July 2021
July 2021 Global Forum

Table of Contents


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Editorial Board

Content stream editors

Translational science
Gary Kelloff US National Institutes of Health
David Parkinson ESSA Pharma, Inc.

regulatory science
Isaac Rodriguez-Chavez ICON plc

Patient engagement
Trishna Bharadia Patient Advocate and Media Contributor
Mary Stober Murray National Minority Quality Forum

Monika Schneider Shionogi

Editorial Staff

Alberto Grignolo, Editor-in-Chief Parexel International

Sandra Blumenrath, Managing Editor, Scientific Publications DIA Scientific Communications

Chris M. Slawecki, Senior Digital Copyeditor DIA Scientific Communications

Regional Editors

David Mukanga Bill and Melinda Gates Foundation

Jin Shun Sandoz

Richard Day University of New South Wales, Medicine, St. Vincent’s Hospital

Judith Glennie JL Glennie Consulting, Inc.

Ling Su Shenyang Pharmaceutical University, Lilly Asia Ventures

Thomas Kühler Sanofi R&D

J. Vijay Venkatraman Oviya MedSafe

Ozawa Goshi Real World Data Co. Ltd.

Cammilla Gomes Roche

Ebony Dashiell-Aje BioMarin

Young Professionals Editors

Kaley Lugo Daiichi Sankyo
Saloni Patel Acorda Therapeutics

DIA Membership

Bringing together stakeholders for the betterment of global health care.

I-SPY 2.2: Evolving the I-SPY 2 TRIAL to Adapt Therapies for Each Patient and Optimize Outcome
Laura Esserman
University of California, San Francisco
Angela DeMichele
University of Pennsylvania
W. Fraser Symmans
University of Texas MD Anderson Cancer Center
Laura van’t Veer
University of California, San Francisco
Doug Yee
University of Minnesota
Denise Wolf
University of California, San Francisco
Christina Yau
University of California, San Francisco
Nola Hylton
University of California, San Francisco

ince opening in 2010, 22 agents or combinations of agents have entered I-SPY 2–a long-standing, adaptive platform trial of neoadjuvant therapy for patients with stage 2-3 breast cancer with high risk for early recurrence. Twelve agents have completed accrual and seven have “graduated” in at least one tumor subtype (indicating an 85% probability that the agent will be successful in a confirmatory phase 3 trial).

Although unproven at its outset, I-SPY 2 is now widely regarded as the archetype platform trial and the design is increasingly being adapted for use in other cancers and indications. We are now at a juncture where advances in care from the first 10 years can be used to reshape the future of I-SPY 2. The steadfast support of key FDA leadership has transformed this novel clinical trial structure into a mainstream approach. In fact, broad acceptance of platform and adaptive trials, including the I-SPY COVID trial (for critically ill patients), by the senior R&D leadership of big pharma demonstrates the acceptance of this new paradigm for accelerated drug development.

Key Advancements of the I-SPY 2 Platform Trial:

  1. pCR is an important prognostic marker for individual patients with molecularly high risk disease, regardless of treatment or subtype received.
  2. We developed an MRI-based “predicted Residual Cancer Burden” (pre-RCB) strategy to predict pCR after each regimen, but before surgery, with high specificity and moderate sensitivity and are testing it prospectively. Furthermore, ctDNA is being developed as an adjunct to improve residual disease prediction and outcome.
  3. Improved classification of tumors improves predicted pCR rates with optimal agent assignment for the molecularly high risk population.
I-SPY 2 is designed for the rapid phase 2 assessment and personalized targeting of promising agents or combinations based on biomarker subtypes defined by hormone receptor, HER2, and MammaPrint (70-gene signature) status. The I-SPY 2 TRIAL is the longest running platform trial and by Q3 of 2021 will have 28 sites across the US. I SPY 2.2 will evolve to a regulatory seamless phase 2/3 design by late 2022.
Choosing Inclusivity: Serving All Patients Through Scientifically Driven Eligibility Criteria
Samantha Roberts
Dylan Bechtle
Katherine Williams
Howard University
Rasika Kalamegham
Genentech, A Member of the Roche Group

he US Food and Drug Administration’s (FDA) 2020 Drug Trials Snapshots Summary Report found that clinical trials supporting the 53 new molecular entities approved by FDA’s Center for Drug Evaluation and Research (CDER) in 2020 included, on average, only 11% Hispanics and 8% African Americans. This lack of diversity in clinical trials can have a direct impact on health outcomes. Events of the past year and the Covid-19 pandemic have brought a renewed sense of urgency to ensure that underserved and understudied patient populations are not left behind in our age of personalized healthcare.

