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Applied Clinical Trials October 2020

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

Any clinical trialists hoping for a softening of insistence on randomized clinical trials in Germany will have been disappointed by declarations made on Monday by Beate Wieseler, head of the drug assessment department at the country's health technology agency, the Institute for Quality and Efficiency in Health Care (IQWiG). "We need comparative data comparing the new drug with the standard of care in a robust study design, which is a randomized controlled study," she told a webinar organized by the European Public Health Alliance in Brussels. This is essential, she said, to be able to judge whether a new drug has any added benefit over the therapeutic standard, to tell patients and physicians what they can expect from it, and to establish a fair price. "If we don't have comparative data, we can't answer these questions," she said. "Other types of study like single-arm studies are not robust data to answer them."

Her views do not align with those of many regulators and HTA bodies in Europe, which are experimenting with adaptive licensing and managed entry approaches that try to work round the challenge of evidence development on innovative medicines, particularly when they are destined for smaller populations. Granting conditional marketing authorizations linked to post-marketing reporting requirements is not a solution where evidence is incomplete, said Wieseler. "We have seen an increase in insufficient evidence," Wieseler said. "We would like to see the evidence we need for decision making at the point the drug enters the market, but our experience is it's not there at this point and we also don't get it fast in post-approval." IQWiG is not, it would appear, moving in the same direction as the UK's NICE, which is exploring managed access programs and real-world data collection already in its Cancer Drugs Fund, and is looking to expand the approach. The European Medicines Agency is also developing its Data Analysis and Real-World Interrogation Network (DARWIN) as a network of healthcare databases across the EU that can provide real world evidence;

Wieseler focused on the notorious difficulties in obtaining companies' compliance with post-marketing requirements, with promised studies often delayed, incomplete, or incapable of resolving the uncertainties that led to only a conditional authorization. Because of this, German legislation has been changed "as an act of self-defense," she said. Requests for post-market data collection can be backed up by restricting prescription to physicians who participate in data collection, and even by the threat of price decreases where uncertainties remain unresolved. And because low levels of compliance are often linked to the sheer cost of running further studies and data collection, Wieseler suggested that a mix of public and private-sector funding could ease those challenges: "In Germany we are spending about €40 billion per year for drugs alone, so we could have a tiny percentage of that to run publicly financed studies to really improve treatment for patients."

Her comments cannot be lightly dismissed. Wieseler is an important figure in the European pharmaceutical landscape, and IQWiG is one of the most influential HTA bodies anywhere. Germany is also by far Europe's biggest—and richest—drug market. So RCT is not going away anytime soon. Like gold, it is not easily transformed.

Articles

Declarations made by Beate Wieseler don't align with those of many regulators and HTA bodies in Europe and will prove tough to transform.  

Gold Standards Remaining Gold Standards for Germany's HTA

There has been much discussion on the move towards decentralized clinical trials (DCTs) amidst the wake of COVID-19, and a new movement (

) is emerging to push clinical operations personnel and biopharmaceutical enterprises to continue with DCT approaches in clinical trials. COVID has forced biopharmaceutical enterprises to move at breakneck speed to implement DCT approaches. However, many biopharmaceutical sponsors with little or no clinical innovation experience and limited resources have implemented poorly designed DCTs in a rush to sustain clinical operations during COVID. This poor implementation manifested in poor clinical quality, non-compliance, and good clinical practice (GCP) related deviations at study sites. In this article, I’ll discuss some of the significant forces currently impacting global operations, FDA foresight on operating clinical studies during COVID, and the subsequent compliance issues manifesting from poorly executed DCT operations.

recently emerged to continue the innovation spurred during the COVID pandemic. This movement’s approach suggests that the clinical trials industry has gotten a glimpse of the future of clinical trials, where clinical operations can run seamlessly, efficiently, and reliably by using future technologies and methodologies that support DCT execution. For example, many sponsors have implemented eClinical and decentralized technologies to keep the patient at home. Examples include eConsent, eSource, telehealth visits, home-nursing visits, and remote monitoring, to name a few.

One of the risks that this movement emphasizes is that the industry will go back to its old ways after the pandemic is over; The reality is that the pandemic is not going away anytime soon, and the world has radically transformed to a point where it is unfathomable to go back to the old ways of clinical trial execution. However, this risk is valid, as the clinical trials industry is very comfortable with implementing tried and true traditional methodologies of clinical trial execution, no matter the cost or impact on clinical trial efficiency.

FDA guidance during COVID-19 public health emergency

on operating clinical trials during the COVID pandemic has pushed sponsors to move towards DCTs. FDA specified in its guidance that “ensuring the safety of trial participants is paramount,” and that sponsors should do whatever it takes to ensure that patients are protected. Recommended strategies branch out to alternative methods of safety assessments (i.e., virtual and decentralized visits) whenever possible, home-nursing visits, shipping investigational medical products to the patients’ homes, modifying protocols to include any changes to visit procedures, and virtual monitoring visits.

The FDA also forewarned sponsors of the potential issues that may come from rapid decentralization, such as missing endpoint data (due to patient discontinuation, changes in study visit schedules, and missed visits), delayed data collection due to healthcare disruptions, and additional safety monitoring for patients who cannot access investigational medical product.

One of the most prominent sections and emphasis in this guidance document includes conducting informed consent remotely; it is clear FDA expected that there would be a significant influx of consent amendments, as they expected many sponsors to amend the protocols to incorporate changes related to operating their clinical studies during the COVID pandemic. The FDA outlines a complicated and convoluted process in its guidance if an eConsent is not available to the patient. For example, study sites are required to send the ICF to the patient electronically, conduct a telephone/video conference call with the patient, and provide sufficient documentation (i.e., identification of personnel on the call, review of the ICF and any questions patients may have, and obtaining verbal confirmation from patients of trial participation). Subsequently, the patient is required to sign a blank piece of paper with a written statement about their voluntary agreement to partake in a specified study and send a photo of that document to the site or mails it. Once received at the site, the study staff are to attach this document to the consent form and generate a note to file explaining the consenting circumstances with this method.

The FDA also expected that major deviations and GCP non-compliance issues would arise due to COVID control measures and monitoring changes. In its document, FDA specified that sponsors should implement alternative and decentralized approaches to monitoring to maintain trial participants’ safety and data integrity, such as enhanced centralized monitoring, phone calls with study sites to review updated study procedures, evaluate trial participants’ status, study progress, and conduct remote monitoring. However, FDA also recognizes that decentralized monitoring could result in missed findings, which would later be identified in on-site monitoring visits. Any missed findings and deviations are to be documented, and the cause for missing the deviations/non-compliance issues should expressly point to the modified monitoring procedures during COVID.

