DIA: Driving Insights to Action
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Listen to former DIA Board President Minnie Baylor-Henry’s special message to DIA members as part of DIA’s 60th Anniversary celebration in 2024.
A few years ago, 8-year-old Autumn noticed a lump on the side of her neck as she was preparing for bed one night. That quiet night opened a new chapter not only in Autumn’s life but in the life of her entire family: Autumn had leukemia. In this interview, Autumn shares the story of her treatment and recovery as a girl who had not yet turned 11. Her experience was also captured in a documentary https://youtu.be/NdUEYypd7iM?si=wxJHo-gFgB9NUJt5. When asked to share her advice to healthcare professionals and researchers as a pediatric oncology patient, Autumn explained: “Every patient is a different case, has a different body, and knows about their body. No matter how amazing you are at the job, keep in mind what children have to say instead of what you already know.”
In April 2023, Professor John Skerritt retired after 11 years of exemplary public service as deputy secretary of the Health Products Regulation Group and head of the Therapeutic Goods Administration in Australia. “What's really changed and what will persist after COVID? First, I think regulators have become a bit more comfortable in dealing with uncertainty. Uncertainty is the biggest challenge rather than benefit-risk,” he explains. “International regulatory collaboration became the basis of working together on these new products: We exchanged information on policies, on how the clinical data was developing, on the real-world performance of these drugs and vaccines, and on safety and post-approval requirements. These are going to persist.”
In part two of this podcast, “ePatients” Dave deBronkart and Stacy Hurt (Patient Advocacy Ambassador, Parexel) discuss new opportunities in the future of patient engagement in clinical research and care with DIA GAM 2023 https://www.diaglobal.org/en/flagship/dia-2023 Patient Engagement track chair Pujita Vaidya. “This advent and acceleration of artificial intelligence (which should be augmented intelligence) and digital biomarkers should not replace the physician-patient relationship but enhance it,” Stacy explains. “Lastly: If you want sustainable patient insights, don't only ask a patient, but invest in and hire patients as internal subject matter experts and full-time employees of your organization.” Listen to part 1. https://diapublications.podbean.com/e/patient-engagement-evolution-of-who-knows-what-part-1/
DIA GAM 2023 https://www.diaglobal.org/en/flagship/dia-2023 Patient Engagement track chair Pujita Vaidya discusses the definition, history, and current state of patient engagement in clinical research and care with cancer survivors and “ePatients” Dave deBronkart and Stacy Hurt (Patient Advocacy Ambassador, Parexel). “Many people were trained for generations to think of patients as poor people who just don't understand how to save their own lives. I'm here to tell you, we are not only eager to help but we're tired of being treated as crash test dummies,” Dave says. “Engagement doesn't just mean invite me into your process. It also means listen to me as a thinking, intelligent person who might have some ideas that you haven't thought of.”
“Healthcare systems obviously have as their primary role the delivery of healthcare,” says Steve Webb, Australian Clinical Trials Alliance board chair. “But we can see big improvements in health outcomes, combined with substantially better financial performance of the healthcare system, if the healthcare system has the dual role of treating patients as well as generating evidence about the most effective treatment options to guide that care.”
For regulators in Brazil, the pandemic’s aftermath includes a backlog of post-approval changes, delayed by emergency development of COVID-19 vaccines and therapies, related to biologic product quality. ANVISA’s new Online Optimized Assessment Project has significantly resolved these pending requests. “The pandemic had already enabled use of online tools for remote assessment of applications and virtual meetings between ANVISA and applicants, and also helped us be closer to other reference regulatory authorities in the process of building trust,” explains project architect Elkiane Macedo Rama, an Adviser of ANVISA’s Third Directorate. “The Online Optimized Assessment Project was a way to gather all these tools in a strategy to speed up the review process of these applications.”
