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Applied Clinical Trials September 2023

Jim Kremidas, former executive director, Association of Clinical Research Professionals, shares his experiences as a patient in clinical trials.

Perspective and Hope From the ‘Other Side’

Senior leaders gather to share insights on the increased investment in real-world data to boost the quality and efficiency of drug development.

Executive Roundtable: The Rise of RWD in Clinical Research

Image Credit: © BillionPhotos.com - stock.adobe.com

The Association of Diversity in Clinical Trials (AOD) has announced its newest partners, Accelerated Cure Project for Multiple Sclerosis and Arab Board for Clinical Research. This strategic collaboration aims to drive diversity and inclusion within the realm of clinical trials, addressing longstanding disparities in healthcare access.

AOD, an advocate for diversity and equity in clinical research, has forged these partnerships to expand its impact on underrepresented populations. Accelerated Cure Project for Multiple Sclerosis, a nonprofit organization dedicated to advancing multiple sclerosis (MS) research, shares AOD's commitment to equal access to treatments and therapies for all patients, regardless of their background. The Arab Board for Clinical Research, renowned for its advocacy work in the clinical research space, joins forces with AOD to enhance diversity in clinical trials on a global scale.

"Our partnership with the Accelerated Cure Project for Multiple Sclerosis and the Arab Board for Clinical Research is a vital step in addressing clinical trial disparities," stated Jeremy Mitchell, AOD's director of business development in a press release. "Together, we aim to improve healthcare outcomes for all by ensuring trials reflect our diverse communities."

This collaboration fosters knowledge sharing and strategies for diverse community engagement in clinical trials. AOD, Accelerated Cure Project for Multiple Sclerosis, and the Arab Board for Clinical Research unite for a more inclusive healthcare future.

Accelerated Cure Project for Multiple Sclerosis and Arab Board for Clinical Research Partner with the Association of Diversity in Clinical Trials.

 (2023, September 28). Cision PR Newswire. 

Articles

Strategic collaboration aims to drive diversity and inclusion within the realm of clinical trials.

Accelerated Cure Project for Multiple Sclerosis and Arab Board for Clinical Research Partner with the Association of Diversity in Clinical Trials

Image Credit: © Blue Planet Studio - stock.adobe.com

ProofPilot has announced a strategic collaboration with Eli Lilly and Company (Lilly) to offer Lilly's patent-pending, sensor cloud platform, Magnol.AI™, a platform that enables management of high-frequency sensor data with security, as part of ProofPilot's technology solution.

For the first time, Lilly is out-licensing its technology. This technology-focused collaboration with Lilly and ProofPilot will enable both companies to help the broader research community to execute digital health research, helping to accelerate pre-competitive biomedical research.

"We are thrilled to collaborate with Lilly and leverage its industry-leading sensor cloud, further strengthening our commitment to provide our customers with the most advanced solutions and enable flawless execution of clinical research" said Chris Venezia, CEO of ProofPilot in a press release. "By integrating Magnol.AI™ into our platform, researchers finally have a one-stop, comprehensive solution to execute digital health research and deliver sensor data-driven insight with the highest quality."

Magnol.AI™ is Lilly's sensor cloud platform that allows for ingestion, visualization, and extraction of high-frequency sensor data with security. It is able to ingest and align a wide array of raw data from wearables, devices, and beyond in a clear time-series format. When aligned with clinician and patient reported outcomes, Magnol.AI™ enables real-time data science capabilities for digital health and digital biomarker research. 

ProofPilot's mission is to perfect clinical research execution by orchestrating technology, tasks, content, and communication through its clinical trial automation platform. When combined with Lilly's sensor cloud Magnol.AI™, ProofPilot delivers a data science solution to digital health and digital biomarker researchers around the world. With this new integration, any researcher can now have access to a digital health research platform that combines data collection, sensor ingestion, device management, and participant engagement.

ProofPilot To Integrate Lilly's Magnol.AI™ Sensor Cloud Into Its Clinical Trial Automation Platform. 

(2023, September 28). Cision PR Newswire.

Platform enables management of high-frequency sensor data with security.

