The average investment in recruiting just one patient for a clinical trial has been 

 to be as much as $6,500. Once patients are successfully enrolled, clinical trial coordinators then face the uphill battle of retaining these patients for the duration of the study. With dropout rates often exceeding 30%, the loss of trial participants is a significant concern for our industry.

Fortunately, hope is not lost—pharmaceutical sponsors and clinical research organizations (CROs) are finding they can improve patient retention rates and bolster trial completion with patient centric trials and patient support services.

Understanding the many barriers preventing patients from trial participation is most essential step to keeping them enrolled. These challenges often include missed work (and subsequent loss of income), complex travel arrangements, time away from home and family, increased childcare needs, and the financial burden of delayed reimbursements. Factors such as the trial duration and a patient's perceived feelings of being valued throughout the trial also impact retention.

Maintaining open and ongoing communication between trial participants, caregivers, and trial staff go a long way in increasing retention rates. Initial, one-on-one discussions help patients anticipate the scope and commitment involved in trial participation while demonstrating the level of support provided throughout the study to overcome potential challenges.

Improving trial outcomes with patient centricity

In recent years, our industry has made a noticeable and advantageous shift towards “patient centricity.” Patient-centric clinical trials improve the patient experience by making trials as comfortable and efficient as possible and removing unnecessary burdens to patients facing a difficult diagnosis. These trials consider the patient's needs from the earliest planning stages, incorporating a patient-first blueprint into the study's design.

In February 2022, the Food and Drug Administration (FDA) released new 

 detailing how drug development teams can implement patient-centric trials. An earlier 

 by The Economist Intelligence Unit found drugs developed with patient-centric processes were:

Nearly 20 percent more likely to launch than drugs developed without a patient-focused approach. This number was consistent across therapeutic areas (neurology, oncology, and rare diseases).

Quicker to recruit 100 participants (4-month time period) compared to other innovation types (6-11 months) and all trials (7 months).

A patient-centric approach makes sense socially, financially, and clinically and is rightfully becoming a standard practice throughout our industry. To improve patient experience, clinical trial teams can assist patients with study logistics, leverage technology to reduce patient visits (i.e., wearable monitors, video appointments, etc.), and establish communication channels to keep patients and trial staff well-connected throughout the entire process. From trial design through trial completion, prioritizing patient needs ensures better outcomes for patients and ultimately brings treatments to market faster.

Initially, when trial teams began using a patient-centric model, they focused on improving the clinical aspects of trials, focusing on providing better patient care. It quickly became apparent that addressing patients' social needs were equally crucial to trial success.

CROs and trial sponsors began asking: How can these studies help patients beyond treatment? Are patients struggling with daily pressures, like finding transportation to and from trial appointments? Are pressures from out-of-pocket expenses causing patients to consider dropping out? The answers to these questions highlighted the need to help patients manage the daily challenges of trial participation.

Today, many clinical trial sponsors look to companies like 

 to manage patient logistics for their trials. Clincierge’s global team of patient coordinators works directly with patients and their caregivers to ensure comfort and safety throughout a trial. Coordinators are local to the patient, ensuring they share a time zone and cultural understanding and providing a high-touch, concierge level of service.

Throughout the duration of a trial, patient care coordinators establish trusting relationships with patients, caregivers, and clinical site staff. Being regionally and culturally aligned from enrollment through the last visit, patients feel they have someone 'in their corner.' This consistency supports better long-term trial retention as patients and caregivers can focus on the patient's treatment, not the logistics involved. It also frees clinical site teams to focus on the data collection and endpoints of the trial and the patient experience during the site visits.

Patient support providers can also alleviate the complexities of multi-country rare disease trials, which often require extensive travel, visas, relocation, language translation, housing, and transport of medically fragile and pediatric patients. Patient coordinators often plan and pre-pay for cross-border travel while navigating the bureaucratic obstacles preventing patients from participating.

In ideal cases, trial sponsors build patient support into the earliest rounds of the trial design, allowing patient coordinators to assist with patient onboarding. This trial model also encourages patient diversity. By communicating with underserved populations and educating them about available compensation and travel reimbursements, patient coordinators assist in enrolling patients who fit trial criteria regardless of their ability to cover participation costs.

By partnering with a patient support services company, clinical trial sponsors ensure higher retention rates while focusing on the needs of the patients involved. Ultimately, patient-centric clinical trials help new therapies get to market faster while supporting the pharmaceutical industry's most significant goal—caring for the health and well-being of patients around the globe.

Case study: Patient support services at work

A review of a multi-year clinical study highlights the impact patient care coordinators have on trial outcomes. The study is researching a new treatment for Duchenne Muscular Dystrophy (DMD), a rare progressive muscle-wasting disease primarily impacting boys.

In rare diseases like DMD, patient populations tend to be small and geographically distributed across the globe. The DMD study spans 35 trial sites in nine countries. Over a five-year period, 18 patient care coordinators have provided support services, including arranging cross-border travel and accommodations for more than 170 trial patients and their caregivers.

These coordinators arrange cross-border transport and accommodation for patients and help them feel comfortable surrounded by new cultures. Speaking the native language of the patient and caregiver and living in the same time zone ensures ongoing communication and personalized support throughout the trial.

Site travel has been provided via airplane, rail, and wheelchair-accessible car service. In total, patient care coordinators booked more than200 airline flights, 250 ground transportation trips, and 530 hotel reservations.

Over 1,300 reimbursements have been distributed to participants after site visits.

Patient carecoordinators have learned the intricacies of DMD to anticipate this patient population's needs and travel preferences. DMD patients often require wheelchairs, so they need ADA-compliant hotel rooms, accessible bathrooms, and living spaces allowing for wheelchair movement.

Likewise, because chewing and swallowing are challenges for DMD patients, many require specific foods and strategically planned mealtimes. Patient coordinators ensure safe and fortified foods are available, allowing patients to adhere to strict dietary guidelines. As patients' medical needs have changed throughout the trial, coordinators continue to tailor logistics to accommodate them.

