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Applied Clinical Trials June 2021

 as Senior Vice President and Managing Director of its global Clinical Services business.

 as Global Head of TalentSource Life Sciences.

 as Executive Vice President of Clinical Research, and 

 as Senior Vice President of Commercial Affairs.

 as Executive Vice President, General Manager, EMEA.

Worldwide Clinical Trials, Inc. announced the promotion of 

 as Vice President of Scientific Strategy and Innovation.

Signant Health announced the appointments of 

 as their Internal Chief Diversity Officer.

 announced the launch of its 2021 International Fellows Program.

 announced an expansion underway at its headquarters in Allentown, Pennsylvania, making the campus to over 300,000 square feet.

 announced continued rapid adoption of its decentralized clinical trial platform to power COVID-19 studies globally.

 is among the top 3 CROs by the number of clinical trials launched in 2020, according to the Russian Registry of Clinical Trials.

 announced that Calyx RIM has supported over 100 COVID-19 vaccine authorizations.

Articles

The latest industry news of the past month, all in one place.

People and Business News — 6/21

Egnyte announced a new product for emerging life sciences companies to manage regulated documentation. Egnyte for Life Sciences Quality is a GxP-compliant product that digitizes the lifecycle of regulated documents, like standard operating procedures (SOPs) and training records. Egnyte for Life Sciences Quality is the third product in a growing lineup of offerings, following the release of Egnyte for Life Sciences in November 2020 and new review and approval workflows.

Egnyte for Life Sciences Quality enables Life Sciences companies to:

Perform e-Signatures: sign off on documents, like SOPs and clinical trial protocols, in a compliant manner, without needing third-party plugins.

Manage effective documents: as new versions are approved, Quality teams can define version numbers for new drafts, set expiry dates, and ensure only effective copies are available.

Scale compliance processes quickly: built with best practices gleaned from 17,000 global customers, Egnyte for Life Sciences Quality implements and validates as it integrates with existing IT infrastructure.

Support for multiple departments and use cases: designed with the ability to support training, continuity, and site readiness documentation.

Egnyte Releases Quality Document Management Offering

Medidata, a Dassault Systèmes company, has announced the launch of the Medidata Decentralized Clinical Trials (DCT) Program, a comprehensive set of unified, secure technologies that enable full decentralization across the clinical trial continuum. Drug, vaccine, and medical device developers (sponsors) and contract research organizations (CROs) can take advantage of the platform offering on the market which combines:

Technology and workflows to virtualize patient participation

Tools that facilitate sponsor oversight of patient safety and data quality

Direct-to-patient services, including facilitation of delivery of study drugs to the home

To date, Medidata has applied its decentralizing technologies across more than 44,000 clinical sites around the world in multiple languages involving more than 600,000 patients with a wide array of illnesses.

Medidata to Offer DCT Platform

Dr. Theodore Leng, MD, Medical Advisor to Verana Health and Director of Clinical and Translational Research at the Byers Eye Institute at Stanford, Stanford University Medical School, speaks about a recent study he led and presented in early May at the Association for Research in Vision and Ophthalmology Meeting.

Podcasts

Dr. Theodore Leng, MD, Medical Advisor to Verana Health and Director of Clinical and Translational Research at the Byers Eye Institute at Stanford, Stanford University Medical School, talks about a recent study he led and presented in early May at the Association for Research in Vision and Ophthalmology Meeting.

Recent Study Brings RWD Front and Center

Clinical trial diversity inclusion has recently been at the forefront of FDA’s initiatives. Sponsors have adopted diversity in clinical trials through 

more traditional methods, such as engaging advocacy groups.

 However, the pandemic has fueled clinical trial decentralization, and some enterprises have used decentralization methodologies to increase clinical trial diversity inclusion by going deep into diverse communities. In this interview, Thad Wolfram, President, Matrix Clinical Trials SVP and Head of Clinical Trials at Matrix Medical Network, will discuss his experiences.

