Mike Straus

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.” 

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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.” 

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

Patient Recruitment Goes High-Tech

Contract research organizations (CROs) have undergone significant changes in recent years, and even more changes are on the horizon. Some of the new and established trends in CROs are the result of technological advances, while others have arisen in response to market pressures or the COVID-19 pandemic. Experts say that spending on research and development has continued to grow over the last 15 years, even as the pandemic has caused biotech stocks to slump. However, CROs continue to face a variety of challenges, from competitive pressure to commoditization to evolving patient engagement models. Market stratification is placing pressure on smaller CROs to niche down or subcontract as larger organizations capture more of the market. As CROs navigate a post-pandemic future, there will be opportunities to implement lessons learned from COVID-19 and adopt emerging technologies that can improve data management, mitigate staffing shortages, or facilitate better patient monitoring and engagement.

The CRO market is in a state of flux, and navigating the changes in this industry will require improvisation and good planning. Here are some of the recent trends and emerging challenges for CROs.

The CRO space has seen a flurry of merger and acquisition activity in recent years. 2016 saw the merger of IMS Health with Quintiles, resulting in the birth of IQVIA. In February 2021, ICON entered into an agreement to acquire PRA Health Sciences. In December 2021, instrument and software supplier Thermo Fisher Scientific finalized a deal to buy CRO PPD.

While these deals have helped the industry’s largest players scale up services, they’re also putting pressure on smaller CROs.

Ken Getz, MBA, is director and research professor at the Tufts Center for the 

Study of Drug Development at Tufts University in Boston, MA. Getz says that these and other deals have enabled large CROs to consolidate expertise and resources.

“In a commoditized service area, scale is important, because it gives you a depth of business development and sales coverage in the market,” Getz explains. “It becomes harder for niche players to function, because without scale, they can’t match the price points and the muscle that larger companies can throw into every project. Some of the smaller CROs are getting squeezed out, while others are becoming subcontractors to larger CROs.”

Getz says that some small CROs may be able to resist this competitive pressure, provided they can specialize in a well-differentiated niche service like a specific type of biostatistics. However, niching down also puts smaller CROs farther away from the end client; these specialized CROs, Getz says, would be selling themselves as subcontractors to the industry’s Goliaths. Still, there may be a middle path forward for small- and mid-sized full-service CROs.

“Some of these smaller CROs will argue that they want to offer outsourcing that’s provided by a vendor similar in size to the client they’re serving,” Getz says. “That’s called right-sizing. Historically, right-sizing has been a successful strategy, but only with select companies—and it’s hard to predict who those companies will be.”

John Kreger, an equity research analyst with William Blair in Chicago, IL, says the pharma industry’s source of innovation has aggressively shifted from large pharmaceutical companies to small biotech startups. This change is prompting CROs to rethink their client engagement model to better target young, aggressively-managed startups. The next two years, he says, will see the industry embracing more innovations.

“The CROs will either be leading the effort to innovate, or they’ll be dragged along by their clients,” Kreger says. “A tangible example would be decentralized trials (DCTs). The old model of a clinical trial had the patient come to the doctor’s office once a month for two or three years. But now, with technology like Zoom and wearables, we can do patient visits from home.”

Kreger says tech-enabled CROs are growing, and they’re more broadly deploying technologies that were battle-tested during the COVID-19 pandemic.

Emerging new technologies could reshape clinical trials over the long term. Kreger says that technology adoption will become more ubiquitous over time; while CROs are only just now starting to look at novel technologies like artificial intelligence (AI) and machine learning, Kreger says this decade will see CROs continue to incorporate more of these technologies. As technological adoption grows, CROs will become less dependent on labor.

“Within artificial intelligence, there’s a field called biosimulation that involves running trials on a computer before running them in the real world,” Kreger explains. “I think technology will make trials and CROs more efficient. But this will increasingly be a biotech landscape. The notion of virtual pharma companies, which was a term thrown around loosely before, is becoming more and more real. You don’t need to be Merck to do this; you can be a small innovator and have outsourcing partners for each functional step.”