Removing the emotional, financial, and logistical burdens of clinical trial participation allows patients, caregivers, and trial teams to focus on life-changing treatments. Although this trial is still underway, it is progressing on schedule and within budget, due in part to a patient retention rate that surpasses industry benchmarks.

 is the founder and CEO of Clincierge. He was featured on a previous episode of the Applied Clinical Trials podcast. Listen 

Articles

Feature Articles

Sponsors can ensure higher retention by partnering with patient support services.

The Role of Support Services in Patient Retention 

The COVID-19 pandemic has laid bare what we already knew about societal inequities in academic medicine. This world-wide disaster is having a disproportionate impact on women, underrepresented ethnic and racial minorities, LGBT scientists, people with disabilities, and those from a myriad of non-traditional backgrounds. As co-authors of a recent 

 commentary, “Pandemic-related barriers to the success of women in research: a framework for action,” we believe it is of upmost importance that those of us in clinical research leadership positions acknowledge this issue and provide a constructive framework for meaningful action. We believe that the timing of this action is now, if we are to successfully prevent more women from leaving the biomedical workforce altogether.

As we detailed in our paper, the data is more than worrisome. Since the onset of the pandemic, significantly more faculty in academic medicine report that they are considering leaving their faculty positions or reducing their hours. Our data has shown that childcare responsibilities are a significant contribution to the attrition of women from science. For example, women with children were more than three times as likely to decline leadership opportunities as women without children. During the pandemic submissions of scholarly papers authored by women to the medical journals decreased, whereas submissions authored by men increased. One department of internal medicine found while that the number of research grants submissions by male scientists to funding agencies increased during the first 12 months of the pandemic, a similar increase in grant submissions by female scientists was not evident. Notably, of the grants submitted by women, lower dollar amounts were requested in these applications. Data from one funding agency, the NIH, shows that while women continue to submit entry level grants in greater numbers, they are not submitting career-advancing higher-level applications. When we think of the clinical research enterprise, inclusive of clinical trials, we know that women are disproportionality represented. Thus, the evident impact of attrition is likely to disproportionally affect clinical research.

While we have documented the problem, the efforts now must be focused on implementing solutions. The solutions are a shared responsibility that will require the buy-in from and engagement of academic institutions, research foundations, government funders, and professional organizations, including Clinical Research Forum. One of several solutions proposed in our commentary centers on providing additional short-term flexible funding for investigators who have care responsibilities and the associated competing demands on their time. For example, the provision of $50,000 to $75,000 per year for junior faculty heavily impacted by caregiving responsibilities would afford opportunities for women to hire additional staff as a way to share the workload and/or may provide funds to offset the cost of childcare and elder care.

Existing programs that provide this type of financial support have been very successful. One such program that existed prior to pandemic, the Claflin Distinguished Scholar Awards at Massachusetts General Hospital, provided $50,000 per year for two years to maintain research productivity during the child-rearing years. The program is competitive, and data indicate that scientists selected had a higher retention rate at their institution (90% vs. 60%) when compared to those who applied but were not selected for the program. Of note, it was a wise investment with a total of $2.1 million provided over an eight-year period, which resulted in the people supported by the program successfully submitting research grants that ended up reaping $51 million in subsequent grant funding—in essence reflecting a 24-fold return on the initial investment.

We exhort more academic institutions to replicate this investment in their basic scientists and clinical investigators—including clinical trialists. While several other similar strategies are funded by foundations, such as the Doris Duke Charitable Foundation and the Rita Allen Foundation, they are not sufficient to address the need. One discrete call to action is for additional organizations to fund similar programs.

Although the COVID crises has highlighted the challenges women face recently in their academic medicine careers, the difficulties women have in being appointed to leadership positions goes back several decades. In fact, the data from the Association of American Medical Colleges indicates a very small increase of only a few percent over the past three decades in women chairs of departments, vice deans, vice presidents, and deans and presidents of medical schools and their teaching hospitals. This is all the more disappointing, considering that women now constitute 50% of the medical student body and junior faculty ranks, and the importance of women role models as leaders and mentors is critical for their career progression. In this regard, it is encouraging that six organizations have recently banded together to form the Gender Equity in Academic Medicine and Science (GEMS) Alliance with the goal of providing specific and practical support for women to advance and be successful in their leadership positions.

As members of the board of directors for Clinical Research Forum, a non-profit professional organization devoted to providing leadership in the clinical and translational research enterprise, we are committed to advocacy efforts that will continue to elevate the importance of the clinical research enterprise and the preservation of a diverse and inclusive workforce. This particular challenge did not just happen overnight, and its solution will take time. The steps we detail are critical right now.

Our hope is that clinical research leaders will commit to financial, operational, and cultural changes to attract and retain women and other underrepresented populations in clinical research. Only by all of us participating can we meet the health and scientific challenges we are facing to improve the public health of our nation and our globe.

, MD, Professor, Medicine and Pharmacology; Vice Dean and Chief Clinical Research Officer; Senior Associate Vice Provost for Human Research; Director, Translational Research Education, Perelman School of Medicine, University of Pennsylvania, and 

, MBBCh, Professor of Medicine, Division of Endocrinology, Diabetes, and Metabolism, University of Pennsylvania Health System

A Closing Thought

With poor retention of women in the biomedical workforce amid the pandemic, industry leaders in clinical research must step up to provide solutions.

We Must Do More to Ensure Women Achieve Their Professional Goals

According to a 2021 Pharma Intelligence survey, only 5% of Americans consent to participate in clinical research. But 81% of survey respondents who had never participated in a clinical trial indicated they would be likely to participate should the right situation arise.

These statistics indicate the current clinical research paradigm is not ideal for maximum patient participation. What are we doing wrong? How can we increase patient participation in clinical trials?

Financial and logistical barriers significantly contribute to low clinical research participation.

 Patients often have high out-of-pocket medical expenditures related to their condition and usually face high out-of-pocket costs when participating in a trial.

 For example, many studies create additional participation costs by requiring testing not covered by insurance and travel to and from specific study sites for procedures and other protocol-related tasks.

 One analysis of a cancer study revealed 99% of patients were covered by insurance, but more than 30% still reported financial concerns surrounding participation.

