The COVID-19 pandemic has hampered the conduct of clinical trials significantly and still creates unprecedented challenges to date. Phase I studies with healthy volunteers are particularly affected as uncertainty on viral spread among the population may call into question safety concerns and potential impact clinical data quality.

Complete lockdown forced stoppage of any new activity

When the pandemic struck in March 2020, stringent government regulations all over the world forced many countries to go into lockdown. As all non-essential movement was forbidden, many businesses were forced to close and everyday activities were reduced to the essentials. Life science companies and clinical trial facilities were
no exception.

Regulatory agencies published guidance on how to manage clinical trials, stating that priority was to be given to COVID-19 studies, in turn slowing down and even halting non-COVID-19 trials. The feasibility and immediate necessity of starting a new clinical trial needed to be
critically assessed.

As a consequence, our SGS Clinical Pharmacology Unit (CPU) in Belgium was closed at the start of the crisis to ease the burden on the healthcare system as much as possible. This meant that the recruitment of any new cohorts was completely put on hold and only minimal activity (necessary for subject follow-ups in ongoing trials) was allowed.

Reopening SGS Phase I unit by adopting COVID-19 risk implementation plan

Following the first pandemic’s peak, with the case rate falling, government restrictions became less stringent. And SGS CPU management reached out to the FAHMP (Federal Agency for Medicines and Health Products) through BAPU (Belgian Association of Phase I Units) to obtain the green light for restarting clinical activities. This would only be granted providing SGS CPU could organize all activities in compliance with local pandemic-related regulations. Therefore, to ensure a safe re-opening of the unit in alignment with rules set by the government, regulatory authorities, local hospitals, the local ethics committee and SGS’s company policy, a COVID-19 risk implementation plan was created.

The local hospital’s Board of Directors and our ethics committee were approached to review the COVID-19 risk implementation plan. Special focus was given to assessing the hospital’s situation, ensuring subject safety could be maintained using hospital facilities, while avoiding the risk of overloading emergency departments and intensive care units. Based on the scheduled trials, the risk of adverse events was evaluated to be low, therefore all parties agreed to SGS CPU re-opening. From June 2020, SGS CPU restarted clinical trial activities (in close collaboration with our clients) at a reduced capacity in line with social distancing guidelines.

The COVID-19 risk implementation plan was based on three key factors, 1) to avoid the potential spread of the virus, 2) to ensure the safety of the trial participants, staff, and visitors, 3) to ensure the quality of trial data.

Hygiene measures were set up for subjects, visitors, and staff, in line with government recommendations. These included regular hand washing and disinfecting with alcohol gel, compulsory wearing of face masks, and social distancing of 1.5 meters (5 feet) at all times. To highlight distancing measures, floor stickers were used to create one-way routes through the facility. Additional measures for staff included signage on doors displaying maximum capacities for offices and meeting rooms. Extra chairs were also removed to avoid exceeding the maximum capacities across the facility. And the staff was instructed to work from home whenever possible.

One precautionary measure was adapting standard operational activities to minimize the risk of potentially infected subjects accessing the site. Telephone interviews prior to visits were introduced using structured questionnaires. Additionally, each CPU reception area was equipped to measure temperatures. Following evaluation, bed capacity was reduced by 20 beds, and plastic screens were put in place where applicable.

Now, instead of the standard screening process, subjects are provided with the Informed Consent Form (ICF) and the CPU in-house rules via email before arriving at the unit. Individual screening appointments are foreseen.

Similarly, upon admission, subjects are invited to individually scheduled appointments. Each ward in the SGS Phase I unit has also been reorganized to enforce a one-way traffic system, with particular attention paid to disinfecting toilets, bathrooms, dining and recreation rooms, and fixed furniture across wards.

To reduce the number of people present at the unit, audits and data monitoring are organized remotely as much as possible. As a rule, the number of monitors, visits, and the length of time in the monitoring room is limited to a minimum. Using eSource in our unit, most data can be
reviewed remotely.

An important asset to control and mitigate the risk of viral spread is consistent COVID-19 testing. After the first pandemic peak, SGS CPU expanded its capacity of state-of-the-art PCR (BioFire, FilmArray), so that testing for SARS-CoV-2 can take place on-site, with results available within one hour. No longer relying on external partners for results has allowed large-scale testing to take place, which has proven invaluable when handling Belgium’s second COVID-19 wave in November 2020.

Upon every admission onto the site, routine SARS-CoV-2 testing is performed, and volunteers are only admitted after a confirmed negative result. During in-house stays, any individual possibly displaying COVID-19 symptoms is immediately isolated, evaluated by a physician (which can also be done by phone outside of working hours), and is nasally swabbed for PCR testing. When the test result returns negative, the subject returns to the ward. If positive, the subject must stay in isolation within the CPU, and the investigator and sponsor mutually evaluate the subject’s safety and continuation in the trial. This means the subject can remain quarantined at CPU for safety reasons or can be sent home to go into quarantine. Follow-up visits can be scheduled as soon as deemed safe. Even though no high-risk contact occurs within the unit, given the permanent preventive measures, all low-risk contacts are still traced and tested as appropriate.

Similarly, staff is instructed to stay at home when feeling the slightest viral symptom or when having had a potential high-risk contact. The medical team then decides on the testing strategy and follow-up steps.

All these steps have been summarized in a decision tree that visualizes the appropriate course of action in the case of a suspected COVID-19 infection within the unit, for both trial subjects and staff.

After the unforeseen lockdown during the first pandemic, the unit reopened implementing a series of measures to assure safe operational activities in uncertain times. Facing the second wave in November, the risk mitigation plan proved to be efficient as only 0.54% of all tests performed were positive, with only 0.27% of tests occurring during clinical trial conduct but with no impact on safety or data quality. The remaining tests occurred during follow-ups and at the end of the trials. It must be noted that during this period, the weekly ratio of positive tests in Belgium reached a peak of 29.2% and 19.2% in Antwerp.

Currently, entering 2021, the positivity ratio has declined again to 5.3% and 4.8% for Belgium and the Antwerp region respectively. However, as a lesson learned, governments are weary to loosen rules too quickly and a semi-lockdown situation is still the default in most European countries, including Belgium. Also, at our CPU, we continue to work with the highest precautions and risk mitigation in place.

Clinical trials are essential, and continuation must be ensured. As infection rates seem to go up and down in waves, and new viral mutations cause concerns, COVID-19 risk mitigation will be part of our common practice for some time. Measures may change in line with the epidemiological situation, but general approaches of social distancing and hygiene appear to stay for the foreseeable future. Only now, with vaccination campaigns being rolled out at speed, can we start looking forward to a more normal life hopefully after the summer.