ProofPilot to Integrate Lilly's Magnol.AI™ Sensor Cloud Into its Clinical Trial Automation Platform

Shalu Chadha, Global Life Sciences Technology Lead, Accenture

Accenture recently issued its Technology Vision 2023 for Biopharma report, which revealed that the industry has embraced AI and invested a lot of money into the technology. Accenture’s global life sciences technology lead Shalu Chadha sat down with 

to discuss the report and the industry’ relationship with AI.

 This is the annual report that we do specific to biopharma. It involved over 65 biopharma executives, and it was focused on the emerging trends we’ve noticed. We’re seeing convergence, like no time before, of technology and science which is driving innovation in a human and machine world. Whether that’s the scientists, the healthcare professionals, the business leaders, or the patients, they’re all driving that. They’re anchored on several trends: performance frontier, AI, data, and digital identity.

The reason why we’ve anchored on those topics is to ground us on what we’re describing as a client imperative over digital core. Our research shows that where there is a deliberate strategy, and where the clients are setting a new performance frontier with their companies, they’re anchored on a digital core.

Our report has stated 93% of biopharma executives actually are surprised at the acceleration of the science and technology. Our research shows us that AI-mediated drug discovery has grown by about 8%, and that is primarily driving over two-and-a-half billion dollars in investments. This paradigm is here and now, and there isn’t a biopharma company today not making the investments in AI in drug discovery and learning to collaborate with many others.

We see this pace, which we call new science, as being here to stay. The questions, what are the implications from a technology standpoint and how do businesses become the new frontier in this space.

PE: The biopharma industry has been slow to adapt new technologies, but it seems that AI is a different story. Would you agree?

 Absolutely. I’ve been here for over eight years, and you’re right. The last three years has driven advancement, whether it’s on the discovery or clinical side. There’s a level of adoption in biopharma that is stacking up higher than other industries.

PE: What lessons can the industry learn from this?

 Using AI as an example, the implications around the new science is that data is critical for any of these novel AI and scientific discoveries. A client’s data management and practices is incredibly important. Secondly, none of this can be done without enough of the partner ecosystem. We’re seeing a very active ecosystem when it comes to partnership that we haven’t seen in biopharma before. Our clients are very clear that the innovation and discovery that needs to be done must be done with platform.

Third, biopharma has traditionally admired itself for working in functions and domains. Now, more than ever, the convergence is causing cross talk between teams. You must be thinking about patient-centricity when considering your supply chain. You must think about your clinical trials and the information you can capture during early discovery. From a culture prospective, those are things that biopharma can learn more from other industries.

On the talent side, there’s a level of cross-skilling there that we’ve never seen before. Every business is now a technology business. The adoption and spread of data and data-based products is ever more important.

PE: How are companies the new importance of data?

 Data is not just within biopharma, it’s in the ecosystem. For example, a patient diagnosed with epilepsy and is anxious for a treatment could be matched for treatment by a drug company using AI by matching genetic information and personalized treatments for rare diseases and providing that back to the patient. When that patient receives options in less than a day for a specific treatment that is similar to their genetic profile and being able to choose that is a remarkable improvement for where we are.

This kind of example shows us that data is the life blood of innovation. It’s not just data curated from within, but more importantly, that data across the ecosystem.

Accenture’s global life sciences technology lead discusses how the life sciences industry has embraced artificial intelligence.

Embracing AI: Q&A with Shalu Chadha

Emily Marden, Senior Counsel, Sidley Austin LLP

Gene therapies have been talked about for years as having the potential to treat and even cure a wide range of previously intractable diseases, including cystic fibrosis, hemophilia, diabetes and many forms of cancer. Yet, despite its promise and the significant investment in research and development, few such therapies have been approved by FDA to date. As a result, few patients have received the benefits of gene therapy.

