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Applied Clinical Trials April 2021

Clinerion has extended its patient coverage in Brazil to four new hospitals with the help of partner iHealth Group. This raises the footprint of Clinerion’s Patient Network Explorer to 17 healthcare organizations and over 7 million patients.

The four newest Brazilian hospitals to join the global community of partner hospitals on Clinerion’s Patient Network Explorer platform are:

Hospital São Lucas—PUCRS, Porto Alegre, Rio Grande do Sul

Hospital Martagão Gesteira, Salvador, Bahia

Centro Regional Integrado de Oncologia (CRIO), Fortaleza, Ceará

They are projected to go online in Patient Network Explorer by the end of May 2021. The hospital network in Brazil comprises hospitals of varied sizes, locations and specializations. 

Articles

Clinerion’s Patient Network Explorer Adds Four New Hospitals in Brazil

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

The European Parliament's health committee is hammering home some of the lessons from the COVID pandemic, which demonstrated so clearly that Europe, both at EU level and among its 27 member countries, "was not ready to deal with public health emergencies." In an April 15 debate, MEPs restated—yet again—the need for changes to the way the EU operates in terms of health policy. Not the first such demand, but the latest in what is becoming a tidal wave of calls for a firmer grip on policies affecting the well-being of its 450 million citizens.

"Despite having experienced previous threats, health structures were not geared towards this possibility," said Spanish socialist Nicolas González Casares, who is leading the parliament's examination of EU plans for upgrading the role of the European Medicines Agency in the wake of the devastation wrought by the pandemic. He attributed the inadequacy to budget cuts that have "diminished the adaptive capacities of our health systems," and pointed to the desperate attempts to cope over the last year as the European Commission and EMA "have had to act by setting up ad hoc structures to achieve a better and more coordinated response."

He told his fellow MEPs that "there is a need for the Union to equip itself with an appropriate institutional framework to deal with emergencies such as the one we are experiencing, without having to improvise, with a clear mandate, and by providing a legal framework for EU institutions to play a more active role." And first up is the proposal for a strengthened mandate of EMA. However, the principal objective of his plea is not to arrange for faster authorization of new medicines to tackle pandemics, not to offer incentives to innovate. Instead, this proposal is limited to bolting additional tasks onto EMA in relation to the specific issue of drug supplies. His draft recommendation is designed to avert the sort of penury in medicines that have hit health services since the crisis began, and he urges developing an institutional framework that defines who does what at any given moment, provides for monitoring and controlling the medicines supply chain, and an agreed definition of drug shortages. He wants to see steering groups set up to overview the production and supply chain for medicines and medical devices. He spoke at length on the need to coordinate and share the knowledge among the member states, the EU institutions and the pharmaceutical industry, and on the merits of creating a European medicines supply database.

"Had a regulation of this nature been in force before the pandemic, some issues such as shortages or the approval of new treatments would probably have been dealt with more deftly during the pandemic," remarked González Casares. He may be right. But readers of ACT will be relieved to be reassured that the EU response to COVID goes further than merely turning EMA into a pill-counting institution. As González Casares acknowledges in the document, he presented to the health committee, there are other EU initiatives underway of a more strategic nature. Another of these was debated and voted through by the committee on April 16: a new procedure to accelerate the EU-wide approval of vaccines adapted to COVID variants. This takes the form of a rapidly-created legal provision to ease the passage of vital new medicines through the EMA's authorization system. It will provide a simplified procedure for vaccines that have already received EU authorization but which are being adapted to be effective against variants of the virus.