 When existing expenses related to their condition are combined with additional spending related to trial participation, the cost simply becomes too great for many patients.

Decentralized clinical research promises to alleviate a portion of these patient burdens and provide broader geographic access to increase overall trial participation; however, decentralized or site-less trials pose participation barriers. In decentralized designs, the first touchpoint with patients is often virtual, which leads to challenges in managing and owning the participant’s experience. Patients may face challenges and require technical support when using decentralized clinical trial technologies.

One participant in a COVID-19 vaccine recently publicly commented, “The trial’s [e-diary] has been such a hassle to deal with. The site couldn’t figure out how to get it to log in, IT couldn’t help, the vendor couldn’t even get it to function! We ended up having to email in the responses daily. We also received calls from the [clinical research coordinator] daily with new troubleshooting steps, which never worked.”

Those who suffer from cognitive decline and those with vision issues may require additional assistance. Patients having to navigate complex platforms or unfamiliar technology to complete trial protocols are less likely to participate. Barriers also include communication, such as language differences, low literacy, and mistrust. More than 30% of the US population has basic or below basic health literacy. This number is likely higher in clinical research, as many studies and their related information are complex.

 If patients do not fully understand the how and the why of a trial, they will be less inclined to participate.

The NIH states the principal challenges of clinical trial recruitment remain, “the lack of awareness and education about clinical trials, availability, and how to participate.”

 Our historical engagement models have fallen short of meeting the needs of individuals interested in clinical research. The common barriers to trial participation are significant. When patients consider enrolling in a study, they weigh the cost- versus-benefit ratio of participation. The substantial costs often win out because there isn’t enough engagement to personally connect individuals with the benefits of participation.

This lack of patient engagement spells disaster for studies: 80% of clinical trials experience setbacks because of enrollment challenges, leading to $600,000 to $8 million in lost revenue every day a pharmaceutical drug or medical device is delayed to market.

 Insufficient patient engagement and the resulting enrollment issues also lead to problems with site coordination and start-up. Like patients, sites need to be ready to go for the start of a trial. However, if there are no patients, the sites sit empty after activation, wasting time, effort, and even more money.

Research from the NIH suggests indifferent or negative attitudes toward participation can improve through education and discussion.

 Therefore, increased education and discussion can potentially lead to higher participation levels. Virtual waiting rooms provide a unique opportunity to do just that.

A virtual waiting room is a virtual location where patients who have expressed interest in clinical research can learn more about clinical studies, manage their enrollment activities, and speak with patient concierge specialists. But, despite the name, virtual waiting rooms do not involve much waiting; patients can express interest in research or specific therapeutic areas of interest independently of site activation or protocol optimization timelines. They combine the function of a patient database with education and engagement, offering participants background information on studies, essential details about participation, and updates leading up to the trial launch. Virtual waiting rooms provide more time for patients to ask questions like “How do clinical trials work?” or “How do you protect my data?” The virtual rooms also enable two-way engagement to explain to interested individuals how best to find a study or answer questions for caretakers.

Virtual waiting rooms have several structural functions that meet the tenets of patient engagement. First, they offer multichannel communication modalities, including phone calls, chat, and email. Multichannel engagement allows patients to receive health information through a communication channel of their preference, thereby increasing the exchange of health information and the accessibility of clinical research. Secondly, they enable patients to intake from various sources into one convenient database, ensuring they are not lost but are converted from interested to engaged. Finally, virtual waiting rooms allow patients to connect with a human to get their questions answered and obtain desired additional information, further boosting engagement.

The most innovative virtual waiting rooms use advanced data-science tools to identify patients through electronic health record (EHR) data. The identified patient’s treating physician contacts them about trial participation, and the patient can express interest and enter the waiting room. There is considerable evidence that clinician recommendations play an important role in helping patients consider clinical trial participation; such engagement can increase the likelihood that patients enrolled in the virtual waiting room will agree to research participation.

For patients, joining a virtual waiting room is as simple as ordering from their favorite local restaurant. Patients text a keyword to a phone number, click a link, or scan a QR code with a mobile device. They are then introduced to the waiting room through an AI-driven virtual assistant, like Elligo’s RootSM or another digital companion. Patients can text questions to the digital assistant about upcoming trials in various therapeutic areas and even receive study enrollment support when the inclusion-exclusion criteria are finalized. If the patient has any issues, they can ask their digital assistant to schedule an appointment with a patient concierge specialist at their convenience.

The virtual waiting room is an effective mechanism for supporting patients from the point of study awareness to consent.

For example, without the virtual waiting room, a patient interested in participating in urinary tract infection (UTI) research would have to search the internet to find a potential study, fill out a lengthy questionnaire, and then wait days or weeks for a call from the site. Once the patient gets a call, the site coordinator asks them additional questions and uncovers that the patient is not qualified for the study because they have not had an acute symptom within 48 hours of study activation. This experience can leave the patient disappointed, frustrated, and perhaps less likely to participate in clinical research in the future.

But with the virtual waiting room, the patient can have a much better experience. Because the patient is already in the waiting room, they can quickly and easily find an appealing UTI study. The patient can scan the study QR code with their smartphone and answer short, carefully written questions designed to reduce dropout and save time. While waiting for the study to start, the patient can read educational materials, ask the concierge questions, and generally feel prepared for participation. Once the study is live, the patient can use the virtual waiting room to inform the site when an acute symptom arises, meeting their enrollment timeline, allowing for participation, and improving the overall study experience.

Virtual waiting rooms also allow patients to become fully educated on the research process. An Antidote Technologies survey found 77% of respondents want the clinical research industry to make it easier to find, learn about, and understand trials, a desire that virtual waiting rooms can efficiently fulfill.

 Virtual waiting rooms offer actionable, regionalized materials at the proper reading level for each patient’s consumption. They provide opportunities for patients to ask questions and engage in clinical
research and their therapeutic areas of interest, helping them become enthusiastic trial participants.

The virtual waiting room helps sponsors efficiently complete clinical enrollment by increasing referral to randomization rates and reducing the cost per randomization as well as overall study spending. They also provide one virtual location for referrals from all partners and ensure no individual is lost in their clinical study journey. Because patients can access virtual waiting rooms from anywhere, they expand sites’ geographical reach and allow for more diversity and trial-participation access.