This situation may be changing. Recently, FDA’s Peter Marks, MD, PhD, director of the Center for Biologics Evaluation and Research (CBER), signaled that the agency intends to “lean in” to approvals of gene therapies and specifically rely on a flexible approach to accelerated approval pathway as a means of bringing therapies to patients sooner in the development process. Even more, Marks suggested that CBER intends to embrace an innovative approach in which FDA would rely on continued follow-up of subjects in a pivotal trial to provide the confirmatory evidence required for accelerated approvals, rather than the more typical approach of requiring that the sponsor conduct an additional clinical study. These developments have the potential to bring more gene therapies to patients, and to speed the timeline for doing so. In addition, this innovative approach to confirmatory studies could bolster confidence in the accelerated approval pathway, and could even finally open the door to incorporating real-world evidence (RWE), alleviating the significant challenges often associated with confirmatory clinical trials.

Accelerated approval allows for conditional approval of therapies for unmet medical conditions

FDA introduced the accelerated approval pathway in 1992, in large part to facilitate the availability of novel therapeutics to AIDS patients even before a sponsor had demonstrated safety and efficacy using standard clinical endpoints. Introduced first in regulations, the accelerated approval pathway was later added as Section 506 to the Food Drug and Cosmetic Act (FDCA) by Congress in 2012. Under the statute, FDA may grant accelerated approval based upon a surrogate or an intermediate clinical endpoint for drugs or biologic products for serious conditions that fill an unmet medical need. A surrogate endpoint, for purposes of accelerated approval, is a marker, e.g., a laboratory measurement, physical sign, or other measure that is thought to predict clinical benefit, but is not itself a measure of clinical benefit; an intermediate clinical endpoint, in turn, is a measure of therapeutic effect that is considered reasonably likely to predict clinical benefit.

FDA has made extensive use of the accelerated approval pathway since its introduction. To date, FDA has approved over 300 accelerated approval applications, including many cancer therapies and four gene therapies.

 In recent years, however, the agency and Congress have expressed frustration about shortcomings of using accelerated approval, including a perceived large number of so-called “dangling approvals” where confirmatory studies were not conducted, or did not show a favorable benefit-risk but the approval product was, nevertheless, not withdrawn from the market. FDA also struggled with the resource-intensive process required for withdrawal of approval of an accelerated approval drug under the statute.

In part in response to such issues, Congress approved changes to the statutory accelerated approval pathway in 2022 including, among other things, that FDA specify conditions for confirmatory trials prior to approval and the introduction of certain “expedited procedures” for withdrawal of accelerated approval where, for example, evidence subsequent to approval “demonstrates that the product is not shown to be safe or effective under the conditions of use.” These expedited procedures largely reduce the process of withdrawing an accelerated approval such that FDA needs only to open a Federal Register docket to publish its proposal to withdraw, open for public comments, followed by a meeting with FDA and, in limited circumstances, an advisory committee meeting. FDA has not yet published detailed guidance on this process, and has only recently initiated the first withdrawal under this process. 

Accelerated approval to facilitate availability of gene therapy products

In recent months, CBER’s expressed willingness to rely on—and even expand use of—the accelerated approval pathway has been reinvigorated, at least for gene therapy products. This renewed reliance holds out promise for significant impacts in the treatment and cure of disease. Specifically, CBER’S Marks has explicitly embraced accelerated approval as a means of ensuring a greater number of approvals of gene therapies in the near future, even opening the door to a more streamlined form of confirmatory data in a manner that seems to implicate reliance on real world evidence rather than just clinical data. 

CBER’s focus on accelerated approval for gene therapy products is particularly noteworthy for several reasons.

Flexible approach to evidence required for approval

First, Marks has indicated that accelerated approval for gene therapy can be flexible, including by taking a flexible approach to the relevant surrogate or intermediate clinical endpoint, depending on the disease state and available measurements. In an interview with Fierce Biotech, Marks stated “[w]e've [got] a better idea over time over the nature of the data that we want to see that can help us feel that there is a compelling case that a given intervention will potentially be associated with a positive clinical outcome.”

 Marks has further used the metaphor of a rubber band, suggesting that the agency can use flexibility in accelerated approvals to the maximum possible level, up to a finite point where the rubber band breaks.

 In this context, Marks has explained that FDA does not “have to get to 100% certainty between an accelerated approval endpoint and a clinical endpoint” and that “[i]If that were the case, there wouldn't be a difference, then we wouldn't have accelerated approval."