Re-Evaluating Eligibility Criteria

Strict eligibility criteria for clinical trials present a clear scientific and evidence-based opportunity to improve diversity in clinical studies. Clinical trial inclusion and exclusion criteria are necessary to define the study population of interest and ensure patient safety. However, many eligibility criteria used in contemporary clinical trials were designed for small molecule drugs and may not be appropriate for studies of therapeutic antibodies or the emerging treatment modalities of the future like cell and gene therapies. Furthermore, many criteria have been defined based on data from predominantly non-Hispanic whites. Nonetheless, several common exclusion criteria, such as laboratory test values, remain a static fixture of trial design. Here we discuss the need to reconsider eligibility criteria and shift from the default state of exclusion to a future state of inclusion in clinical trials.

White Paper Podcast

Neta Bendelac headshot
White Paper by 4G Clinical
DTP Emerging as Practical Patient-Centricity
One of the most basic aspects of critical trials, helping patients maintain their therapeutic regimens, was greatly impacted by the travel and social restrictions of COVID-19: Delivering and distributing investigational drugs to maintain the trial while keeping patients and site employees safe in the process. “The pandemic forced everyone to think differently. We were all running a crisis and the main challenge was how to keep patients under treatment. Direct to patient (DTP) means shipping the drug to the patient home, or to patient location according to his choice, instead of having the patient coming to the clinical site. That allows patients to stay at home. There is no need to go anywhere and jeopardize their immune system in a pandemic,” explains Neta Bendelac, Senior Director of Strategy, 4G Clinical. “Flexibility is the name of the game here. 4G’s model for DTP allows different configurations of the solution. A study may want to allow DTP, but a patient may prefer not to have DTP and they would prefer to come to the site. Our RTSM (randomization and trial supply management) can be set up to enable each patient to choose between DTP and the traditional settings. That is being patient-centric.”
Digital Endpoints Must Meet Patient Needs
Multi-Stakeholder Effort Required – One Size Does Not Fit All
Bray Patrick-Lake
Evidation Health
Christine Manta
Elektra Labs
Jennifer Goldsack
Digital Medicine Society

echnological advances are speeding the development of digital measures and endpoints throughout drug development and across therapeutic areas and patient populations. While regulators encourage stakeholders to pursue patient-centric approaches, few actionable guidances or standards exist.

Digital measures of health offer enormous promise to transform how we define health and disease, and in turn improve health outcomes, economics, and equity. However, it is expensive and time-consuming to develop digital measures of health for use in healthcare and clinical research. Disjointed and undisciplined digital measure development that takes a signal chasing approach rather than measuring what matters most to patients can exacerbate the inadequacies of poor assessments in use today. It ultimately costs us the early promise of digital measures to improve the lives of patients in meaningful ways.

White Paper Podcast

Serena Barker headshot
Stephen Tait headshot
White Paper Podcast by Calyx
CTMS Key to Unlocking Clinical Data Power
Clinical trial management systems (CTMS), which have historically been large clinical data repository and management systems, are responding to changes in research necessitated by the pandemic. “We demand data to work much harder for us now. We want things to be intuitive and at our fingertips. We firmly believe a CTMS solution shouldn’t be any different. Data needs to work hard to support the client’s business, provide a seamless, interoperable solution that users and stakeholders find intuitive and drive the success and velocity of the clinical trial,” suggests Serena Barker, Vice President, eClinical Operations for Calyx. “We see CTMS as just one of a number of important components that now exist in a much more integrated and interoperable system that spans everything from the drug discovery process, trial operations (where the CTMS sits), through sales, marketing enablement, and all the way into manufacturing,” concurs Calyx Vice President of Engineering Stephen Tait. “We see the CTMS continuing to be a really important player within that trial operation section. But we see the data that contains, and the workflows and the information within, being used in all those other parts of the clinical process in ways that we as the supplier of the CTMS system cannot even imagine.”