Some large biopharmaceutical sponsors were prepared and had the budgets to implement DCT measures, such as rolling out eConsent using established technology systems, adjusting their centralized monitoring practices, and implementing remote monitoring using specific technologies. These methods protected sites from non-compliance because these methods have been tested in clinical innovation pilots, have less room for human error, and could rapidly be verified by monitors. However, many other sponsors with minimal or no DCT or clinical innovation experience were left to scramble to put poorly designed methodologies together, which exposed study sites to GCP non-compliance and major protocol deviations.

For example, some sponsors have followed FDA guidance on conducting consent remotely and have not relied on eConsent technology. The implementation of such methodologies has resulted in poorly designed consenting case report forms (CRFs), a lack of proper consenting documentation, missed consent form signatures, and sometimes consenting couldn’t be verified due to staff turnover. Furthermore, monitors could not identify these deviations for several months, as sponsors did not equip their monitors with the appropriate technologies to properly perform remote monitoring visits. Now that new COVID safety procedures are implemented, and monitors can physically access sites, they discover a slew of major protocol deviations and GCP non-compliance issues.

How to make clinical innovation and DCTs work

Some large biopharmaceutical sponsors have enjoyed stepping into the future by implementing novel technologies that support DCT execution and seeing them work. Nevertheless, many sponsors who could not afford DCT technologies (do not know the return on hiring DCT vendors) and lack clinical innovation experience are left behind with major non-compliance issues and protocol deviations amidst the pandemic. Implementing DCTs must be done with the latest technologies and clinical operational design expertise to minimize human error. The examples I see first-hand prove that implementing DCTs using traditional methodologies will result in significant issues. Biopharmaceutical sponsors who have had a good experience with DCTs will likely support moving forward and #NOGOINGBACK, whereas sponsors who did not risk going back to traditional methodologies.

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

A discussion of the forces currently impacting global operations, FDA foresight on operating clinical studies during COVID, and the subsequent compliance issues manifesting from poorly executed decentralized clinical trial operations.

New Compliance Issues Emerge Amidst COVID Clinical Operations

The much-anticipated meeting of FDA’s vaccine advisory committee this week is slated to address a number of critical issues related to testing and approval of vaccines to prevent COVID-19 infection. Although the Vaccines and Related Biological Products Advisory Committee (VRBPAC) will not review an application for any particular product, this panel of virologists and scientists will discuss 

policies and data requirements for determining that a pandemic vaccine can be considered safe and effective

, particularly when based on more limited, early clinical trial data.

Shaping the discussion is the current halt in two major vaccine trials due to unspecified safety issues. U.S. investigators continue to seek more information on patient illness in the AstraZeneca vaccine study announced in early September, although enrollment has restarted for AZ trials in the United Kingdom and other countries. Johnson & Johnson more recently paused its massive COVID vaccine trial due to an “unexplained illness” in a patient. The safety committee for the study has stated by examining whether the ill individual received the vaccine or was in the placebo arm. The sponsors emphasize that these research halts demonstrate their excessive caution and importance of calling on outside monitoring boards to fully investigate such cases.

FDA standards for documenting vaccine safety is an important topic for VRBPAC review, particularly as it relates to granting Emergency Use Authorization (EUA) to an experimental vaccine, an approach that agency officials consider likely and appropriate given the high costs of the pandemic in terms of public health risks and economic hardship. The Center for Biologics Evaluation and Research (CBER) specified in its 

 that it expects an EUA application to provide two months or more of safety data for at least half of the participants in a trial following completion of the full vaccination regimen. As most serious side effects appear within six weeks of individual vaccination, this timeframe is designed to provide a sufficient period for detecting events such as vaccine-induced enhanced respiratory disease and to distinguish such conditions from coronovirus disease.

A particularly challenging issue for the advisors is the how granting EUA status to an initial product could interfere with further assessment of the vaccine’s safety and with ongoing trials for other preventives. FDA says that the sponsor of an authorized vaccine should continue blinded follow-up assessments for months following an initial distribution, but there some authorities believe that an EUA sponsor should shift all participants in the placebo arm to receive treatment. While that might appear a more ethical decision, it could block efforts to gain further information on vaccine efficacy and side effects, including rare adverse events and fuller comparisons among patient groups with differences in age, sex, comorbidities and ethnic characteristics. And because of limited information about how long immunity will last from initial vaccines, both manufacturers and regulators look for additional guidance on determining what data needs to be collected further to indicate when boosters or additional vaccination would be advisable.

Most analysts expect that some vaccines likely to gain approval in subsequent months may be more effective or provide stronger protection than the early products. However, continued development of alternative vaccines may be hindered by difficulties in enrolling new subjects in randomized trials when a vaccine is on the market. Scientists and vaccine developers emphasize that it’s vital for research to continue on multiple preventives, as certain products may affect certain populations differently, and varying formulations may be more suitable for distribution in certain regions.

These issues raise important ethical considerations for the research community and health authorities. While randomized, placebo-controlled clinical trials are necessary to understand the true effects of a medical product on larger populations, individual participants may gain limited benefit and added risk. And in the face of a lethal pandemic, the risks are even more stark. An alternative research approach may be to use a newly authorized vaccine as a control in testing subsequent preventives, a form of noninferiority trial. Such studies may take much longer and cost more to produce results but could reduce the need for large placebo control arms that deny treatment for thousands.

This week's much-anticipated meeting of FDA’s vaccine advisory committee will address critical issues related to the testing and approval of vaccines to prevent COVID-19 infection.

Early Vaccine Authorization Raises Ethical & Logistical Challenges for Trial Sponsors

In March, Clinical SCORE began a series of surveys with clinical trial site staff to better understand the challenges they were facing during the COVID-19 global pandemic, and how sponsors and clinical research organizations (CROs) could help. Results from the first survey, 

painted a bleak picture. Subsequent surveys showed 

for sponsors and CROs. After another three months, we reached out again to see how those challenges were evolving and if those needs were being met.

In total, 202 Principal Investigators (PIs) and Study Coordinators (SCs) responded. As in previous studies, about half of respondents were from sites in North America (55%), with site staff in Eastern Europe being the next biggest contributor (17.8%).

31% of respondents were from clinical practices and academic hospitals each, with the latter showing a response rate now similar to that seen in the first survey after significant declines in the second and third surveys. PI respondents, again, represented a variety of specialties, with cardiology having the largest influence (31%). What they had to say was both promising and consistent.

In looking at the responses from the first survey when the pandemic began through to this current survey, it appears that trial activity has increased. In the first three waves of the survey, only about 25% of sites had 10 or more active trials. In this current survey, nearly 60% of respondents reported having 10 or more active trials. Yet the overall mean number of trials per site remains lower than in April.