Continued follow-up as confirmatory evidence

. Second, Marks has suggested that confirmatory evidence can come from continued follow-up of subjects, rather than a separate confirmatory study. To this end, at a recent meeting of the American Society of Gene & Cell Therapy (ASGCT) Marks stated, “[w]ith gene therapy under the regenerative medicine advanced therapy designation, a confirmatory trial could simply be following the cohort you have enrolled in your registration trial.”

 This suggestion is consistent with reliance on intermediate clinical endpoints, and alleviates one of the main challenges to accelerated approval—namely enrolling a confirmatory study once a drug has been approved. It also provides a manner of ensuring that further data on the clinical endpoints will be gathered in a timely manner. Marks appears to be open to such data confirming benefit in a broad sense, rather than pursuant to a narrow understanding of the intermediate clinical endpoint.

Taken together, these approaches recapture the sense of urgency that gave rise to accelerated approval in the 1990s, and have the potential to reinvigorate use of the pathway for gene therapy, and perhaps more broadly. FDA and sponsors have long struggled with the challenges of enrolling confirmatory trials once a drug has been approved, with some sponsors proposing the use of RWE as an avenue for further insight into the safety and efficacy. Marks’ indication that FDA would consider continued follow-up of clinical subjects as confirmatory evidence, could be seen as a first step in incorporating RWE into the accelerated approval pathway. Such a move would be highly significant for sponsors.

It is worth noting that FDA has indicated that it is fostering approval of gene therapies in other ways as well. For example, FDA and sponsors have long acknowledged that manufacturing is a key challenge for the approval and widespread availability of gene therapies. Manufacturing changes in the development of a biological product, and particularly gene therapies, pose challenges because of the potential impact on the safety and efficacy of the therapeutic product. FDA is now tackling this issue head on for gene therapy products with the publication of a recent draft guidance, “Manufacturing Changes and Comparability for Human Cellular and Gene Therapy Products.”

 In that guidance, FDA makes clear that it that it is open to innovative approaches in manufacturing gene therapies and that it acknowledges that manufacturing processes may be subject to modification even after approval. The new draft guidance focuses on establishing “a robust framework” for managing these manufacturing changes, including attention to risk management, product stability, and comparability studies.

Marks’ high-profile commitment to greater use of the accelerated approval pathway and this recent focus on gene therapy manufacturing issues are a welcome and positive sign that FDA is committed to approving additional gene therapy products. These developments also promise renewed interest and flexibility in using the accelerated approval process to bring promising products to patients.

, JD, is senior counsel at Sidley Austin LLP

FDA, Accelerated Approval Program. May 30, 2023 

https://www.fda.gov/drugs/nda-and-bla-approvals/accelerated-approval-program#:~:text=The%20FDA%20instituted%20its%20Accelerated,based%20on%20a%20surrogate%20endpoint.%22

The Future of Accelerated Approval for FDA's Marks? More Rare Disease Drugs and No 'Hanging Chads.' Fierce Biotech. July 28, 2023. 

https://www.fiercebiotech.com/biotech/peter-marks-says-fda-now-has-better-sense-rare-disease-biomarkers-will-more-accelerated

Cell/Gene Therapies: US FDA Wants ‘Quantitative Correlation' Between Surrogate and Clinical Outcome, Former Reviewer Says. Pink Sheet. July 10, 203.

FDA 'Leans In' to Accelerated Approval for Rare Disease Drugs. Pharma & Healthcare Monitor Worldwide. May 22, 2023.

FDA, Manufacturing Changes and Comparability for Human Cellular and Gene Therapy Products: Draft Guidance for Industry (July 2023). 

https://www.fda.gov/media/170198/download

Exploring the implications of FDA’s renewed focus and commitment to expand the use of accelerated approval for gene therapy products.

Accelerated Approval and the Promise of Gene Therapy

Clario, a healthcare research technology company, and CellCarta, an organization focused on integrated sample management and specialized laboratory services, have announced a strategic partnership aimed to improve clinical trial sample handling. Additionally, the companies hope to streamline the handling of tissue and samples and subsequent digitization in support of clinical trial endpoint generation across multiple therapeutic areas, including oncology, hepatology (e.g., NASH), and gastroenterology (e.g., UC and Crohn's).