Medical Director, Clinical Pharamcology Unit, SGS Life Science Services

Articles

Feature Articles

Life sciences companies challenged by need to minimize health risks without sacrificing data quality during pandemic.

Impact of COVID-19 on Phase I Clinical Activities

A prominent goal for biopharmaceutical research has been to broaden the range of participants in clinical trials to fully assess the impact of new therapies on different ethnic, racial and age groups. FDA has pressed for more inclusive research programs for drugs and medical products for decades to enhance the understanding of how medications affect certain populations differently. An early aim was to reverse established limitations on testing new products on women and both very young and elderly patients. More recent policies aim to offset years of under-enrollment of minority groups by expanding enrollment criteria, including more research sites in minority communities, and engaging investigators with diverse backgrounds. The visibly high impact of COVID-19 on minority populations in the US has focused added attention on the importance of including racial and ethnic minorities in clinical trials for pandemic vaccines and therapeutics.

Over the years, FDA has issued multiple guidance documents to encourage broader data reporting on research subjects of different races and ethnicities. In November 2020, the agency spelled out a range of strategies in a final document on 

“Enhancing the Diversity of Clinical Trial Populations”

. It supports broader eligibility criteria for Phase III studies and outlines ways to make it easier for individuals to participate in clinical studies, such as utilizing adaptive trial designs and enrichment strategies to facilitate broader ethnic group participation.

The importance of more inclusive clinical trials, moreover, has been emphasized for developing drugs and biological products for combatting COVID-19, as seen in a broad 

 issued in May 2020. This advisory, which FDA staffers have augmented several times over recent months, supports a range of strategies for studying drugs and medical products during the pandemic, such as arranging for more decentralized clinical trials, fewer clinic visits, virtual check-ups, alternative monitoring processes, and remote data collection and informed consent processes. FDA extended these policies to early stage clinical trials and cites international standards for conducting diverse research developed under the International Council for Harmonization.

New vaccines to combat the pandemic similarly should test these critical products on a broad spectrum of patients, FDA advises in a June 2020 guidance that spells out regulatory expectations for assessing vaccine manufacturing processes and facilities and both nonclinical and clinical data. The agency specifies that to ensure that vaccines are safe and effective for all indicated populations, 

sponsors should enroll individuals most affected by COVID-19

, specifically racial and ethnic minorities, elderly individuals and patients with medical comorbidities. And subsequent 

 published in October 2020 to clarify data requirements for requesting an Emergency Use Authorization (EUA) for a COVID vaccine notes the need for broad clinical data for a medical product intended to be administered to millions of individuals. The intense public focus on the conduct and results from vaccine clinical trials prompted sponsors to take steps to meet expectations in this area; some trials were even halted at times due to difficulties in attracting sufficient numbers of minority patients to participate.

FDA has also sought to promote research diversity through its Drug Trials Snapshots program, established in 2015 to increase the visibility of clinical trial enrollment by age, sex, ethnicity and race. Under this program, the Center for Drug Evaluation and Research (CDER) posts a brief “snapshot” on demographic participation in clinical trials for each newly approved new molecular entity and biologic therapy. According to a recent report on the program’s impact, though, there still may be a ways to go for clinical trials to reflect the diversity of the US population.

 shows that while participation by sex has become evenly balanced in recent years, and sponsors are including more elderly patients, most studies still enroll relatively low percentages of Black, Asian and Hispanic patients.

The Snapshot report and related issues were discussed at a recent FDA 

 on Diversity in Clinical Trials. Richardae Araojo, FDA associate commissioner for minority health, emphasized the importance of more inclusive clinical trials to reduce distrust of medical treatment by minority groups and offset vaccine hesitancy.

View from Washington

FDA emphasizes importance of inclusion in trials.

Diversity in Clinical Trials Gains Ground Amidst COVID

One day after his inauguration, President Joe Biden unveiled a lengthy program for combatting COVID-19 by ramping up distribution and inoculation of millions of Americans over the next three months. This comprehensive pandemic response began with the President signing a packet of executive orders that expand COVID-19 testing and required mask-wearing on federal property and in public transportation and makes wider use of the Defense Production Act (DPA) to reduce shortages of supplies such as protective equipment, lab equipment and vaccine production and delivery materials.

One of the initial executive orders signed by Biden calls for issuing a high-level plan for developing and testing promising COVID-19 treatments. The President calls for the secretary of Health and Human Services (HHS) and the director of the National Institutes of Health (NIH) to devise a plan supporting large-scale randomized trials and other studies able to identify promising treatments that can be “easily manufactured, distributed, and administered, both domestically and internationally.” In emphasizing the need for randomized trials, the provision highlights the administration’s emphasis on relying on science in medical decisions, as opposed to the promotion of untested products by the Trump administration.

 of the National Strategy, which seeks to mitigate spread through expanded masking and testing and an increased medical workforce, also supports accelerated research and clinical development of new treatments. Starting with a comprehensive preclinical drug discovery and development program of treatments that can be readily scaled and administered, it also calls for diverse clinical trials to ensure that new therapies address the needs of communities of color, children, pregnant women, and high-risk populations. And it aims to improve access to more affordable, high-quality treatments by preventing shortages through investment in advanced biopharmaceutical manufacturing, advanced purchase agreements, and strengthened surveillance systems.

The comprehensive vaccination campaign also supports ongoing vaccine R&D as a way to bolster vaccine access. Important goals are for the government to fund research and testing of vaccines for adolescents and children and the development of formulations that may be easier to deliver and administer. To assess whether current vaccines remain effective against new viral strains, NIH, FDA and BARDA will evaluate the need to alter current vaccines. FDA is cited as key to authorizing effective vaccines for rapid delivery, for assessing emerging viral mutations, and for establishing recommendations for dosing and expanding vaccine supply.

President unveils lengthy program for combatting COVID-19 immediately following inauguration.

Biden Pandemic Plan Highlights R&D Support

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Applied Clinical Trials, January/February 2021 Issue (PDF)

The COVID-19 pandemic has severely impacted the conduct of clinical trials back years due to restrictions on in-person visits to investigator sites. Over the past 11 months, the industry has responded with an accelerated adaptation to decentralized trial methodologies.

In December 2020, Decentralized Trials & Research Alliance (DTRA) was launched to unite trial stakeholders with a mission of to make trial participation more accessible by advancing policies and best practices. In this interview, co-conveners of DTRA, Amir Kalali, MD and Craig Lipset discuss the new alliance as well as how COVID-19 has impacted the industry.

Andy Studna: How did the idea for starting DTRA first come about?