Kreger hypothesizes that as technology grows, the CRO model may change from a labor-driven model to a technology-driven one. If this were to occur, CRO operations would rely less on people and more on software. The competitive differentiator between CROs, then, wouldn’t be who has the best people, but rather, whose technology can best capture, sort, and utilize data.

Pandemic, worker shortage demand flexibility

The COVID-19 pandemic and a shortage of skilled workers have put pressure on CROs to change the way they conduct studies, and new technology is already making research more flexible. Eric Coldwell, managing director, equity research at R.W. Baird in Chicago, says that while other technologies like machine learning and AI are growing, DCTs are the single-most important trend in the CRO space today. AI and advanced data analytics may offer future innovations, but Coldwell says that DCT technology is solving a current problem.

“The most important topic of 2022 is DCTs, full stop,” Coldwell says. “If you can’t do research at a traditional site, you have to be able to do it somewhere else. What’s really interesting is that different CROs have different approaches to DCT. IQVIA claims it can do just about everything internally with its proprietary technology. Covance has traditionally worked with outside vendors, but they bought snapIoT in 2020. But then you have other companies that would rather partner with channel-agnostic technology leaders, or just be flexible and work with everyone.”

Coldwell cites the examples of CROs PPD and Syneos. Both organizations have partnership agreements with Science 37, a clinical research firm specializing in DCTs. Syneos also has a deep relationship with Medidata. Coldwell says most CROs will forge partnership agreements with DCT software developers, but three or four of the world’s largest CROs are building DCT technology in-house. These technology solutions, Coldwell says, are part of a larger trend that aims to increase the flexibility of clinical trials.

“I don’t think you can plan for COVID-19 interruptions, other than to be as flexible as possible with your approach to a trial,” Coldwell says. “We’re two years into the pandemic now. We’ve found ways to keep important trials going. Trials went from 90% closed at the start of the pandemic to 80% open today, but the reality is that 20% of study sites have always done 80% of the world’s work. We can survive with 80% of study sites open. But the big change has been this incredible growth in tools that allow a patient to visit a study site less frequently.”

Coldwell says governments and review boards have been very flexible with new technology and methodology solutions that enable fewer in-person study visits. The message from the review boards is that researchers should do what makes the most sense to keep a trial running—especially when patient welfare is at stake.

“If you have a patient who will be severely harmed if they’re denied access to an investigational drug, then you need to change the protocol,” Coldwell says. “The review boards have said, ‘don’t ask for permission, tell us what you did and then ask for forgiveness.’”

While technology has enabled CROs to conduct hybrid clinical trials involving online and in-person components, these trials come with their own challenges. Despite offering the advantage of fewer study visits and easier patient access, Getz says hybrid trials are demanding and difficult to run because they require CROs to juggle multiple different patient preferences and execution models simultaneously.

“Hybrid clinical trials aren’t making research easier for anyone,” Getz says. “A hybrid trial requires a more agile mindset, where you can adapt quickly and prepare to manage multiple executional models that you deploy at the same time. Sponsors and CROs are struggling with it.”

Getz says that while CROs have been trying to move clients away from traditional methods and toward emerging tools, these efforts have historically resulted in significant pushback. Sponsors have typically expected that CROs will fall in line with the sponsor’s own standard operating procedures. While some CROs have forged deep enough relationships with clients to gain a certain degree of latitude, Getz says that the CRO is still required to follow the sponsor’s procedures and operational requirements in many cases. This trend has continued despite hard evidence demonstrating that more flexibility from sponsors would create better results.

“We’ve gathered a lot of data at the Tufts Center that consistently shows that CROs are faster and more efficient than comparable studies managed by sponsors’ own internal teams,” Getz says. “We’ve been sharing those findings for decades, and it doesn’t seem to have influenced sponsor preferences for when and when not to outsource. The general position that most pharma companies take is that they need to provide a level of oversight where they limit the CRO’s ability to take latitude, to do things that are novel and different.”