"This collaboration brings together Clario's cutting-edge scientific expertise and unrivaled clinical trial endpoint solutions with CellCarta's unparalleled sample processing and management expertise," noted Joyce Suhy, PhD, EVP, medical imaging, and specialty solutions, Clario. "This partnership advances Clario's ability to support histopathology studies, providing our customers with full visibility for biopsy sample logistics and significantly accelerates delivery of centralized assessments for eligibility and efficacy endpoints."

: Clario teams up with CellCarta to transform clinical trial sample management for histopathology studies. 

September 26, 2023. Accessed September 27, 2023. https://www.prnewswire.com/news-releases/clario-teams-up-with-cellcarta-to-transform-clinical-trial-sample-management-for-histopathology-studies-301937860.html

Joint venture aims to streamline handling of tissue and samples and subsequent digitization in support of clinical trial endpoint generation. 

Clario, CellCarta Strike Partnership to Improve Sample Handling in Clinical Trials

Image Credit: © Production Perig - stock.adobe.com

Emmes has announced the addition of telehealth capabilities within Advantage eClinical. The new application means any scheduled visit can become virtual with video calls augmented directly through the platform and patients signing in through their existing participant portal.

The addition of telehealth capabilities is part of a much wider development plan for Emmes' third generation clinical data platform. The platform accommodates all trial modalities—traditional, decentralized including hybrid and fully virtual—as well as the needs of patients, sponsors, and sites. It also includes all tasks from data capturing, cleaning, monitoring, to workflow management, sample tracking and even clinical assessment and engagement tools.

"What we are building with Advantage eClinical is more than an EDC or eCOA/ePRO. It's a platform to accelerate the delivery of all types of trial designs through one unified, modular system. 90% of respondents in the Center for Information and Study on Clinical Research Participation's (CISCRP) 2021 Perception and Insights Study stress the importance of having options for completing study visits, such as virtual and home visits. By eliminating the need for sponsors to procure and set up additional point decentralized trial (DCT) systems, we hope more studies will offer patient-centric options for patients to participate," commented Ching Tian, chief innovation officer at Emmes in a press release.

Ashley Davidson, Emmes associate vice president, product management and operations, explained that the telehealth application makes workflow far simpler for site staff because all information is on screen at the same time, including assessment forms and patient records. In a press release, she commented: "It gives that real world feel of an in-person visit and enables simultaneous note-taking and record-checking. On a more practical level, operating a decentralized or hybrid trial design means we can also open up trials to more diverse groups of participants, which has been a big driver from the regulators."

Emmes Introduces Telehealth Capabilities into Advantage eClinical. 

(27 September, 2023). Cision PR Newswire.

Scheduled visits can become virtual with video calls augmented directly through the platform and patients signing in through their existing participant portal.

Emmes Introduces Telehealth Capabilities into Advantage eClinical

Image Credit: Adobe Stock Images/Olivier Le Moal

Thread Research revealed in a company press release that it has officially launched a suite of new complex electronic clinical outcome assessment (eCOA) features, including an expanded global library, to its decentralized research platform serving global researchers. Reportedly, the new features enable the platform to process complex eCOA data collection while presenting only relevant data to the site teams and participants.

Thread stated that with these new features, clients can now:

Eliminate 100% of custom development activities for eCOA and related study quality risks.

Reduce eCOA implementation costs by up to 54% leveraging Thread's no-code platform.

Decrease data capture clicks by up to 90% for participants to increase patient retention.

Launch studies with complex eCOA in nine weeks or less.

Increase compliance consistently above 94% by eliminating unnecessary technology burden.

"The launch of these enhanced eCOA features provides our clients with the next-generation functionality needed to increase speed, scale consistently, and reduce study risks," said John Reites, co-founder, CEO, Thread, in the aforementioned release. "These features bring us closer to bringing research to everyone, everywhere with our innovative approach to Patient-First eCOA."