The focus of active trials has also changed. COVID-19 vaccines and treatments now make up 25% of the reported active trials, with the majority being conducted at academic hospitals. Interestingly, the specialties of the PIs at sites conducting COVID-19 studies extends well beyond the pulmonologists and allergists one may expect.

*Percent of all sites conducting COVID-19 studies.

These data from the fourth survey show a far lower percentage of respondents reporting that COVID-19 has had a substantial effect on the ability to conduct trials (33%) compared with the first and second surveys (56% and 52%, respectively). The burden of managing study supplies has also decreased, from 23% and 31% in wave one and two, respectively, to 16%. This overall trend in the easing of pandemic’s negative effect on staff is capped by the difference in the percent of PIs and SCs reporting that COVID-19 has had a substantial effect on site staff, which was as high as 73% of respondents in waves one and two, respectively, now down to 36%.

Sponsors responded but sites need financial support

Study site staff were vocal about their needs during the early months of the pandemic. As we reported in 

, the pandemic posed an opportunity for sponsors and CROs to demonstrate a commitment to front-line site staff and study participants.Financial support and protocol flexibility were most often requested by site staff facing economic uncertainty and difficulty in obtaining supplies, getting labs, and conducting visits.

Based on results of this recent survey, it appears that many study sponsors were listening to these calls. PIs and SCs rated sponsors overall as doing a middling job in their response to the pandemic, with a mean rating of 4.3 on a 7-point scale. These ratings did not differ significantly by type of site, geographic region, or number of ongoing clinical trials. Sponsors were given higher ratings for their willingness to create protocol amendments for conducting home or remote monitoring, and for home delivery of investigational medications. As one PI from North America said, “I think they did what they could. Let’s not forget that this pandemic took us all by surprise.” Ratings of sponsors’ willingness to deliver other forms of support was less favorable.

For example, 43%–55% of respondents said that sponsors made no attempt at all at providing assistance. As shown in the graph, there were several areas where this lack of response was notable:

Increasing the budget for home/remote monitoring

Increasing the budget for study subject travel

Increasing the budget to retain study participants in ongoing trials

Financial concerns and budgetary issues are clearly still plaguing site staff. For example, while sponsors made protocol adjustments for home delivery of medication, financial allowances were not made. “They should improve their budget to send medications to homes and encourage safe transportation,” said one PI from South America. With nearly 40% of respondents noting that COVID-19 has negatively affected the finances of their clinical trial site, it is a definite cause of concern for sponsors moving forward.

What lies ahead with clinical trial development is as uncertain as any facet of life in this pandemic era. But, as described in a perspective recently published in the 

, site staff are discovering adaptations that can benefit the industry beyond just those trials of COVID-19 treatments. We can continue look to what has and hasn’t worked in the past six months to help inform changes in the coming months. Some lessons and needs remain timeless and persistent:

Modifying the requirements for in-person visits is a relief on CROs, site staff, and patients alike and can help substantially in a trial’s ability to stay the course

With the healthcare industry competing with the general population for PPE, sponsors and CROs can help sites acquire the materials needed to safely conduct trials

The financial effect of COVID-19 shut-downs and delays may have yet to be fully experienced, but sponsors play a pivotal role at helping to mitigate the damage now

Honest, transparent, and timely dialog between sponsors, CROs, and site staff may be the linchpin in maintaining the relationships needed as trial programs look to continue or start in 2021

Surveys like this, and the insights gleaned from them, are a step toward fulfilling that later need. 

To read the full results report and uncover other ways sponsors can help, visit 

The authors would like to acknowledge Kristie Walters for her editorial assistance in preparing the article.

Lessons from six months of conducting clinical trials during the COVID-19 pandemic

Where Do We Go From Here?

COVID has caused many study disruptions, and the clinical innovation investments that big pharma companies put in before the pandemic are now coming into play. The concept of clinical innovation has changed, as have cultures on adopting clinical innovation. In this interview, Hassan Kadhim, Director, Global Head of Clinical Trial Business Capabilities, Clinical Innovation & Industry Collaborations at Bristol Myers Squibb, will discuss his perspectives on how the pandemic has shifted clinical innovation.

Moe Alsumidaie: How has COVID impacted the clinical trial environment?

When COVID began emerging, it impacted the workforce because we could not meet in person and collaborate with our stakeholders and designing studies and in planning for study timelines. From logistical and organizational perspectives, it has already affected the pharma industry and many different industries. As a result, there was an adaptation going from in-person schedules to fully remote collaboration for a long, sustained time. But on top of that, where it impacted clinical research the most is the patients. First of all, healthcare institutions, especially at the peak in March and April, were getting overwhelmed with COVID cases. Suddenly, what we observed was that the hospital networks had to rightly prioritize the acute crisis by treating COVID patients and patients suffering from life-threatening diseases rather than from other indications and conditions.

For clinical research, patients started thinking twice before going to the sites, which created the situation for us in pharma to find solutions and quickly address recruitment, enrollment, and retention. Despite that, many pharma companies put a halt or a pause to their clinical research portfolio, which has delayed many study starts, study enrollment, and forced everyone to rethink what we can change to adapt to this new environment.

What was that experience like internally?

 They say necessity is the mother of invention—and by the same token, innovation. COVID has created the necessity for innovation. It has forced everyone to think differently because the entire environment around us has changed, and we all realized that clinical innovation was a necessary tool to enable new approaches for designing and implementing clinical trials. Organizations that had a head start (i.e., they had vital clinical innovation programs, had experimented in many different approaches and technologies, whether it’s decentralized trials or remote monitoring, or really anything that in the past (pre-COVID) was considered maybe a nice-to-have at the time) experience an easier transition to the recovery efforts compared to organizations that did not invest in clinical innovation. 

Nonetheless, for everyone, this experience reinforced and emphasized the need for innovative trial approaches as it really came down to portfolio continuity. If you want to continue doing clinical trials, you likely cannot continue doing them in the old paradigm and ignore the impact of COVID-19. Maybe you can do it for some sites, for some regions, but on an enterprise level, on a global level, knowing that the pandemic was a global occurrence, we noticed a varying degree of impact in different countries and different regions.

MA: What is it like for managing in-person visits, say from patients to monitoring visits?

When there are surges in COVID cases, you will find that patients will have the valid question come back to their minds: “Should I go to my clinical trial visit? Is it that important? Should I risk myself of being infected?” So, anything that enables patients to participate remotely will be critical. Anything that allows the transfer of data directly from the electronic source (i.e. eSource) will be a difference-maker. Remote monitoring has also become increasingly important; CRAs, for example, may be asking: “should I go to the site and expose myself?” or, “can I do monitoring activities differently or remotely?” If we enable remote monitoring, that could also be a difference-maker from an efficiency perspective for running trials. When we are forced to think about how we adapt those components to enable clinical research, we will likely see that the long-term impact of the COVID crisis may be further adoption of innovative trial approaches and hopefully sustaining that kind of flexibility in clinical trials to drive real change.

