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Applied Clinical Trials October 2021

New support models range from flexible software platforms, IROs, and DROs.

The Evolution of Site Selection

Thursday, October 21, from 4:30 to 6:00 p.m. MST

 – Southwest educational event will cover the Los Angeles, Dallas/Houston, Phoenix, Denver, Las Vegas areas with a specific focus on these therapeutic areas and medical conditions:

https://www.ciscrp.org/event/aware-for-all-southwest-virtual-event/

Events

AWARE for All Southwest — 10/21

THREAD, a technology and service provider supporting decentralized clinical trials (DCTs), has announced the company's expansion into the Europe, Middle East and Africa (EMEA) region to support location-specific clinical trials and meet the demand for global studies.

To support this global reach, THREAD opened an office in Dublin, Ireland in early 2021 and has hired more than 50 team members with plans to hire additional positions across Europe, including Ireland, U.K and Sweden, to amplify its regional presence.

More on THREAD’s expansion into EMEA Market

Articles

THREAD Expands into EMEA Market

Before the pandemic, a December 2019 Industry Standard Research survey found that 38% of pharmaceutical sponsors and contract research organizations (CROs) expected virtual trials to be a major component of their portfolios, and 48% expected to run a trial with most activities conducted in participants’ homes. One year later when attendees at McKinsey’s Clinical Operations Roundtable were asked the same questions, the responses were 100% and 89%, respectively.

Today, most are asking what trials and what aspects of trials can be effectively decentralized and to what degree. Fully virtual or decentralized clinical trials (DCTs) typically handle all enrollment processes and assessments in a patient’s home, enabled by end-to-end digital tools and involve the self-administration of medicines. This model is gradually migrating from smaller, early-phase and post-approval studies toward larger pivotal trials, such as Otsuka and Click Therapeutics’ landmark fully remote clinical 

 to investigate the effectiveness of digital therapeutics in reducing symptoms in adults diagnosed with major depressive disorder (announced in Feb 2021).

In the near term, sponsors, investigators, and CROs expect fully virtual trials to remain limited to a narrow set of use cases, such as a well-characterized drug with few adverse events in a mild indication, with end points suited to remote measurement. Long-term, however, fully virtual trials will be more widespread—especially in certain therapeutic areas such as rare disease, mental health, central nervous system, neurodegenerative and others that require patient populations that can’t physically travel or don’t live near a site. 

Ultimately, the therapeutic area alone shouldn’t determine a trial design. Rather, each trial should be designed for-purpose and centered on patients. The target patient population, treatment, and indication will primarily determine whether a trial is fully virtual, hybrid or a traditional site-based trial. Even so, there are defining patient population characteristics in many therapeutic areas that can make some studies more likely candidates for all-virtual research.

Here are five therapeutic areas that are particularly apt for an all-virtual research approach, and that can serve as an entry point for hesitant sponsors interested in exploring this growing DCT model.

 have diabetes and one in three or 88 million adults are prediabetic. Given the disease’s prevalence and its widespread geographic reach including many rural areas, diabetes is ripe for fully virtual research. Blood glucose values can be monitored continuously with wearable devices attached to the patient’s skin and automatically uploaded to a central platform in the cloud for easy access by trial investigators, sponsors, and the patients themselves.

In addition, the propensity of patients with Type two diabetes to be elderly or struggle with obesity can make it difficult for patients to travel to trial sites. These patients often have vascular problems which also can also hinder mobility. Further, diabetes is rampant in certain demographics such as Native Americans who are 

 to have diabetes as whites and often live in remote rural areas far away from the nearest clinician. Virtual trials bring lifesaving treatment to these patients and further the development of treatments that reflect the unique needs of a more representative population.

—With wearable devices, including Apple watches, that monitor increasingly more sophisticated and wider range of cardiovascular endpoints remotely, research focused on cardiovascular diseases are apt for a fully virtual trial design. These devices accurately monitor and measure cardiac events and catch issues, such as atrial fibrillation (a common type of sustained cardiac arrhythmia) and ventricular tachycardia (abnormally fast heart rate) to alert the patient and remote physician in real time. Even some clothing items, such as bras, have sewn-in heart monitors! There are other devices that can be worn continuously for months at a time to capture more sophisticated measurements and automatically send data into the cloud. The same is true when it comes to managing blood pressure.