: THREAD LAUNCHES SUITE OF NEW FEATURES AND EXPANDED LIBRARY TO MODERNIZE ECOA SOLUTIONS. 

September 26, 2023. Accessed September 27, 2023. https://www.prnewswire.com/news-releases/thread-launches-suite-of-new-features-and-expanded-library-to-modernize-ecoa-solutions-301938170.html

Platform includes an expanded global library. 


Thread Introduces New Electronic Clinical Outcome Assessment Suite 

Peter O'Donnell is a freelance journalist who specializes in European health affairs and is based in Brussels, Belgium.

The latest promise held out by the European Union to rare disease patients comprises not only “new capacities and capabilities to execute innovative trial designs,” but also “solutions to address scientific gaps and technical and operational challenges.” The outcome, according to the proposal’s assurances, should be “dedicated, rare-disease specific and sustainable infrastructure” for rare diseases with high unmet medical needs. But the promise is conditional. It comes in the shape of a new research program—and the condition is that the EU will provide the money while a chosen team will do the work.

 aims to optimize drug development through clinical trials conducted for small populations and clusters of diseases with commonalities. It will focus on a subset of the 95% of underserved rare diseases—the “white spots” constituted by those conditions for which there is no approved treatment option and where development is not currently commercially viable.

Among the novelties it brandishes, the program will engage regulators and health technology assessment (HTA) bodies in validating recommendations for the use of registries driven by electronic health record (EHRs) and longitudinal natural history studies, and seek closer alignment on the uses of real-world evidence (RWE)—issues currently so lacking in European consensus as to trip up many innovative studies. It is also targeting the particular problems in accessing trial sites that are scientifically and operationally qualified and with readily available pools of patients, especially in the area of advanced therapies. And it is aiming to ensure closer compatibility and alignment on some of the classic pinch points between regulators and industry.

It is a serious attempt to tackle the limited understanding of disease etiology, biology and natural history handicapping progress, and the lack of established endpoints for use in clinical trials. It links to the EU “moonshot” program on rare diseases, the European Reference Networks, and the registries they are each developing in their own specific disease areas, the European Joint Program on Rare Diseases, and to the European Platform on Rare Disease Registration Platform for clinical data management, as well as the the Accelerating Clinical Trials in EU initiative. It will also tie into a new cluster of Horizon Europe projects on developing therapies for rare diseases with no approved options expected to start in the fall, and the EU Partnership on Rare Diseases that is expected to start in mid-2024.

The plethora of EU initiatives in this field (the team that wins this latest contract is also expected to “partner with existing projects/initiatives, including the Innovative Medicines Initiative, Screen4Care, conect4children…” and half-a-dozen other EU programs on rare diseases) might be seen as a strength. But it also holds the risk of being a weakness—as this proposal acknowledges (without any apparent irony) with its additional aim “to help overcome the fragmentation of the clinical trial environment across Europe.”

The proposal also has an explicit link to boosting the innovation culture in the EU, and in a remarkable display of optimism states: “Europe is becoming more attractive for the clinical development of medicines for rare/ultra-rare diseases thanks to the uptake of innovative methodological approaches for conducting successful clinical trials for rare/ultra-rare diseases.” That is a point of view not universally shared: CEOs of international Big Pharma firms have spent much of 2023 denouncing the barriers to research investment posed by EU regulation, backing their criticisms with threats of relocating their drug development programmes away from Europe. And even the EU itself admits that more must be done to attract and retain innovation in Europe.

This is perhaps the core of EU challenges in driving innovation—reconciling the many distinct but inter-related bodies, agencies, authorities, interest groups, and stakeholders in Europe. It is not just the 26 member states with their own competing views and priorities, but the jockeying for power and position among the EU institutions themselves—the European Commission that proposes laws, the European Parliament (with its multiple political groupings among its 700+ members) and the Council (where national ministers and their diplomats deliberate) that jointly decide on legislation, the European Medicines Agency (EMA), and the parallel Heads of Medicines Agencies. Behind each of these formal actors there lies a complex web of indirect influences—often pitting industry against payers or regulators, or consumer and patient groups, or scientific or medical societies, or health professional organizations.