The prioritization of the patient experience through the virtual waiting room can also diminish site burden and infrastructure, identification, and enrollment costs. Virtual waiting rooms boost site enrollment capacity and support coordinated efforts throughout the enrollment, further streamlining the study and reducing spending. Because waiting rooms allow patients to become fully educated on the research process and further evaluated on likely screen-fail issues, they also improve patients’ likelihood of randomization and retention throughout the trial.

Most importantly, virtual waiting rooms offer early patient engagement to educate and retain patients. The earlier and more comprehensive engagement is, the earlier patients can ask questions about the study, understand what to expect from the protocol, a then make a cost-vs.-benefit decision of participation.

Elligo Health Research provides a virtual waiting room model and is currently running a study to demonstrate that patients presenting to the screening visit and consenting process after spending time in the virtual waiting room are more likely to agree to the research requirements and to adhere to the protocol procedures and timeline. While the study is not yet complete, the early results hold promise that virtual waiting rooms are a solution to patient engagement and, therefore, research participation.

, Executive Director of Digital Strategy, Elligo Health Research

Pharma Intelligence. Patient Perspectives on Clinical Trial Participation Report. Accessed through: Informa Business Intelligence. Patients Rate their Clinical Trial Experience Positively, but Trial Locations Still Pose Barriers to Enrollment. Accessed April 11.2022.

Zafar SY, Peppercorn JM, Schrag D, et al. The financial toxicity of cancer treatment: a pilot study assessing out-of-pocket expenses and the insured cancer patient’s experience. 

 2013;18:381-390. Accessed March 28, 2022.

Narang AK, Nicholas LH. Out-of-pocket spending and financial burden among Medicare beneficiaries with cancer. 

. 2016;3:757-765. Google Scholar. Accessed March 28, 2022.

Nipp RD, Powell E, Chabner B, Moy B. Recognizing the financial burden of cancer patients in clinical trials. 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4571792/

Stump TK, Eghan N, Engleston BL, Hamilton O, Pirollo M, Schwartz JS, Armstrong K, Beck JR, Meropol NJ, Wong Y-N. Cost concerns of patients with cancer. 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3770507/

Van Norman GA. Decentralized Clinical Trials: The Future of Medical Product Development? 

. 2021;6(4):384-387. Published April 27, 2021. Accessed April 14, 2022.

Crane Cutilli C, and Bennett IM. 2010. Understanding the health literacy of America: Results of the National Assessment of Adult Literacy. Orthopaedic Nursing 28(1):27-34. 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2668931

National Institutes of Health. NIH Clinical Research Trials and You – Opportunities for Education and Awareness. 

https://www.nih.gov/health-information/nih-clinical-research-trials-you/opportunities-education-awareness

Desai M. Recruitment and retention of participants in clinical studies: Critical issues and challenges. 

. 2020;11(2):51-53. Accessed April 15, 2022.

Hargreaves B. Clinical Trials and Their Patients: The rising costs and how to stem the loss. 

http://www.pharmafile.com/news/511225/clinical-trials-and-their-patients-rising-costs-and-how-stem-loss

Clark LT, Watkins L, Piña IL, et al. Increasing diversity in clinical trials: overcoming critical barriers. 

 2019;44:148-172. Accessed April 7, 2022.

Antidote Technologies, SCORR Marketing. 2018. 

https://www.antidote.me/blog/what-role-does-health-literacy-play-in-clinical-trial-participation#:~:text=In%20addition%20to%20health%2Drelated,to%20participate%20in%20clinical%20trials

Exploring their unique opportunity in increasing study enrollment levels.

A Primer on Clinical Trial Virtual Waiting Rooms

Patient recruitment has long been a challenge for clinical trial investigators, with low recruitment being the single-largest cause of terminated trials. One 2015 analysis found that 19% of all clinical trials are terminated early due to poor recruitment. In the US, one study of 41 NIH-registered clinical trials found that only one-third of studies meet their patient recruitment goals. This same study found that as many as 24% of all NIH-registered trials fail to get even halfway to a full patient sample.

Clinical trial patient recruitment is arguably the most difficult aspect of pharmaceutical development, because it involves a variety of factors beyond study sponsors’ control. Yet in spite of this lack of control, sponsors, investigators, and service providers are finding creative new ways to identify and recruit patients that are made possible through advances in medical technology.

The COVID-19 pandemic has accelerated the adoption of these technologies, and now, the innovators and disruptors responsible for creating patient recruitment tools say further tech advancements and refined processes will dissolve barriers to trial participation and accelerate research. Here are some of the emerging new ways that sponsors and contract research organizations (CROs) are conducting patient recruitment.

Patient recruitment challenges have long hamstrung rare disease research. Now, though, direct-from-electronic medical record (EMR) patient recruitment technology is enabling trial administrators to locate rare disease patients anywhere in the world. Jason Baumgartner, MBA, is the founder and CEO of BEKHealth in New York City. BEKHealth is a software company that manufactures EMR data processing, feasibility, site selection, and patient-trial matching software. Baumgartner says that EMR aggregation is enabling investigators and sponsors to rapidly identify patients with rare diseases, a pool of patients traditionally difficult to find.

"Just yesterday, we had a company send us a protocol,” Baumgartner tells

 last month. “Through our network of research sites, we identified about 100 patients. Technologies that can evaluate entire networks of practices with a high level of precision, that enable CROs to tell the drug companies how many patients are in which locations in a centralized manner, that’s what’s emerging.”

Baumgartner notes that patients are often rendered ineligible for studies as a result of medication history or comorbid conditions. In the past, he says, out-of-date or incomplete information has often resulted in prospective patients being dropped from studies due to previously unknown comorbid conditions or medication histories. With rare diseases, in particular, researchers may face the added challenge of trying to locate patients without having an ICD-10 code. Now, though, recent advances in EMR technology have enabled investigators to conduct a type of predictive analytics called disease modeling. By aggregating various pieces of medical data into one centralized repository and then analyzing that data, emerging new technologies can predict whether or not a given patient has a particular rare disease—no ICD-10 code needed.

