Perfect Harmony

November 1, 2004
Donna Beasley

Donna Beasley is vice president of operations with Praxis, 5141 Virginia Way, Suite 450, Brentwood, TN 37027, (615) 312-8207, fax (615) 312-8208, email: info@gopraxis.com.

Applied Clinical Trials

Applied Clinical Trials, Applied Clinical Trials-11-01-2004,

A skillful mix of marketing and management savvy together with scientific expertise makes a recruitment campaign sing.

A skillful mix of marketing and management savvy together with scientific expertise makes a recruitment campaign sing.

Effective subject recruitment is a cornerstone of clinical research. In 2001, over 85 percent of all completed medical research studies experienced enrollment delays, and 34 percent were delayed for more than one month.1 Such postponements can cost pharmaceutical companies millions of dollars in missed sales. For example, according to The Pharmaceutical R&D Compendium, delays in getting a drug to market in 2000 were estimated to cost companies around $1 million per day.2 In 2003, a month-long delay cost sponsors an estimated

$47 million in unrealized revenue.3 Because of these realities, developing effective subject recruitment programs has become even more critical to the industry. With less than 10 percent of eligible patients participating in clinical trials at any time, subject recruitment programs can increase a sponsor's capability to reach those who have never considered participating in clinical research.4

Effectively raising awareness of the need for clinical research subjects must be handled methodically and with integrity. To understand what makes a subject recruitment campaign successful, one can view the procedure as a five-step process that includes subject profiling, market segmentation, marketing communications planning, centralized pre-screening, and trial management. All of these steps are integrated and interdependent, and effective subject recruitment can only happen when all of these elements work together.

The following case study will illustrate how all of these fundamental aspects come together to create an effective subject recruitment campaign. A cost-effective campaign to recruit qualified participants for two separate clinical research studies was to be executed for Pharmacia. Both studies focused on the treatment of a socially sensitive pediatric condition. The overall recruitment goal of the multimonth study required identification of 225 qualified subjects across 32 sites throughout the United States.

Here is an overview of the five-step process and how it was implemented for these studies:

Subject profiling
Subject profiling includes understanding the subject population; utilizing demographic, psychographic, and statistical research sources; and consulting with medical professionals. Both clinical expertise and marketing expertise are required to describe the target population for a recruitment campaign. Just as every indication is different, every protocol is different. Various exclusion and inclusion criteria create a distinct subject profile for every study. After developing a subject profile, source mapping and recruitment planning can be done to determine which outreach programs will be the most effective in identifying subjects.5

With some indications, potential subjects are not in control of their own healthcare decisions, and their caregivers are the targets of the awareness campaign. For example, in clinical research studies regarding pediatric or elderly conditions, a parent or caregiver is most likely to be the one making the health care decisions for the subject. In such instances, both subject and decision-maker profiling are crucial in creating an effective campaign.

For profiling in the pediatric studies, target populations had to be examined on a variety of levels. Since the subjects sought were children, the caregivers were the decision-makers and the target audience for the recruitment message, due to their responsibility for making the healthcare decisions for the study candidates. For profiling purposes, it was critical to determine who these caregivers were. The research revealed that women between the ages of 25 and 49 are most likely to have children ages 5 to 10 years old, and that women are typically the healthcare decision-makers. Thus, the person targeted was a young woman with a young child. This profile allowed for investigation into the sites where the study was going to be conducted, in order to determine the designated market areas with the greatest incidences of both the target audience and the subject population.

Market segmentation
Market segmentation involves researching the optimal locations to find qualified subjects. Markets are ranked to pinpoint where the highest concentrations of potential subjects are. There are many variables used in this analysis, including population counts, incidences of target demographic households, and the prevalence of the disease in the market.

From the beginning, the protocol must be analyzed not just from a clinical standpoint, but also from a demographic perspective. This includes evaluating the target subject population, determining the incidence of the condition based on geographic location, establishing site qualifications, and confirming subject accrual timetables and rates based on prior studies.6

The values and norms of the target audience must be known intrinsically: What factors influence individuals to enter themselves or someone in their care into a clinical research study and what elements make them shy away from it? What are their priorities? Where do they get their information? When do they consider participation in clinical research a viable option? This information aids us in finding the target audience in specific locations and determining the best methods to reach them.

In the pediatric campaigns, a national database was used to uncover demographic information, media usage, audience psychographic information, product usage, and media consumption. The research provided knowledge about the media use habits of adult women with children between the ages of 5 and 10 years old, since, as previously discussed, these women were making the health care decisions for their children. We learned that our target audience obtained information through personalized sources, such as direct mail and communication with their pediatrician.

Markets with higher populations of children were also identified, since a greater population of children indicated not only the presence of more potential subjects, but of more mothers who might be receptive to the recruitment message. Some markets were more successful in their recruitment efforts than others, simply because some areas had a higher potential subject population. For example, the Jackson Hole, Wyoming site had a very small population of women with children within a 60-mile radius, so subject recruitment was a challenge. The Louisville, Kentucky site reached its recruitment goal very quickly because of the high population of women with children in the market.