The ultimate example of this “fragmented” landscape alluded to in this latest proposal is the current plan to reform the EU’s rules on pharmaceuticals, of which this column has already offered some thoughts.

 It, too, amounts to a promise—a promise that is in many respects self-contradictory in its desperation to emulsify the conflicting views underlying almost every issue it touches upon. Unfortunately, the EU’s record in fulfilling its promises in the pharmaceutical and clinical trial sphere is not without blemish. This column will be delighted if it can report on some whiter rather than darker spots in upcoming columns.

is a freelance journalist who specializes in European health affairs and is based in Brussels, Belgium

https://ec.europa.eu/info/funding-tenders/opportunities/portal/screen/opportunities/topic-details/horizon-ju-ihi-2023-04-04-two-stage

https://www.appliedclinicaltrialsonline.com/view/playing-catch-up-with-europe-s-decline-in-attracting-clinical-trials

https://www.appliedclinicaltrialsonline.com/view/european-legislative-proposals-presage-new-rules-for-clinical-trials

EU proposal focuses on a subset of underserved rare diseases—exploring the gaps in those conditions for which there is no approved treatment option.

Reaching for the ‘White Spots’ in Rare Disease 

New technologies are changing the ways that life sciences and regulatory agencies approach the collection and analysis of data. Scott Cleve, vice president of regulatory operations, information, and compliance at Daiichi Sankyo sat down with 

 at the Veeva R&D and Quality Summit 2023 in Boston to discuss these topics.

 What are the current struggles with the regulatory environment right now?

 For regulatory, we are so focused with understanding the regulations for delivering our products to market and working with FDA. For us, that’s dictated by FDA requirements and guidance, which are more scientific in nature. Those change from time to time, from health authority to health authority. Understanding what those changes are is part of our remit. We translate those to the organization and develop the processes and systems in order to make sure we’re compliant.

 There are new regulations and new technologies to address those regulations. Where do you see the industry heading in the next few years?

 There’s a couple of factors. One is: what are the regulators asking of us? The trend in the industry has been data driven. Especially from FDA, and we assume that other health authorities are going down this path as well. Our data practices are certainly something we must consider going forward. We’re moving from a narrative-based submission to more of a data-based submission. Historically, we’ve created large summaries and clinical study reports.

Those contain narratives. How did we analyze our study data? What are our conclusions? We’re going to continue to shift towards presenting a data set, our analysis, and having agency analyze it and seeing if we come to the same results.

How do you ensure that discussion of the results, benefits, and risks continue to happen in those filings? That’s going to drive us a lot.

The second issue is the collaboration of multiple health authorities. From an efficiency standpoint, does that help us make our submission? Does that help us then move towards approvals in a quicker manner? Having more integration and discussion between health authorities is helpful.

 How do you deal with data privacy concerns, especially during clinical trials?

 It’s the next step for the industry. If you think about decentralized clinical trials, that allows more patients to participate in trials. It doesn’t force them to come to a center to collect data or meet with the investigator. We’re able to meet with a wider population who may not be able to physically come there.

As we collect that data, however, that poses different challenges. How do we provide the technology to the patients? How do we have a secure way to collect it and ensure that there’s the right security and handling of the data? This applies to the data pertinent to the trial along with the protected data. There are privacy concerns.

We must have controls in place with technology to ensure the patient’s privacy is protected. The audit trail from the device to our systems is all there. There are companies that are doing that effectively, but it’s still early days.

 You mentioned getting the technology into the hands of the patients. Is there concern about patients accurately collecting their own data?

 There’s such a wide range of patients. Depending on what disease or affliction that you are collecting data on, do the patients have the dexterity to enter in into a phone? Is there a voice capture? Whose validating on either the CRO or clinical side? There’s a lot of thought that goes into that. We’re trying to make that as easy as possible, but we’re only as good as the users are.

The onus is on the CROs or the people that are providing the technology to provide a level of training. That’s going to help the data collection be successful, but it’s an extra step, especially when they’re not in the clinic and instead in the care of a clinician or an investigator who’s used to filling in forms and other information to collect the data.