Meeting Highlights: DIA China 2021

Meeting Highlights from DIA China 2021

Meeting Highlights: DIA China 2021

China GVP: Lifecycle Pharmacovigilance and Patient Safety
Monica Juping Xu
Taimei Medical Technology

n May 2021, the National Medical Products Administration (NMPA) in China issued an announcement about Good Pharmacovigilance Practice (NMPA/Decree No.65/2021), hereafter referred to as GVP, the first pharmacovigilance guideline issued in accordance with China’s new Drug Administration Law of the People’s Republic of China. The expected official version of GVP has been released in final form and will be effective on 1 December 2021.

This is the first time the term “pharmacovigilance” is officially reflected in the Drug Administration Law of China, which provides its context in Article 12: “The State establishes a pharmacovigilance system to monitor, identify, evaluate and control adverse reactions or other problems related to drug use.” Article 1 of the China GVP clearly mentions that, “The Practice is formulated in accordance with Drug Administration Law of the People’s Republic of China, Vaccine Administration Law of the People’s Republic of China and other relevant provisions for the purpose of regulating the pharmacovigilance activities throughout the lifecycle of drugs.”

White Paper Podcast

Jason Monteleone Headshot
Dr. Lingshi Tan Headshot
White Paper Podcast by dMed Global-Clinipace
dMed Global/Clinipace Building Bigger Business Than Both
dMed Global, a full-service clinical contract research organization (CRO) headquartered in China, and Clinipace Incorporated, a full service clinical CRO with US headquarters, announced the merger of the two companies in April 2021. “Western biotech companies increasingly recognize their need for a strategic partner who can stay on the leading edge of fundamental changes in the global clinical landscape,” explains Dr. Lingshi Tan, Founder and Chairman of dMed Global and Global CEO for dMed/Clinipace. “We know that the drug development market in China is growing at greater than 20% a year per annum, and that is almost three times as fast as clinical research in the rest of the world,” says Jason Monteleone, Clinipace CEO, who will serve as Chief Business and Strategy Officer for dMed/Clinipace. “We can partner with biotech companies, truly partner with them, be a solutions provider with them, and continue to provide the level of service they would expect out of a mid-size CRO but also bring them the size and scale of a little bit bigger business than both of us combined.”

Meeting Highlights: DIA China 2021

Global Pharmaceutical Regulation Evolving and Modernizing to Protect Public Health
Handsome Ji

he key priorities to modernize regulatory science are to optimize the regulatory system, encourage scientific innovation, and develop cross-cutting talents. By opening interdisciplinary conversations and studying the similarities and differences among regional regulatory policies, health authorities and scientists will be able to protect and promote the health of all populations.

The Global Regulatory Modernization Town Hall at DIA China 2021 aligned with the conference theme of Integrating into Globalization, New Journey to Innovation as representatives from four major regulatory authorities–the (China) National Medical Products Administration (NMPA), the US Food & Drug Administration (FDA), the European Medicines Agency (EMA), and the (Japan) Pharmaceuticals and Medical Devices Agency (PMDA)–shared strategies for building regulatory capacity building during the next three to five years.

Meeting Highlights: DIA China 2021

Preparing for Unknown Risks in Exploratory Clinical Trials: Guideline from China CDE
Yuan Yao
Takeda Development Center Asia

ew treatment areas including gene therapy, cell therapy, oncolytic virus, and proteolysis targeting chimera (PROTAC) products are growing into hotspots for early drug development in China. The recently issued Center for Drug Evaluation (CDE) Technical Guideline for the clinical trials of the oncolytic virus products emphasized methods of risk control in exploratory clinical trials for these products.

White Paper Podcast

Lorraine Marchand Headshot
Robert DiCicco Headshot
White Paper Podcast by IBM Watson Health
Future of Life Sciences: IBM Watson Health’s Vision for Smarter Healthcare
The global pandemic, even with its disruption and tumult, helped the healthcare industry rediscover that necessity is the mother of invention. “It probably catapulted the life sciences industry forward by at least five to 10 years,” suggests Lorraine Marchand, Vice President and General Manager, IBM Watson Health. But are we where we should be, and what’s next? Join us to learn how data and technology will shape the future of healthcare, and how IBM Watson Health plans to tackle some of the most critical challenges facing Life Sciences today.

Around the Globe

Decentralized Clinical Trials in APAC Here to Stay
Serene Ong
Marken APAC
Gaurang Majmudar

he face of clinical trials has been changing rapidly, and while decentralized clinical trials have been explored by the industry for many years, the COVID-19 pandemic has exponentially accelerated the shift towards such trials with increased urgency. The most dramatic shift in this direction has been on logistical and at-home services, as they were needed to support the ongoing studies.