“The pandemic had a substantial impact on community understanding of clinical trials. Having said that, the sort of ambient level of community knowledge of clinical trials is still substantially lower than it needs to be,” explains Australian Clinical Trials Alliance Board Chair Steve Webb. “Community awareness of the difference between evaluation of experimental interventions, about which relatively little is known regarding safety and effectiveness, compared with comparative effectiveness research, is an important distinction often with limited understanding in the community, in government, and amongst policymakers.”
From microphysiological systems and digital pathology to next-generation-sequencing and diversity in foundational genomic data sets: In this iteration of our annual year in review podcast, Global Forum https://globalforum.diaglobal.org/?_ga=2.145203060.1598158086.1639673102-473981677.1619533007 Co-Editors for Translational Science Gary Kelloff and Lanny Kirsch discuss emergent technologies and approaches that are upending clinical development, diagnostic, and patient care in oncology and beyond.
While the African Medicines Agency (AMA) plans and plants its inaugural headquarters in Rwanda, the European Commission, the European Medicines Agency (EMA), several EU Member States, and the Bill and Melinda Gates Foundation continue to mobilize more than €100 million in support. “The idea is to use the AMA as a platform that will further advance the capacities of the African continent to regulate medical products as a collective. It's a network approach to regulation of medical products on the continent,” explains David Mukanga (Deputy Director, Africa Regulatory Systems, Bill and Melinda Gates Foundation) in this conversation with EMA Head of International Affairs Martin Harvey Allchurch.
Clinical trials struggle to enroll eligible patients, while interested patients have difficulty finding pertinent clinical trials. Can technology help solve this people problem? “Typical patient recruitment happens based on historical data at research sites and that usually does not help, given the number of competing clinical trials trying to reach out to the same patients,” explains Indegene Senior Vice President for Enterprise Clinical Solutions Ram Yeleswarapu. “But today, tools and techniques to mine electronic health record data, clinical data, molecular data, allow us to look at sites and patients in a much more precise manner.”
Actions to increase patient diversity in clinical research initially addressed racial and ethnic demographics but are expanding to address gender identity. “Further research can only help us better understand the differences in our bodies and illnesses and how combinations of certain medications and existing treatments can improve everyone's lives,” explains Liam Paschall (Parexel, TransCanWork, DEIBA thought leader). “This will not only help transgender people. It's going to teach us about how the human body works.”
Digital technologies are rippling through clinical research and care, promising deeper links between healthcare research and delivery. In her interview with Global Forum https://globalforum.diaglobal.org/ US Editor Ebony Dashiell-Aje (BioMarin), Digital Medicine Society CEO Jennifer Goldsack expresses concern about the lag between producing evidence that something is fit for purpose and the conversations that need to take pace with payers and HTA experts. “We don't want to demonstrate, using the best, most novel measures possible, that new therapies are making a meaningful change for patients in ways that we haven't been able to measure before but are critically important, then delay going to market because additional evidence is required by our payer colleagues because we haven't taken time to take them with us.” Jennifer served as a panelist in the Paying for Digital Health: What Evidence is Needed? discussion at DIA Global Annual Meeting 2022.
DIA Global Forum https://globalforum.diaglobal.org/’s annual review of new drug approvals in China has shown growth in both the number and types of new drugs approved in China from 2019 https://globalforum.diaglobal.org/issue/may-2020/new-drug-approvals-in-china-in-2019/ through 2021 https://globalforum.diaglobal.org/issue/may-2022/new-drug-approvals-in-china-in-2021/: from 34 new chemical drugs and 19 biological products in 2019 to 37 new chemical drugs and 24 biological products in 2021. This podcast explores this growth in the context of the regulatory reform begun in China in 2015. “The annual number of new drug approvals reached a record high of 61 in 2021,” explains Global Forum China Regional Editor Ling Su (Shenyang Pharmaceutical University Yeehong Business School; Venture Partner, Lilly Asia Ventures). “In 2021, among the 61 new drugs approved, 31–slightly over 50 percent–were developed by local companies, and this was the first time that domestic companies received more new drug approvals than foreign companies in a given year.”