The need for more diversity in clinical trial participant populations is long overdue. From your experience, how has

diversity in clinical trials improved over the last year,

and what can we expect in the future moving forward in a post-pandemic world?

 It’s been known for quite some time that there’s a lack of diversity among clinical trial participants, but it really wasn't until COVID-19 shined a light on the lack of equity around healthcare, as well as the lack of diversity in clinical trials, and what that could mean for a potential vaccine and treatment, that regulators finally stepped in. This put additional pressure on sponsors, along with public pressure on diversifying participant populations, and I. In response, several sponsors presented new landing pages around diversity in clinical trials and new recent strategic statements, saying, "“We're only going to partner with those who have their own strategy for addressing this.” We, as a society, and the regulators and the industry, as a society and the regulators, and the industry, we all recognized the problem and knew we needed to solve this moving forward.

Matrix Medical Network brought clinical trials to

underserved communities during the most critical times throughout the pandemic. How did you connect with these communities to encourage enrollment,

pockets that reject clinical trials and reject new medicines, especially vaccines?

 I think first, it ties back to the fact that Matrix has seen some hesitancy amongst the underserved populations because of how they have been treated in past clinical research. We were able to talk to and educate folks on what's happening with COVID-19, since, as an enterprise, we were also part of screening and testing, and eventually become a part of vaccination efforts. Similarly, we were a part of clinical trial efforts. Our ability to run small, compact mobile health clinics allowed us to cover a lot of much ground within urban areas to get to these underserved populations as well as, for instance, large mobile health clinics out on Native American reservations helping reach those communities. So, I think it’s the combination of the reach, the flexibility, the fact that we really value our relationships with the folks in those communities, and our ability to build trust and confidence in what we're helping to bring to them that allowed us to have such a strong impact.

Let’s talk more about that education around clinical trials and the vaccine.

As a decentralized clinical trial healthcare provider, could you talk about some of the initiatives

 One of the challenges, historically, and this goes back to the diversity aspect for trials, is there's a lack of awareness of the availability of a clinical trial. We’re bringing all that information to underserved communities to promote that dialogue. We start with local community leaders to really help them to understand what we’re doing with patient recruitment for a clinical trial, specifically, how we go about that and what value clinical trials bring. One of the examples I like to give is if you take oncology, for example, for a patient who doesn’t have any other treatment options available, a clinical trial can actually become a treatment option for them. We’re helping to look at ways we can bring those treatment options to the underinsured, the uninsured, and to populations that otherwise would not have that option of care. We’re helping to facilitate those local conversations around what a clinical trial really is, how we can help individuals and what it can mean for their livelihood.

Can you tell me about the benefits of using mobile health clinics for recruiting patients and conducting clinical trials? What are the shortcomings?

 From a benefits perspective, the first is that it allows us to meet a patient anywhere, and that which really does help. For these underinsured and uninsured populations that are not going into a physician's office, they don't have a physician who is talking to them about a clinical trial to frame it as something they can take part in. So first and foremost, it's it’s about enabling the conversation to happen, to give them any line of sight into a clinical trial. And the mobile health clinic gives us provides us with that mobility to get into the community and enable conversations that otherwise wouldn’t have happened. That's That’s one of the big significant benefits; just providing the awareness, access, and the opportunity. There are some risks and some downsides. For instance, we are limited to whatever tests, imaging, or screening we can bring along with us. To mitigate for that, one of the things we're we’re working on is to figure out how can we figuring out how we can further diversify the breadth of screening we bring into the community to support the broadest patient population possible.

talking about Matrix initiatives, could you tell me

about how those initiatives and priorities are coming how those initiatives and priorities come

into clinical trial design, particularly in the mobile setting?