 Craig has been actively leading and advocating for decentralized research for more than a decade now, while I have been supporting convening and knowledge-sharing on decentralized trials for years through the CNS Summit. These conversations have been thoughtful and productive, but barriers to meaningful adoption have remained. We founded DTRA to go beyond the conversation by creating a neutral and sustaining space for collaboration to address the barriers to decentralized research. As a result, the organization and our approach draw on my experience in global clinical development, and creating non-profit and neutral collaborations, Craig’s experience in decentralized trials and leading consortia in clinical research, and both of our trusted networks of leaders that seek to go farther together.

AS: Would you have come up with the idea for DTRA if COVID-19 had never happened?

 Actually, like it has done in so many cases, COVID-19 complicated the effort. Planning for DTRA preceded the pandemic, COVID-19 delayed the DTRA in several ways as leaders in the field were heavily focused on executing study continuity strategies across the biopharmaceutical industry relying upon decentralized research tools. By mid-year, however, the urgent need for the benefits that could result from DTRA’s collaborative effort was clear, and leaders were ready to step forward.

AS: How do you anticipate achieving maximum collaboration between stakeholders involved in clinical trials?

 I think that our ‘big tent’ approach is an accelerator for collaboration. While some collaborations convene a single stakeholder group in order to address their specific challenges, DTRA is a multi-stakeholder initiative, which includes regulators, pharma sponsors, service providers, technology companies, site networks and patient organizations. Among our first needs as an organization was to establish our priority areas, a process which could have been challenged by our stakeholders potentially having highly divergent needs. But the priorities for decentralized research across stakeholders proved to have a remarkable degree of consistency, which provided DTRA with a shared vision and strong focus moving forward.

AS: What problems within clinical trials do you think COVID-19 has amplified and how can they be solved?

 Well, it’s clear that COVID-19 has underscored how fragile the clinical research enterprise can become–and it has contributed to that fragility. Despite the degree of shared resources and infrastructure across the sector, no single stakeholder owns or controls all of the components necessary for a successful drug development program. And, when pandemic-related lockdowns took hold across the globe, many study sites were unable to remain open and research participants were unable to leave their homes for study visits. But the research community was able to maintain continuity by drawing on other stakeholders that stepped forward, and embracing decentralized research solutions that had been available, but had struggled for adoption. We think this experience demonstrates how collaboration makes our shared ecosystem stronger, reduces risk, and drives progress.

AS: What are your goals for DTRA moving forward?

 DTRA goals include progressing shared solutions to common challenges while creating a community among the leaders in decentralized research, and to that end, the membership of DTRA has identified four priority areas. These include definitions, removing the ‘Tower of Babel’ created through sector—or organization-specific jargon by commonly endorsed archetypes of decentralized research, as well as key performance indicators. We must also use our collective experience to understand and share best practices that reduce risk and improve decentralized trial execution.

 They also include gathering data and information from across the community to promote knowledge sharing/education by providing educational resources for all stakeholders to improve awareness and appreciation for the impact of decentralized research; and identifying and removing remaining barriers to the global conduct of decentralized research, charting pathways to resolution. It’s truly exciting to see the dedicated support for these priorities and the collaborative effort needed to move forward from a group that now includes more than 100 committed stakeholders.

is an Assistant Editor for Applied Clinical Trials. He can be reached at

Co-conveners of the newly formed Decentralized Trials & Research Alliance, Amir Kalali, MD and Craig Lipset discuss the alliance as well as how COVID-19 has impacted the industry.

New Alliance Seeks to Bring Increased Accessibility to Trials

COVID-19 has radically transformed society and has especially transformed the potential for drug development’s acceleration. For rare and ultra-rare disease populations, the pandemic has shown these groups the potential to create, test and conditionally approve an effective therapeutic for a disease that’s killed over 400,000

 Americans as of January 2021. While an infectious disease is biologically different from a genetic disease, the framework of rapid development, testing and conditional approval is one that can be used by society to advance therapeutics for orphan and
rare diseases.

The concept of rapid prototyping, testing and approval for small populations is one that Cure Rare Disease has pursued for its rare and ultra-rare disease patients who lack effective treatments since its start in 2018. Cure Rare Disease is a unique organization–a nonprofit biotechnology company dedicated to creating an ecosystem supportive of N=1 (or a few) drug development–an ecosystem including payer reimbursement and clear guidelines from our regulators.

Key to this ecosystem’s development is the interdisciplinary collaborative network that Cure Rare Disease forged. A collaboration that includes leading academic investigators, preclinical, regulatory and manufacturing expertise alongside disease luminaries. Rather than traditional clinical trials with a varying number of patients, the therapeutics under development are designed to remedy the individual’s genetic mutation–starting with the neuromuscular disease class. These N=1 (or a few) trials will forgo the traditional placebo–a questionable practice for fatal pediatric diseases with well-established natural history–and instead treat the pre-treated individual as a control when combined with rich natural history data. Improvements or stabilization of the disease’s progression are the ultimate determinants of success and are driven by both biomarker and functional endpoints based on the individual. This means that for non-ambulatory patients there will be no exclusion from participation but rather a trial whose endpoints are centered on upper-limb improvements and pulmonary capacities alongside increases in dystrophin (in the case of Duchenne muscular dystrophy) protein. The freedom to experiment with new and potentially impactful endpoints is an advantage of nonprofit drug development–a chance to experiment with the status quo in hopes of finding a better alternative that allows more patients to participate rather than be excluded based on factors out of their
own control.

As a lean organization, the power of collaboration has continued to catalyze the speed of therapeutic development. An example of this is the ability of the team to understand how one’s role as a collaborator contributes to the primary mission downstream rather than a more traditional silo structure of talent with barriers separating discovery to preclinical development and beyond. Through a collaborative structure, individual therapeutics are designed in a holistic manner with inputs from downstream processes such as manufacturing and regulatory support inputted into the initial construct design aimed at avoiding pitfalls further down the development path and ultimately save the most precious resource to patients: time.

Though a young organization, Cure Rare Disease is preparing for its first clinical trial in 2021–a single patient CRISPR-based transcriptional activator targeted to rare mutation on the dystrophin gene for a 25-year-old patient. As a first-in-human for this therapeutic modality, the speed with which this drug was designed is notable. The approach began in 2018 with an initial muscle biopsy. By 2019, proof of principle was established and by 2020 proof of efficacy was shown in-vivo. Engaging the FDA from an early time point helped to paint a confident development roadmap as did the trailblazing work from an earlier program led by Dr. Timothy Yu at Boston Children’s Hospital.

 Through this collaboration, a new way of advancing life-saving medicine is born–a furthering of the template first forged by Dr. Yu in an effort to define a path for families, academics and clinicians to treat even a single patient impacted by a genetic disease.