The World Health Organization has initiated a pilot coordinated scientific advice (CSA) procedure https://www.who.int/activities/optimizing-research-and-development-processes-for-accelerated-access-to-health-products/who-coordinated-scientific-advice-for-health-product-r-dwhereby product developers may obtain WHO advice on the most appropriate way to generate evidence on a product's benefits and risks. “WHO has been interacting with health product developers for many years but there wasn't a standardized or formalized approach to do it. We're quite well-positioned to be a coordinated and single entry point to initiate that dialogue,” explains WHO Science Division Unit Head Anna Laura Ross. “We have additional considerations around the needs of lower- and lower-middle-income countries or settings with limited resources,” says Science Division Technical Officer Mercedes Perez Gonzalez. “For example, the need for inclusion of specific populations, where you would find certain concomitant infections not necessarily present in higher income settings.”
In 2021, the 74th World Health Assembly adopted the Global Patient Safety Action Plan (GPSAP) 2021-2030 https://www.who.int/teams/integrated-health-services/patient-safety/policy/global-patient-safety-action-plan towards eliminating avoidable harm in healthcare. “Here in the United States, the Office of the Inspector General reports that one in four Medicare patients suffer harm in US hospitals,” says Sue Sheridan, a founding member of Patients for Patient Safety US, formed to advance this global plan in the United States. “Medication error is a huge global issue,” continues US founding member Soojin Jun in this interview with Mary Stober Murray (National Minority Quality Forum).
In April 2022, FDA issued new draft guidance on Diversity Plans to Improve Enrollment of Participants from Underrepresented Racial and Ethnic Subgroups in Clinical Trials https://www.fda.gov/regulatory-information/search-fda-guidance-documents/diversity-plans-improve-enrollment-participants-underrepresented-racial-and-ethnic-populations. Because this guidance applies to all medical products, CDER, CBER, and CDRH all contributed, but this draft was led by Project Equity from FDA’s Oncology Center of Excellence (OCE). “It is important that we be able to evaluate new therapies in the context of a diverse population that will use these medical products because the diseases for which these products are intended present in variable fashion across the population and because populations respond variably to medical products,” explains OCE Project Equity Lead Lola Fashoyin-Aje. “But we should reconsider the question regarding why diversity in clinical trials is important. Because the question really ought to be: What are we missing when trials are not diverse, when the study population in the clinical trial is not diverse? What are the missed opportunities for advancing science or advancing clinical medicine and, ultimately, for driving improvements in population outcomes?”
The Cancer Moonshot launched in 2016 with a Blue Ribbon Panel Report featuring 11 recommendations, including creation of human tumor atlases and a national cancer data ecosystem, for improving cancer research and care in the US. In February 2022, the White House announced that the Cancer Moonshot was being reignited. “The ecosystem has vastly improved the efficiency of the nation's cancer research efforts. They're bringing powerful computational methods of vast amounts of data in an organized fashion to enable treatment decisions and prevention,” explains Global Forum Translational Science Editor Gary Kelloff, special advisor to the National Cancer Institute, US NIH. “The ecosystem is complementary to the other efforts and provides the tools and methods to implement this sharing of large amounts of new data that's coming.”
In March 2022, the Tufts Center for the Study of Drug Development (CSDD) issued an impact report that examines clinical trial budgets and factors that drive commonly observed variations and cost. “Part of the focus of all of these studies is to understand how complexity, how increased customization in our trials, more fragmentation as we have different parties involved, contributes to longer cycle times and larger budgets than comparable studies when we control by therapeutic area,” explains Tufts CSDD Executive Director and Professor Ken Getz, who also serves as board chair for the Center for Information and Study on Clinical Research Participation. “Not only are we seeing longer timelines today, and larger budgets, but we see more variation around the mean for any of these measures, which means that it's getting more difficult for companies to predict or to anticipate and manage an expected timeline or an expected budget.”