“The EMR as a source of truth is becoming the mandate,” says Baumgartner. “I’d say that within five years, most research and health institutions will be leveraging automation to do research. If you look at an 80-hospital health system, they might be using 20 EMR systems. The aggregation of data across 80 hospitals and 20 systems, for the purpose of understanding patients, doing feasibility studies, or engaging in decentralized recruitment, is the trend we’re seeing.”

Baumgartner predicts that in the near future, feasibility studies and recruitment will no longer be coordinated at the hospital level. Rather, aggregated EMR solutions will enable feasibility and recruitment to be their own centralized functions. Today, though, he says the most exciting development in recruitment technology is metadata.

“There are multiple products that exist today that will tell you in real time how many patients have been identified for your study,” he says. “But reports are now existing that provide metadata around why specific patients are, or are not, being considered for a study—which criteria are knocking patients out of the trial. Organizations are also getting direct feedback from clinical research staff about why the patient isn’t a good fit. That information is becoming more available to sponsors, which enables better collaboration.”

EMR data aggregation and modeling are also helping investigators and sponsors to create a more individualized and welcoming patient experience. The benefits of this individualized approach are most immediately noticeable at community sites, such as a pharmacy. Baumgartner says pharmacies have unique and growing data sets that typically rely on prescription data to determine whether patients may be eligible for studies, but this approach can be problematic. When recruiting using prescription data alone, it isn’t always clear which condition the patient has.

“A depression drug may not be used to treat depression,” explains Baumgartner. “It may have been prescribed for anxiety. Or Crohn’s disease versus [irritable bowel syndrome]. You can’t have people show up to a pharmacy and get a text or call about a disease they don’t have. So how do you use predictive disease models to determine what disease a patient has when their medication is indicated for four different conditions?”

BEK Health has solved this problem by aggregating EMR data from 25 million patients into approximately 2,000 disease models. Baumgartner says that for about 1,000 of those models, BEK Health can predict with 90% accuracy which disease the patient has. It’s this type of predictive analytics that Baumgartner claims can help to improve both individual access to clinical trials and enhance the patient experience during a study. (Listen 

Social media effective with younger patients

Investigators and CROs were dabbling with social media for trial recruitment long before the COVID-19 pandemic, but it wasn’t until the pandemic shut down study sites that social media became a viable strategy at scale. Nimita Limaye, PhD, is the vice president of research for the life sciences R&D strategy and technology division at the International Data Corporation (IDC), a market research and advisory firm specializing in the technology industry and headquartered in Boston, Mass. Limaye says social media recruitment has come a long way in the last 10 years.

“The first so-called “virtual” trial was run in 2012, for overactive bladder,” says Limaye. “The trial’s objective was to recruit 600 patients across 10 states. They used multiple novel strategies, including online recruitment, screening and consent; at-home study drug delivery; mobile- and web-based tools for data reporting; online identity verification; and a centralized investigator site. But the study failed because the trial population wasn’t comfortable with using so much technology; (the study’s failure) may also have been related to the severity of the disease.”

Since then, however, it appears that changing patient demographics have made social media a viable recruitment strategy. Two years after the overactive bladder trial, explains Limaye, Sanofi implemented a social media recruitment strategy for its Phase IV VERKKO trial investigating a 3G-enabled wireless glucometer. In this instance, Sanofi recruited 60 subjects through Facebook, and the study sample had an average age of 56; several subjects were 70 years of age or older. The study boasted high patient satisfaction scores (over 4 out of 5), despite the elderly population, and a dropout rate of 9%.

“Social media has had a high success rate when recruiting younger patients,” Limaye points out. “I also think today’s patients are more digitally savvy. At IDC, we refer to them as the ‘patient sapiens’—the digitally savvy patients of today. A few years ago, I thought decentralized trials (DCTs) were more of a fashion statement than anything; most companies were just toying with it. Now, everyone is going down that path.”

The COVID-19 pandemic also increased public awareness of clinical trials. Limaye explains that the high visibility of the COVID vaccine trials has helped to change public perception of clinical trials in general; patients are now more aware of clinical trials.

Limaye says the rise of social media-based patient recruitment has opened the door for sponsors and investigators to mine real-world data and to give patients a more central focus in research. Sponsors and investigators are also now more willing to adopt a variety of other new technologies that will further broaden recruitment efforts.

“We’re seeing technologies like Amazon’s Alexa coming in,” says Limaye. “So imagine [as a patient] asking Alexa if she can find a trial that you can participate in. Traditional recruitment hasn’t vanished, for sure, but the scale and reach of digital solutions makes ‘digital-first’ the future of patient recruitment.”

Limaye says the future of clinical trial recruitment technology will involve tapping into what’s increasingly being referred to as the Metaverse. Technologies like augmented reality and ambient intelligence will enable remote patient monitoring and drive deeper patient engagement. Limaye notes that while these technologies are still in their very early days, some companies are already exploring these opportunities.

Beyond technology solutions, though, companies are increasingly going directly to the patients with a more humanized appeal.

Says Limaye: “Most companies are starting to build out patient advocacy groups. There’s now a position called the ‘chief patient experience officer’ that some companies are rapidly introducing.”

All of these emerging new trends, according to Limaye, are driving a patient-first paradigm where the patient is the central focus. Recruitment communications are now more cognizant of patients’ emotional journeys, which is something Limaye says must continue to be prioritized. Moreover, she adds, models are shifting from patient-centric to participant-centric, with clinical researchers focusing on the larger ecosystem of care surrounding the patient.

“Patients have seen the advantages of accepting these new technologies, but the personal component shouldn’t be forgotten,” says Limaye. “It’s critical to keep in mind that we are dealing with human beings, and that the emotional component needs to be woven into the technology as well.”

Large retail pharmacy chains are increasingly acting as clinical trial recruitment sites, with pharmacy brands like CVS and Walgreens now working with DCT providers to stand up trials. Liz Beatty is the chief strategy officer and a member of the board of directors at Paris, France-based Inato, an online clinical trial platform provider for pharmaceutical companies that matches study sponsors to community-based trial sites. Beatty explains that pharmacy chains are in the process of determining which aspects of clinical trials can be performed virtually with patients at home, as well as which aspects can be done in a pharmacy.

