Recruiting Special Patient Populations

Effective subject recruitment is the cornerstone of clinical research. Delays in patient recruitment cost pharmaceutical companies time and money. According to a recent report in Cutting Edge Information, clinical trials last 42% longer than expected in Phase I, 31% longer in Phase II, and 30% beyond planned deadlines in Phase III—all because of recruitment delays.¹ Each day a drug is delayed from market, sponsors lose up to $8 million.²

While it can be challenging to reach a general audience for clinical trials, it is much more difficult to target "special populations" and motivate them to participate. Special populations are defined as specific ethnic and demographic groups, such as women, seniors, children, African Americans, Native Americans, and Hispanics.

As clinical trials become more complex and specific, protocols increasingly require recruitment of special populations. While these groups have been historically underrepresented in clinical research, their participation is critical to the success of many medical research studies and to the evaluation of marketed pharmaceutical and medical products.

Percentage of special populations without insurance

Furthermore, it has been mandated that minorities be adequately represented in clinical research.³ The National Institutes of Health (NIH) Revitalization Act went into effect in 1993, requiring that NIH-sponsored clinical research include women and members of minorities and their subpopulations to determine whether the investigational product will affect them differently.⁴ Although this mandate does not apply to all clinical research, it does emphasize the importance of ensuring diversity in clinical research.

Despite this mandate, special populations are still not being recruited into studies efficiently and effectively. According to Michael Kritschgau, director of late-phase feasibility and development at Radiant Research, a recent Medstat survey entitled "What Patient Recruitment Methods Work Best for Women and Minorities" found that: "Industry efforts to enroll minority volunteers in trials remain unsystematic and unsophisticated."⁵

This article outlines specific strategies and important issues to consider when recruiting special populations. It will discuss the importance of recruiting special populations, the barriers to recruiting them, and some solutions for effectively recruiting these groups into research studies.

Popular mediums for audiences

The importance of special populations

There is a view that the industry has historically taken a "one-size-fits-all" approach to clinical research and drug development. For instance, children have traditionally been given smaller doses of medications that were approved for use by adults but never tested in children. Women have been treated with medications tested mainly, and sometimes exclusively, on men. There is now a realization that children might not be treated most effectively with an adult medication and that medication that works on a man may not work on a woman in the same way. As a result, "the current research climate encourages the active recruitment of groups that have often been neglected in research. Examples include the inclusion of women and ethnic minorities."⁶

There are many factors that make patient recruitment of special populations particularly difficult, including distrust, ethics, cultural issues, the population pool, health insurance issues, and the role of caregivers.

Where to find special populations

Problems and barriers

Distrust. Trust—or rather, a lack of it—is among the many issues that sites, sponsors, and patient recruitment partners must consider when undertaking recruitment campaigns for targeted populations. First, they must address the basic distrust for research expressed by these groups.

Each ethnic and racial community brings a distinctly different history to clinical research. Researchers must be familiar with each group's experience with unethical research and find solutions that address distrust and fear to ensure optimal conditions that foster participation.⁷

Among American Indian and Alaskan native peoples, there is a longstanding distrust of government rooted in a history of disease, coercion, broken contracts, and denial of basic rights. In the African-American population, there is the case of the Tuskegee syphilis study. Among Hispanics, women have often been the target of the most blatant unethical research and medical practices. These practices indicate a climate of unethical medical practices and the violation of the reproductive rights of poor women and women of diverse ethnic groups. As for Asians and Pacific Islanders, there is a history of U.S.-funded research conducted in the countries of origin, as well as the overall oppressive political conditions to which this population has been exposed.⁸ Given this history, it is no surprise that these groups may view clinical research somewhat skeptically.

Recent research indicates that this cycle of distrust may be changing, but researchers are far from the point of declaring it a nonissue in the recruitment of special populations. The NIH recently released research findings indicating that minorities participate in health research studies at the same rate as Nonhispanic whites when they are made aware of the study and they meet medical requirements. This brings to the forefront the issue of making information accessible to all special populations.