Behind the first patient are several other patients with varying genetic deletions and duplications –primarily on the dystrophin gene but not exclusively. In using the first patient as a proof of concept for not only the modality but for the framework, Cure Rare Disease marches forward with a trove of experience and insights regarding the development of tailor-made (mutation-specific) therapeutics. It would be a disservice to the collaborative network not to mention the lengths to which these collaborators are willing to go to support this vision–all giving some to support the growing realityof customized therapeutics.

The collaboration has led to additional questions that seek to challenge the status quo regarding the potential for investigators and drug developers to innovate in how preclinical testing and development are done. Concepts from as the potential for 2D and 3D tissue modeling in lieu of an animal model to test efficacy to common delivery platforms in the case of AAV reducing the need for repetitive vector toxicology. These concepts are those that the regulators and NIH are now considering

 and concepts that Cure Rare Disease is putting into action to shift from the theoretical to the practical.

Essential to a patient-centric collaboration is the patient and patient family. Through Cure Rare Disease’s drug development program, the patient and patient family are key contributors to enabling the successful development of a customized therapeutic. Patient families are required to contribute biological samples to enable the research team to understand the mutation, its break points and other aspects as if a custom drug is to be developed, the target needs to be well defined and characterized. Beyond the contribution of biological samples, the patient and patient families are kept frequently informed of progress in an effort to reduce the anxiety and uncertainty that families face in the race to develop a therapeutic. Ultimately, the goal is to have an aligned team aware of the challenges and unified around the singular goal of developing a customized drug.

The outbreak of COVID initially forced drug makers to shift R&D focus and delay non-COVID clinical trials even though disease progression does not slow. Now almost a year later, the drug development industry has become far better at managing development and clinical trials that are in-part remotely conducted. For Cure Rare Disease, which began as a virtual company, the segue into a forced virtual environment was a relatively seamless one as it relates to preclinical development. Rather than conducting efficacy studies through our academic collaborators, it became essential to shift these studies to facilities deemed exempt in order to maintain continuity of research. Zoom and Microsoft Teams became even more essential technologies to allow our multi-national collaboration to continue to drive progress.

While preclinical development was able to be shifted with limited impact, two areas that were not as fortunate in the current climate are logistics and clinical operations. In shipping high-value materials domestically and internationally, the already-stressed shipping channels proved to be challenging. It was here that extreme attention to detail became especially important. For Cure Rare Disease, this meant continuously tracking various shipments in coordination with the recipient party and even a Christmas Eve FedEx handoff to ensure material integrity. As the world begins to return to “normal”, issues surrounding shipping and logistics will likely be reduced but the learnings remain that contingency plans are critical when time-sensitive materials are on the move–insurance, extra packaging, dedicated resources to tracking and resolving issues as they arise and a clear line of communication between the senders and recipients.

Beyond the logistical challenges that COVID-19 has brought came the potentially larger challenge of conducting clinical trials. For Cure Rare Disease, patients undergo immune suppression to enable the delivery of AAV-mediated therapeutic. Therapeutic administration is conducted in either the PICU or the ICU. During the height of COVID-19, ICUs across the US became inundated with COVID-19 patients thereby forcing the delay of gene and cell therapy trials. A recent report by McKinsey cited that 45% of respondents (cell and gene therapy companies) expected delays of 3-6 months on average for development programs.

 Diving into the details, delays regarding site activation for clinical trials, patient recruitment for trials and follow up appointments of enrolled patients were top areas of delays with 55% of respondents citing these three areas as delayed.

While these delays are temporary, the lessons learned from the COVID-19 experience are not. Lessons such as allowing virtual trials visits informed by diagnostic tests being done locally rather than having the patient go to a clinical trial site thereby limiting visits, trial burden and potential exposure (even in a post-COVID world). For instance, to what degree is it possible to have trial participants have diagnostic scans and blood draws done in their hometown (or nearby city), and then have that information transmitted to the trial site for accumulation for the trial sponsor? This is known as decentralizing clinical trials. This suggested change may ultimately benefit the trial sponsor in enabling greater enrollment for families who previously would not enroll due to the trial burden and traveling. Only time will tell but COVID has brought an opportunity to challenge traditional status quos.

In the same light as modifying clinical trials so too is the need to discuss the advancement of regulatory thinking as it relates to therapeutic development. With overlapping phased trials and streamlined preclinical development conducted for COVID-19 vaccine trials–to what degree can we apply these lessons to future efforts that are not directed at infectious diseases but rather genetic diseases? A piece of the answer lies with the flexibility that the incoming FDA commissioner will have vs. his or her predecessors. Under Commissioner Scott Gottlieb, MD, the FDA approved a record number of novel drugs, especially for orphan indications. Several of the learnings from COVID-19 will likely not be applicable to drug development such as the parallel tracking of clinical trials; however, components such as regulatory flexibility are ingredients that may well be applicable to rare disease broadly to help speed development, especially as it relates to bespoke drug development (N=1). Another aspect that could be considered for adoption is the increased leveraging of real-world evidence (RWE) by analyzing real-world data sources as was seen with COVID therapeutic and vaccine development and accelerating this initiative. These learnings present only a subset of the opportunities available for implementation into non COVID-19 drug development efforts moving forward.

Ultimately, COVID-19 has presented an opportunity for drug development to reimagine the status quo. As the saying goes, necessity breeds innovation and society stands at a cross roads now to conduct business as usual or attempt to adopt these painfully garnered learnings to improve the speed with which drugs are developed, tested
and approved.

https://www.nytimes.com/interactive/2020/us/coronavirus-us-cases.html

https://cen.acs.org/business/Milasen-drug-idea-injection-10/97/i42

https://fnih.org/what-we-do/programs/bespoke-gene-therapy-consortium

https://www.mckinsey.com/industries/
pharmaceuticals-and-medical-products/our-insights/
covid-19-and-cell-and-gene-therapy-how-to-keep-innovation-on-track

Non-profit biotech organization Cure Rare Disease utilizes collaboration amidst COVID-19 pandemic to catalyze speed of therapeutic research.

Improving Drug Development for Rare Patients Post-COVID

I could promise that I’m not going to write another editor’s letter this year about decentralized trials, but I don’t make promises I can’t keep. While so many issues related to COVID’s impact on clinical trials rise to the top of the news stream, it has pulled decentralized trials along its wake since the pandemic’s start. I can promise, however, that we are encouraging contributors to rise above the urge to blanket everything under the decentralized trials-per-COVID umbrella. We are much happier to offer the readers of 

 actual, concrete solutions or dialogue that furthers the conversation. We can keep pointing to the past, but not learning from that past and putting lessons into future practice, the industry runs the risk of falling back into reactive clinical trial habits.