 Decentralized trials saw a great tremendous shift in adoption during the last year or so. When a participant is in a clinical trial. Historically, when a participant is in a clinical trial, they’re taking place at a research center. And so, the historical view is really based around this idea of a site, an investigator, and the research taking place. Now, we’re at a pivotal point where we’re shifting the paradigms to recognize that a clinical trial takes place 24 hours a day, seven days a week, wherever the participant is. And so, what we're we’re doing with the decentralization of trials is we're following that patient, whether they’re at a site, whether they're at home, whether we're we’re managing a virtual visit, or whether we're monitoring with wearables, the trial is always happening. What the mobile health clinic does is it offers yet another lever, if you will, that we can pull around the flexibility of the trial to meet the needs of the patient experience. If the participant isn’t comfortable with us going into their home, the mobile health clinic allows us to bring the clinic to them. We can set up a clinic in an area that otherwise wouldn’t have a research site, which allows for allowing several people to participate at once via that clinic. We wouldn’t want COVID-positive patients going into a medical facility, so we operated as a contained extension of that site with strict safety protocols to be able to enable these trials to happen, but in the safety of that environment. It's all about the flexibility of a trial.

Speaking of the flexibility of trials, can you tell me about the challenges that sponsors faced

in the beginning of the pandemic and what was so challenging with implementing decentralization through virtual techniques or through the decentralized techniques that at the beginning of the pandemic and what was so challenging with implementing decentralization through virtual techniques or through the decentralized

 Over the last five to 10 years, there have been many different capabilities and techniques that have been brought into the market that there’s this huge vast, fragmented ecosystem. At the beginning of the pandemic, many trials were flat out halted. Many trials were flat-out halted at the pandemic’s beginning because the participants couldn't couldn’t go into a research site. Other trials that were intended to begin were delayed or halted stopped because recruitment couldn't couldn’t take placeoccur in an in-person environment. I think sponsors see our capability to quickly shift to the best option and adapt a trial design or protocol to take advantage of decentralized capabilities as a huge benefit. Secondly, it’s beneficial to work with regulators, to really understand what the regulators would accept,to understand what the regulators would accept because the downstream risk was always regulatory acceptance. We saw regulators also willing to say, "We’re going to learn through this process. We’re going to actually to understand what does and doesn't work through decentralization.” I think what we're we’re seeing coming out the other side is a lot of adoption willingness. We have sponsors, CROs, and regulators who have learned what we can do and where it does work.

that things are opening up again, of course,

do you see a shift back? Do you see a hybrid? Where do you see decentralization fitting in here?

 I think sponsors, CROs, and regulators learned so much over the last year about what we can do and what we can do differently. What we do on a clinical trial, even from a standard-of-care perspective, even from a standard-of-care perspective, what we do on a clinical trial generally reflects what the standard-of-care in the real world looks like. The other thing that's that’s happened this year is that everyone has gotten much more comfortable with virtual visits and with not needing to necessarily go into the doctor's office go into the doctor’s office necessarily. We’re really at a jumping jumping-off point where we're we’re going to continue to build on this decentralization. And I think that while there will always be gold standards in clinical trials that are tied to traditionally run trials wrapped around clinical research sites, I think at a minimum, hybrid studies between site-based and decentralization is here to stay, and it's it’s only going to grow moving forward.

, MBA, MSF, is a thought leader and expert in the application of business analytics toward clinical trials, and Editorial Advisory Board member for and regular contributor to Applied Clinical Trials

Thad Wolfram, President, Matrix Clinical Trials SVP and Head of Clinical Trials at Matrix Medical Network, speaks about his experience utilizing decentralization methodologies to increase clinical trial diversity inclusion by going deep into diverse communities.

How the Pandemic Facilitated Clinical Trial Diversity Inclusion

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

Growing evidence of deficiencies in clinical trial reporting in Europe has impelled the authorities to—somewhat dilatory—action, and discussions on how to improve the situation are now beginning among national regulators, the European Medicines Agency and the European Commission.