Like diabetes, cardiac patients are in all corners of the world and often many hours from central research sites and—due to their condition—may have mobility challenges and concerns. Virtual trials extend access to the millions living with heart disease and high blood pressure. Further, the data gained from continuous and multiple-symptom monitoring of cardiac patients is dramatically more useful in comparison to the less-reliable, one-hour, single-symptom testing completed at a site once a month or every few months. Heart arrhythmia often occurs only intermittently so it may not be picked up at the occasional site visit. Today’s wearable devices monitor blood pressure, heart rate and rhythm, and oxygen saturation levels as well as activity level (steps taken) so researchers can superimpose different measurements depending on what endpoint is being studied or combine multiple measurements for more meaningful information.

Parkinson’s Disease, Multiple Sclerosis, Alzheimer’s disease, and other CNS diseases may dramatically impact patients’ mobility as well as hamper caregivers’ ability to bring affected loved ones to frequent clinician visits. All-virtual trials open these patients up to potential opportunities they might not otherwise ever have for a treatment.

Like cardiac wearable devices, there are an increasing number of new technologies that allow researchers to measure novel endpoints of patients in the comfort of their own homes and in more realistic life settings outside of a doctor’s office. Devices can continuously measure number of hand tremors per minute, for example, so a novel endpoint could be the reduction of hand tremors which was not as easily studied in traditional trials.

An electroencephalogram (EEG) is a widely used non-invasive method for monitoring the brain but has historically been a large and bulky technology, restricted to the monitoring of subjects in a lab or clinic while they are stationary. Today, we can use a wearable EEG, which overcomes these limitations and allows the long-term, non-invasive recording of brain signals at home.

—Like patients with CNS disorders, patients struggling with neuromuscular diseases, including Duchene Muscular Dystrophy may have severe mobility challenges that make it difficult to make regular clinician visits. Fortunately, there are advanced activity monitors that do not interfere with movement on these patients such as ankle bracelets that can record various measurements continuously to, say, show how much activity a person takes part in over a period. Red Nucleus Clinical’s iTakeControl platform is a clinically approved solution that enables HIPAA-compliant video assessments of patients, live video research visits and audio recording to provide richer audio/visual data that is also auditable for compliance purposes.

“We have used our platform in various ways across different clinical trials, but it has proven particularly effective in trials of boys with Duchenne Muscular Dystrophy,” explained Chris Jones, partner at Red Nucleus. “Rather than forcing parents to spend hours on the road or in flight for site visits, leaving everyone exhausted, iTakeControl platform allows parents to administer video patient assessments at home that can be reviewed by an objective clinician and quantified as clinical evidence.”

According to Jones, the video assessments also provide recorded evidence that can be compared over time to assess change. This is especially important in neuromuscular disorders where changes can be ambiguous or imperceptible to an untrained eye. Disease area expert researchers can review the videos to look for the smallest fluctuation in movement or function. “We can assess and compare pediatric developmental milestones, like communicating or playing with blocks, over time,” he added.

The technology has also been used to assess validated instruments, such as the Clinician Global Impression of Change or Severity, for real-world function data that is meaningful to the trial. “We can also conduct live video tele-research visits between researchers and participants and their caregivers within a GCP-compliant application that includes components seamlessly integrated with the study including an audit trail and recording options,” explained Jones.

—Chronic obstructive pulmonary disease (COPD), asthma, and other pulmonary diseases share common characteristics that lend themselves to fully virtual trials. Virtual Contract Research Organizations (VCROs) can engage patients through central virtual sites and leverage advanced HIPPA-compliant technology platforms to capture all necessary information that’s automatically uploaded in the cloud. This is especially prevalent for patient recruitment, where remote coordinators (nurses, principal investigators, research assistants) engage with patients via telemedicine or secure video to interview patients and review medical records to determine trial eligibility and obtain informed consent.