Their vote—which now needs to be endorsed by the parliament as a whole at a future plenary session—comes after the release of an EMA reflection paper in February, and discussions in recent weeks with senior members of EMA, including Marco Cavaleri, head of its office on biological health threats and vaccine strategy. They received assurances on the criteria and operation of the new mechanism—including requirements that variant vaccines must be based on already approved/in use vaccines, and justification for the relevance of the variants included, based on disease surveillance and characterization of strains circulating at the time of selecting the variants. The efficacy of a monovalent or a multivalent variant vaccine against the variant strains may be inferred from provision of immunogenicity data after primary vaccination with the variant vaccine; and after a single dose of the variant vaccine when given to subjects who previously received primary vaccination with the parent vaccine. And as soon as a global forum is established to support SARS-CoV-2 strain selection for vaccines (such as has been discussed at the World Health Organization), the recommendations made should be consulted when selecting the variant strains.

This may prove a more effective measure to bring the pandemic under control—but it also underlines the growing conviction among many Europeans—and their politicians—that there is a need for more Europe in the field of health, and for progress towards a health union to match the EU's other major achievements such as its monetary union that created the Euro and its customs union that permits free trade across the internal borders between its member states.

Parliament's health committee is answering calls for a firmer grip on policies affecting the well-being of its 450 million citizens.

Dragging the EU into a More Health-Conscious Post-COVID Dynamic 

FDA is halting enforcement of a policy that limits prescribing and dispensing of Mifeprex (mifepristone), a widely used drug to induce a medical abortion in the very early stages of pregnancy. The revision allows doctors to authorize the pills via telemedicine and to make them available to patients through mail-order pharmacies while the pandemic continues, as a way to facilitate treatment while minimizing risky personal contact. And it puts FDA in the middle of the abortion debate.

Since approving Mifeprex for market in 2000, FDA has required women to obtain the drug directly from certified healthcare providers in certain clinics, medical offices and hospitals. The shared risk evaluation and mitigation strategy (REMS) program for the drug and generic equivalents calls for patients to be evaluated by trained medical professionals and blocked product dispending by retail or mail-order pharmacies or over the Internet. While medical professionals and women’s health advocates have opposed these restrictions for years, the limitations appeared more egregious when the Trump administration dropped similar distribution restrictions for a number of high-risk medicines to ease patient access to treatment during the pandemic—but did not extend such flexibility to mifepristone, despite its strong record for being safe and effective.

Now FDA is modifying the requirement for in-person consultation, stating that the agency will exercise “enforcement discretion” regarding dispensing limitations during the public health emergency and will be flexible in permitting Mifepristone dispensing through the mail.

 FDA acting commissioner Janet Woodcock confirmed the change in letters to the American College of Obstetricians and Gynecologists (ACOG) and the Society for Maternal-Fetal Medicine.

FDA’s move was praised by ACOG leaders, who sought and gained federal court approval in July 2020 for FDA to suspend its restriction on mifepristone dispensing directly to the patient in a clinic or medical office.

 The judge cancelled the prescribing restrictions on the basis that requiring women to travel to clinics in person to obtain the pill put them at risk of COVID infection. However, the Trump administration appealed the ruling, and the Supreme Court overrode that decision in January 2021, restoring the requirement that individuals seeking medication abortions to obtain the pills in person.

Now FDA has moderated the in-person prescribing requirement, supported by evidence from continued review of adverse events related to Mifeprex during the six months last year when the more liberal dispensing policy was in effect. Woodcock explained in her letter that FDA reviewed studies related to mifepristone safety and adverse event reports from January 2020 to January 2021 and found no evidence that remote patient consults raised serious safety issues, such as sepsis infection, bleeding or ectopic pregnancy.

The debate reflects how Mifeprex has become more widely used to halt unwanted pregnanciesas state and federal policies have made surgical abortions more difficult to obtain. Abortion opponents seeking to limit access to mifepristone claim that a telemedicine appointment to discuss such treatment raises grave safety risks to patients. Several states are considering bills to ban the pills or make them even harder to obtain. However, state restrictions could become moot with more flexible video consultation policies that enable patients to obtain a prescription from a physician in another state and to receive the drug through the mail. Some women may be reluctant to take a pill that is banned in their home state for fear of arrest and charges, even though most doctors consider mifepristone safer than many common over-the-counter pain medications.