MA: What kinds of technologies are now in demand to be used in clinical trials?

Anything that enables patients to participate remotely, providing flexibility for patients to be in the trial. We noticed that with COVID, many sites, especially big institutions, have now adopted eConsent as a platform for trials that they conduct. This was also in some cases a mitigation measure in a pandemic to keep trials running. To emphasize, this is the site adopting eConsent, not the sponsor pushing eConsent to the site. We realized many sites are not only interested but are going full-blown implementation with eConsent in their practice. As a sponsor, it’s time for us to consider eConsent as a commodity and not an innovation, and address working with sites that have eConsent versus those that don’t and how do we create this ecosystem, where multiple eConsenting modalities are all considered valid is something sponsors will need to adapt to.

The same is true for telemedicine. We know that several healthcare institutions were already using telemedicine in their familiar healthcare setting, but now the necessity created with the pandemic brought an immediate need to use telemedicine in their clinical trials as a mitigation measure. Some sites already had telemedicine solutions; others didn’t. Sponsors are thus left with the optionality of using the site’s own telemedicine technology, or push telemedicine as a solution to the sites. I think a flexible ecosystem is probably the happy medium we as an industry need to strive to, where the site will use their own telemedicine platform when available and get the sponsor’s telemedicine provided solution where the site doesn’t have one available. And all of that in the same study! This “trial-with-options” mantra is where we need to adapt to as an industry.

And then, of course, it raises again to the forefront the approach of decentralizing clinical trials, so allowing a fully remote approach in some cases or a hybrid in other cases, or just a flexible model where for the majority of visits in a study, the patient has the choice to do the visits in person at the clinic, or remotely using technology.

MA: How has COVID changed the culture of adopting innovation in big pharma?

I'm sure you probably know about the innovation adoption life cycle, where whenever there's some innovation that's introduced in any industry or any market, there's usually the innovators that introduce it, then there's the early adopters, the early majority, the late majority and then the laggards. If an innovation is really good and provides real benefit, with time everybody adopts it and that time could take months to years, but it's generally a question of time. I think what COVID did, is change the culture of innovation, where for some of these innovations, we were probably in the pharma industry at a stage of, having a good portion of early adopters, but the early majority hadn't really joined. What COVID did is it pressured the system so much that it accelerated the transition from early adopters to early majority. By the same token within clinical innovation, there has been a culture shift towards accelerating many of the innovations that were in the pipeline to help us prepare for the future. I think this is the cultural shift that everybody recognized is needed to mitigate the very real (and now realized) risk of disruption of clinical research due to a pandemic. The rest remains on us as an industry from a tactical perspective and change management on implementing and enabling the adoption those innovations to work for our studies, sites, and patients. There’s still much work to do, but what changed is the perception of the culture and its sentiments.

MA: What will clinical innovation look like in the future?

Innovation means different things to different people, and what’s an innovation today, may no longer be called innovation in 10 or 15 years (or less). For example, EDC, which 20 years ago, was the innovation of the hour is now a standard technology that is essential for every trial. I think what COVID has done is that it propelled all the things that we call innovation today in 2020; it has accelerated their trajectory to no longer stay in the “innovation” category for too long. In the future, I think that decentralized trials may become the norm in the industry. Post-COVID, I think there will still be innovations that perhaps we haven’t thought of today.

I think when the dust settles and we as a society come out of this pandemic, we will look back at this period as a period that really pressured everything to accelerate the innovation of its time (for many different industries).

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

Hassan Kadhim, Director, Global Head of Clinical Trial Business Capabilities, Clinical Innovation & Industry Collaborations at Bristol Myers Squibb, discusses his perspectives on how the pandemic has shifted clinical innovation.


COVID Shifts Clinical Innovation in Big Pharma

has joined the company as Senior Vice President, Europe and Managing Director, Germany.

 has been appointed CEO of Raremark and former Head of Product, 

as Vice President of Human Resources and Culture.

Medable Inc announced several new hires including 

as Head of Site and Investigator Network, 

as VP of Decentralized Trial Innovation, 

announced that more than 500 in over 30 countries are using Veeva SiteVault Free.

, for the 4th year in a row, has been named a “Leader” in the Everest Group Clinical Development Platforms Products PEAK Matrix Assessment 2020. Oracle also maintained its position as the highest positioned vendor in “Vision and Capability” and took the highest position for “Market Impact.”

announced that it was awarded the Society for Clinical Research Sites (SCRS) Eagle Award

The latest happenings of the industry from the past month.

People and Business News

In the face of the pandemic, more coronavirus clinical trials are being planned and initiated, while a large number of studies for non-COVID-19 indications are suffering delays. Much of the disruption can be attributed to measures taken to ensure patient safety, such as strict lockdowns and social distancing, as well as the high demand for medical professionals to treat and manage COVID-19 patients.

Across the clinical research community, we’re seeing a direct impact on trial site activation and patient enrollment. Many investigative sites are either being reallocated to assist in front-line COVID-19 care or have been temporarily closed, with much of their staff presently furloughed, making it harder for existing, pre-pandemic trials to continue. Consequently, many sponsors have implemented alternative ways to conduct trials or components of them, incorporating remote and virtual activities, which aim to bring studies directly to patients via a range of technologies.

While the pandemic has presented the industry with a host of operational challenges, COVID-19 has also given us the opportunity to reflect on how we can improve the clinical trial experience.

A focus on better understanding patients’ journeys through the clinical trial process and their interactions with investigative sites in the midst of the coronavirus crisis has prompted an important question: How can sponsors set up sites for success in a post COVID-19 world?

The answer largely lies in addressing existing pain points for investigative sites, pain points that predated the pandemic, including those around protocol development, staffing, payment schedules and, last but not least, patient engagement.

A true partnership between sponsors and investigative sites must emerge that prioritizes proactive planning and listening, enabling the development of solutions that allow critical clinical trial work to not only continue, but expand, accelerate, and thrive.

Whether independent or an academic medical center, investigative sites have long been asking for changes to overcome the many pain points that delay or hamper clinical research. Essentially, these are old problems, but now they present themselves with a new twist because of COVID-19 and there is an impression that the issues are completely different from those clinical trial sites have always faced.