Cleve talks about the future of the industry and how data remains a key focus.

Veeva R&D and Quality Summit 2023: Q&A With Scott Cleve, Vice President of Regulatory Operations, Information, & Compliance at Daiichi Sankyo

Discussions on current European legislative initiatives edge forward in drug approval and the use of health data, and the potential for exploiting real-world evidence (RWE) is receiving increasing attention from researchers and regulators. European innovators are looking forward to what they see as "a large number of high-quality data sets that can be accessed and shared for research and innovative purposes that ultimately improve the lives of European patients." That is the view of The European Confederation of Pharmaceutical Entrepreneurs (EUCOPE), the body representing smaller biopharmaceutical research companies in Europe.

The legislators' intention is clear enough as a concept. The draft regulation on reforming the EU authorization process

 says that the companion proposal on the European Health Data Space (EHDS)

"will provide a common framework across member states for access to high-quality real-world health data (RWD)," it says, going on to speak of promoting “progress in R&D, comparative clinical assessments, and regulatory decision-making."

For industry, there is evident merit in the use of RWE to complement clinical studies, and particularly in the case of many novel therapies to provide answers to questions that cannot be addressed by randomized clinical trials. A EUCOPE working group on digital health has been energetic in its exploration of the possibilities—and pitfalls—of regulation in this area, and the group's Leander Vranken recently outlined his view of how the opportunities can be best taken advantage of.

As he puts it, EHDS could optimize and widen the secondary use of health data through its envisioned electronic health data sharing mechanism, which would allow industry innovators to request access to health data from the new category of “data holders,” such as hospitals, for the purposes of science, research, and innovation. And because EHDS will set up a health data ecosystem with clear data collection standards, it will—if it comes into effect in an optimal fashion—provide for the robust RWE generation requires from the routine collection and analysis of large numbers of high-quality data sets. For the smaller firms in EUCOPE's membership, the common network of health data sharing would lower the barriers for the use and reuse of high-quality health data.

Another of the prominent examples of this growing engagement is a group styling itself RWE4Decisions, created by the Belgian health insurance body INAMI, but comprising a broad range of the European healthcare community, including notably more than a dozen national health technology assessment (HTA) bodies, payers, and regulatory agencies, but also extending to clinicians, patient groups, researchers, registry-holders, data analysts, industry, and academic experts. Its focus is on the sharp end of using RWD—where decisions are made on whether to reimburse new medicines. Its extensive stakeholder membership is allowing it to explore what RWD can be collected for highly innovative technologies—when, by whom, and how—so that it can be used to generate RWE for decision-making by healthcare systems, clinicians, and patients. It works on the basis that RWE generation is a shared responsibility and should be pre-specified and planned with all stakeholders.

The prospects for using RWE have also been welcomed by leading members of the European Parliament. Stelios Kympouropoulos, a Greek psychiatrist who is one of the center-right European People’s Party (EPP) group—and who, as a spinal muscular atrophy patient, understands well the challenges of rare diseases. A champion of RWD as a source of "invaluable insights into the effectiveness, safety, and value of medical treatments and interventions when applied in real-world settings," he sees the combination of RWD within EHDS as a valuable support for research.

Specifically, he recognizes the benefits that can occur in rare disease research, notably in the creation of rare disease registries, to improve rare disease diagnosis and treatment and to enhance patient engagement and participation in research. But he raises what he calls a "pivotal question": are the member states adequately prepared to confront the challenges of infrastructure, policies, and regulations on data sharing and technical capabilities? "It is crucial," he concludes, "for stakeholders to join forces and work together."

It is a conclusion that, regrettably, seems to encapsulate so many of the dilemmas in European health policy.

is a freelance journalist who specializes in European health affairs and is based in Brussels, Belgium. 

https://health.ec.europa.eu/publications/proposal-regulation-laying-down-union-procedures-authorisation-and-supervision-medicinal-products_en 

https://health.ec.europa.eu/publications/proposal-regulation-european-health-data-space_en

Legislative efforts seek a common framework in accessing and applying real-world data and evidence in clinical studies.

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