“Once you get into advanced and serious diseases like cancer, patients still need to go to a physician or oncologist,” says Beatty. “So that’s why we think community doctors have a strong role to play in the future. But [the community pharmacy approach] works for a lot of basic health procedures. We’re seeing CVS and Walgreens trying to provide access [to trials] where they can.”

Beatty says trial sponsors are increasingly looking at larger catchment areas for patients in rural areas, particularly in the middle states. Clinical trials, she explains, used to be heavily concentrated on the east and west coasts. The community pharmacist is also a new resource for trial sponsors, particularly as patients have still been visiting pharmacies during the COVID pandemic even when they may have delayed visits with their primary care providers.

Pharmacies also offer the advantage of more convenient locations for patients. Beatty says that prior to COVID, it was typical for American trial participants to travel two or more hours to reach a trial site. Since the pandemic started, however, participants are no longer willing to travel long distances. Bringing clinical trials into the pharmacy environment, Beatty explains, was an effective means of reaching patients where they are.

In December 2021, CVS Health published the results of its COVID monitoring and testing study, a case-control study, in a research letter in 

Journal of the American Medical Association

. From May to August 2021, CVS administered COVID polymerase chain reaction tests to over 1.2 million symptomatic individuals at over 4,000 locations across the US. The study determined that vaccination with any number of doses of any FDA-approved COVID vaccine was associated with a lower risk of infection, with people who had received two doses of an mRNA vaccine having the lowest risk across all timepoints.

Recruiting patients directly from pharmacies may also solve another recruitment problem sponsors face: competition.

“Sponsors typically go to the same clinical research centers as everyone else,” says Beatty. “If everyone is at a major health center and there are only so many patients included there, it slows recruitment because that site needs to distribute patients across trials. A lot of companies will also have internal competition; they have multiple trials for the same disease in their portfolio, so they’re competing with themselves. The solution is to expand access to clinical research centers.”

While patient recruitment technology has come a long way, maintaining a focus on patient engagement and viewing recruitment as a journey are two of the ways that trial sponsors and clinical researchers can improve the onboarding process. Beatty says that technology can help patients better understand the clinical trial process, and it gives sponsors the ability to translate complicated medical language into more accessible material. When technology is applied in this way, it moves patients through the participation journey in a faster and easier manner.

“Any way that we can use technology to keep patients engaged will help,” explains Beatty. “If we can use technology to remind patients what to do if there’s a problem, or tell them what to expect next, that helps. Even the informed consent process has been enhanced through technology. Consent forms are very technical, and they’re written in medical language. It’s difficult material to understand and digest. Using video or [interactive] glossary terms to better explain things when getting consent can help.”

The patient recruitment and onboarding process is rapidly undergoing a digital revolution. Patient opt-in solutions, EMR funnels, and community site-based data analytics are making it easier for sponsors and CROs to find, evaluate, and recruit patients from a wide geographical area without the need for the patient to visit a trial site. The next evolution of patient recruitment will involve tapping into the metaverse, with recruiters leveraging Amazon’s Alexa and virtual or augmented reality technology to find and recruit patients in a combined online-offline environment. This technology has even enabled pharmacies to step into the trial space, which has improved access for patients. While there remain concerns around competition for the patient base with more players starting trials in major clinical research centers, emerging patient recruitment technologies are enabling sponsors to sidestep this challenge by starting trials in smaller communities.

The future of recruitment technology will enable more DCTs, help companies streamline recruitment efforts, and expand clinical trial access to a broader segment of the general population. Over time, the benefits will be better access to care for patients and a higher trial completion rate for investigators.

Carlisle B et al. “Unsuccessful trial accrual and human subjects protections: An empirical analysis of recently closed trials.” 

Charlson ME et al. “Applying results of randomised trials to clinical practice: Impact of losses before randomization.” 

 (Clinical Research Edition), vol. 289 (1984): 1281.

Sundgren M et al. “Using real-world data in patient recruitment.” 

Tabak YP et al. “Incidence and estimated vaccine effectiveness against symptomatic SARS-CoV-2 infection among persons tested in US retail locations, May 1 to August 7, 2021.” 

Emerging tools in data analytics, automation, EMR aggregation, and even social media are enabling faster and easier patient recruitment.

Patient Recruitment Goes High-Tech

The Critical Path Institute’s (C-Path’s) Electronic Clinical Outcome Assessment (eCOA) Consortium was created in 2011 as the Electronic Patient-Reported Outcome (ePRO) Consortium, the change of name occurring in early 2022 to reflect the expanded scope of expertise of our membership and the Consortium’s interests. Our mission is to advance the science of clinical trial endpoint assessment through collaborative research, education, and development of best practices for eCOA data collection to the benefit of all stakeholders, including trial sites and participants.

The Consortium has a strong history of analyzing what is necessary to ensure effective eCOA system implementation. Our membership is formed from a range of organizations—from global contract research organizations (CROs) to smaller-scale mobile health technology firms—but we maintain equity in voice with all members empowered to help improve the experience for all who use eCOA systems in clinical trials, and to define the future state of eCOA data capture.

The current energy around digital health technologies (DHTs)—bolstered by FDA’s recent draft guidance

—is intriguing, as our membership includes firms that innovated in DHTs. We are exploring the interface between “traditional” ePROs and DHTs and identifying where our membership’s established operational and scientific expertise can help develop consensus-based approaches to DHT adoption.

Consistent with the collaborative mindset, the eCOA Consortium partners closely with the sponsor organizations within C-Path’s Patient-Reported Outcome (PRO) Consortium, specifically those firms with a key interest in eCOA systems. This relationship is pivotal to the eCOA Consortium’s success in developing industry-level recommendations; doing so in isolation would attenuate the utility and effectiveness of our output.