For example, sponsors notoriously leave sites out of protocol development, which we are well aware of in the industry. Every clinical investigation begins with the development of a protocol that describes how a clinical trial will be conducted—encompassing the objective(s), design, methodology, statistical considerations, and organization of the study—and ensures the safety of the trial subjects and integrity of the data collected. These documents are already quite complex, and now amid the pandemic, sites are expected to add requirements like negative COVID-19 tests as a prerequisite for patient participation and to do so without any support from trial sponsors.

Being left to navigate new requirements and complexities, and somehow still find the right patients for a clinical study is not an entirely new challenge for sites. We often hear sites say things along the lines of: “this inclusion/exclusion criteria is going to yield zero patients because we can’t find patients who meet the protocol requirements,” whether, for example, that is a specific cholesterol test or body mass index (BMI). Rather than expecting sites to just ‘figure it out” on their own, sponsors must focus on optimizing protocol design by better matching the right types of sites with the right types of studies (e.g., institutions for oncology vs. independent sites for vaccines).

Similarly, staffing challenges at clinical trial sites have always been a source of frustration, but amid the pandemic, these frustrations are being heightened. Where studies went on hold, new COVID-19 treatment and vaccine trials continue to start and, more recently, non-COVID-19 studies are ramping up again. Many independent sites, as well as academic institutions that conduct trials, suffer from staffing bottlenecks, which are intensifying because of COVID-19. For already overloaded study coordinators, who generally are without the support of a dedicated team or on-site resources, the workload has increased to a point where it has become nearly impossible to manage without additional support from service providers.

An increasing number of independent sites are offloading administrative functions so that their staff can concentrate on more clinically-focused activities. However, while independent sites are scrambling to do this quickly, larger institutions are unable to pivot and adapt at the same pace. Particularly in urban areas where hospitals are doing all they can to stay afloat, many studies have been put on the backburner and research team members, such as trial nurses, have been reassigned to help manage everyday healthcare needs, including those that involve COVID-19 triage.

That said, where staffing for clinical studies continues to be prioritized within hospital settings are cases in which research is the only care option for patients who are terminally ill, such as those enrolled in certain oncology trials.

COVID-19’s impact on clinical trial sites is much more nuanced than simply stating “the study went on hold.” A giant pain point has to do with the fact that many sites, particularly hospitals, are struggling financially. Elective and other non-essential procedures and surgeries are still a challenge to schedule and perform because of the coronavirus. This leaves hospitals and other investigative sites with the bleak reality of having to deal with reduced profitability and, consequently, furloughs, a slimmed-down staff, and even less flexibility to leverage service providers for resourcing needs.

Financial stress is a well-known challenge to clinical research site success and, again, the pandemic has simply exacerbated this pain point. Limited operating cash, manual invoicing processes, untimely payment frequency, and lack of financial transparency negatively impact site engagement and, for the most part, stem from antiquated payment terms and triggers. Investing in technologies and processes that ensure payments are accurate and on time will go a long way to resolving these issues and improving site productivity. Additionally, rather than using payment “holdbacks,” sponsors can employ alternative methods, such as better and more transparent monitoring plans to hold sites accountable for resolutions to queries.

Effectively tackling the industry-wide issue of delays in the execution of clinical trial agreements (CTAs) between sponsors or their CRO partners and sites is another measure that can be taken to meet the needs of sites in a post-COVID-19 world. Currently, we’ve seen a 10% increase globally and 13% increase in the U.S. to finalize a CTA for large research institutions. What’s interesting is that independent sites have seen a decline in the overall time of negotiations (for all trial types). Furthermore, most COVID-19 CTA negotiations are completed in less than a week, when the typical timeframe for non-COVID-19 trials can be more than three months. These differences between trial and site types need to be captured in sponsors’ templates and expectations. Standardizing legal language and streamlining the process with solutions—which address the needs of both independent sites that have limited legal resources and academic institutions more concerned with IP, indemnification, and government funding requests—would speed up study start-up by weeks, if not months.

The urgency around developing treatments and vaccines for COVID-19 has also made it clear that existing technologies can be better leveraged to address trial inefficiencies, reduce the burden on both patients and sites, and accelerate progress in clinical development. As a result of the pandemic, we will see more hybrid trials that combine site and remote patient visits. More clinical trial protocols will be written with decentralization in mind, as sponsors have now seen first-hand how positively sites have responded to working with technologies—such as telehealth tools, electronic patient-reported outcomes, and wearables, for example—that enable this approach and simultaneously reduce the burden on sites and their patients.

The decentralization of clinical trials, of course, comes along with challenges for investigative sites as well. Putting new standard operating procedures and processes in place for the conduct of remote visits adds complexity, as does incorporating and adjusting to technology designed to support them and improved patient engagement and retention. Again, at their core, these are not inherently new challenges, but the pandemic has provided an opportunity to revisit our approach to tackling pain points. In forcing the research community to be more open to using different tools to ensure vital research continues, the pandemic is driving the beginning of a new era of patient and site engagement—one in which a more proactive and efficient approach ensures the lines of communication remain open and data is collected appropriately and with greater speed.

On the flip side, sponsors will need to carefully manage which and how many technology tools they ask investigative sites to use in a given research study. Imagine a site with 10 studies from different sponsors and how many different technologies and systems they need to learn how to use in order to be successful. That problem only gets compounded as a site runs more trials for more sponsors, and some sites have as many as 400 studies ongoing at once. What it comes down to, in this case, is less is generally more. Investing in best-in-class technologies that are consistently and more commonly used across the industry, rather than customized systems, will reduce the burden on sites, especially as the disruption caused by the pandemic lessens and the volume of non-COVID-19 trials increases.

Finally, with the more open mindset the pandemic has brought about, sponsors should be more willing to use new sites for different indications. The decreasing number of primary investigators conducting research means we cannot only rely on sites we have worked with previously. Sponsors and CROs must embrace research-naïve sites in order to hit FPI (“first patient in”) and enrollment goals.

Additionally, to ensure patients in clinical trials are representative of the population, an emphasis must be placed on diversity. We know this is an issue today, so we must do all we can to introduce new sites into the mix, in locations that represent the demographic diversity of the populations we aim to serve. In doing so, we will help to move the needle and meaningfully improve outcomes for more and more patients.

Vice President, WCG Study Start-Up & Administration, 

Recognizing pre-pandemic pain points, such as patient engagement and protocol development, could lead to post-pandemic trial success. 

Addressing the Needs of Clinical Trial Sites in a Post-COVID-19 World

The COVID-19 pandemic has been a lengthy, and uncomfortable pressure test for our global healthcare system. In the long term, we hope that 2020 will prove to be an inflection point for positive change, an urgent call to action to address the bottlenecks that have gotten in the way of a more efficient and effective way of improving human health. In the short-term, however, there have been more immediate and acute concerns about the ability of clinical development to continue in the face of widespread infection; how will patients continue participation when leaving home poses a significant risk?; what happens to patients who are relying on speedy development of life-changing, even life-saving, treatments? 