Remote monitors can be worn by pulmonary patients to capture breathing patterns, coughing episodes, and oxygen saturation measurements in real time and continuously for more meaningful information. Additionally, patients can use clinically compliant apps on their mobile devices to record how they are feeling compared to using clunky paper questionnaires. These apps can be programmed to remind patients to complete their ‘homework’ to reduce the burden and use symbols or leverage games to help pediatric patients comply. All collected information from the app will then be fed into the central virtual site platform for review by the research team, yet the patient never leaves the comfort of their home.

The same is true for sleep disorders like sleep apnea or insomnia. Connected devices that monitor oxygen saturation can be used anywhere and the data collected can be automatically uploaded to the cloud. Withings, for example, has a clinically compliant Sleep Tracking Mat that tracks and analyzes sleep cycles (deep, light and REM), heart rate, and snoring. Withings can also monitor the intensity of breathing disturbances, thanks to an algorithm that analyzes interruptions in breathing patterns that occur during the night. Patients not only benefit from staying in their own homes during a trial but also see their own symptoms’ impact on night sleeping.

Today, nearly every therapeutic area performs clinical research where at least some aspects can be decentralized. Even certain aspects of complex oncology trials can be decentralized to improve patient access and data capture. For instance, the National Cancer Institute’s Cancer Moonshot program funded a DCT managed by Medable calledthe Digital Biomarkers for Clinical Impact (DigiBioMarC) study. This study aims to understand and improve the quality of life for patients receiving cancer therapy.

Even so, DCTs are still relatively new to many life sciences sponsors and researchers, causing some companies to be cautious. The COVID-19 pandemic forced many companies to leverage more virtual approaches to research, and many promise that there is “no going back” to traditional trials. The advantages that research virtualization can bring to key therapeutic areas must be carefully considered by each sponsor, researcher, CRO, and academic institution as they evaluate what approach, or combination of approaches, is most effective for their purpose.

As the industry becomes increasingly comfortable and knowledgeable about virtual research and DCTs, this new model will become more mainstream. The advantages to both researcher—i.e., faster patient enrollment, richer real-world data, use of digital biomarkers—and patient—i.e., more access to life-changing treatments, less burden, faster results—are simply too important to ignore.

“Globally, the clinical research landscape will increasingly incorporate new technologies into their trials,” concluded Jones. “COVID cracked open a new mindset across the entire life sciences industry where even the wary are embracing digital innovation to advance healthcare. The future looks bright.”

is Co-founder and Chief Medical Officer of Curavit

Five therapeutic areas that are apt for an all-virtual approach, and that can serve as an entry point for sponsors who are hesitant yet interested in exploring the growing DCT model.

Decentralized Clinical Trials: What Therapeutic Areas are Ripe for All-Virtual?

The Bristol Myers Squibb Foundation, together with its partners, National Medical Fellowships and the American Association for Cancer Research, has announced the first group of 52 physicians selected for its Diversity in Clinical Trials Career Development Program. The early-stage investigators are the first of 250 community-oriented clinical trialists who will be trained through the program by 2027.

The 52 physicians selected by an independent selection committee are an accomplished group working at a broad range of healthcare institutions in 22 states across the U.S. The physicians include 34 women and 18 men who represent a diverse cross section of races and ethnicities and bring a widely varied perspective and range of experiences to the program, as well as to their therapeutic focus areas of cancer (hematologic or solid tumors), immunologic disorders and cardiovascular diseases.

The first cohort of scholars will begin their two-year participation in October 2021 with a program orientation, followed in early November by a six-day intensive educational workshop on clinical research, called 

BMSF-AACR Design and Implementation of Clinical Trials Workshop

Diversity in Clinical Trials Career Development Program

Bristol Myers Squibb Foundation Diversity in Clinical Trials Career Development Program Announces First Group of Physicians

Mary Costello, Head of Site and Investigator Network at Medable, and Pat Larrabee, CEO of Rochester Clinical Research, discuss their extensive careers in the clinical trials industry, as well as talk about their article in our October issue, “

Podcasts

Mary Costello, Head of Site and Investigator Network at Medable, and Pat Larrabee, CEO of Rochester Clinical Research, discuss their extensive careers in the clinical trials industry, as well as talk about their article in our October issue, “Why Siteless Trials Won’t Work.”