To that end, the two consortia—with input from FDA—initiated a collaborative effort in 2019 called the 

. This initiative covers a range of critical eCOA-related topics from developing a common eCOA Lexicon

, through to exploring the opportunities for bring-your-own-device (BYOD) implementation, a project that has produced a recent podcast. We will soon begin a detailed analysis of the challenges around eCOA translations and licensing, a persistent pain point in clinical trial execution, alongside a project to give direction on the practical considerations for the implementation of wearable technologies in clinical trials, which will leverage the deep experience of our members in clinical technology implementation.

The mutual sharing and collective analysis of our members’ real-world experiences and their established processes in a neutral arena is central to gaining consensus and alignment. Developing common methods and standardized processes benefit all stakeholders, and allow the viability, integrity, and robustness of systems to be what defines a trusted eCOA and DHT provider. Alongside the PRO Consortium, we are exploring a potential project under FDA’s ISTAND Pilot Program

 to assess standardized methodologies for the use of mobile devices for remote image capture in specific clinical applications. This is an example of where a pre-competitive alliance in the context of developing consensus-driven standards for COA use—in this case clinician-reported outcome assessments—is not just preferable, it is arguably necessary.

The value of pre-competitive alliances is indisputable, especially where we can help advance medical product development, but a culture of standardization along with operational and scientific rigor must prevail. We look to the successes of CDISC, which was borne of a need to support regulatory submissions and enable informed decision-making, and yet in the context of eCOA systems we have a long way to go. In 2021, we administered surveys to trial sponsors and eCOA providers that clearly illustrated that CDISC-based standards are not yet dominantly central to eCOA data requirements; this is exactly what we must work to address.

This regular column, on behalf of the eCOA Consortium, will explore some of the challenges to and opportunities for eCOA and DHT systems and what our members collectively agree is the best path forward. We will share more detail on BYOD, eCOA systems, the Conformité Européene (CE) mark, the general value of back-up systems in eCOA, and much more.

https://www.fda.gov/media/155022/download

https://c-path.org/wp-content/uploads/2022/03/GettingBetterTogetherInitiative_eCOALexicon_v2.pdf

https://www.fda.gov/drugs/drug-development-tool-ddt-qualification-programs/innovative-science-and-technology-approaches-new-drugs-istand-pilot-program

News

Consortium looks to advance endpoint assessment through the development of  eCOA best practices.

The Power of Collaboration: Introducing the eCOA Consortium 

Functional service partnerships (FSPs) allow pharmaceutical and biotech companies the ability to outsource support within certain functional areas of clinical trial management, either to supplement their own internal capabilities or those they have outsourced to another contract research organization (CRO). This approach helps enable more flexible ramping up or down of resourcing as client portfolios change. It also allows for the opportunity to leverage the provider’s technology if they choose, meet new or changing geographic capacity needs, and take advantage of the provider’s experienced staff in areas such as regulatory affairs, pharmacovigilance, clinical operations, data management, etc. However, making an FSP model work takes coordination and accountability. One solution is the inclusion of an implementation lead.

Biopharma companies often use CROs to run their trials in whole or part. If in part, a CRO may provide FSP support to augment client staff in a particular function through dedicated resources. Traditionally, these resource-allocation efforts are overseen by an operations delivery lead (ODL), but some CROs, including PPD Clinical Research Services, take a different approach. By adding an implementation lead (IL) to support the process, responsibilities are divided and efficiencies gained in the critical early phase of the partnership.

 catches up with Brian Ford, director, functional service partnership solutions, PPD Clinical Research Services, Thermo Fisher Scientific, to answer some frequently asked questions about how ILs contribute to the successful use of FSP models.

An implementation lead is a role whose responsibility it is to coordinate the internal workstreams and client collaboration required in order to assess the resourcing scope of the client, then manage the process of identifying and allocating the right resources at the right time in the right geographies to meet their needs.

In some dedicated resource FSP engagements, an ODL is typically assigned to coordinate all efforts between the client and the CRO (or CROs) providing a functional service. But when the scope or volume of the work is significant, because of the heavy workload upfront to establish and drive the partnership and resource allocation process, efficiencies are gained when the service provider supplements the work of the ODL with someone focused on making sure there is a strong foundation for resourcing success. This is the IL.

ILs work closely with ODLs, but their focus is different. While the ODL aligns with the sponsor on timelines, strategies, and operational delivery, the IL is more involved in the initial onboarding of resources. The IL makes sure the project is on track and processes are in place for successful onboarding of resources. A big part of this work involves the coordination with other internal stakeholders in talent acquisition, HR, finance, IT, legal, and others to manage the preparation, allocation, and timely onboarding of requested resources.

Early input from ILs is critical to setting a foundation for project success. Even before the bid defense, ILs are instrumental in creating an implementation plan, which serves as a proactive, relationship-building springboard to strategic dialogue. The implementation plan provides guidance relating to resourcing and the strategies the CRO will use to meet the client’s objectives. From there, the client can review resource allocation strategy and timelines, then refine the outlined approach as needed in collaboration with the IL.

While clients and ILs often do communicate in the early days of the project, the primary client interaction is typically through the ODL. Whatever level of interaction there is between the IL and client tends to decrease as the project matures and processes become better established. The IL remains a presence, but by the time the project is firmly underway, the ODL often becomes the exclusive point of contact for the client. The timing of the transition depends on the volume of the project, its level of complexity and any changes to its scope.

ACT: How does having an IL drive better outcomes?

Having a divide-and-conquer approach between the ODL and IL provides for a more focused level of effort in each key area of the partnership. The IL is able to concentrate on developing and executing resource-allocation strategies, while the ODL is then able to provide high-level project delivery oversight, planning and partnership-building with the client.

In this Q&A, ACT catches up with Brian Ford, director, functional service partnership solutions, PPD Clinical Research Services, Thermo Fisher Scientific, to answer some frequently asked questions about how ILs contribute to the successful use of FSP models.

The Role of Implementation Leads in Successful FSP Projects

It's three months since the European Union's clinical trials regulation came fully into force (and eight years since the legislation was adopted), but knowledge and understanding of the new rules is still—to say the least—patchy, and compliance, consequently, far from guaranteed. The European authorities are, however, taking a softly-softly approach to getting the clinical trials community up to speed, and since January the European Medicines Agency (EMA) has been providing weekly titbits of information and advice about the regulation, in order to woo trial sponsors into learning to live with it. The metrics of this service provide an interesting surrogate endpoint for measuring engagement of those who need to know.