The move was prompted by a recent letter from transparency and health campaigners that documented widespread failures by trial sponsors to meet the requirements for reporting results. This alleged that more than 4,000 clinical trials of medicines—nearly a third of all trials undertaken in Europe—are missing results on the European trial registry, in violation of long-standing transparency rules. The University of Amsterdam has run 195 drug trials, but marked only 14 as completed—and posted results for none of them. Germany, France, Italy and Spain also stand accused of regulatory inaction, with data from EMA in late 2019 showing that results were missing for over 500 applications linked to drug trials involving children in those countries.

The letter, to the Heads of Medicines Agencies—the national regulators in the EU, urged the creation of a process to ensure that national competent authorities adopt and implement common minimum standards for promoting sponsors’ compliance with clinical trial results reporting requirements. "Despite significant improvements in sponsor compliance in recent years, thousands of due clinical trials are still missing results," it said. "The persistent failure of many sponsors to meet their obligations indicates that the European medicines regulatory system is currently neither effective nor efficient," it continued. It suggested that even minimal engagement by national authorities could rapidly improve sponsors’ compliance rates.

The Heads of Medicines Agencies have now confirmed that they discussed the letter, and there was wide recognition of "the importance of the sponsors fulfilling their obligation to make trial results public." However, the responsibility under European law lies with each national regulator, and “HMA is not in a position where the organization can impose standards on the national competent authorities.” So, it promised to "reach out to the European Commission and the European Medicines Agency with a view to initiate joint actions to improve clinical trial sponsors’ compliance."

TranspariMED, a civil society organization that has played a leading role in tracking non-reporting, welcomed the HMA engagement, while urging it to immediately provide a forum for national regulators where common standards could be developed for following up on unreported trials. Till Bruckner, founder of TranspariMED, said his organization "hopes that HMA will now actively work towards the creation of a regulatory system that no longer idly stands by when rules are broken, taxpayers’ money is wasted, and patients’ interests sidelined.”

He added that some national medicines regulators are already acting. He cited Denmark and Austria as recent examples where attention has led to significant improvements in trial reporting. But he raised questions over how energetic the authorities were being in Germany, France, Italy, Spain, the Netherlands, Belgium and Ireland. Bruckner says that the failings often result from ignorance among sponsors of the reporting requirements, and that national authorities could achieve some easy improvements simply by issuing alerts: many regulators are not even contacting those that break the rules, let alone enforcing compliance. “Running a single clinical trial can cost millions of Euros, but that money is wasted if the results are never made public. Is it really too much to ask regulators to send out a few hundred reminder letters to prevent valuable medical knowledge from being lost forever?” he asked.

The pressure for change is backed by Cochrane. It's Karla Soares-Weiser pointed out that without access to reliable information from all clinical trials, the evidence base on which to make judgements is incomplete—which "limits the scientific community’s ability to learn from research findings and can lead to patients being harmed.” Bettina Ryll, founder of Melanoma Patient Network Europe, another signatory to the initial letter to HMA, said that protection of future patients is being neglected, and "regulators must stop turning a blind eye."

Allegedly more than 4,000 clinical trials of medicines are missing results on the European trial registry, in violation of transparency rules. 

Putting the Squeeze on Trial Reporting Failings in Europe

 BIO Digital 2021 will spotlight biotech’s transformative role and impact on today’s four key challenges – COVID, social justice, the economy and climate change.

https://www.bio.org/events/bio-digital/schedule-overview

Events

BIO Digital 2021 — 6/14-18

FDA’s surprise decision this week to approve Biogen’s treatment for Alzheimer’s disease has raised serious questions about the validity and value of the agency’s accelerated approval process. The 

 Aduhelm (aducanumab) based on data from one clinical trial that shows some effect on reducing amyloid beta plaques in patients with mild cognitive impairment. Unlike most surrogate markers supporting early approval, that effect has not been linked to clinical benefit, challenging its validity for anticipating patient gains.