Ethical considerations. There is a natural conflict between the researcher's desire to recruit patients to fill a study and the right of subjects to not be coerced into participating in a study. Ethical practices must be in place to ensure that special populations, who have historically been at risk for abusive and exploitive practices, are protected.⁹ The issue of placebos must also be addressed and is especially important if a subject is required to discontinue his or her current medication to participate in a study. If the study is testing an investigational drug against a placebo and the patient is receiving a placebo, that person is not being treated for his or her condition. During the informed consent process, there must be full disclosure made to all subjects that they may be receiving a placebo.

Cultural issues. Sites, sponsors, and patient recruitment partners must also consider cultural issues, often exacerbated by socio-economic disparities. Culturally sensitive communication vehicles in the subjects' language and vernacular must be used to foster a rapport. Also, it is critical to determine which communication vehicles and which communications media will reach a particular target audience most effectively.

Researchers need to be aware that recruitment materials that are effective with one ethnic group might not be successful for recruiting subjects from another culture or demographic. Translation is an issue. It is important to preserve the original meaning of the study materials, so the translator must have a clear understanding of the study.

Population pool. Another important factor to address is population breakdown. Because special populations represent a smaller population pool nationwide than the general population, there are fewer individuals from these groups available for studies. The total population of the United States is 281,421,906 according to U.S. Census statistics.¹⁰ African Americans comprise 13% of the U.S. population, senior citizens comprise 12% of the U.S. population, and women ages 25 to 44 comprise 14%. Sponsors must consider the availability of any special population when formulating patient recruitment goals for a protocol.

Health insurance. Special populations tend to be more medically vulnerable than the general population. The percentage of individuals in all special populations that have health insurance is lower than in the general population. For instance, in 2000 only 19% of African Americans had health insurance. Since many protocols require patients to have used certain medications or at least be diagnosed with a particular indication, many individuals will not participate because they may be unaware of their condition or may not have had the opportunity to use a certain medication. In addition, if due to lack of insurance a potential participant does not see a physician regularly, the opportunity to learn about a study from a medical professional is considerably limited.

On the positive side for sites and sponsors, the inexpensive and sometimes free medical care that patients receive during clinical research may draw these special populations to the study as an option for affordable, accessible health care. Subjects that are seen by an Investigator have the potential to be treated for their condition. Subjects may also receive medical exams that can diagnose and detect other medical issues. They can then be referred to other physicians and specialists for follow up. This is one way for the underinsured to possibly obtain medical care for a condition that would otherwise have gone undetected.

Caregivers as decision makers

It is important to keep in mind that with many special populations, the target audience for the recruitment message might not be the actual patient. In fact, the likely target is the patient's caregiver.

An adult caregiver for a senior citizen, usually a relative, is most likely to make the decision to place the senior in a medical research study. Families can be very hesitant to have their elderly relatives participate in clinical research because they do not want to put their loved ones through procedures or experimental treatments that may not work. Another key factor to consider is that many seniors are dependent on others for assistance, since more than 50% report having at least one disability that limits their daily activities. This may make it too difficult to participate without the assistance of others. They are also often hesitant to report their illnesses and frequently under-report their symptoms.

Parents may be reluctant to allow their young children to participate in clinical trials, especially if the condition is not life-threatening or if other viable treatment options are available. Recruitment is even more challenging if it is for a double-blind study where some subjects will receive a placebo, or if the research involves a painful procedure. Parents want to make sure that their children are receiving effective treatment. Furthermore, they don't want to expose them to the pain of something like a blood draw if the procedure does not clearly benefit their child's health.