The so-called Clinical Trials Information System (CTIS) was launched on Jan. 31, when the legislation entered into force. Sponsors could, from that date, log in to use CTIS to draft and submit new clinical trial applications, and could also transfer into CTIS trials that were initiated under the now superseded Clinical Trials Directive. It had a slow start. Over the first week, the number of logins to CTIS was just 1,260 a day, and just 53 draft applications were made, with just one actual application submitted—small beer in a region where some 4,000 clinical trials a year are conducted, according to the EU.

However, by the following week, logins were running at 2,000 a day, 87 applications were in draft form, and there were three submitted applications—one of which was the first multinational clinical trial in the system, and also the first trial to use CTIS to transition from the regime of the old directive to the new regulation. By late February, there were 4,000 logins a day, 185 draft applications, and seven applications submitted—including the first by a large pharmaceutical company. In addition, three of the applications passed validation by the regulatory authorities—the first step in the clinical trial application evaluation process in CTIS, when a check is made that the application dossier documentation is complete. The trend continued: as of mid-March, over 6,000 logins to CTIS had been recorded, more than 220 applications were in draft,and14 clinical trial applications for assessment by the regulatory authorities had been submitted—most of them from academic sponsors.

By early April, with numbers still rising steadily, the first clinical trial was authorized through the new system. This trial had been ongoing under the clinical trials directive and was transferred to the regime of the clinical trials regulation. And in line with the provisions of the CTIS, details were publicized indicating that it was a randomized Phase III trial in Sweden of vasopressin and steroids in addition to adrenaline in cardiac arrest. The sponsor was Tiohundra AB, a Swedish healthcare company listed as "non-commercial." CTIS also provided details on the inclusion and exclusion criteria for recruitment, primary endpoints, the full trial protocol, the planned number of subjects, the trial sites, the informed consent form, and the CV of the investigator. The information is open and accessible to all—patients, healthcare professionals (HCPs) and clinical researchers—and equally to the general public.

One of the key elements of CTIS is the additional transparency it brings to trials. Part of CTIS is a searchable database (euclinicaltrials.eu) that is open to patients, HCPs, and the general public. Patients can find clinical trials that are recruiting participants within their country and therapeutic area of interest and can obtain sponsor contact information to request more information about joining specific trials. And when trials have ended, the sponsor must upload a summary of the results of the trial in lay language, making clinical trial results easily understandable to the public.

Late April saw a continuing rise in engagement, with 13,000 logins a day, 366 draft applications, 31 submitted applications, and one more authorized application—this time for a completely new trial rather than a transition from the previous regime. And, again, details were listed on the public section of the CTIS website.

This time the trial is a prospective Phase II study of calcium electroporation in combination with irreversible electroporation and immunotherapy in patients with pMMR metastatic colorectal cancer, conducted by Zealand University Hospital in Denmark. It is described as an investigator-initiated study involving CE approved devices and an EMA approved drug, to determine the efficacy and safety of Ca-EP performed concurrently with IRE followed by a PD-1 inhibitor (pembrolizumab). CTIS also lists eight secondary endpoints, and recruitment is due to start in June.

The CTIS listing provides for similarly public information (as it becomes available) on unexpected events and urgent safety measures, as well as summary results, a lay person’s summary, and clinical study reports. Reports on any corrective measures and the results of inspections are also provided for.

As from May, monthly reports will replace the weekly bulletins that EMA has been publishing in order to familiarize the clinical trials community with the new system, to offer alerts to obligations and rights, and to track the evolution of take-up. But EMA will continue to provide the range of advisory services that have been set up to ease the implementation of the new system.

And for anyone apprehensive about the extent of information being divulged to the public, some reassurance—or at least clarity—may be found in provisions that allow sponsors to upload “for-publication” and “not-for-publication” versions of certain documents, including the protocol and the investigator brochures so as to protect personal data and commercially confidential information.EMA is currently preparing guidance on this protection in CTIS, and has published a draft 

 for open consultation, with a deadline of Sept. 8 for comment.

View from Brussels

EMA continues to familiarize industry with new clinical trial legislation.

Dragging the Clinical Trials Community into Conformity

Patient recruitment remains the largest impediment to clinical trials progress. Barriers to participation are numerous and as noted in this 

, can be broken down into these buckets on the recruitment progression cycle—awareness, identification, information and consent, patient-centric operations, and accelerated regulatory approval. Each of these buckets or progressions contain a plethora of ideas, strategies, technologies, and choices. And at any one of these progressions, a potential participant can be lost.

The reality of patient recruitment is that its success depends on those myriad factors under the buckets, in addition to an individual’s behavior or personal beliefs. According to survey results in this 

 from IQVIA, “When asked what prevents them from participating in a trial, fears about their health and safety (62%) far outweighed concerns about time (37%), logistics (18%), and negative press about research (8%).” Further influences can be analyzed by gender, race, and ethnicity, all coalescing around choosing to participate.

In this issue, we present a fraction of the exhaustive list of options that currently exist to foster recruitment. 

, for example, where potential participants can learn, discuss, and express interest in a clinical trial for a near-future opportunity to participate and remain engaged. Sharing clinical trial results with 

ACT presents solutions to foster greater participation in May issue.

Applied Clinical Trials-05-01-2022

The Role of Support Services in Patient Retention

We Must Do More to Ensure Women Achieve Their Professional Goals

A Primer on Clinical Trial Virtual Waiting Rooms

Patient Recruitment Goes High-Tech

The Power of Collaboration: Introducing the eCOA Consortium

The Role of Implementation Leads in Successful FSP Projects

Dragging the Clinical Trials Community into Conformity

Patient Participation is a Team Sport

Applied Clinical Trials May 2022 Issue (PDF)

Clinical Trial Diversity Advances in Regulatory Agenda

Measuring Patient Satisfaction as a Primary Outcome for Patient-Centric Initiatives

Sharing Clinical Trial Results with Pediatric Participants