Keeping Sites at the Center of Clinical Research

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

This column has commented previously—and occasionally scathingly—about the gap between words and action on personalized medicine in Europe, but a new straw has appeared in the wind that may mean something more substantial will emerge than the customary rhetoric.

It isn't the planned European Partnership on Personalized Medicine, reported on here last March. For all its fine aspirations, the latest update on its genesis is a disappointment. A "basic information" website for the project reports: "No network description provided." It lists participants as "0", countries involved as "0", joint calls as "0", funded projects as "N/A" and period as "N/A". According to the official EU website, the start is now scheduled for 2023/2024—adding merely "more details will be provided at a later stage".

Nor is it the EU-backed IC-Permed, whose next step is to hold—in early November—the first “ICPerMed family meeting”, which "aims to explore cooperation and synergies" in "different areas of personalized medicine" and "possibly other related projects." Besides establishing a forum for discussion, the aim—says an IC-Permed announcement—is "to harmonize future activities, to expand cooperation and to jointly develop strategies for fostering PM research and implementation of PM approaches in healthcare and health systems." So not exactly a fast-track operation there…

Not much either can be expected in the near future from the EU's new pharmaceutical strategy, currently stuck in a seemingly endless round of consultations and impact assessments. Although the outline is full of warm words about how "personalized therapies dramatically improved the prognosis of patients with some cancers", citing trastuzumab, or how "initiatives such as the ‘1+ million genome’ are exploring ways to access genetic data with the potential to improve disease prevention and allow for more personalized treatments". There is a promise of a legislative proposal in 2022 – which will no doubt take at least a year, and probably more, to turn into legislation - that would include "flagship initiatives on innovation", including personalized medicine. And there are plans for access to 10 million genomes across borders for personalized medicine by 2025. But that all remains for the present in the lap of the EU gods.

Even the European medicines agencies' strategy for 2025, while positive about the concept, is non-committal in its approach. Commenting on "innovations in patient-centered healthcare, and precision/personalized medicine", it says these "often do not fit properly into existing regulatory systems” and suggests only that "protecting public health while providing a regulatory environment that can support such steps towards precision medicine is key if EU patients’ needs are to be better addressed."

The clue in fact springs not from the familiar world of EU medicines policy, but from the more robust realm of EU data policy. It comes in the shape of an announcement at the beginning of October that the Council—that is, the ministers of the EU member states—has agreed its position on a draft law known as the Data Governance Act. The agreement means that the Council can now start negotiating the final shape of this critical piece of legislation with the European Parliament – the co-legislator in the EU. In short, this opens up the prospect of stronger European data-sharing mechanisms. As the Council said in its announcement, "The aim is to promote the availability of data that can be used to power applications and advanced solutions in artificial intelligence, personalized medicine, green mobility, smart manufacturing and numerous other areas."

The outcome should be easier access for the reuse of certain categories of protected public-sector data—including on health, and an increased trust in data intermediation services. This will give a much-needed boost to the EU efforts to bring digitalization and data use into practical operation—prizing open the door to the wealth of information that constitutes one of the fundamental resources of shifting personalized medicine from an idea into a reality. The fact that this announcement comes within the framework of the EU's data policy makes it all the more encouraging, since – with no disrespect to the many EU officials working in the health area – the EU's data policy is flying, because there is a strong legal base and plenty of budget and political momentum for it, while EU health policy remains hobbled by its absence of any real place in the EU treaties, reluctant member states, and piecemeal budgeting.

Now, of course, it will be necessary to follow up these—and other health- and medicine-related—developments in EU data policy, and that is yet another task for the clinical trial community already burdened with keeping up to speed with a constantly-changing evolution of regulatory and legislative challenges in Europe. This column can't promise to solve all those challenges—but it will, in its own modest way, do whatever it can.

A new straw has appeared in the wind that may mean something more substantial will emerge than the customary rhetoric...

Is Personalized Medicine Finally Gaining Traction in Europe?

Medidata, a Dassault Systèmes company, has announced that Translational Drug Development (TD2), a precision oncology contract research organization, has signed an agreement to adopt Medidata’s Rave CTMS (Clinical Trial Management System) and eTMF (electronic Trial Master File) solutions, offerings within Medidata’s Unified Platform.

