Figure 1. Active clinical studies (active INDs).

Patient recruitment efforts are becoming increasingly sophisticated to accommodate enrollment demands linked to the rising number of global clinical trials. Active investigational new drug (IND) applications are approaching 4,000 (Figure 1), the number of subjects per NDA currently exceeds 5,300 (Figure 2), and approximately 80,000 clinical trials are ongoing in the United States alone.¹ Attracting, enrolling, and retaining study subjects in all of these trials is a challenge, and meeting that challenge successfully and in accordance with established timelines requires well-designed initiatives by trained staff or professional recruitment providers.

Figure 2. Average number of evaluable patients per NDA.

Professional recruitment and retention Since the early 1990s, there have been remarkable changes in approaches to patient recruitment and retention. Rudimentary recruiting methods have given way to the development of professional, well-orchestrated strategies led by dedicated staff at larger independent sites, site management organizations (SMOs), some academic medical centers, and patient recruitment providers. At the same time, sponsors are understanding the need for procedures to support patient recruitment initiatives, and are investing significant resources in the development of staff and programs internally to provide recruitment services. Therefore, the environment now includes providers external to Pharma and internal to the sponsor company.

CenterWatch, a publisher and information service for the clinical trials industry, estimates that in 2002, $500 million were spent on mass media promotion, up from $400 million just two years earlier.⁴ According to CenterWatch, these figures represent dollars allocated to central campaigns and individual site initiatives. With so much at stake, spending dollars wisely, productively, and ethically is at the heart of the recruitment industry which is dedicated to meeting or beating enrollment targets in the allotted time frame.

Figure 3. Market share of industry-sponsored trials by site type (2002E = $4.53 billion).

Industry insiders have long recognized that retention of study subjects is a direct reflection of how much they understand about the clinical trials process and the importance of protocol adherence. Educating study volunteers about the process in which they are about to engage, explaining their responsibilities to them as study candidates, and always showing respect for them increases their sense of buy-in, and should improve retention.

A word about metrics Metrics are heading toward center stage as patient recruitment initiatives become more scientific. This is a significant change from the 1990s when the practice of keeping metrics was very much in its infancy. At that time, there were few benchmarks and a limited body of literature dedicated to recruitment. In an industry where formal, budgeted recruitment efforts have historically taken a back seat to laissez-faire recruiting practices and in-house database screening, metrics have been either nonexistent or amounted to little more than counting the number of calls generated from various advertisements. Their approach is no longer accepted by sponsors paying the bills, nor should it be.

With increasing pressure to accelerate clinical timelines, more dollars are flowing into recruitment. With them comes the understanding that recruitment success has to be measured, and that accountability is destined to become standard practice. Accountability involves a complete tracking of each point of contact, starting with the prescreening call through scheduling of the first screening visit, then recruitment, enrollment, retention, and linking these actions to the referral source. Through continuous measurement of these actions, meaningful metrics will take shape.

Figure 4. Clinical trial enrollment forecasting.

Market research Sponsors are just beginning to recognize this reality which challenges their long-held expectation that investigators will be able to achieve all or most of the enrollment target from in-house databases, requiring little or no additional marketing effort. This raises the question as to what sorts of efforts are most effective in spurring timely patient enrollment. Broad-based multimedia patient recruitment campaigns can be developed but before allocating big dollars, sponsors are increasingly using market research to understand which techniques attract the types of patients needed for specific studies.

Market research is a way of finding out what people believe, think, want, need or do. Original or "primary" market research employs systematic, objective techniques to obtain this information which may not be available through existing or secondary resources. The collected data are analyzed and then used to support decision-making and judgment by providing a basis in fact (Figure 5). The purpose of conducting market research is to reduce risk in product or service development, thereby increasing likelihood of success.⁷

Figure 5. Steps in the market research process.

Jim Kremidas, of Eli Lilly and Co.'s Clinical Trial Enrollment Services, says that major Sponsors are expanding recruitment capability in-house. At Eli Lilly, Kremidas heads a central group that provides support to study teams in identifying appropriate interventions for each trial, based on the protocol design, the countries in which the study will take place, and the available budget. "The central group is capturing knowledge continuously about the impact of study design and communication tools across a wide variety of trials and therapeutic areas to help us do our job more effectively. This will include better selection of providers and types of media for specific trials. The knowledge will be contained in a database that Lilly intends to build to help predict effectiveness of different types of recruitment tools," Kremidas explains. As part of that effort, Kremidas says his group has already developed metrics showing that in individual studies, various supplier interventions based on those data have proven successful.

One of the more unique trends involves making patient recruitment proficiency a core competency of the clinical research associate's (CRA) job. Merck & Company launched this type of initiative in 2001. According to Susan Tempest, Pharm.D., site implementation and training manager, this innovation grew out of a recognition that the monitor's job entailed more than reviewing data. "The monitor's role at Merck began changing from that of a data manager to a site manager. This required a review of job competencies needed to perform the new role effectively and it coincided with our interest in supporting our research sites with their recruitment efforts. So we opted to enhance the skill set of the field monitors in this area, as they are on the front lines." As part of this pilot-stage initiative, Merck's monitors, known as medical research associates, or MRAs, receive recruitment training starting with the concept that the company and the site are forming an alliance to facilitate a successful trial.

MRAs ensure that a recruitment plan is in place, and once the study begins, adherence to present objectives is monitored regularly. Tempest says the idea is to be proactive in terms of recruitment, and not wait until two weeks before the end of the enrollment period to recognize that current strategies will not lead to a site enrolling the targeted number of subjects within the designated enrollment period. Investigative sites that are more sophisticated in terms of their recruitment abilities may require less intervention than sites that are struggling.

A look to the future The number of clinical trials is on the rise around the globe, and meeting enrollment targets is delayed in most of them due to difficulties in finding qualified volunteers. This is hardly news, but what is new is the degree to which Sponsors are embracing professional solutions.

Apparently, the educational efforts are working as the recruitment industry is seeing an influx of cash earmarked for well-designed campaigns dedicated to attracting, recruiting, and enrollment study subjects. Current estimates of media spending peg the number at $525 million, a figure that continues to grow. And as the industry becomes more sophisticated, there is a realization that successful patient recruitment is about much more than placing targeted, IRB-approved advertising and counting the number of responses. It is about adding a scientific element to the process by measuring results in a consistent way that leads to the creation of databases of information that will eventually be used to predict success with some degree of certainty. Also, metrics tallied on an ongoing basis enable proactive changes in media placement throughout the campaign instead of waiting until the end of the study, when it is too late. It is also about the basics.....working closely with sites.

Key takeaways

• With resources pouring into patient recruitment, professional, organized approaches to recruitment and retention are key to meeting or beating enrollment targets and timelines.
• The use of metrics to measure success of various recruitment efforts adds a scientific element to patient recruitment practices.
• Focusing greater attention on patient retention may serve to reduce the nearly 25% dropout rate of enrolled study volunteers.
• Sponsors are starting to understand the value of using market research as part of developing multifaceted recruitment campaigns that reach the targeted audience more effectively.