As clinical trial sponsors faced unprecedented roadblocks, many quickly realized that speed and agility would be key if they were to steer their way through COVID-19 and ensure that research, discovery, and patient care were not completely obstructed. One critical area of focus was maintaining a strong site relationship strategy, and as countries move beyond the initial disruption of lockdowns, it is clear that the lessons learned in this area will be critical for ongoing efficiency and productivity in the “new normal.”

Without a doubt, the pandemic experience has exposed a number of shortcomings, some directly related to the current situation, but others more systemic. The subsequent assessment has left some sponsors reimagining what strong site relationship strategies in the future may (or rather, should) entail.

An effective and agile site strategy starts with viewing trial sites as valued partners throughout the entire clinical development process, not just a single stop on the way. By maintaining deep, ongoing relationships with sites and their patients, sponsors and their clinical research partners are able to quickly incorporate innovative approaches to adapting to obstacles at hand, like COVID-19, or increase efficiencies within the trial process.

It can be extremely valuable to categorize sites based on several partner factors to determine optimal ways and times to consider involving them in trials of interest. In a sense, this can position sponsors to assess their “go-to” site networks based on needs as they arise.

 An elite clinical trial institute or site network has a long-standing relationship with the sponsor and CRO, with each heavily dedicated to ensuring growth and pushing innovation through mutually agreed upon key performance indicators. Such elite networks often work across multiple therapeutic areas or in singular, but high-volume therapeutic spaces and go above and beyond industry benchmarks to meet a trial’s requirements. In some cases, sponsors and sites have dedicated relationship managers to oversee and grow the alliance, ensure quality delivery of various trials within the portfolio, and continuously seek new opportunities to collaborate further. For some organizations, including IQVIA, these institutions are already informed and fully engaged in leveraging our tech-enabled solutions and data insights to meet our customers’ key study deliverables.

 On another level, sponsors and CROs may partner with a research institution or site network with a proven track record of quality performance in managing studies and the ability to meet anticipated needs within varying therapeutic spaces. They may have some experience with a sponsor or CROs’ solutions, but will work to perform at or above industry standards for varying trial needs, such as site start-up and recruitment. And therapeutic sites can continue to expand research capabilities to include additional specialties. The history between site and sponsor can organically help with that expansion.

 Lastly, it is essential to develop therapeutic network strategies in specialist areas, such as rare disease and cell and gene therapy. These networks work with expert sites and investigators in a specialized field to ensure the appropriate capabilities are in place to meet the trial and patient needs.

In these times, we see how strategically important it is for sponsors to maintain several diverse partnerships to maintain trial continuity for patients in need.

As some countries experience resurgences in COVID-19, some sites may need to close or make quick changes over the coming months. It is helpful for sponsors to adjust quickly by knowing what sites they can turn to and keep trials on track. In a long-term strategy, sponsors need to anticipate challenges in their pipeline programs and address them with foresight. Maintaining diverse partnerships can help match up trial needs with individual site capabilities, as part of a proactive strategy.

Enhancing patient-to-trial matching capabilities

In traditional clinical development, investigators guide patient recruitment. During the initial months of the pandemic, when almost every aspect of clinical development was on hold, patient recruitment proved to be a tremendous concern for sponsors. With patient interest in trials increasing, it was essential to carve another path to reach them and connect them to trials.

As an example, to optimize patient recruitment, IQVIA uses a layered approach, efficiently utilizing our relationships with partner sites. First, recruitment starts with sites that have strong, comprehensive patient databases. These sites are highly qualified research sites. Because of the access to large numbers of potentially qualified patients onsite, staffing levels may be a limited concern in quickly contacting and qualifying patients within its systems.

To secure additional patients, we also rely on proprietary healthcare data assets and modeling algorithms using artificial intelligence and machine learning to create a direct-to-patient recruitment model. This approach allows sponsors to aid sites with recruitment by providing additional qualified patients for ongoing trials from our trial matching capabilities. By broadening the identification of patients beyond the site’s database, we are able to rapidly recruit participants and execute hyper-targeted multi-channel campaigns (e.g., social media, pharmacies, labs, patient communities, etc.) to also raise awareness of trials in their local markets. Delivering the right message at the right time is a key component of this model, which can be a productive way to engage patient populations quickly during downtimes and with limited resources.

To keep up with the potential volume of patients for ongoing trials, it is important to maintain the appropriate staffing levels when multiple protocols are enrolling at the same time. During the pandemic, maintaining appropriate staffing became a challenge for some sites. In these cases, qualified research staff were assigned to work at the direction of the principal investigator. Augmenting the staffing model played a key role in accelerating recruitment.

As sites reopened and targeted patients opted-in for participation, it was useful for sponsors to consider relying on the expertise of the global site network teams to provide experienced study support to reduce site burden and continue high-quality patient care throughout the trial.

Also, during the pandemic, routine patient visits with their providers decreased due to their own safety concerns and restricted access to critical patients only. The reduced patient volumes and corresponding billing reduction led many sites to furlough staff and/or reduce staff numbers and hours, creating more trial onboarding delays.

Another creative way IQVIA dealt with these delays was to re-engage furloughed site staff using sponsor funding, and temporarily engaging these staff through the global site network infrastructure to return and focus on specific protocol tasks.

This sponsor-funded approach allowed study sites to retain/bring back trained employees who know the appropriate trial protocols and steps to reduce onboarding time. By working with sites to augment staffing, sponsors know that trials remain on track despite roadblocks. If sites were bringing in new staff, these individuals would need to be trained on both research protocol and site-specific policies and practices, which would add time and cost to an already delayed trial process. As soon as the site research and patient care levels returned to normal rates or immediate protocol needs were fulfilled, staff would be able to return to regular activities, where funding would revert back to sites, not from sponsors.

The future is still uncertain, and while we don’t know exactly what a “post-COVID-19” world will look like, we do know that sponsors will need to consider trial site networks as partners to continue bringing important therapies to patients in need, both in the aftermath of this pandemic and in preparation for others in the future. Maintaining a thorough site relationship strategy for ongoing programs is part of a more holistic approach to trial design that is proving to be useful during the pandemic and may help shape the future of clinical development.

Vice President, Global Patient and Site Solutions, IQVIA

Evaluating the lessons learned about trial sites from COVID-19 to form new strategies and improve patient safety for the future.

Shifting Perspectives on Site Networks to Create Positive Change

While participation in clinical research offers potential access to promising new treatments, it can also be a challenge for patients due to the burden of trial appointments and the need to travel to a clinical research site that may be far from home. These challenges can become overwhelming, especially if the study participant is seriously ill or is a child. For many study participants, in-home visits from a clinical trial nurse may be a welcome alternative to on-site visits. These in-home visits may also benefit sponsors as they can enhance recruitment and retention without sacrificing data quality, all while increasing patient centricity.