On the other hand, parents are very willing to have their children participate in clinical trials for life-threatening conditions like cancer, when nonstudy treatment options are limited. A study conducted at the Walter Reed Army Institute of Research in conjunction with the National Cancer Institute (NCI) found that pediatric patients were recruited into clinical trials at high levels; whereas after adolescence, only a small percentage of cancer patients were enrolled in clinical trials. This suggests an aggressive stance by parents to find lifesaving treatments for their children. In fact, more than half of all children attracted to NCI-sponsored trials are between the ages of 5 and 9, compared with less than 1% of adults ages 75 to 79. The highest percentage of adult patients accrued are between the ages of 40 and 55.¹¹

And, in some populations, while the patient ultimately makes the medical decisions, family members may be quite influential and should be considered when targeting these groups. Within the African-American population, for instance, 47% of families are headed by a female, who is likely to be making medical decisions for the entire family.

Given these challenges, there are certain steps that sites, sponsors, and patient recruitment partners can take to effectively recruit these groups for clinical research. Assessing population and demographic information is critical.

Solutions

Understanding the process. It is important to note that study sponsors, including major pharmaceutical and biotechnology companies, are providing the funding for the majority of clinical research studies. These sponsors are deciding who the patient population is and what the inclusion/exclusion criteria will be. Thus, it is essential for sites, sponsors, and patient recruitment partners to know the audience they are recruiting. It is critical to understand their motivations, influences, and media habits to reach them in the most efficient and effective manner.

Informed consent and ethical concerns. Informed consent can be particularly difficult with special populations. For one thing, language barriers must be overcome. Although informed consent requirements vary across the country—and in some cases consent may not even be required—potential subjects should be given an official form written in their own language.

Another issue is that immigrants may not understand the basic human rights afforded to them in the United States. They may feel coerced into participating because they fear retaliation if they do not. Social status is another factor. Some members of special populations, such as Asians and Pacific Islanders, sign a consent form simply because the person who asked them to sign it is influential. As a result, they may not understand the risks of the study.¹²

Informed consent is the primary mechanism of protecting subjects against unethical treatment. The NIH, IRBs, and investigators must work together to tailor the consent process so that it will be effective for all special populations. This means avoiding any appearance of inducement to participate in clinical research, monetary or otherwise.¹³

Sponsors can integrate tools into the recruitment process to increase the autonomy of subjects. Recruitment materials should include effective educational components that explain clinical trials and the medical research process in a simple, easy to understand manner. Informational Web sites that share valuable information about a particular condition and effectively outline study specifics can play an important role in informing subjects about the trial.

In addition, the purpose of IRBs is to protect medical research participants and to look out for the patient's best interests. IRB contact information is distributed to all subjects at the outset of the study so participants have an outlet to go to if there are concerns or questions.

Implementing these measures ensures that all subjects are fully informed about their participation in the trial process.

Market research and media consumption patterns. The proper medium must be selected to reach the target audience, whether it is the patient, family, caregiver, or parent. It is imperative to know which medium influences the target audience (see sidebar).

The right communication vehicles. Market research and media consumption patterns are then used to develop the right message, visuals, and tools to reach the target audience. For example, for an African-American audience, the message and visuals need to connect with a strong image of family and community. Also, because research shows that in general, African Americans are not heavy newspaper readers, a television or radio advertisement or news segment may be more effective than a newspaper advertisement in informing them about the clinical research study.

Geographic considerations. The recruitment industry must also take geography into account when focusing on special populations. If there is the opportunity to choose markets, it is crucial to select markets where individuals in the target population largely reside (see sidebar). While it may seem as if the differences in population size are insignificant, remember that the overall size of these groups is smaller compared to the size sought in a general recruitment campaign. Choosing geographic regions with more potential participants is therefore in the best interest of the study.

Case study

The following case study illustrates how population and demographic information can be effectively used to recruit special populations.

A clinical research study to test the safety and effectiveness of a dual cardio drug in African Americans was implemented by a major pharmaceutical company. The purpose of this dual cardio drug was to treat high blood pressure and high cholesterol with one pill. The six-month study took place in 100 sites across the United States. The goal was to randomize 500 African-American subjects aged 18 to 80 years. The purpose of the study was to test the investigational medication in African Americans for effectiveness.