Unanticipated deviations to clinical research protocols became unavoidable, as subjects were unable to attend study visits due to travel restrictions, clinic closures, and quarantine requirements. Regulatory bodies around the world were forced to quickly revise their regulations or guidances to minimize disruptions to clinical research.
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Around the Globe

Enhancing Patient Engagement in Clinical Trials by Pharmaceutical Companies and Patients in Japan
Atsushi Kitamura
Pfizer R&D Japan

atient engagement in clinical trials in Japan has been progressing steadily in the last few years. Pharmaceutical companies and patients who have not realized its value until recently have had more opportunities to hold discussions on clinical trials, with DIA contributing to and promoting such discussions. Currently, many pharmaceutical companies are trying to incorporate patient insight into their protocols and informed consent forms (ICFs). On the other hand, there remain a number of challenges to overcome in promoting these activities.

  • Environmental changes brought about by the COVID-19 pandemic have served as an opportunity for pharmaceutical companies and patients to communicate with each other.
  • A considerable number of pharmaceutical companies that have implemented patient engagement activities have examined ways of inviting the most appropriate patients to obtain input.
  • Obtaining patient insight is key in implementing decentralized clinical trials (DCTs) as a near-term solution to the COVID-19 pandemic and as a longer-term solution to make it easier for patients to participate in clinical trials. On the other hand, the process of utilizing patient insight from individual countries in global trials has not been optimized.
  • Medical institutions involved in clinical trials in Japan often use their own informed consent form (ICF) template. In this regard, it is necessary to explore ideas on how to implement patient-friendly ICFs at all clinical study sites.
  • To overcome these obstacles, cooperation of not only pharmaceutical companies and patient groups but also government and academia/medical institutions is indispensable.

White Paper Podcast

Thaddeus Wolfram headshot
Brandi Buzzetta headshot
White Paper Podcast by Matrix Medical Network
Decentralization Bringing Research and Patients Closer
As clinical researchers, like other professionals, learned to work virtually and remotely during the pandemic, the biggest impact on clinical trials might be summed up in the word decentralization. “A traditional clinical trial is focused around research sites and the principal investigators managing the trial. A decentralized trial flips the lens to fully focus on the participants. Instead of a trial being about a site, it becomes about a participant who’s actually living and breathing that trial, all day, every day,” explains Thaddeus Wolfram, Senior Vice President, Matrix Clinical Trials. “Equally important is removing or lessening that intimidation and hesitancy of signing up as a participant of a potential trial,” continues Brandi Buzetta, Matrix Director of Account Management. “Participants were hesitant to go to a large academic medical center. They felt intimidated. A mobile health clinic helps with not only awareness, but lessens that hesitancy to join the trial, too.”

Around the Globe

Interview with Saudi Food and Drug Authority (SFDA) CEO Hisham Bin Saad Al-Jadhey
Saudi Food and Drug Authority (SFDA) CEO Hisham Bin Saad Al-Jadhey
Saudi Food and Drug Authority (SFDA) CEO Hisham Bin Saad Al-Jadhey

rof. Hisham Bin Saad Al-Jadhey, CEO of the Saudi Food and Drug Authority (SFDA), outlines the SFDA’s key priorities under its current strategic plan. He also touches on why domestic pharma and medtech manufacturing is important to the SFDA, pricing issues for innovative new therapies, and the role of the Authority within the Saudi “Vision 2030” plan.

White Paper Podcast

RIM Whitepaper V2 and RIM Reference Model: Advancing Regulatory Science
In April 2021, the Regulatory Information Management (RIM) Working Group of DIA’s Regulatory Affairs Community issued Version 2.0 of the RIM Whitepaper that provides insights relating to 11 key regulatory capability areas including RIM implementation considerations, processes, and best practices. The Whitepaper also provides context for the RIM Reference Model in development. “One of the key aspects of the model is standardizing terminology and relationships between information,” explains IQVIA Senior Regulatory Affairs Director Donald Palmer in this conversation moderated by Ennov Director of Product Management Kathie Clark. “It puts the stake in the ground in terms of the basic data elements required to support regulatory in its business process and also other functional areas which depend on regulatory,” continues Venkatraman Balasubramanian, Senior Vice President, Life Sciences, Orion Innovation. “If we can put the best practices out there, we all align on the hope that this will allow industry to bring life-saving or life-improving medications and therapies to patients faster. We’re hoping to make a big difference,” concludes Pat Shafer, Managing Director, FTI Consulting.
We Are DIA
Clinical Research and Bioethics: Looking at COVID-19 as a Turning Point