FDA announced its more flexible approach to Mifeprex prescribing as a deadline neared for a federal appeals court to decide a challenge to the Trump requirements upheld by the Supreme Court. A long list of leading medical societies, including the American Medical Association, the American Academy of Family Physicians and ACOG, sent a letter March 1 to President Biden and Vice President Harris urging “swift action” to end the prior administration’s “unscientific and discriminatory policy” that forces patients prescribed mifepristone for pregnancy termination to pick up their medications at a health center. They point out that such requirements contradict actions by FDA and other federal agencies to promote the use of telemedicine during the pandemic to ensure access to health care while limiting unnecessary contact.

Separately, the Biden administration has moved to repeal regulations instituted by the Trump administration that bar family planning clinics that receive federal funds from offering abortion referrals and counseling. That move was widely hailed by women’s health advocates, but strongly opposed by anti-abortion forces.

https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/questions-and-answers-mifeprex

https://www.acog.org/news/news-releases/2021/04/acog-applauds-fda-action-on-mifepristone-access-during-covid-19-pandemic

FDA is halting enforcement of a policy that limits prescribing and dispensing of Mifeprex (mifepristone), a widely used drug to induce a medical abortion in the very early stages of pregnancy.

FDA Lifts Restrictions on Access to Abortion Pill

 as Global Vice President of Partner Sales, and 

Worldwide Clinical Trials announced that 

, has been promoted to chief scientific officer, Early Phase Development.

MedVector announces that it has appointed 

, as strategic advisor, pharma relations and clinical protocol.

 as Associate Director of Pharmaceutical Development.

 has been recognized by Everest Group as one of the top global companies providing Pharmacovigilance and Complaint Management Operations services.

The latest people and business news of the industry, all in one place.

People and Business News — 4/21

Parexel and Veeva Systems have announced a collaboration to accelerate clinical trials through technology and process innovation. The collaboration combines each company’s experience across thousands of studies worldwide.

As part of the partnership, Parexel is standardizing on Veeva’s suite of clinical operations applications, including Veeva Vault eTMF, Vault CTMS, and Vault Study Startup. Veeva Vault CDMS for clinical data management will also become a standard offering available from Parexel to its customers.

Parexel and Veeva Partner Aim to Accelerate Clinical Trials

eClinical Solutions LLC has announced that Translational Research in Oncology (TRIO) has selected eClinical’s elluminate clinical data platform for its trial processes across its network of 700+ cancer centers.

The variety of digital health data now collected in clinical research have provided tremendous opportunities for scientific breakthrough. In the last decade, the volume of clinical data has grown by 183%, with over two-thirds of sponsors now using or piloting at least four different data sources in their trials. Despite significant innovation in data collection platforms and capabilities, including those for decentralized clinical trials (DCT), there has been less innovation on the process of ingesting, reviewing, organizing and analyzing these data streams. 75% of companies still rely on existing excel and SAS infrastructure to organize their data once it has been collected.

TRIO and eClinical Solutions to Power Digital Transformation in Cancer Trials

Precaution continues to dominate EU thinking on science and technology–with politics intervening to offer some intriguing impacts on human health. Amid the heated COVID-driven controversies over vaccination that are ruffling Europe, a specialized European advisory group on ethics has just issued a cautious opinion on the use of gene editing–including a call for a global guarantee that heritable human genome editing is not prematurely clinically applied. In addition to the intrinsic interest of the subject and of the opinion the group presents, the views it expresses offer an interesting comparison to–or contrast with–the apparently haphazard decisions by EU countries over recent weeks in respect of the AstraZeneca vaccine against COVID.

The European Group on Ethics in Science and New Technologies (EGE) is tasked with advising the European Commission with “high quality, independent advice on all aspects of EU legislation and policies, where ethical, societal and fundamental rights issues intersect with the development of science and new technologies.” In a 

new and broad-ranging opinion on genome editing

, the group urges a degree of caution–notably that this technology should not be applied “for purposes other than against serious diseases that cannot be prevented or treated otherwise.” And it stresses the need for safeguards against enhancement or de-enhancement of traits, and to ensure that investments in research on germline genome editing have the purpose of protecting health. But at the same time, the opinion acknowledges that somatic genome editing has the potential to alleviate suffering from diseases that could not be treated effectively before, and recommends pursuing its use, along with providing access to clinical studies and clinical application in healthcare.