While COVID-19 sharpened global understanding of the importance of efficient medicines review and regulation, the Pan American Health Organization (PAHO) has been systematically assessing national medicines regulatory authorities in the Americas since 2010. "It's inevitable that we reflect on what happened during the pandemic but also that we take that as an enormous opportunity to move forward in a way that can take the lessons out of regulation in a time of crisis to prevent crisis," suggests PAHO Medicines Health & Technologies Unit Chief Analía Porrás in this conversation with Susan Zavala Coloma (DIGEMID, Peru) and Global Forum https://globalforum.diaglobal.org/ Regional Editor for Latin America Cammilla Gomes (Roche). “The idea of the assessment is not just to showcase what's going well in a regulatory authority but, with the regulatory authority, to decide on the priorities for opportunities for improvement. We gained the trust of our regulatory authorities and our other stakeholders like the industry; with that trust, the authorities know that we're going to push them to be their best.”
“The ground is shifting in terms of how we will continue using randomized clinical trial data and real-world data in many different disease settings,” says Veronica Miller, co-author of Use of External Controls in FDA Regulatory Decision Making https://link.springer.com/article/10.1007/s43441-021-00302-y. In this research article, Miller (Forum for Collaborative Research) and Adora Ndu (Bridgebio Pharma, Inc.) describe where and how FDA has used external controls to support development and approval of drugs for rare and pediatric diseases. “We're seeing, not just in rare diseases but in many other diseases, this coming together of what used to be totally separate silos. In part, that's facilitated through electronic health records and other mechanisms of capturing data and being able to follow data at a bigger level, but also just because of understanding the importance of clinical data.”
In Part 2 of this interview, Chief Executive Officer Francisco Nogueira discusses the practicalities of data capture, data management, and machine learning within the framework of Accumulus Synergy’s proposed global cloud-based platform for regulatory submissions. “In terms of enthusiasm and shifting to database- from dossier-based submissions, this work had started before Accumulus was even conceived,” he explains. “Many companies already have data lakes in how they gather and collect and house the data that they are working through today. What I'm seeing in the ecosystem, both our sponsors and nonsponsors, is a high level of enthusiasm and high level of engagement towards what we define as data-centricity.” Listen to Part 1 of this interview. https://diapublications.podbean.com/e/sharing-cloud-based-data-as-they-emerge-accumulus-synergy-part-1/
In January 2021, 10 of the world’s leading biopharmaceutical companies announced the formation of Accumulus Synergy, a nonprofit corporation intended to enable global, real-time collaboration and data exchange and submission between industry and health authorities. “Our aim is to be at the intersection of where those who develop medicines, and those who approve them, can interact differently,” explains CEO Francisco Nogueira. “Our technology will provide the ability for a sponsor to work with as many regulators as that sponsor chooses to in a much more streamlined fashion. We will enable the platform. We will enable it with the know-how and the technology. But ultimately the business rules remain with the business.” Listen to Part 2 of this interview. https://diapublications.podbean.com/e/sharing-cloud-based-data-as-they-emerge-accumulus-synergy-part-2/
Global Forum https://globalforum.diaglobal.org/?_ga=2.145203060.1598158086.1639673102-473981677.1619533007 Co-Editors Gary Kelloff and David Parkinson discuss translational science milestones in 2021 against the backdrop of disruptive technologies advancing disease diagnostics and therapies. “The sensitivity of the diagnostic assays is getting better and better, and so is the analytical validation,” says Gary. “We have now the opportunity with liquid biopsies that allow from 20 cc of blood whole exome sequencing, whole transcriptome sequencing, and therefore deep DNA and RNA interrogation, real biology characterization. And that has fantastic opportunities for drug development, for patient diagnosis and prognostication, but also for the longitudinal monitoring of patients,” concurs David.