Because of recent sponsored projects, the editors are privy to information we can’t attribute yet on decentralized trials, but safe to say, many industry stakeholders are open to change and to further the cause. Observations include:

The pandemic has truly accelerated the adoption of patient-centric technologies, as well as expectations for accelerated timelines.

Leaders that believe in taking action and who enable adoption of technologies or practices is essential for the industry—or at least their organizations—to thrive.

When the regulatory decisions on submissions during the COVID timeframe are made, many will look to those as signals for FDA readiness.

At press time, we are putting the final touches on 

“Clinical Trials Operational Successes Post COVID-19”

. The event is live on February 11 and 12. If you can’t make it, however, the symposium will be available on-demand, and we encourage you to watch at your leisure. You can also submit questions on-demand, and they will be forwarded along to the respective presenters for their response.

For the rest of the year, any topic we write to will include a component of COVID. For example, site feasibility will include aspects of ensuring sites can recruit participants from a diverse population, as indicated by the need borne out of COVID vaccine trials. Patient centricity and diversity again would not be complete without including the natural outcome of patient-centric solutions expected to take deeper roots post-COVID.

2021 has just begun, but thankfully, it looks like a promising year.

 is Editor-in-Chief of Applied Clinical Trials. She can be reached at 

From The Editor

A look forward to 2021 for the clinical trials industry.

2021 Promises for Clinical Trials

, when the impact of the COVID-19 pandemic was in its early stages. Voices from stakeholders, including vendors and other organizations are presented, along with data from recent surveys. They provide insight into how the industry is adapting to new approaches to clinical trial conduct during the COVID-19 era, largely with the aid of virtualizing tools, strong partnerships, and regulatory guidance. Despite the upheaval in the past year, they share a sense of optimism that at least some of the systemic changes leading to the remarkably quick development of several vaccines will remain. This could involve expanded use of already popular technologies, which according to a new survey by the Society for Clinical Research Sites (SCRS) and Medidata, includes electronic clinical outcomes assessment (eCOA) (used by 72.9% of respondents), email notification (64.3%), online recruitment (63.3%), and more.

 But, for an industry that is notoriously slow-moving, not enough time has passed to determine which process changes will ultimately become standard practice post-COVID.

One key finding from the interviews was that hybrid models, as compared to fully virtual or traditional trials, are widely expected to assume a prominent role in the clinical trials landscape, as they facilitate the growing emphasis on patient centricity. There are also lessons learned, mainly involving the realization that stakeholders need a strong foundation to transition to decentralized clinical trials (DCTs), whether they are fully virtual or a hybrid of remote, in-home, and onsite visits. The foundation is rooted in strategic partnerships with contract research organizations (CROs), vendors, and associations who share collective wisdom to develop best practices or apply knowledge acquired from clinical care to the clinical trial realm. Stakeholders weigh in on the critical importance of building this foundation in order to move ahead with revamping clinical trial operations.

 presents current thinking on how sites are becoming more comfortable with an evolving industry. Jim Kremidas, Executive Director of the Association of Clinical Research Professionals (ACRP) comments, “Sites recognize that things are changing, and they have to be looking for people with new skill sets or developing people within their organizations to leverage these new skill sets.”

So, the sector is in flux, as evidenced by the rising use of technology, greater reliance on remote visits and partnerships, and a work force that is a better fit to the new reality of conducting clinical trials during a pandemic and beyond.

Status of decentralized clinical trials (DCTs)

When the pandemic first hit, there was a sudden awareness across the industry that if existing clinical trials were to resume, and if there was any hope of a vaccine being quickly developed, processes had to be adopted that would allow the safety of patients and site staff to remain top priority. With patients increasingly reluctant to visit sites, “safety” meant instituting at least some remote or “televisits”, a key aspect of DCTs. In the last few months, DCT uptake has grown dramatically, and is slated to continue. A recent analysis suggests that the global market for DCTs is expected to reach $10 billion by 2026, rising at a 6.5% compound annual growth rate between 2020–2026.

 As evidence of this growth, the SCRS/Medidata survey found that televisits, already used in the past two years by 45.1% of the 204 respondents, are likely to be adopted by an additional 39.2% of respondents in the next two years.

 The survey also reported that only 15.5% of respondents participated in decentralized or completely virtual trials in the past two years. But, 42.1% stated that they expect to implement them in the next two years–nearly a three-fold increase.

Research from the Tufts Center for the Study of Drug Development (CSDD) indicates that during the pandemic, telemedicine has become the most frequently used approach for supporting DCTs.

 Its use by more than 80% of companies reviewed for a recent 

 suggests that its growth is due mostly to the relative speed and ease of implementation. This was the finding of a CSDD analysis of the 50 largest pharmaceutical companies, based on published information, virtual conferences, and detailed interviews with 23 pharmaceutical companies conducted in August and September 2020.

Melissa Nezos, Vice President of Clinical Operations at Firma Clinical Research, a provider of in-home health services, comments on the ongoing shift toward DCTs. “What I’m hearing from big pharma is that they are setting corporate goals going forward to have a decentralized clinical trial component. Many of the large companies have innovation groups where DCT is a focus for the future. Before the pandemic, they were slowly inching toward the goal of performing more DCTs, but the pandemic has forced these innovation groups to immediately become engaged. They’re now working with partners like Firma on how to pivot their ongoing trials, and how to strategize on incorporating DCTs into their future trials,” Nezos explains.

Regarding the use of more home-based visits, Rasmus Hogreffe, Vice President of Decentralized Clinical Trial Innovation at Medable, a provider of a DCT platform, says, “We are seeing rising decentralized trial adoption in the industry on a daily basis, including home visits. Before, patients were going to the site, and now, we are seeing sites going to the patient. It’s a patient-centered approach, rather than a site-centered approach.”

To make this happen, site staff need to be trained in how to conduct a DCT. A 2019 survey of 340 site professionals conducted by SCRS in collaboration with VirTrial revealed that 60% of respondents had no experience in remote trials or any type of virtual processes, 37% claimed to have conducted a hybrid trial, and only 3% had participated in a completely virtual trial.

 With protocols embracing more virtual components, these statistics are concerning, but they were collected pre-COVID, and since then, site professionals have gained exposure to virtualizing tools and are incorporating them into ongoing studies. Kremidas of ACRP remarks, “Now that people have been forced into using virtual technologies, they’re realizing that it’s not as scary as they thought. They’ve become accustomed to using these tools, and that’s half the battle. The analogy is—when you get a new computer with unfamiliar software, you first move a little slower than you’d like, but as time passes, you get used to it, then you start to like it, and finally you can’t live without it. That’s where we are now.”