Particularly striking is the treatment of expertise in the opinion. This, it says, is vital to “ensure adequate competencies in expert bodies.” As it observes, genome editing technologies are evolving quickly and expertise to assess research and application has to keep pace with new developments, so it is important to widen the basis of expertise and broaden what counts as relevant knowledge at the level of expert committees, fora and other bodies established to examine and set guidelines and standards for research and application of genome editing technologies. It extends the advice to providing due guidance for ethics committees charged with approving and supervising clinical trials involving genome editing, covering safety assessments and risk/benefit determinations of clinical trials are developed, along with training modules for research ethics committees and other involved bodies “to ensure high-standing and consistent application of ethical standards.”

With a view to promoting broad alignment, the group has asked the European Commission to engage in global discussions on regulation of this emerging field with the World Health Organization and the World Medical Association, covering universal adoption of standards on the ethical use of genome editing in human beings. And within Europe it wants to see the creation of a specifically European platform to exchange information and promote “a broad and open public debate” on the ethical and social implications of germline genome editing in human beings. It stresses that this will require a “basis of sound and evidence-based information,” and a heightened awareness of the implications of widely used terminologies and distinctions such as somatic and germline editing, or prevention, therapy and enhancement.

What might the group have said if it had been asked to give an opinion on the EU’s recent performance in the use of vaccines–and specifically, the AstraZeneca vaccine? Not the squabbles between the UK and the EU (and even within the EU!) on delivery, which are almost too unseemly to merit attention here, but on the more sensitive area of efficacy and safety judgments concerning innovations. From the outset, there was disunity among the member states about whether, in the absence of trial data from the elderly, the vaccine should be given to older people–with France, notably, withholding it from those over 75 years of age. But then anecdotal reports of blood abnormalities among a handful of recipients sent national authorities in the EU into paroxysms of incoherent indecision, destroying any semblance of EU alignment on evidence-based decision-making, as some countries suspended use of the product pending the outcome of a European Medicines Agency (EMA) review of the case reports, others imposed some limitations relating to age, and others carried on with administration regardless. And when EMA delivered an interim clearance of the product, many countries still refused to use it.

The picture was of politics replacing evidence-based decision-making, as governments responded to public (and often ill-informed) anxiety rather than to scientific evaluation. The summit of incoherence was reached when member states subsequently reverted to following expert advice: governments that had ignored the advice of the EMA and suspended the use of the AstraZeneca vaccine then reinstated its use–in line with the advice from the same institution. It was another example of action driven by a European tendency to bow to uninformed public opinion, playing safe politically rather than scientifically. It epitomized a question that has assumed growing importance over the last 50 years: how to take account of public sentiment while science itself evolves. The exploitation of gene technology in food and agriculture from the 1980s has manifestly been impaired in Europe by public concerns, not always on the basis of a good understanding of the subject. A similar cloud already hangs over the development of nanotechnology. The debates have often not been edifying, since they have frequently relied on acute emotion rather than on accurate information. And the risks from widespread misinformation and even from conspiracy-driven dis-information are currently crystallizing conspicuously in vaccine hesitancy and frank anti-vaccination movements, frequently linked to the relative novelty of
mRNA vaccines.

The disarray among national governments in Europe will have done nothing to inspire confidence either in science in general, or in Europe’s regulatory institutions–and least of all, confidence in vaccines. Governments’ knee-jerk responses to lurid headlines, with the principal aim of avoiding blame if things go wrong, do not constitute a noble strategy in times of crisis. Defensive appeals to that “precautionary principle” beloved of many European policymakers are not necessarily the right approach to public debate on the relative risks and benefits of alternative courses of action. The advice of the EGE about ensuring “a broad and open public debate” on the “basis of sound and evidence-based information” might be a better guide. And above all, for those utterly obsessed with the precautionary principle, it should have been evident that seeking to protect the public from a minimal risk of vaccine side effects would in any case expose people to an even greater risk–of contracting a serious disease that has already killed hundreds of thousands across Europe.