Rave CTMS aims to address struggles that study teams experience in trying to manage and oversee clinical trials due to the fragmented and rapidly changing trial ecosystem. In 2021, Medidata released enhancements to Rave CTMS including ad hoc reporting and proactive risk management support.

TD2 and Medidata Partner in ClinOps

In the face of a host of contentious and controversial policy decisions, President Biden appears poised to bring in an experienced and well-regarded hand to lead FDA. The agency has lacked a permanent leader for more than eight months, as the White House has been unable to identify a new commissioner acceptable to the politicians and interest groups on all sides.

So, as the clock has ticked down on the Nov. 15 deadline for Janet Woodcock to vacate her acting commissioner role, potentially forcing Biden to appoint another acting commissioner, word is out that the White House will name cardiologist and research pro Robert Califf to the top job, a position he held for almost a year at the end of the Obama administration.

Califf’s appointment will bring much-needed stability to FDA as it contends with a host of difficult policy decisions involving vaccines, new anti-COVID therapeutics, access to e-cigarettes, accelerated approval programs and budget priorities. Califf may face opposition in the Senate, as partisan politics has come to the fore on all sides. Although hewins plaudits for his experience in medical research and his familiarity with FDA operations and requirements, some consumer advocates and liberals criticize his close ties to industry and pro-development attitude. He will need support from Republicans, which may be more tenuous in today’s hotly divisive climate on Capitol Hill.

Another factor driving the FDA nomination is the recent announcement of retirement plans by Francis Collins, long-time director of the National Institutes of Health (NIH). Biden will want to name a new leader for NIH before the end of the year, and that provides an opening to bring a woman scientist into the administration’s health and science leadership cadre.

Hopefully, the politicians will recognize the importance of experienced leadership for the nation’s leading health agencies and put aside partisan politics to agree on a new FDA commissioner, and then a new leader at NIH. FDA has been well-served by acting commissioner Woodcock, but her tenuous position has exposed her to criticism and second-guessing on all sides. With a global pandemic still raging, a seasoned hand is needed to stabilize FDA’s exhausted workforce, ensure funding continuity, and steer debate and decisions on many difficult scientific and policy issues.

Rumor has it the White House will name cardiologist and research pro Robert Califf to the top FDA job, a position he held for nearly a year at the end of the Obama administration. But he may face opposition in the Senate.

Can Califf Bring Clarity and Enhanced Credibility to FDA?

 joined Castor as Chief Clinical Development Officer and 

 as Chief Financial & Development Officer.

AiCure has added the following new senior team members: 

, as Senior Director of Digital Biomarker Development; 

as Director, Strategic Partnerships; and 

Curavit Clinical Research announced the appointments of 

Worldwide Clinical Trials announced the appointment of 

, as Vice President, Scientific Solutions, Hematology & Oncology.

 as the company’s Executive Vice President, Clinical Data and Digital Services.

 as the company’s first chief marketing officer.

Anju Software hired a new Vice President of Operations, 

 to run its FM71 study in Eastern Europe and the USA.

 platform is the industry’s first patented trail-audited real-time risk-based quality management system.

PHASTAR was announced as a joint winner of the 

2021 Innovation in the Management of Clinical Data Award

 by the Association for Clinical Data Management.

Anju Software has been named by Gartner as a sample vendor in four categories in its 

2021 Hype Cycle Life Sciences Research and Development report

Elligo Health Research was named winner of the 

 at Society for Clinical Research Site’s recent 2021 Global Site Solutions Summit for their virtual AI-powered clinical trial engagement assistant, Root.

The latest industry happenings of the last month, all in one place.

People and Business News — 10/21

Considerations for sponsors outside of the UK and the EU27

“Move to EU to avoid Brexit costs, firms told.” This was the news in UK a couple of weeks after the signing of the Trade and Commerce Agreement, as reported by 

 The recommendation, directed at all companies of the United Kingdom that export to the European Union (EU), also applies to sponsors of pan-European clinical trials located outside of the new EU27—such as the United States.