Supply chain disruptions prompt anticipatory planning

The COVID supply chain crunch has affected nearly every sector. In June 2021, the White House published a report explaining the various factors affecting supply chains, from labor shortages to low inventory and beyond. In September 2021, McKinsey & Company noted that the pharmaceutical industry is vulnerable to region-specific supply chain interruptions like natural disasters. Disruptions are increasingly common and increasingly global, and high inventory alone is insufficient to guard against supply chain shocks.

Kreger says that CROs are hired to solve problems and keep trials on track. While all trials come with challenges, and while the pandemic has meant nearly every clinical trial has had some kind of crisis, Kreger says that solving problems is—or ought to be—the core skill of CROs.

Getz says that managing supply chain disruptions involves anticipatory planning, and several of the larger CROs are already quite effective at anticipating and resolving shortages. However, smaller CROs are more likely to struggle with these issues:

“The larger CROs have the resources to stockpile supplies or accommodate for when things get pinched down the road. The smaller CROs don’t have the resources or the infrastructure to monitor supply chains and mitigate shortages.”

Despite challenges such as controlling sponsors, a labor shortage, and market consolidation, the CRO industry will continue to be buoyed by growing demand for outsourced R&D services. Coldwell says that the main factors driving CRO performance over time have involved Big Pharma outsourcing more of their work, new biotech startups gaining financing, and regulators asking for more data and imposing more protocol requirements. He points to several other economic drivers that are also contributing to the growing need for CROs, including a more crowded pharmaceutical marketplace and a push by pharma companies to find better competitive differentiators.

“I’ve covered CROs for 27 years, and I don’t think we’ve ever seen a year where outsourcing didn’t either hold ground or gain ground in terms of market penetration,” Coldwell says. “There was a mass acceleration of outsourcing due to COVID-19, and I don’t see pharma companies bringing work back in-house. I also don’t see regulators asking for less data. What I don’t know, and where there is some debate, is what will be the ultimate impact of this rapid transition toward more fully decentralized trials.”

Coldwell expects that over time, as CROs become more effective at running DCTs, those studies will become faster and more efficient. While this shift would mean less revenue from an individual trial, Coldwell says it would also mean fewer delays, fewer change orders, and less clean-up work. As DCTs become faster and less expensive to run, he says, pharmaceutical companies may spend more money on DCTs to get more drugs to market faster.

“The debate isn’t whether there will be a lot of activity,” Coldwell explains. “There will be. The real debate in five or 10 years is whether decentralized trials will be successful enough and rolled out broadly enough to increase revenue.”

While the jury is still out on DCT revenue, past investments in mRNA, antibody therapies, autoimmune products, vaccines, oncology, and various other fields have already created tremendous demand for outsourced services. Coldwell says this increase in demand is reflected in the CRO industry’s revenue growth numbers.

“The publicly-traded CROs are looking at a 2021 revenue growth that’s close to 30%,” he notes. “The aggregated year-over-year growth of those companies is going to be in the mid-to-high 20s, which is pretty amazing. Before the pandemic, a typical growth expectation was about 6% to 8%. We’re seeing growth rates in 2022 that are beyond what was expected in 2018.”

The CRO industry is undergoing rapid growth and significant changes. While growing investment in pharmaceutical R&D is creating more opportunities for CROs, smaller players are facing competitive pressure from larger companies that have undergone recent mergers. Supply chain disruptions and labor shortages are contributing to a more challenging environment, but analysts say that CROs have the tools and creativity to solve these problems—if sponsors will accept the need for innovation. Still, the emergence of DCTs and advanced technologies are giving CROs new tools to meet demand.

In the near term, the future of the CRO industry will see companies learning lessons from COVID and implementing more technology-driven solutions. By the end of this decade, analysts say CROs will invest in AI-powered biosimulation, consolidate clinical and commercial divisions, and ramp up hybrid trials. While there will be pressure to differentiate or niche down, and to ensure services are competitively priced, a smaller slice of a bigger pie is still more pie.

How CROs have adapted to recent challenges—and how they’ll continue 
to evolve in the future.

Mike Straus

Articles

Patient Recruitment Goes High-Tech

CRO Update: Where are Contract Research Organizations Headed?