Innovations in therapeutic product development will only be effective when patients can access and use them. But establishing and explaining the value and price of these innovations among so much unmet need, and ensuring access by patients who need them, has proven difficult throughout Europe and elsewhere. “Policymakers more often or too often have a short-term view, short-term perspective, rather than a long-term perspective, and sometimes are driven more by political goals than promoting patient access in a real way,” suggests Andras Incze, Akceso Advisors. “We want the breakthrough innovations to reach patients throughout Europe. We want the best products and to get them to patients as fast as possible,” explains Rick Vreman, Utrecht University, the Netherlands. “But then it gets a bit more tricky when we start to think about what we need to make that happen.”
“There are good reasons to explore the use of artificial intelligence in pharmacovigilance. There are an increasing number of sources of drug safety information, and efficient screening, processing, or evaluation of them would benefit from accurate automated methods,” explains Gerald Dal Pan, Director, Office of Surveillance and Epidemiology (OSE), CDER. “First, there’s the potential application of AI to the processing of case reports. Second, there’s the potential application of AI for assessing causality in a case report. Third, we’re exploring the use of AI in real-world data as part of the Sentinel Initiative.”
COVID has demonstrated the importance of regulatory systems that ensure the safety and efficacy of therapeutic products as well as patient access to these products, especially in the complex network of healthcare, scientific, pharmaceutical, regulatory, and patient communities in Europe. “Regulators and industry have worked day and night over the last two years to bring vaccines and therapies forward. We know very clearly that sustainability of the system is an issue. More regulatory resources and simpler processes are desperately needed,” explains Isabelle Stoeckert, Bayer AG vice president and head of regulatory affairs for Europe, Middle East, and Africa. “Many countries have learned that reliance and collaboration between regulators is a really good thing. COVID-19 has really shown that,” suggests Henrik Nielsen, Novo Nordisk vice president of global regulatory sciences. “And I think this will stay, so we will see more reliance between regulatory sources, and we'll probably see increased use of different collaboration schemes around the world.”
How are clinical research and clinical care industries in Japan responding to the new challenges emerging in the post-pandemic world? “During 2020, it became a very difficult time to initiate a clinical trial, a difficult time to recruit patients to clinical trials which were ongoing, especially if those were clinical trials in patients who were elderly or in cancer therapies. Patients were a little bit reluctant to go to hospitals, even though we had very few cases in Japan,” explains E. Stewart Geary, global safety officer and senior vice president, Eisai Company Limited. “The healthcare system in Japan has one big challenge in that a lot of people are concentrated in large cities, and that's also where healthcare professionals are concentrated. But you have a large elderly population which is still in the countryside in towns which are kind of dying off, are very small, and are probably underserved by healthcare professionals. Because of that, there had been ongoing debate about telehealth.”
“We're moving toward an era of truly personalized medicine where research is uncovering the genetic basis for disease as well as mutations and biomarkers that can be targeted with drug and biologic therapies. We need to continue to identify the right patients for these innovative therapies, and this is where companion diagnostics has a foothold,” explains Tiffany Levin (55th Parallel). “One of the key challenges for drug sponsors is the timing of the development and review of companion diagnostics when they're intended to accompany an accelerated therapeutic development program,” continues Megan Doyle (Amgen). “We know regulators have developed or are developing accelerated regulatory pathways for drugs that are intended to address areas of high unmet need. But we don't have a similar accelerated pathway in most jurisdictions for the companion diagnostic.”
The Pharmaceutical Benefits Advisory Committee (PBAC) is an independent expert body appointed by the Australian Government to recommend new medicines for listing on the Pharmaceutical Benefits Scheme. How have advanced therapies impacted the cost and cost effectiveness of pharmaceuticals, and the work of PBAC, in Australia? “Our decision making is becoming harder because we're being asked to make decisions with substantially more uncertainty about the benefits and safety and the value propositions because medicines are coming to market earlier,” explains PBAC Chair Andrew Wilson to Ric Day, Global Forum https://globalforum.diaglobal.org/ Regional Editor, Australia/New Zealand. “I don't think the quality of the information has fallen. It's just that we're seeing it earlier in the drug development program process to be considered, and so there is more uncertainty associated with it.”