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

European Group on Ethics in Science and New Technologies issues cautious opinion on the use of gene editing amidst COVID vaccination controversy.

Europe's Eternal Struggle with Safety and Innovation

, “Technological Impact on Accelerating Vaccine Trials, Development and Delivery.” With panel members from the leading vaccine manufacturers, it offered interesting behind-the-scenes insights into how these vaccines went through the development process with flying colors.

Marie-Perre Hellio Le Graverand, SVP, head of clinical development and operations from Pfizer, brought the numbers—266 days from the announcement of the pandemic to first EUA; 44,000 enrolled participants; four months to enroll; and 150 sites in six countries; with over 50 million electronic diaries; 7.5 million data management records and 34 million total data points.

To paraphrase Hellio Le Graverand, this was only possible because of digital technologies. The volume and speed of data they managed in real time, all the while maintaining quality, was totally unprecedented.

Similarly, Janssen’s trial included 45,000 participants. Terry Murphy, the company’s COVID-19 clinical development relaunch leader, said they recruited 3,000 patients in one day alone.

Again, unprecedented. But not unpredictable. The two core technologies that pharma and CROs used were predictive analytics and dashboards.

Rachel Berria, VP and medical head of AstraZeneca (US), said that predictive analytics and data from a variety of sources to heat-map where COVID was going, to open up sites in those areas and enroll patients accordingly, was key to the speed.

All of the participants noted that the immediacy and transparency of the dashboards coming from internal and external data sources, allowed for quick decisions, fostering improved trial conduct and data quality. These examples included: applying new strategies to enrollment; shifting focus for diverse populations; and providing site support.

Tal Zaks, chief medical officer for Moderna, concedes that while the company is built from the ground with a digital infrastructure, the tools for collaboration that exist today would have been challenging five to 10 years ago. “As a small biotechnology company that is highly leveraging CRO partners, that was really a key enabler. Where we lack the infrastructure, technology has enabled us to tap into the infrastructure of our CROs partners to achieve what we have.”

But outside of technology, the one factor that helped the unprecedented speed is what Berria pointed to, the rolling regulatory review process...which wouldn’t have been possible without data provided to regulators on an ongoing basis. Technology and science for the win.

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

Behind-the-scenes look at vaccine development.

How Did Clinical Trials Move at the Speed of COVID?

The challenges of finding a large, representative patient sample for a study remain the biggest in drug and vaccine development. Identifying patient candidates via electronic health records (EHRs) has become increasingly powerful. However, complex study protocols, strict patient definitions, along with the mandatory sample size often require investigators to look for patients outside of the healthcare provider system to complete the study on time. A combination of real-world data (RWD) sources can be used to identify proxy measures enabling outreach for a study without jeopardizing privacy rules or directly targeting individuals.

The growing availability of RWD, including EHR, claims, disease registries, and device-collected health data, alongside new data science techniques to combine, protect, and share health data, have led to multiple applications in the new drug development process and in the management of a drug’s lifecycle. For example, in clinical research and operations, RWD is used to validate hypothesis, write clinical development plans, support study design, validate study protocols, and obtain information on study feasibility. This synopsis is focused on applying RWD on patient recruitment for a clinical study.

EHR adoption in clinical care has become more prevalent globally. EHR systems are also an integral part of clinical research. Systematic enhancements enable investigators to search for patients matching the study criteria. The federated EHR (FEHR) research model, developed within the European Innovative Medicine Initiative (IMI; EHR4CR project 2011-2016), provides trustworthy, real-time services via de-identified, aggregated EHR data from a growing network of healthcare organizations (HCO). The FEHR model provides a new level of HCO engagement since the data remains where it was created and in full control by the individual HCOs in the network.