Our research shows a consensus that as the pandemic rages on, DCTs are clearly trending toward the hybrid model. While some trials may be fully virtual, and some may remain traditional, many more will be hybrid, as they are well-suited to a customizable patient-centric mix of on-site and remote visits. Ken Getz, Executive Director and Professor, at CSDD, explains, “About 55% of all trials moved to remote or a model with support from virtual technologies during the pandemic. I think once the pandemic is behind us, and there is more familiarity with these approaches, the hybrid approach is the most likely model because it’s defined by patient preferences. We are giving patients the option to come into the center or have virtual visits. Why wouldn’t we offer that for any trial?”

Similarly, Nezos of Firma comments, “Most of our current studies are hybrid. We aren’t seeing or working with companies performing fully virtual trials yet. A lot of technology would have to be in place for studies to be fully virtual and that’s something that most stakeholders don’t have. As for hybrid, sponsors are asking us to look at the protocol to see what they can do to bring in more virtual elements, so they can maximize the amount of visits that can be done in the home.” As part of this effort, she points out that many protocols include assessments and items that could be performed in the home with the help of home health practitioners, such as sample collection, blood draw, and EKG.

But there is still a vital role for site visits. For example, the first and last study visits may be more extensive, and may involve imaging, which would require visits to the site or to an imaging facility. Also, patients may want to have at least some face-to-face visits with the principal investigator and study coordinator, so to enable this, the protocol could be designed to move items originally planned for a remote second visit into an on-site first visit.

Amy (Nordo) Cramer, Global Product Development Operations Strategic Partnerships at Pfizer, sees the movement toward DCTs as operating along a spectrum, reflecting the specifics of various therapeutic areas and patient populations. “On one end is the fully virtual, completely decentralized trial, and at the other end is a study with maybe just one virtual tool, such as ePRO, with hybrid in the middle. Out of cautiousness, portions of the research community will opt to move slowly from one end of the spectrum, maybe starting with one functionality of a DCT, and as they become more comfortable, they’ll start moving across. I think other companies, like Pfizer, will be innovative and lead the industry by utilizing the full spectrum of DCT,” Cramer says.

The discussion about DCTs is also a discussion about patient centricity. DCT momentum was fueled by the COVID crisis, but their growing acceptance suggests that they are offering solutions to long standing challenges for the clinical trials sector, such as patient recruitment, enrollment, retention, and compliance. Current thinking indicates that if potential subjects could more easily enroll and participate in study visits from the convenience of home, retention and compliance might improve.

Getz from Tufts CSDD remarks, “I think the term ‘DCT’ does not go far enough in conveying what we need to do as an industry. Calling studies ‘decentralized’ is still putting the site at the center of the trial. We should be thinking about this as patient-centric. This would mean that patients who are more anxious may want to have at least some in-person visits, whereas others may want to mostly interact using a hand-held device.”

Jeremy Price, Director, Clinical Innovation & Strategic Partnerships at Pfizer, says, “We are proactively meeting with study teams and reviewing their protocols with them to see if including remote visits makes sense. If we can add some remote visits, even one or two over the duration of the study, it’s a huge win from the patients’ perspective, and they are more likely to stay in the study. It can also be a win for diversity and inclusion, as we can increase access for participants from a variety of backgrounds and locations that may be further from study centers.”

To boost patient centricity in clinical trials, Medable launched its Patient Advisory Council (PAC) in February 2020.

 It is a nationwide network of advocates who are advising the company and its biopharma customers on how to improve patient access, experience, and outcomes in clinical trials. The PAC is a network of patient advocates, advisors, and caregivers with diverse backgrounds in patient engagement and a strong understanding of patient preferences. The goal is to improve clinical trial access and efficiency by embedding patient voices and perspectives into aspects of clinical trials, and identifying and prioritizing potential hurdles that patients face. Medable is incorporating those perspectives into its DCT platform.

As greater use of DCTs unfolds, the logical next question is—which of the current changes will remain once the pandemic winds down? It is fair to say that no one knows for sure, but there are smart initiatives underway that are looking at the infrastructure and partnerships needed to make some of the changes stick.

Pfizer has been active in the DCT space for a long time, according to Price. He says the company has strong strategic partnerships with many types of clinical research community members, including those with telehealth capabilities. “Early in 2020, adoption of telehealth for clinical care increased exponentially, so we were able to jump on that and utilize those tools for visits in our trials.” Cramer adds, “We had already done a significant piece of work in trying to form a better bridge between clinical care with clinical research, so when we got into the COVID situation, and needed to find alternatives, we knew the options clinical care was using, and our strategic partnerships helped us understand how we could use existing functionality in clinical care in clinical research. Our partnerships were a large part of our ability to pivot so quickly.”

For Pfizer, the importance of partnerships is being played out in a new initiative called Vulcan. Launched in August 2020 by Health Level Seven International (HL7), Vulcan seeks to use a model for collaboration among diverse stakeholders in the translational and clinical research space to define a common set of standards that can be implemented globally, using the HL7 Fast Healthcare Interoperability (FHIR) standard for data exchange.

 The intent is to optimize the design, conduct, and reporting of clinical studies. Cramer, the group’s co-chair, mentions, “We have this opportunity as a collective group of the entire research community to work on solutions together. No longer does clinical research sit at its own table. We’ve joined a table of all of healthcare, and the benefits of this collaboration are exciting. We are actually working together in a way that I haven’t seen in my career. This is a game changer for clinical research.”

In December 2020, the formation of another alliance—Decentralized Trials & Research Alliance (DTRA)—was announced.

 The goal of DTRA is to unite a wide range of stakeholders, namely healthcare companies, regulators, patient groups and research organizations to enhance patient-focused trials and remove barriers to participation by advancing practices and technologies for decentralized studies. According to a recent DTRA press release, there hasn’t been a forum in which a diverse group of stakeholders could collaborate on this subject.

 As evidence of the strong interest in this initiative, there were 50 founding members, growing to nearly 70 members by early January 2021, just weeks after the organization’s launch.

The movement toward greater patient centricity and the adoption of decentralizing tools that enable it has been brewing for a while, but in recent months of the pandemic, there has been a dramatic uptick. So, the tide is clearly turning, and the industry’s embracing of DCTs is a silver lining. But will this momentum last?

Getz comments, “It’s hard to envision how it will play out because the pandemic forced a very abrupt change in design. Regulatory guidance has accommodated that abrupt shift. Basically, the door has been opened, and a lot of patients are going to say now that they’ve seen the light, why would they revert to only having in-person visits?”

He expects the path to a DCT world to be far from smooth, as most everything that’s been done in response to the pandemic has added more complexity and customization to clinical trials. This in turn increases cycle time, inefficiency, and cost, and the industry needs to figure out how to
manage this.