The marketing communications plan
Once the target audience is described and more is known about its media consumption habits, the best way to reach the subject or decision-maker profiled in the identified market segment is determined. Various tactics are taken into consideration, including newspaper, television, and radio advertising; Internet banner ads; direct mail; brochures; posters; investigator education materials; and public relations services.

As specific tactics are implemented, creativity becomes a large part of the process. Because of today's hectic lifestyle, a creative message is imperative to attract attention and gain awareness. Direct messages are formulated and customized to the target audience. Materials are designed and produced. Public relations activities can be conducted to show the positive impact of medical studies and to educate the public about the condition, as well as to attract potential subjects. Direct marketing and media advertising plans are implemented. All recruitment and advertising materials and initiatives must be IRB-approved prior to implementation to ensure that the materials accurately portray the study. The role of the IRB is to protect the interests of potential subjects.

Creativity plays a critical role in attracting the right individuals. Each study requires different tactics, depending on how the target audience receives their information. The goal is always to attract, inform, and retain eligible subjects. Research indicates that higher response rates are received by advertising that has a consistent look, that reinforces the recruitment campaign message, and that is strategically placed through effective media buying.7

Formulating the message for the pediatric studies was a challenge because of the sensitive nature of the condition. The focus of the recruitment message was a reflection of the thoughts and emotions felt by someone impacted by this condition.

Tactics included print advertising, primarily in parenting magazines; two direct mail campaigns, one to pediatricians within 20 miles of each site and one to households near each site; Web site development; and public relations. Only households with children ages 5 to 10 were targeted.

In the interest of raising consumer awareness of clinical trials, the Web site that was run in accordance with this study included some general questions and answers on medical research studies. An informed individual is more likely to be interested in a study, and is also more likely to follow the study regimen, take an active part in their care throughout the study, and remain enrolled for the duration of the study.

Centralized prescreening
Centralized prescreening means that there is one centralized location for all information regarding potential participants. The goal is to ensure that only the most qualified potential trial participants are scheduled with various research sites. The centralized procedure facilitates accurate tracking and analysis of recruitment activity as it occurs.

Systems such as interactive voice response (IVR) streamline the subject screening process. IVRs are utilized to prescreen candidates and to collect data throughout the study. Call centers with toll-free numbers collect subject information at a central source, and the IRB-approved prequalifying questionnaires can be used to prescreen individuals. Customized Web sites are now being used to post the prequalifying questionnaire and to pre-screen candidates online through a secure network setup.

The comprehensive Web site for the pediatric studies served two purposes: first, to inform and educate the public about the studies; and second, to prequalify potential trial participants. Because individuals are often reluctant to submit personal information over the Internet, Secure Socket Layer technology was used to ensure the security of the information presented online through the prequalifying questionnaire. The prequalifying questionnaire incorporated the inclusion/exclusion criteria to screen subjects for the studies. In this manner, individuals could be automatically qualified or disqualified from the candidate pool. Fifty-four percent of all prequalifying questionnaires were completed on the Web site, the balance via telephone.

In accordance with HIPAA and IRB regulations, it is imperative to respect the privacy of potential subjects and their medical information. In the pediatric studies, whether the inquiry came via telephone or the Web site, all inquiring individuals were asked to grant permission to collect information before completing the prequalifying questionnaire. When subjects prequalified, they were instructed that, with permission, their information would be sent on to a research site. For those who did not qualify, or did not wish to have their information sent on, the information was destroyed.

Trial management
The trial needs to be managed once the subjects are recruited, have qualified for the study, and have given their consent to participate. Hands-on subject support and personal attention must be implemented. Study coordinators need to stay energized and motivated, and principal investigators must stay well-informed and subject-focused.

Indeed, to ensure subject retention, the focus should remain on the subject throughout the trial. Nearly 40 percent of all prequalified volunteers fail to enroll due to inconvenience and lack of responsiveness from investigative site personnel. In an analysis of more than 1,700 prequalified study volunteers for Phase II and Phase III projects, CenterWatch found that 13 percent never enrolled because there was no conveniently located investigative site, 14 percent of prequalified subjects lost interest following their initial interactions with call center or study staff, and 23 percent of prequalified volunteers were never randomized because no one contacted them after the initial phone screen.8

The success of a clinical research study involving a lengthy time commitment by the subject depends greatly on the perceived value of the care the subject is receiving. Careful consideration should be given to reimbursement methodology and retention strategies. It is important that the study participant understand the commitment and responsibilities required for participation in a clinical research study. Reimbursement and retention strategies must be more frequent, creative, and varied when an extended time commitment is involved.

Every subject who enters into a clinical trial is valuable. There are many reasons why eligible subjects refuse to enter a study, or drop out once they have enrolled. Some of these reasons include: misperceptions about clinical trials in general, concerns over the protocol, perceived complexity of the protocol, poor motivation to continue, and lack of support and guidance during the study.

Subjects who adhere to a study regimen are those who are informed about the study and the condition. They have regimen aids and support for transportation arrangements. They also have a commitment enhanced by a sense of community within the study, and they receive appreciation items throughout the study.