Investigators using the FEHR model can mine the data and identify patients beyond their own clinic to others within the network. To help investigators go beyond the source of patients already known by HCOs, one complementary option is RWD-driven digital advertising to reach suitable study candidates. Whereas traditional digital advertising often results in burdensome screening activities for sites, RWD-driven digital outreach allows for enhanced targeting of suitable and motivated leads that can be referred to sites. This combination of FEHR technology and RWD-driven advertising offers synergies to boost the capability of finding and recruiting patients.

Accessing a growing RWD ecosystem, including consumer and behavioral data, and applying new data science techniques to protect, connect, and securely exchange matching data records, provides sponsors and researchers innovative ways of depicting a holistic patient view beyond clinical profiles found in an EHR system. Researchers can now isolate representative clinical cohorts using EHRs followed by a smart modeling technique matching the clinical cohort with predictable consumer markers, resulting in an expanded “look-a-like” pool of potential trial participants. The enlarged audience can be transitioned through a multiple-step matching approach using self-assessment questionnaires, healthcare professional interviews, and structured data matching against a patient’s medical record retrieved digitally.

The ability to model a suitable cohort using RWD and safely connect, qualify, and scale with measurable outcomes is a critical step forward in further improving the precision of isolating the right audience for a trial. Access to a large number of patients combined with smart-matching techniques are means for researchers to ensure a diverse study population and allow for a more strategic approach to clinical study management. Additionally, it represents a new way of connecting the general public with opportunities to learn and engage in clinical research as one option of care. This approach is particularly attractive for sponsors and CROs using virtual sites and conducting decentralized studies since it requires global reach of prospective subjects without borders.

Director, Health Informatics, Data Science & Artificial Intelligence, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden, 

Assoc. Prof., Carlanderska Hospital, Gothenburg, Sweden, 

Assoc. Prof., Chief Strategy Officer, Trialbee AB, Malmö, Sweden

Growing availability of RWD leads new drug development process.

Using Real-World Data in Patient Recruitment

The COVID-19 pandemic has been credited with exposing longstanding challenges in clinical trials,

 including the perpetually inefficient site feasibility process. Finally, this critical step is receiving the attention it deserves, maybe even an overhaul, as the wave of clinical trial decentralization surges on. This effort involves re-thinking the kinds of questions to ask in feasibility questionnaires, now that sites have reopened, and are coping with unprecedented numbers of remote study visits, and increased reliance on digital tools.

Determining a site’s digital readiness is essential, as the pandemic seems to have created the opportunity for access to a broader range of patients, beyond those who live near a site, to include those in rural or in lower income areas, allowing sponsors to meet diversity and geographic targets. Complementing this trend is the growing use of investigator digital platforms designed to eliminate the repetitive nature and drudgery associated with site feasibility.But according to Jeffrey Kingsley, founder and CEO of IACT Health in Columbus, Georgia, there is still a long way to go. “So far, few sponsors and contract research organizations (CROs) are leveraging their databases to eliminate a lot of the questions we get all the time. For example, we are still constantly asked, ‘Do you have a freezer?’ We get this question even from companies we’ve done many clinical trials for. Fortunately, since COVID, this is slowly starting to change,” he explains.

To explore the changes happening to the site feasibility process, 

 interviewed several experts in this field, representing a site, investigator platforms, and vendors. They offer decades of experience and insight into pre- and current COVID efforts to revamp this pivotal first step in increasing the likelihood of a successful trial.

Site feasibility starts by understanding the responsibilities of sponsors and investigators as defined in the International Conference of Harmonisation-Good Clinical Practice (ICH-GCP) Guidelines,

 Notably, these guidelines explain what a qualified investigator is, and the requirement of sponsors to select those investigators to carry out a clinical trial in accordance with a protocol. With this regulatory foundation, the site feasibility process involves choosing sites that not only conform to these requirements, but can also offer the best fit for specific studies, based on past performance, access to a database of appropriate patients, and the bandwidth to perform the study at hand. And with the shift toward decentralized clinical trials (DCTs) or hybrid versions, assessing a site’s familiarity with technology is being added to the process.