The broad labeling approved for the new drug, moreover, has generated heated debate among scientists, researchers, patients, and payers as to the long-term impact of the approval decision on the credibility and independence of FDA decisions. Coming in the wake of an assessment of several cancer therapies that gained accelerated approval but failed to document long-term benefit, the decision has raised questions about approving new drugs and biologics based on preliminary evidence of possible benefit that awaits later confirmation. FDA emergency use authorizations (EUAs) for some questionable and harmful anti-COVID-19 treatments already have eroded public confidence in the scientific and medical validity of some agency actions, and many research leaders fear this recent decision will heighten those concerns.

The very high price tag set by Biogen for the treatment also is heightening the debate over pharmaceutical costs, reimbursement, and prescribing. In setting a price of $56,000 a year, way above the cost-effective threshold of $2500 to $8000 calculated by the Institute for Clinical and Economic Review (ICER), Biogen stands to earn some $17 billion a year from the drug, according to Wall Street analysts, particularly with a label that opens prescribing to both early and severely debilitated Alzheimer’s patients. All eyes are on how Medicare and health and drug plans will set coverage parameters and how doctors and medical authorities will identify those individuals most suitable for treatment. 

 the drug’s appropriate use and insurance coverage at a meeting on July 15, 2021. Biogen says it has begun to negotiate value-based contracts with major payers such as Cigna and CVS Health to support access to the drug. But just how the parties will link payment to treatment outcomes remains to be seen.

 was launched in the 1980s to provide early access to treatment for dying AIDS patients with no available treatment. Since then, it has been used to speed approvals of new therapies, primarily for AIDS and cancer where validated surrogate markers have provided evidence that a drug has potential for curbing disease. Many accelerated approval products have been able to document continued benefit from post-approval studies, building support among industry sponsors and patient advocates for the process. Some consumer groups and health care providers, though, complain of long delays in confirming benefit and have questioned the often high cost of paying for unproven treatments.

 of its Oncologic Drugs Advisory Committee to evaluate supplemental indications for several leading cancer therapies where confirmatory trials provided only limited evidence of ongoing clinical benefit. Although FDA revoked the added indication for only one product, it continues to examine these therapies and to struggle with the difficulties in conducting postapproval trials. Biogen is not expected to provide confirmatory data from a postapproval study for years, if not decades, further undermining the accelerated approval paradigm.

It remains to be seen whether the flexibility applied by FDA reviewers to the new Alzheimer’s drug reflects a broader, less rigorous approach to approving treatments for devastating conditions with urgent need of treatment. The significance of FDA’s action is apparent in a personal message from Patrizia Cavazzoni, director of the Center for Drug Evaluation and Research (CDER). She notes that 

CDER reviewers carefully vetted highly complex data

 to reach its conclusion that the surrogate endpoint is “reasonably likely” to predict clinical benefit. Cavazzoni acknowledges “residual uncertainties” about the drug and its potential for reducing clinical decline from Alzheimer’s disease, but critics maintain that this and earlier studies show no link between reducing amyloids in the brain and improved health. In basing its approval on “potential benefit,” as opposed to clear clinical benefit, FDA has angered and confused both its critics and advocates.

Some industry analysts predict that this more flexible approval standard will drive a surge in R&D for additional Alzheimer’s drugs as well as other experimental treatments for rare and lethal diseases. Several leading pharma companies are testing new Alzheimer’s treatments that also aim to reduce amyloid in the brain or to clear other invasive substances. But many scientists fear that approvals based on limited evidence of clinical benefit may generate confusion and uncertainty that only deters investment in R&D.

One outcome, though, is that FDA analysts and pundits no longer will assume that agency reviewers will follow the recommendations of its advisory committees, as usually is the case. The advisory committee that assessed the Biogen drug last November voted almost unanimously against approval based on the limited evidence of effectiveness, but FDA reached its own conclusion.