Whether it be the location of the legal representative, the submissions of applications to responsible regulatory agencies, the pharmacovigilance duties to assure the safety of medicines, or the delivery of Investigational Medicinal Products (IMP) to clinical sites: After Brexit, new procedures must be set in place to address all these aspects. There is plenty of guidance information available. Both the European Medicines Agency (EMA) and the British Medicines and Healthcare products Regulatory Agency (MHRA) are continuously publishing and updating relevant information.

 In this article, we summarize the most important changes for sponsors located outside of the EU27 that wish to conduct clinical trials of medicinal products in the EU27 and the UK (Figure 1).

 Considerations for Sponsors outside of the UK and the EU27. Additional ways for submissions and reporting in Europe after Brexit have increased the workload to conduct an international trial taking place in the UK and EU.

Starting with the location of the sponsor or legal representative of an EU clinical trial: US pharmaceutical companies have traditionally looked to the United Kingdom for competent and capable partners to conduct clinical trials in Europe owing to the ease of communication that the shared language brings. Unfortunately, solely UK-based CROs can no longer conduct clinical trials in the EU on behalf of sponsors from the US or other non-European locations. EU law demands that the sponsor or legal representative be established in the EU.

In contrast, EU Sponsors or CRO partners based in the EU can conduct a clinical trial for medicinal products in both the EU and the UK. In 2019, in its Human Medicines (Amendment etc.) (EU Exit) Regulations,

 the UK introduced an approved countries list that defines where a clinical trial sponsor or their legal representative may be established to be allowed to conduct a clinical trial for medicinal products in the UK. This list initially includes all EU and European Economic Area (EEA) countries and will be reviewed at least every three years by the British government.

Acting as legal representatives for non-EU sponsors—whether from the UK or other parts of the world—CROs must be legally integrated in the EU to be able to conduct clinical trials there. UK-based CROs must establish a presence in the EU if they do not want to be left out.

Over the lifecycle of a clinical trial, various submissions such as initial applications, substantial amendments, or end of trial notifications must be made. Sponsors or CRO partners of clinical trials for medicines in the EU27 and UK are responsible for these submissions. They can no longer solely use the EU portals—currently still the Common European Submission Portal (CESP) and, from Jan 31, 2022, onward, the Clinical Trials Information System (CTIS). Instead, they must use the British MHRA gateway, as the MHRA is now the standalone medicines and medical devices regulator for the UK.

Similarly, the EU/EEA and the UK are now separate regulatory entities with regards to drug safety. Thus, parallel reporting through the appropriate channels in the EU (EudraVigilance gateway) and UK (MHRA gateway) is necessary.

Accordingly, marketing authorization holders have increased responsibilities in terms of assuring the ongoing safety of marketed products in both regulatory systems. They are required to keep two pharmacovigilance system master files (PSMF) up to date. And although the UK allows the qualified person for pharmacovigilance (QPPV) to be located in the EU or EEA, it is still necessary to define a national contact person for pharmacovigilance in the UK.

CROs representing sponsors in clinical trials taking place in both the EU and the UK therefore have a higher workload, as an additional regulatory agency must be addressed.

Time and costs for IMP logistics between EU and UK

An important issue for sponsors is how to ensure continued and unrestricted supply of IMPs to the clinical trial sites. Sponsors of EU and UK clinical trials that import IMPs into Great Britain from outside the UK must reassess their study supply chains after Brexit. They are required to create assurance systems to control whether the IMPs have been duly certified by a qualified person (QP), before release of the IMPs to trial sites. The UK will continue to recognize QP Certification of IMPs from countries on an approved list, which currently includes all EU and EEA countries. As for the abovementioned list of accepted countries for the sponsor’s location, this list of approved countries will also be subject to review at least every three years, introducing a new level of uncertainty in the long-term planning of clinical trials.

For the export of IMPs from Great Britain to the EU, on the other hand, sponsors must organize a new importer and batch releaser, plus a new QP declaration. The only workaround for this is to have the IMP manufactured in Northern Ireland and then ship it to the EU, as it is then not considered an imported IMP under the Northern Ireland Protocol.

This issue will be for CROs coordinating the logistics of the IMP supply to deal with. The simplest scenarios are those in which the IMP is manufactured, packaged, and distributed either in the EU or the UK alone. Sponsors wishing to ship IMPs between the EU27, and the UK should factor in the longer timeframes and additional organizational issues at the very beginning of planning the clinical trial.