Because of the unsettled landscape, CSDD is more cautious about making statements about process change being sustainable. “We aren’t convinced of that. Historical precedent would suggest that the speed and incredible collaborations and success we’ve had in developing COVID-19 vaccines may be more of a one-time occurrence unless there are a whole host of fundamental areas that are addressed,” Getz warns.

Still, this is an amazing time for the clinical trials sector, as recent success in developing several vaccines is a testament to what this industry can accomplish. But, it is shifting, so it will be critical to re-visit this subject periodically to determine which changes become permanent.

Neuer A. Patient Centricity and Virtualizing Technologies in a COVID-19 World. Society for Clinical Research Sites and Medidata. December 2020. Available at: 

https://myscrs.org/learning-campus/white-papers/

Global Virtual Clinical Trials Market By Study Type, By Indication, By Region, Industry Analysis and Forecast, 2020–2026. KBV Research. December 2020. Available at: 

https://www.reportlinker.com/p05999876/Global-Virtual-Clinical-Trials-Market-By-Study-Type-By-Indication-By-Region-Industry-Analysis-and-Forecast.html?utm_source=GNW

Lamberti MJ, Smith Z, Wilkinson M, et al. Impact Report. Global Clinical Trials Transition to Decentralized Models Abruptly, in Nuanced Ways. Tufts Center for the Study of Drug Development. November/December 2020.

Impact Assessment of Decentralized Clinical Trials (DCT) Awareness in the Clinical Research Industry.Society for Clinical Research Sites and VirTrial. May 2020. Available at 

Marklein T. Medable Forms Patient Advisory Council to Advocate for Patient Access, Experience, and Outcomes in Clinical Trials. Medable Press Release. February 19, 2020. Available at: 

https://www.businesswire.com/news/home/20200219005346/en/Medable-Forms-Patient-Advisory-Council-Advocate-Patient. Accessed December 31, 2020

Ribick A. HL7 Starts Project Vulcan FHIR Accelerator Program. HL7. Press Release. August 11, 2020. Available at: 

http://www.hl7.org/documentcenter/public/pressreleases/HL7_PRESS_20200811.pdf. Accessed January 3, 2021

Decentralized Trials & Research Alliance (DTRA) Launches to Democratize and Accelerate Clinical Trials. Decentralized Trials & Research Alliance. Press Release. December 10, 2020. Available at: 

https://dtra.org/dtra-launches-to-democratize-and-accelerate-clinical-trials/

MBA, President, Medical deScriptions, LLC

Hybrid studies, patient-centric tools, and collaborations create big changes for clinical trials and stakeholders during COVID-19.

Sharpening the Focus on Patient-Centricity as Pandemic Continues

Big pharmas join clinical research marketplace

Inato, a global industry marketplace that matches research sites to the right clinical trial protocols, announced over 500 sites across more than 30 countries are participating in its Marketplace. Sanofi and Merck KGaA, Darmstadt, Germany have also joined the Marketplace, which Inato says will further its mission to accelerate the pace of medical innovation to improve people’s lives.

Using a data-driven approach—coupled with a high-touch qualification and support process—the Inato Marketplace provides research sites the opportunity to search and match for trials based on their qualifications, interests, and patient needs. By matching sites and trials on a global scale, the Marketplace enables trial sponsors to work with a broader range of qualified sites and rapidly expand the pool of patients engaged in their trials.

Senators Edward J. Markey (D-Mass.), Thom Tillis (R-N.C.), Gary Peters (D-Mich.), and Susan Collins (R-Maine) have introduced the Research Investment to Spark the Economy (RISE) Act to authorize nearly $25 billion in support to US researchers who have been impacted by the COVID-19 pandemic.

Although coronavirus-related research is a current federal government priority, most other research has been delayed due to closures of campuses and laboratories. The people who comprise the research workforce—graduate students, postdocs, principal investigators, and technical support staff—face financial and other hardships from the disruption of their research activities. The RISE Act would provide necessary relief to preserve the current scientific workforce and ensure that the US is prepared to continue its global scientific leadership once this crisis ends.

GCSA Intrinsic is supporting the UK clinical research industry by providing an internationally-recognized quality benchmark for sites focused on attracting commercial clinical trials.

The GCSA gold standard has been ratified by a global advisory board of industry experts from a broad range of global and UK organizations. According to Board members, GCSA will either enhance existing standards that some UK research centers have, or it will help improve and raise the standards of those centers that are trying to build their research capacity, thus allowing these centers to promote themselves as global competitors

Jazz Pharmaceuticals plc and GW Pharmaceuticals plc have entered into a definitive agreement for Jazz to acquire GW for $220 per American Depositary Share (ADS), in the form of $200 in cash and $20 in Jazz ordinary shares, for a total consideration of $7.2 billion, or $6.7 billion net of GW cash. The transaction is expected to close in the second quarter.

The combined company will be among the leaders in neuroscience. GW has a scientific platform and a deep pipeline of cannabinoid product candidates, as well as highly specialized manufacturing expertise. GW’s lead product, Epidiolex oral solution, is approved in patients one-year and older for the treatment of seizures.

News

A compilation of recent notable news developments that pertain to the clinical trials industry.

News Notes (January & February)

While Europe and its citizens, like much of the rest of the world, continue to reel under the assault of COVID-19, the focus of many health authorities is understandably on vaccines, and the related research, development and–particularly as 2021 gets underway–production issues. But work is nonetheless continuing on planning for the health challenges that will still be there even when COVID-19 is under control. Late January saw Emer Cooke, the new executive director of the European Medicines Agency, fresh from a tough debate on vaccines in the European Parliament’s health committee, switch her attention to cancer, with an appearance at another of the parliament’s specialized committees.

Cooke was speaking at the parliament’s temporary committee on cancer, which has been set up specially in response to Europe’s Beating Cancer Plan–one of a number of health initiatives now emerging from the EU. Establishing her credential with the committee, she pointed out that EMA had approved 116 new cancer medicines over the 26 years of its existence, and in 2020 alone this included 11 products with new active substances–about a quarter of the 39 cancer medicines approved during the year.

The many challenges she identified in cancer medicine development are matched, she said, by “many solutions that we can see from our perspective.” And at the top of her list was improving clinical trials collaboration with downstream decision makers, as well as providing support to innovation. And she had some clear ideas on how this should be done, with a powerful emphasis on patient benefit as a priority.

In her view, “when talking about supporting innovation, we need to make sure that clinical trials are designed to answer the right questions.” For her, this means appropriately designed trials that not only promote innovation, but that also address the needs of cancer patients. “It’s only in this way that will be able to meet the evidence needs of regulatory authorities and downstream decision makers such as health technology assessment bodies, insurers, healthcare professionals and patients.” Cooperation is needed with those decision makers, and to ensure transparency of processes, and that requires better communication of information.