FDA’s approval of Biogen’s treatment for Alzheimer’s disease has raised questions about the agency’s accelerated approval process.

New Alzheimer’s Drug Heightens Debate Over FDA Accelerated Approval Process

BIO Digital 2021 will spotlight biotech’s transformative role and impact on today’s four key challenges – COVID, social justice, the economy and climate change.

BIO Digital 2021 — 6/10-6/11

Following a three-month review of vulnerabilities in the US supply chain for products important to national security, the Biden administration has rolled out a broad initiative to promote domestic production of critical materials, including medicines and their ingredients. The initiative calls for the Department of Health and Human Services (HHS) to establish a public-private consortium for advanced pharmaceutical production to strengthen domestic competitiveness and supply chain resilience in this area.

A detailed report presents strategies for preventing supply chain disruptions in several key industrial sectors. The broader aim is to ensure ready access for U.S. manufacturers to semiconductor chips, rare earth elements and large capacity batteries for electric vehicles, as well as pharmaceutical ingredients.

 Such gains will bolster America’s economic and national security and address transitory supply chain challenges. Continued US dependence on key pharmaceutical products and active pharmaceutical ingredients (APIs) from overseas has been driven by pressures to lower costs, the report acknowledges, a situation that leaves the medical supply chain vulnerable and warrants new approaches to support domestic production.

FDA acting commissioner Janet Woodcock applauded the announcement, noting that the COVID-19 pandemic revealed “just how vulnerable the supply chain is” and that it is “essential for the national and health security and economic prosperity of the United States.”

 The report recommends actions long backed by Woodcock and other FDA officials, including a boost in local pharmaceutical production, R&D to advance innovative manufacturing technologies, robust quality management maturity to support reliable drug manufacturing, and leveraging data to improve supply chain resilience.

To start, the HHS consortium will select 50-100 critical drugs from the “essential medicines” list established by FDA, as part of an earlier federal initiative.

 The aim is to advance the development of novel platform technologies for domestic production of active pharmaceutical ingredients (APIs), particularly those for widely used generic drugs. The initiative will be able to tap $60 million provided by the American Rescue Plan to spearhead investments in advanced manufacturing technologies, such as systems with on-demand manufacturing capabilities, to increase production of key pharmaceuticals and ingredients.

FDA anticipates playing a prominent role in advancing these and other supply chain resiliency initiatives and is working with other HHS agencies to develop a further plan for designing and building the long-term capability for US manufacture of supplies to combat future pandemics and biological threats.

 And to increase transparency of product sources throughout the pharmaceutical supply chain, HHS will seek legislative authority in two areas:the ability to track API sourcing and production by facility, and a requirement that all pharmaceuticals sold in the US identify the sources of APIs and finished dosage forms on labeling.

The supply chain security report acknowledges that the shift of drug manufacturing overseas, particularly for generic drug APIs, has reduced US costs by trillions of dollars in the past decade, but has left the American health care system vulnerable to shortages of essential medicines. Change is needed, as the COVID-19 pandemic has highlighted the critical importance of a resilient US healthcare manufacturing sector and of the nation’s ability to rapidly develop and strengthen production of vital vaccines and medical products.

https://www.whitehouse.gov/briefing-room/statements-releases/2021/06/08/fact-sheet-biden-harris-administration-announces-supply-chain-disruptions-task-force-to-address-short-term-supply-chain-discontinuities/

https://www.hhs.gov/about/news/2021/06/08/biden-administration-recommends-policy-changes-secure-us-pharmaceutical-supply-chain.html

https://www.fda.gov/about-fda/reports/executive-order-13944-list-essential-medicines-medical-countermeasures-and-critical-inputs

https://www.fda.gov/media/143406/download

https://www.fda.gov/about-fda/reports/executive-order-14017-americas-supply-chains

The Biden administration has rolled out a broad initiative to promote domestic production of critical materials, including medicines and their ingredients.

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Applied Clinical Trials June 2021