Industry guidelines advise sponsors to reduce the emotional and physical burden of study participation and to consider the convenience of participation for both patients and their caregivers.

With mobile research nursing, a nurse goes to that patient’s home —or any other location that is convenient for the patient—to conduct off-site visits and perform study-related assessments and data collection. These off-site visits ease the burden of study participation by allowing clinical trial obligations to be completed in the comfort of the home and at the convenience of the patient and their caregivers. Bringing the trial to the patient also offers the opportunity to strengthen study engagement, especially if the patient is visited regularly by the same nurse who is familiar with their health and circumstances.

According to the Deloitte Center for Health Solutions, more than 70% of all clinical trial participants live more than two hours away from the clinical research site. The need to travel long distances for frequent follow-up visits may deter eligible patients from enrolling in a study. Offering the attractive option of off-site visits with a mobile research nurse expands the patient population available for recruitment by making study participation accessible even for those with limited mobility and those who do not live near a clinical research site.

 Even the most motivated clinical trial patients may find traveling to sites inconvenient or difficult, especially if they feel unwell. The COVID-19 pandemic and associated travel restrictions have made site visits even more challenging. With mobile research nursing, clinical research visits can be performed where and when it best suits patients and their caregivers.

At Illingworth, we augment our mobile research nursing services with patient concierge services that help patients get to site visits when they are required to do so. These services, which may include travel bookings, expense reimbursements, and other customized features, are uniquely configured to take into account the patient’s specific needs and limitations.

 Reducing the burden of trial participation often goes hand in hand with improving retention. In fact, one survey of clinical trial participants found that 38% of those who dropped out of a study did so because they found site visits to be stressful.

Mobile research nursing contributes to reductions in patient stress without compromising study design or data quality. Indeed, throughout the COVID-19 pandemic, mobile research nursing has enabled patients to continue to participate in clinical trials even when sites were locked down.

 When they need to travel long distances to sites, patients may be exposed to conditions that affect their ability to perform certain physical assessments. Even the disruption of typical routines can impact data quality as patients may become fatigued or exposed to other illnesses while traveling. Mobile research nursing can alleviate these confounding factors by eliminating the need to travel or rearrange daily life activities. In addition, mobile research nursing visits enable site staff to assess the safety of their patients at timepoints when they might not otherwise be able to due to scheduling conflicts or unforeseen circumstances, such as the current coronavirus public health emergency.

Over the past two decades, there has been a significant shift within the clinical research industry regarding inclusion of off-site data acquisition options. This is due, in part, to increasing emphasis on patient-centricity and wider acknowledgement of the patient as a partner in clinical trials—not just as a participant. Researchers today are more likely to engage with patient advocacy groups, and what they are hearing is that patients welcome the opportunity to participate in clinical trials as long as the experience is not overly burdensome. Mobile research nursing helps address that need.

Taken together, the benefits associated with mobile research nursing can help sponsors complete trials on time, with improved recruitment and retention and increased patient and caregiver satisfaction. When the cost of mobile research nursing is balanced against the cost of dropouts and delays, having the ability to offer in-home visits may be appealing to all stakeholders.

With the emergence of COVID-19 and the associated site closures and travel restrictions, many clinical trials came to a halt. Sponsors of existing studies that did not have off-site capabilities turned to mobile research nursing as an option to keeping studies on track. In turn, mobile research nursing providers were tasked with adapting their processes and procedures to ensure the safety of both their nursing staff and study participants. This agility and flexibility in times of uncertainty is invaluable for keeping studies moving forward.

Patients are surrounded by caregivers and families whose lives are also impacted by participation in a clinical trial. On-site visits can put stress on a patient’s support network in terms of time away from home, school, work, and potentially lost wages. In many cases, such as rare diseases, pediatrics, and conditions with limited treatment options, patients and their caregivers will enroll in clinical trials regardless of the inconvenience involved. Participation, however, takes its toll over time.

Technological advances, such as electronic patient reported outcomes, wearables, and telemedicine, have broadened the spectrum of procedures that can now be performed off-site or in the home. With technology, the number of clinical trials that could be conducted with the option of mobile research will continue to increase.

Having a nurse come to the patient eliminates the time a patient, and in some cases their family, would otherwise have to spend traveling and sitting in waiting rooms. Altogether, it makes the mechanics of clinical trial participation less disruptive to a patient’s family life, as well as to their educational and professional lives. Moreover, mobile research nursing offers the patient-centric features of customization and personalization of the clinical trial experience, delivering care in a manner that reflects a patient’s individual preferences and personal situation.

Mobile research nurses are an extension of the team at the study site. A best practice for integration with site staff is to have every nurse approved by the site and named on the delegation of duties log. As these nurses will be performing activities on behalf of the site, it is important for the nurses to engage and build strong relationships with site staff. In-person meetings with site staff are optimal, as this creates opportunities for the mobile research nurses to share their background and expertise. It is also critical to establish a consistent flow of communication between site staff and the mobile research nurses throughout the course of the study.

Another best practice that can help make the clinical trial experience seamless for study participants is for principal investigators (PIs) to discuss the mobile research nursing option and explain how in-home visits will work. Keep in mind that it is entirely up to the patient whether to opt in for mobile research nursing.

A rigorous onboarding process is also essential to successful integration. In an ideal situation, the study participants and their families are invited to meet the mobile research nurse at the clinical research site in advance of the first in-home visit so everyone can become familiar with each other. Of course, adjustments should be made when patients/families cannot travel to the site for these introductory meetings, for example, in the time of a pandemic.

Close communication between the mobile research nurse and the site team to discuss details of the upcoming visit, such as adverse events to follow up on and changes to medication, enhances the quality of care and the nurse’s role as an extension of the site team. Further examples include handling all visit requirements, coordinating with the pharmacy and the courier delivery of the investigational product to the visit location, bringing all equipment necessary to perform the required assessments, and transferring any samples to a courier for delivery to the laboratory. If any serious adverse events are noted, the nurse must immediately report them to the PI and take appropriate action where necessary.

Selecting a mobile research nursing partner

For those exploring mobile research nursing as part of their clinical development plans, here are a few key questions to ask a potential mobile research nursing provider:

Look for providers who offer registered nurses with not only many years of clinical experience, but also specific clinical trial experience in your therapeutic area of interest. You should also ask if the mobile research nursing provider can serve all the geographies where off-site visits may be needed.