Small parenthesis: business as usual for data protection

At the end of June 2021, the European Commission determined that the UK provides an adequate level of data protection and formally adopted adequacy decisions for the UK under the General Data Protection Regulation (GDPR). These allow for the continued unrestricted personal data flow from the EU to the UK. Personal data flows in the opposite direction also remain unaltered, as the British government has similarly decided not to impose additional safeguards. With regard to data protection issues, no adaptation is required by sponsors or CROs after Brexit, regardless of whether they are UK or EU-based.

CTIS simplifies submissions, but not in the UK

As early as in 2014, the EU members adopted the clinical trials regulation (Regulation (EU) No 536/2014), which provides for the central submission of study applications and of documents for European studies. Since the end of 2014, a clinical trial application for multinational studies in the EU can be submitted in accordance with the Voluntary Harmonized Procedure (VHP). In a single submission, a sponsor can simultaneously submit a clinical trial application to the competent authorities in all participating member states of the European Union. But the VHP is only an intermediate solution for a centralized submissions system. On January 31, 2022, the new EU-hosted portal, Clinical Trials Information System (CTIS), will go live. The EMA website states that “CTIS will become the single-entry point for clinical trial application submission, authorization and supervision in the EU, and in the European Economic Area (EEA) countries Iceland, Liechtenstein and Norway.” Through CTIS, sponsors and/or their CRO partners will be able to apply for clinical trial authorization in up to 30 EEA countries with one single application. The same requirements and deadlines will apply to all EU member countries, resulting in a harmonized electronic submission and assessment process for clinical trials conducted in multiple member states. With CTIS, information sharing will be ensured and decision-making processes between and within member states will be expedited. The activation of the new portal will allow Clinical Trials Regulation (Regulation (EU) No 536/2014) to come fully into force at the beginning of 2022—thereby making it easier for trials to be conducted in the EU across multiple member states and making the EU much more attractive for sponsors worldwide. As submissions in the UK will have to be carried out separately via the MHRA, they will not benefit from the simplifications provided by the new CTIS system.

In summary, the workload to conduct an international trial taking place in the UK and EU has become heavier. Whereas Brexit has increased the complexity of conducting pan-European clinical trials including the UK, in the EU the Clinical Trials Regulation will make it easier for trials to be conducted across multiple EU member states.

As every clinical project is different, sponsors must carefully select the right European countries in order to bring the clinical trial to successful completion. This success depends on many aspects, including not only the availability of patients in the respective countries but also the availability of dedicated investigators and the treatment praxis.

 The UK is still an important player from a health economics point of view. Nonetheless, sponsors will not automatically include the UK in their clinical-program-planning and will always evaluate whether the extra effort involved is worth it.

Additionally, regardless of a certain level of economic integration assured by the EU-UK Trade and Cooperation Agreement concluded in late December 2020, insecurities about a stable British partnership remain that may also affect clinical research. Sponsors and CROs should keep a watchful eye over future legislative changes in the United Kingdom. One thing is certain: Planning and successfully performing clinical trials in the EU and UK involves higher costs and more work after Brexit. Sponsors from the US and other non-European countries should take this into account at the earliest possible time point when planning their clinical program for the EU.

, DVM, is Chief Executive Officer and Founder, all of SSS International Clinical Research.

Article (British government officials advise companies to expand to EU.)

https://www.theguardian.com/politics/2021/jan/23/brexit-hit-firms-advised-government-officials-set-up-shop-in-eu

https://www.ema.europa.eu/en/about-us/brexit-uk-withdrawal-eu/brexit-related-guidance-companies

The Human Medicines (Amendment etc.) (EU Exit) Regulations 2019, SI 2019/775

Interview with Lars Behrend from 21.07.2021 by P. Ledesma, Sofpromed, https://www.sofpromed.com/sss-cro-for-clinical-trials-in-germany/

A summary of the most important changes for sponsors located outside of the EU27 that wish to conduct clinical trials of medicinal products in the EU27 and the UK.

Featured Content

Applied Clinical Trials October 2021

The Evolution of Site Selection