage their supply-side packaging, labeling, and distribution operations.

New free-picking capabilities included in latest IRT release will be used for patient randomization and supply chain management.

Suvoda Announces Free-Picking for JIT Clinical Trial Distribution

ObvioHealth announces the launch of ObvioGo, a decentralized clinical trial platform and mobile application.

ObvioGo's tech stack has been designed to capture and integrate multi-source data. The system incorporates digital instruments, real-world data, artificial intelligence, as well as integration with clinical systems via APIs and industry standard interfaces.

DCT platform to deliver stronger evidence of therapeutic efficacy and safety.

ObvioHealth Introduces ObvioGo

Director of Digital Engagement & Optimization, ClinOne 

One of the key reasons for poor recruitment lies in the general lack of trial awareness among both patients and healthcare providers (HCPs). Throughout the history of clinical research, recruitment has largely been focused on patients living in relatively close proximity to major academic study centers—specifically, large hospitals affiliated with prominent universities.

Not only has this created a great deal of homogeneity in enrolled patient populations, but it has also served to keep most clinicians outside of these hospital networks in the dark about trial opportunities for their patients. And while enormous budgets are spent on direct-to-patient outreach, connecting with physicians can provide indirect access to dozens or hundreds of patients through already existing trusted relationships, likely leading to a lower screen failure rate based on the HCPs’ understanding of the individual and inclusion/exclusion criteria.

The influence HCPs have with their patients cannot be understated. Most patients choose a primary care doctor and remain with them for years. Patients with specific conditions likely rely on the same specialists for the duration of their care. The result is that patients trust their doctors. In fact, a 2021 Pharma Intelligence article states that 81% of patients who had never participated in a clinical trial would be likely to do so if referred by their doctor.

The clinical research industry can do more to reach out to clinicians working outside the central academic center bubbles. By connecting with and informing clinical leaders in smaller communities, rural communities, economically-disadvantaged communities, and others, sponsors can exponentially expand their reach to more—and more diverse—patients.

Following are a few strategies to help reach more HCPs and, through them, their patients...

Make It Easy for Busy Clinical Trial Site Teams—

This is a key reason why there have not been strong pushes to reach out to physicians outside traditional research networks. They simply do not have the time to conduct a trial. Luckily, solutions and technologies exist that can help get recruitment materials out to more HCPs with targeted messaging without adding new tasks for the site teams. The best solutions literally run in the background, educating clinicians, and providing them with information to share with their patients while site teams continue to focus on other trial responsibilities. One example is Trial Awareness by ClinOne, which curates a proprietary network of HCPs by therapeutic specialty and geographic region, then informs them of clinical trials that may be of interest to their patients (and connects them with local enrolling sites). Using solutions like these, sites can increase and optimize recruitment activity without hurting their team’s productivity by adding labor burden.

Today’s digital marketing technology allows for automation to keep messaging moving and keep potential patient recruits coming into the enrollment funnel. Keeping with ClinOne Trial Awareness as an example, study teams can map out their messaging and recruitment campaigns, including protocol information, inclusion/exclusion criteria, site information, and custom content. The platform reaches out on a consistent basis to HCPs to keep study opportunities top of mind as they meet with patients—and provide them with multiple options to learn more about the trial or speak directly with site contacts. Automated regular outreach with actionable links helps ensure coverage, understanding the need to reach different HCPs at different times and with different types of messaging.

Digital recruitment strategies that focus on patient outreach often require multiple messaging changes, multiple touchpoints, and high frequency to try and reach the numbers of patients needed to enter the enrollment process. HCP outreach, on the other hand, can be much more efficient. Physicians, obviously, will more quickly understand what a clinical trial is trying to accomplish and how it may benefit their patients. They will, generally, require less explanation regarding study protocols and eligibility criteria than a patient would need. Because physicians have the best interests of their patients in mind, they are likely to share information about clinical trials if they think a patient will benefit. The fact that referrals from trusted physicians are much more likely to be taken seriously versus recruitment ads seen outside their doctor visit, means that a digital campaign to reach HCPs is likely to be much more cost-effective than patient-targeted campaigns. An idea is to use an eNewsletter to showcase the trial for local HCPs and include a study-specific landing page for more information.

Engaging HCPs is not a miracle cure. Patient recruitment is a complex, nuanced and multi-faceted challenge, and no single solution will solve all issues instantaneously. It will, however, raise awareness within the local medical community which can have both a measurable direct and a qualitative indirect impact. By raising your study’s profile, you will generate increased word-of-mouth and conversations between physicians and patients. And by providing site contact information, you will encourage physicians to reach out directly to counterparts they know at nearby institutions to discuss individual patients—often leading to highly qualified peer-to-peer referrals. The success of such a program should consider a number of metrics including engagement rates, visits to your trial’s study page, and feedback from sites in addition to any uplift you experience in screenings, referrals, and enrollment.

When HCP outreach is used to expand access to patient pools that are geographically diverse and located further from the clinical site, it can be beneficial to both recruitment and retention to include ways to make participation easier for them. That’s why ClinOne provides not only virtual visits, but also partners with Uber Health for a Patient Ride solution. In fact, a 2022 

 survey found that 95% of sites believe providing transportation improves recruitment efforts. Patients and caregivers are faced with challenges that include consistent access to vehicles, the expense of driving and parking, physical or mental hardships, the anxiety of scheduling, and traffic. Providing patient rides together can unlock the full value of awareness.

Better recruitment can have a positive cascade effect on any clinical trial. Getting more eligible patients into the enrollment funnel more quickly can help studies start on time. This can help sponsors get their new drugs and therapies to market faster where they can help more patients while allowing sponsors to maximize their opportunities for market exclusivity.

Digital recruitment campaigns that focus on HCPs allow sponsors to greatly expand the number of clinicians in the loop about their studies, in turn giving them access to much larger groups of patients. The trust those patients have in their HCPs can lead to higher-quality referrals more quickly than patient-targeted digital recruitment strategies. Further, these higher-quality referrals are more likely to lead to high patient retention versus less targeted recruitment approaches, helping to keep studies on track.

, Director of Digital Engagement & Optimization, ClinOne 

Increased outreach is necessary to combat poor recruitment and large focus on patients near study centers.


Build Relationships with HCPs to Reach Potential Clinical Trial Patients

Trialbee will introduce a real-time monitoring module now available in its SaaS-based Trialbee Honey™ platform.

Honey Analytics is optimized for study teams to monitor recruitment and enrollment efforts in real-time, aggregating end-to-end recruitment and enrollment data into a single dashboard. The module provides users with “status-at-a-glance” metrics and the ability to perform a detailed “drill down” into recruitment and enrollment data. Honey Analytics comes packaged in Trialbee Honey™.

Real-time monitoring module now available in SaaS-based platform.

Trialbee Introduces Trialbee Honey™ Analytics

WCG announced the expansion of its Phase I review services. Launched in conjunction with the opening of Dr. Vince Clinical Research’s (DVCR) research complex in Overland Park, Kansas—these services are intended to improve timelines in the clinical trial process while maintaining necessary human subject protection for early stage and clinical pharmacology research.

Read more about the expansion and partnership 

Expanded services will provide faster timelines in the clinical trial process for early stage and clinical pharmacology research.

Featured Content

Applied Clinical Trials September 2022

‘Record’ Gains in Bringing Research Closer to the Patient

Salary Survey: The Age of COVID