It all sounds so simple, but in practice, site feasibility has long been awkward and slow, and often more about checking boxes than turning to sophisticated databases and cloud-based solutions that could eliminate much of the redundancy.

 Today’s thinking suggests that if less time were devoted to repeatedly asking the same questions, more time would be freed up to build relationships and improve communication with sites that have a proven track record in various therapeutic areas.

A recent article by Kurbegov et al. of the American Society of Cancer Oncology (ASCO) describes a Task Force that was convened to evaluate the burdens and challenges of site feasibility, which often lead to delayed study start-up and act as a barrier to site participation.

 With input from sites, sponsors, and CROs in the form of surveys and in-person meetings, the Task Force developed three recommendations for improvement, with a goal of speeding patient access to clinical trial participation, and ultimately, much needed new treatments, as shown in Table 1 below. The third recommendation—leveraging technology to centralize the feasibility assessment—is a nod to performing as much of this process as possible by teleconference due to the pandemic.

The site survey found that the 103 site respondents spent a median of 264 hours annually completing feasibility assessments, with all sites spending a combined 27,192 hours, at a conservatively estimated cost exceeding $1 million for input from the study coordinators alone. Importantly, the stakeholders agreed that standardization will reduce burdens associated with site feasibility, and most thought that sponsors and CROs should use the same set of standardized questions for this process, except for those linked to specific protocols.

These findings align with work from Alliance for Clinical Research Excellence and Safety (ACRES). The organization launched a Site Accreditation & Standards Initiative in 2013, with a goal of addressing the inefficiencies in the clinical trials process, and the lack of uniform standards.

 ACRES promoted the idea that without an accepted, consistent set of standards and accompanying metrics, it is impossible to compare performance across sites, a factor that is critical to site selection. In 2018, ACRES, in collaboration with the British Standards Institution, published its principles for developing standards in 

 with an eye toward site accreditation, and the importance of viewing high performing sites as a critical resource.

At first glance, the changes spawned by the pandemic seem mostly focused on adding questions to the feasibility questionnaire about the status of technology adoption, and whether potential patients are able to participate in televisits, or use apps for patient reported outcomes (ePRO) or eConsent. A closer look, however, reveals those questions as a first step toward using the site feasibility process to expand the geographic area of patients available for study participation.

Mary Costello, head of Site Investigator Network at Medable, a provider of a DCT platform, describes the kinds of pre-qualifying technology questions to be asked for achieving this goal. “These questions might include asking if they have a patient database that tracks details, such as whether patients have smartphones. Do the patients have reliable high-speed internet? If they aren’t comfortable with technology, do they live with someone who can help them log on? We’re in a new era, and you don’t want to leave this information to chance. Successful feasibility is becoming more about anticipating and planning. Anyone who is getting ahead of these questions has a competitive advantage,”
Costello mentions.

She adds further that the pandemic has provided sites with a unique opportunity to expand their outreach beyond patients who live close to a site. “This is a turning point for the industry. Sites have existed on single digit margins for years, and have been limited to a drivable catchment area. Now, a patient might do a one to two-hour drive to an appointment if the rest of the visits can mostly be done remotely. I would suggest enhancing marketing efforts to broader, more diverse communities, as DCT imagines that we can bring in a whole new crop of clinical trial participants,” explains Costello.

Similarly, Diane Carozza, VP, clinical strategic solutions, study planning & site optimization at WCG, comments on how for the first time, site feasibility strategies are having to consider ethnic diversity and inclusiveness for patient recruitment. “We’re on the cusp of a big shift in diversity inclusion that the pandemic is fueling. It’s turning into something that isn’t just a ‘nice to have’. The FDA is calling out sponsors who are submitting applications for indications that have proven epidemiological prevalence data that certain ethnicities have a higher prevalence than others. Carozza explains they are asking, “What are you doing from the beginning to ensure that you include those groups in your trial?”