Study coordinators and principal investigators (PIs) also need proper training. Not only does the investigator meeting need to present the inclusion and exclusion criteria and specifics about adverse event reporting, but the PI also needs to address how to treat study participants as valued customers rather than merely research subjects. Site staff need to know what materials are going to be available for recruitment, as well as the goals, objectives, timeframes, and projected milestones for the study.

Subject retention is the key to the clinical trial process. Subjects want and deserve personal attention from everyone they are in contact with at the site. Retention tools such as newsletters, reminder postcards for appointments, appreciation items delivered throughout the study, and follow-up phone calls are essential in making individuals feel like they are an integral part of the study. These communication tools can also educate participants about their condition.

Subjects will also want their questions answered: What are the side effects of the medication? How many office visits will I have to make? Is there a stipend for participating in the study? What about transportation and childcare? Study site staff members need to be properly trained to answer these questions and to make follow-up calls with subjects. Site staff should receive a list of frequently asked questions and designated responses.

Web-based information systems are now being developed to assist research sites and pharmaceutical companies in subject recruitment and tracking analysis. These systems facilitate a single tracking log for all subjects and potential subjects. Clinical research site staff, pharmaceutical company sponsors, and clinical research organizations utilize one system with a specific username and password. This identification system determines which study data may be accessed and at what level of access. The subject log can be retrieved and updated by clinical research site staff. Sites benefit from this arrangement because they can immediately update candidate information on one simple electronic form as changes occur in the candidate's status. Once a candidate prequalifies, the subject's information can automatically be added to the system and updated throughout the study. Site staff can also retrieve graphs pertaining to enrollment and candidate outcomes for their site. As subject information is updated, site staff, sponsors, and clinical research organizations can have constant, real-time access to an analysis of the recruitment plan using secure HIPAA-compliant platforms.

Flexibility is key in effective subject recruitment. In the pediatric studies, sites that offered early morning, evening, and Saturday hours for appointments were more successful in their subject retention efforts. It is important to make it easy for subjects to stay with the study program.

Conclusion
The program is evaluated throughout the process to determine any necessary adjustments and to monitor responses. Following the culmination of the recruitment period, a comprehensive review is done to determine the success of the campaign and the specific tactics, such as advertising, direct mail, public relations, and referrals from doctors or friends. A comprehensive report is issued to communicate the results.

The recruitment goals were exceeded for the two pediatric studies. Exactly 435 prequalifying questionnaires were completed and 256 children successfully prequalified for participation. Evaluation of each referral source vividly illustrates how the integrated communications approach effectively met the goals of the recruitment effort. Qualified candidates were referred to the studies from all recruitment tactics implemented.

Public relations initiatives netted newspaper placements; talk radio interviews; segments with local ABC, NBC, and CBS affiliates; and post-air story placements on station Web sites. Conveying the recruitment campaign in a news-type format enhanced the credibility of the message, because of the value the public places on news stories. The news stories focused on the condition and the study was mentioned as a sidebar.

Subject recruitment is a process that relies on the integration of subject profiling, market segmentation, market communications planning, centralized prescreening, and trial management. A puzzle is not complete without all of its pieces, and subject recruitment campaigns can only be as effective as the sites supporting them.

Treating the potential subjects with the respect and courtesy that they deserve, and giving them the information to make informed decisions, is integral to successfully recruiting an interested and cooperative pool of subjects.

Also, it is imperative to realize that subject recruitment is an intricate process requiring marketing and management expertise together with the scientific expertise. Experience and research are required to analyze the protocol, to find optimal site locations, and to understand the demographics surrounding the media habits of the target subject population. Tying it all together creates a cost-effective recruitment and retention program for each study.

Experts in these fields should be engaged to take on these campaigns and are available through centralized subject recruitment and retention companies. These firms are skilled in incorporating the local level experience of the study coordinators and doctors with marketing research, media planning, and a creative message that allows them to prepare, execute, and manage a successful recruitment program.

References
1. V. Gamache, "Minimizing Volunteer Dropout," CenterWatch Monthly, 1, 9-12 (December 2002).
2. F. Kermani and G. Findlay, The Pharmaceutical R&D Compendium (2000); available at www.cmr.org/publications/books.html.
3. S. Space, "Site Strategies to Improve Recruitment Advertising Effectiveness," CenterWatch Monthly, 1, 9-13 (October 2003).
4. K. Koreith, "Taking Patient Recruitment In-House," CenterWatch Monthly, 1, 5-9 (February 2004).
5. B.D. Harper and L.-O. Eriksson, "One Size Does Not Fit All," Applied Clinical Trials, 42-48 (November 2002).
6. F. Kilpatrick, "Rev Up Patient Recruitment," Pharmaceutical Executive (April 1, 2002).
7. S. Space, "Site Strategies to Improve Recruitment Advertising Effectiveness," CenterWatch Monthly, 1, 9-13 (October 2003).
8. A. Neuer, "Treating Study Volunteers as Customers," CenterWatch Monthly, 1-7 (March 2003).

Donna Beasley is vice president of operations with Praxis, 5141 Virginia Way, Suite 450, Brentwood, TN 37027, (615) 312-8207, fax (615) 312-8208, email: info@gopraxis.com.

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