The focus must be on “trials fit for purpose from a patient perspective, and that ensure that patient views are systematically considered through the development process.” This is all the more true when research is confronting the particular challenges of rare and pediatric medicines, she underlined. But she saw this could be an opportunity, a chance for the EU to optimize the research effort by ensuring access to clinical trials and facilitating participation in them.

While remaining diplomatic, Cooke left no ambiguity in her estimation of the current degree of coordination at European level. “To do this we need to leverage the resources for conducting high quality research in Europe.” There is insufficient access to clinical trials—“and if we don’t facilitate access these trials just take too long to conduct.” At present, she pointed out, the majority of trials are conducted in only a handful of EU countries, and often only in a few centers. “There really are opportunities to bring trials closer to EU patients by promoting and enlarging the development of competences and trial readiness across Europe,” she said.

She also favors encouraging collaborative clinical trials by leveraging interaction between academia and scientists linked to regulatory bodies. This, she said, is necessary to address rapidly emerging regulatory science research questions, and to make a reality out of the concept of treatment optimization. “The EU needs to support clinical research into cancer treatment optimization with respect to all important clinical outcomes, real world effectiveness and safety. This will help to identify the population that is most likely to benefit. The continuation of data generation is necessary to inform the optimal use of medicines and the choices of patients and doctors,” she argued.

As she emphasized, clinical trials and drug development do not stop when a product is approved or reimbursed. “Evidence generation is a continuum which helps us to refine the understanding of what is the optimal use of new cancer medicines in clinical practice.” This she sees as a major opportunity for the EU to develop a learning healthcare system, which can maximize data generation in the real world by federating data from different sources–such as electronic health records and cancer registries. Regulators have a particular role in this, by identifying the open issues and helping to design the research questions that are needed.

But, she acknowledged, this needs the right infrastructure for systematically collecting, federating and sharing key data from different sources–and at present that is something lacking in Europe. That is why EMA is collaborating with the European Commission in the creation of the European health data space–another of the EU’s new initiatives.

It is also time to “refocus on designing quality into clinical trials.” For her, this includes applying risk proportionate approaches that systematically involve patients and a wide range of stakeholders in trial design. She said that EMA, along with other international regulators in the International Council of Harmonization, are making progress on this through updating of the fundamental good clinical practice guidelines for clinical trials.

Better communication could also decrease time lags and differences of view between approval decisions by regulators and access decisions by health technology assessment bodies. That in turn will benefit from progress on the EU’s now long-delayed HTA regulation, which should widen the scope for EMA to engage with HTA bodies. The right changes to pharmaceutical legislation–also up for EU review in 2022–and smarter regulatory practices can provide tools to help incentivize innovation. It should be possible to shorten review times, to make more use of priority schemes for innovative medicines, and targeted support through orphan designation.

“We are fully committed to delivering on the ambition of creating an enabling environment for the development, evaluation and access to new and re-purposed cancer medicines in the EU, and we stand ready to support the implementation of the European Beating Cancer Plan,” she concluded.

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

View from Brussels

Cancer still a primary focus of EMA in light of COVID and vaccine development.

EMA’s Cooke Reviews European Cancer Prospects

The results of several studies published in 

 and elsewhere have demonstrated the impact of growing clinical trial data volume and the increasing diversity of clinical data sources on study timelines and inefficiencies.

New benchmarks show that the increase in data volume and diversity is accelerating. The typical late-stage protocol, for example, now collects on average 3.6 million data points, three times the number collected 10 years ago.

In collaboration with and funding from IBM Watson Health, Tufts CSDD has now completed a study assessing how the clinical data management function—internal teams in collaboration with their electronic data capture (EDC) partners—are managing, collecting, organizing, storing and analyzing their clinical data. This article summarizes the results of this collaborative study and provides more granular cycle time measures, experience with EDC solutions, insights into challenges and opportunities to optimize clinical data management practice.

A global survey was conducted between September and October 2020.In total, 194 verified unique individual responses were received and analyzed. Respondents had an average of 10.8 years of experience working in a variety of roles including clinical operations, data management, executive leadership, clinical development and others. The mean number of clinical trials performed per year was 54. In the discussion that follows, we’ve classified organizations into two primary subgroups: those conducting 50+ trials/year are designated as “Larger” and those conducting fewer than 50 trials/year are designated as “Smaller.”

Clinical data management and EDC solution pain points

More than twelve different EDC solutions were identified by respondents. Most organizations (73.9%) report using two or more and the remaining 26.1% of respondents report using only one EDC solution.

Table 1 below shows the wide range of clinical data management pain points reported. The typical respondent noted 3.3 different pain points associated with their primary EDC solution. Managing mid-study updates and their associated delays topped the list followed by flexibility and customization challenges.

Nearly one third of respondents reported challenges with database go live delays and the lack of integrated patient engagement and electronic clinical outcome assessment (eCOA) applications. Slightly more than 30% reported challenges with the cost of their primary EDC solution. Pain points that were reported the least frequently included data incompatibility between platforms, customer support problems and solution complexity (slow user learning curve).

Although a relatively high percentage of respondents cited database go live delays as a key challenge, it is interesting to note that the cycle time between final protocol approval and the database go live milestone has not changed during the past three years.

 Figure 1 below shows that the average duration from final protocol approval to the database go live milestone has increased by one day.

The results of this study also show that the average study close-out cycle time—from last patient last visit to database lock—remains unchanged between 2017 and 2020 with organizations reporting an average duration of 36.8 days. Mid-study updates represent a time intensive challenge.Managing a mid-study update requires about half of the total time needed to achieve the initial go live release of the database, as shown in Figure 2 below. This helps explain why planned and unplanned study updates are the top reported pain points.

Looking at each of these cycle times individually, and comparing smaller vs. larger organizations, there were some notable differences. The results show that smaller organizations (<50 trials/year) are faster at early-stage data management processes whereas larger organizations (≥ 50 trials/year) are faster in late-stage processes.

Despite the challenges noted, respondents report a high level of satisfaction with their EDC solutions, as shown in Table 2 below. Database design and data collection tasks received the highest satisfaction levels with over 90% satisfied. Database closeout, the overall end-to-end process, and data processing and cleaning abilities also received high levels of satisfaction. Managing mid-study updates and the overall study cycle time received the lowest relative satisfaction scores.

2020 Tufts CSDD – IBM Watson Health benchmarking study highlights need for new functionality from EDC solutions and providers.

Applied Clinical Trials-02-01-2021