Attempts to improve site feasibility efficiency have been underway for several years among a handful of organizations, as shown in Table 2 below. Generally, uptake of these efforts was slow,

One of the most visible initiatives is the Shared Investigator Platform (SIP), which was created by TransCelerate BioPharma as an industry-wide solution to the problem of sites having to learn, access, and maintain excessive numbers of portals. SIP was designed with and for sites so they would have a centralized platform for providing information that would be available to multiple sponsors, and would eliminate the burden of repeated duplication of responses. In 2019, TransCelerate considered their SIP project to have met its initial objective, and as originally agreed, ownership of the platform and the intellectual property transitioned to Cognizant. Since then, the company has made significant progress towards establishing SIP as a core platform for clinical operations teams.

Larissa Comis, product owner of the SIP at Cognizant, explains that with the permanent changes to clinical trials brought on by the pandemic, sponsors are keenly interested in sites’ technological abilities to enable virtual collaboration and communication through SIP. As evidence, platform use has grown substantially in the past year, as shown in Chart 1 below. According to Comis, “We now have 146,000 users of SIP, which represents 125,000 site researchers. The rest are sponsors, including 21,000 study teams. SIP is used in 98 countries, in about 25,500 different locations.”

Comis explains that Cognizant was already seeing an uptick in adoption before the pandemic that extended into the early months of 2020. “What was interesting was that other than the first few weeks of the lockdown in March 2020, we did not see a huge fallout of adoption, which amazed us. We were expecting the activity to significantly drop, but it picked right back up really quickly. Now, we see 2021 as totally taking off on the site side and on the sponsor side. We attribute this to the growing use of decentralized clinical trials,” she says.

Jeffrey Kingsley explains that IACT Health is part of an investigator platform through hyperCORE International, a legal partnership of 10 high performing companies. IACT is a founding partner of hyperCORE, which started in 2019, and has evolved into a large, global clinical research site organization with more than 90 sites. To improve efficiency in site feasibility, all of the companies are mandated to use Devana Solutions, a site feasibility technology built on the Salesforce platform. Devana can instantly display and report trial performance metrics on all historic and currently running studies captured in the system. Kingsley remarks, “Within that software, we know everyone’s performance on specific types of trials, and with that transparency of the data, sponsors and CROs can easily see the best sites for their studies.”

Looking forward, Kingsley comments, “It’s about data, data, data.My wish for the industry is that we use data to eliminate all of the waste in the feasibility process. Stop wasting our time asking if we have a freezer. Let’s take steps to address all of the barriers from the site side, such as listening to our input as to how protocol design will impact recruitment and enrollment.”

To secure overall improvement to site feasibility in the long term, stakeholders are focusing on asking the right questions once, rather than repeatedly, all in an effort to speed the finding of the right sites with the right patients and digital readiness for DCTs. Technologies such as electronic health records, internal databases, and investigator platforms will be key as sites use this opportunity to meet enrollment goals by expanding their outreach to patients in underserved and more distant communities.

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https://www.appliedclinicaltrialsonline.com/view/covid-exposes-the-cracks-in-trial-problems

Cotliar J. How a Pandemic Accelerated the Adoption of Virtual Trials. 

https://globalforum.diaglobal.org/issue/may-2020/how-a-pandemic-accelerated-the-adoption-of-virtual-trials/

ICH Harmonised Guideline: Integrated Addendum to ICH E6(R1): Guideline for Good Clinical Practice ICH E6(R2). International Conference on Harmonisation. Available at: 

https://database.ich.org/sites/default/files/E6_R2_Addendum.pdf

Code of Federal Regulations. Subpart D—

Responsibilities of Sponsors and Investigators Electronic Code of Federal Regulations

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MBA, President, Medical deScriptions, LLC

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