he impact of the COVID-19 pandemic was palpable throughout the drug development pipeline. Many of the policies, practices, and principles that emerged during 2020 will continue to shape clinical research and drug development practices for years to come. In addition to operational hurdles, COVID-19 also brought us new ethical challenges that will continue to resonate throughout the drug development community.

White Paper Podcast

James McCormick Headshot
Melanie Owen Headshot
Patricia Mann Headshot
White Paper Podcast by PPD
Master Protocols: Expanding Research, Compressing Timelines
As an important tool in developing COVID-19 vaccines and treatments, the increased visibility of master protocols has added to interest from sponsors pursuing master protocols in other therapeutic areas. “This pandemic required transparency in drug development research outcomes and collaboration between regulators and drug developers. This necessitated rapid global adaptation of innovative trial designs, such as master protocols. Clearly, drug development has shifted based on that successful model,” suggests Pat Mann, Senior Director, Regulatory Affairs, PPD. “These designs allow study teams to flex midstream to add or remove indication cohorts, drug combinations, and to conduct other investigations in response to early findings without having to create a new study design, write a new protocol, or set up additional studies,” explains Melanie Owen, Senior Director of Early Development in PPD’s Hematology and Oncology Therapeutic Unit. “What is perhaps more relevant is that the development timeline can be compressed, as seen with the COVID crisis,” continues James McCormick, Senior Director, Regulatory Affairs, “thus empowering the sponsor with more information in a shorter timeframe to optimize their IP selection, target the therapeutic area, and deliver a meaningful clinical indication for the label.”
Career Column
Making Technology Personal
Enhance personal growth and career development
Megan Larison
Merck & Co., Inc.

uring the pandemic, many people recognized the need to significantly accelerate innovation to help ensure the future of our collective work, health, and advancements in medicine. Similarly, through developing a growth mindset and maximizing technology advancements, one can also evolve and enhance their personal growth.

We Are DIA
DIA Welcomes New Fellows and Congratulates Our 2021 Award Winners

New Fellows of DIA

Fellow Rebecca Vermeulen

Rebecca Vermeulen (Chair), Hoffmann-La Roche Ltd.

Fellow Peter Bachmann
Peter Bachmann, Federal Institute for Drugs and Medical Devices (BfArM) Germany
Fellow Guido Rasi
Professor Guido Rasi, Clinical Trial Center of Gemelli Polyclinic Institute; Tor Vergata University of Rome
Fellow Janet Woodcock
Janet Woodcock, US FDA

White Paper Podcast

Michael Agard Headshot
Franciska Darmer Headshot
White Paper Podcast by NNIT
Digital Business Transformation: Technology Plus Culture Equals Innovation
The power of emerging technologies and data (re)use can help organizations transform business processes, respond to rapid market development, and decrease time to market. “Transformation of the business is related to being able to reuse your data and your documents to optimize the process,” explains Michael Agard, NNIT Managing Consultant for US. “Most companies focus on their internal business users, meeting the needs of their requirements. It really takes an outward look to the patients and the investigators: How can we support their journey?” “We see data-driven technology-enabled clinical trial conduct as being core for how we want to use digital technology to improve our clinical development,” continues Franciska Darmer, Advisory Director, Global Head of Clinical, NNIT. “Technology is just one component of that transformation. It’s much more focused on developing a culture of ongoing innovation. Technology is there to enable us as part of the business transformation. It’s extremely important to focus on not just the technology, not just business transformation via optimization, but focus on developing this culture of innovation.”
Regulatory Affairs: The IND, NDA, and Post-Marketing Advertisement
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Views and opinions expressed in Global Forum are those of the authors alone and do not necessarily represent those of DIA or any other agency, organization, employer, or company. DIA does not guarantee the accuracy or completeness of any information published in Global Forum and will not be responsible for any errors, omissions, or claims for damages, including exemplary damages, arising out of use, inability to use, or with regard to the accuracy or sufficiency of the information contained in Global Forum.