2. How are nurses trained to conduct the assessments specified in the protocol in an off-site setting?

The mobile research nursing provider should also have a robust onboarding and training process. In addition to being thoroughly trained in good clinical practice, mobile research nurses should be trained in study-specific procedures.

3. How does the company ensure the quality of the data captured by the mobile research nurse?

Ask about the mobile research nursing provider’s standard operating procedures and the processes they utilize to oversee their nursing staff. Ideally, the provider will prepare and train all nurses on a home care manual that explains all the procedures to be performed at each specific time point. Ongoing data reviews to ensure accurate completion of source documentation with feedback to the nurses enhance data quality and good documentation practices.

The provider should be able to demonstrate a high level of nurse oversight, comprehensive training approach that ensures their nurses can function independently in the field, and a commitment to only hiring nurses who are eager to be integrated into the on-site trial team and dedicated to patient safety and patient centricity.

Fewer than 10% of clinical trials are completed on time. Many studies simply get shelved due to incomplete enrollment. Consequently, study sponsors are continually searching for ways to overcome obstacles in recruitment and retention.

For many, reducing patient and caregiver burden related to clinical trial participation is a top priority.

The rise of mobile research nursing using highly trained practitioners with a diverse skill set harkens back to the bygone doctor’s house call, when care was home-based. Whether at home, school, work, or elsewhere, mobile visits reduce patient and caregiver requirements, providing flexibility and giving study participants more control while addressing key issues for sponsors.

International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use: “Addendum to ICH E11: Clinical Investigation of Medicinal Products in the Pediatric Population,” Aug. 18, 2017. Available at 

https://database.ich.org/sites/default/files/E11_R1_Addendum.pdf.

Forte Research: “Retention in Clinical Trials: Keeping Patients on Protocols,” Jan. 23, 2020. Available at 

https://forteresearch.com/news/infographic/infographic-retention-in-clinical-trials-keeping-patients-on-protocols/.

With the assistance of mobile research nursing, in-home visits provide solid alternative to trial participants, especially during COVID-19.

When Trials Stumble, Mobile Research Nursing Lends a Helping Hand

Nearly two-thirds of clinical research sites say they are willing to conduct hybrid or virtual clinical trials, and more than half say they would do “whatever is required” to conduct a virtual study.

 Patients are also eager to participate. In a recent study, 75% of patients say that collecting all study data from their own home is appealing and 73% like the idea of a hybrid trial.

While the convenience, speed, and potential data quality improvements that come with decentralized clinical trials (DCTs) are inspiring, implementing DCTs can seem intimidating to investigators who haven’t participated in largely virtual studies.

“Consider how to embrace DCTs in a way that creates opportunity for your site and your patients. We must innovate to meet patient needs,” said Amanda Wright, vice president of partnership development at Javara, an integrated research organization that, in partnership with Wake Forest Baptist Health, is working on a Phase III clinical research study to evaluate the safety and effectiveness of mRNA-1273, a vaccine candidate against COVID-19 sponsored by Moderna. “You don’t have to decentralize every element of every study. Start where you’re comfortable. Carefully evaluate which components of each study can be decentralized, such as using remote monitoring devices to collect vitals such as weight and blood pressure without an in-person visit.”

With proper evaluation and planning, sites can avoid unexpected obstacles and reap the benefits of a DCT. Here are five key considerations to enable an easier transition to decentralized research.

1. Change management: Know what to expect

DCTs do not mean studies are entirely virtual, and often follow a hybrid model that leverages digital technologies like eConsent, telemedicine, wearable devices, electronic clinical outcome assessments (eCOAs), and electronic health (eHealth) records for various parts of the process. These technologies can improve patient centricity by reducing the burden of in-person visits and manual activities like paper diaries. Additionally, DCTs provide patients with interpersonal reassurance and support with technology to enable interactions at a time and place that suits patients and caregivers, which often leads to a better-quality interaction.

The obstacles to DCTs for sites range from fear of irrelevance, difficulty transitioning from paper to technology, the potential for patient resistance, patient populations without access to the internet, and concerns about data security and privacy.

Sites can overcome those challenges to improve outcomes and experience for all stakeholders. DCTs benefit sites by providing

Expanded trial access and diversity of participants

Improved patient engagement and retention

Expedited patient identification and cost reduction

Increased capacity for additional studies

As sites become more comfortable with DCTs, they may realize that DCTs can actually enable a closer patient-physician/site relationship than a traditional, randomized clinical trial can. DCTs enhance the patient-physician/site relationship in a virtual world by providing modular options and more choices.

Even so, a thorough change management process is imperative. Map out the options best for your site and include those that are already part of your infrastructure (see Figure 1 below). When creating messaging to staff and patients about the new options, for example, reinforce that it is an opportunity to ease burden and improve the workflow for everyone. Highlight to study teams, investigators, and patients that there will be choices about how to participate in a study.

“Preparation is key. You may need to customize your strategy for subgroups that are less comfortable with technology. It’s also imperative to understand your population’s access to the internet. This will help inform your search for the right technology partner and your implementation plan,” explained Patricia S. Larrabee, founder and CEO at Rochester Clinical Research. “Staff will be excited that data collection is faster, in real-time, and that the risk of losing paper documents will diminish. Televisits are not without challenges, but they have allowed us to continue studies during the pandemic. We always need to be ready to see patients remotely and sometimes after hours, particularly to assess adverse reactions. DCTs make it possible.”

2. Technology:What to look for in partners and solutions

There are several technology solutions in the marketplace, so it can be challenging to evaluate what is best for each individual organization. Of course, a DCT technology solution must support principal investigators in managing the care and safety of patients, but what else should be considered? Should it be an end-to-end product that covers all your technology needs? Does the solution accommodate hybrid studies? What is important to look for in the user interface?

Typically, there’s no need to do a complete technology overhaul. The best approach is to integrate all systems, including existing systems, and ensure your primary solution is built modularly. It allows sites to customize which studies, or parts of a study, to decentralize, as not every site or patient is ready to digitize every element of the process. As critical, the platform must seamlessly integrate with wearables and patient-collected data.

“No one needs one more piece of technology that doesn’t talk to your other systems; it needs to integrate,” said Larrabee. “And even more so, it should not require a software engineer to use it.”

When it comes to ensuring patient centricity, opt for a solution that has a simple, single sign-on to provide patients with ‘one way in and one way out,’ as Wright suggests, to minimize the learning curve. This will also significantly reduce tech support burdens for sites. Another important consideration for patients is internet access. Look for a system and provider that can meet the needs of participants without consistent internet access. For example, some DCT vendors provide devices that can work as hot spots.

Decentralized clinical trials (DCTs) have ignited clinical transformation while the COVID-19 pandemic has fueled their rapid expansion.

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Applied Clinical Trials October 2020