The American Heart Association reports that African Americans are at greater risk for cardiovascular disease and stroke-related death than Caucasians. For African Americans age 20 and older, 36.7% of men and 36.6% of women have high blood pressure. Among African Americans, 45% of men and 46% of women have total blood cholesterol levels over 200 mg/dl.¹⁶ Research has confirmed that, although the prevalence of the conditions is high in this population compared to other groups, the use of prescription drugs to treat the indications has traditionally been below average.

Through syndicated research, individuals taking high blood pressure medication, cholesterol medication, or a combination of both were targeted for the study and an age profile was analyzed. It was determined that individuals taking separate medications for both conditions would be most likely to take a dual cardio drug for convenience sake. Since many individuals in the target do not take medication, the media consumption patterns of the target age range of 30 to 64 years was also researched in an effort to reach potential study participants that were not captured through the research on medication. Although African Americans in general are light readers of newspapers, these particular audiences are heavy readers of African-American publications.

The strategy was to develop messages that would communicate the high incidence of the disease in African Americans by appealing to the family as well as the patient. The text was written to provide a sense of comfort, familiarity, and trust in the research and the FDA-approved study medication. Also developed were materials that explained what clinical research studies are and answered frequently asked questions. Astute planning also ensured that the sites were located in communities with high African-American populations.

Recruitment materials included a study logo, consumer brochure, print advertisement, community outreach materials, and site tools. African-American publications were targeted for print advertising. These publications are published directly for the African-American audience, offer an effective readership profile, and allow for the use of a more cost-effective local media outlet. The study sites were mainly located in large to mid-sized markets in which African-American publications were available. All materials prominently showed family-oriented visuals to appeal to the strong sense of family in the demographic.

A community outreach program was also critical for reaching the African-American audience. The community outreach initiatives addressed the cultural barriers and the distrust issues presented by the study. Research determined that African Americans tend to be regular churchgoers and that pastors and the church communities wield a strong influence. A pastor or church administrator mentioning the study to the parish, or a study poster displayed on a church bulletin board, constituted a strong and credible third-party endorsement.

To that end, churches were used as outlets to reach the target audience. Sites were given brochures and posters to send to the churches, along with a letter to church administrators explaining the clinical research study.

Doctors were also sent a letter that they could customize for their patients to inform them about the study. In this way, the distrust factor was also addressed, since the message was coming from a personal physician—someone they trust.

Overall, the recruitment goal was met and the study time was shortened by 128 days.

Conclusion

Recruiting special populations for clinical research studies requires a targeted approach that takes into consideration the clinical research process, informed consent, market research and media consumption patterns, population information, cultural issues, and geographic considerations. Effective patient recruitment techniques for these groups will become more and more critical as sponsors continue to recognize the importance of including these previously underrepresented groups in medical research and as the FDA continues to mandate participation by these special populations in clinical studies.

Donna Beasley is vice president of operations with Praxis Communications, Inc., 5141 Virginia Way, Suite 260, Brentwood, TN 37027, (615) 312-8207, fax (615) 312-8208, email: info@gopraxis.com

References

1. Cutting Edge Information, "Accelerating Clinical Trials: Budgets, Patient Recruitment, and Productivity," May 2004.

2. Cutting Edge Information, "Accelerating Clinical Trials: Budgets, Patient Recruitment, and Productivity," May 2004.

3. NIH guidelines on the inclusion of women and minorities as subjects in clinical research, 59 Federal Register 14508–14513 (1994).

4. K. Korieth, "CenterWatch Survey: Study Volunteers Satisfied with Trial Experience," The CenterWatch Monthly Newsletter, 12, (9) 1–11 (September 2005).

5. K. Korieth, "CenterWatch Survey: Study Volunteers Satisfied with Trial Experience," The CenterWatch Monthly Newsletter, 12, (9) 1–11 (September 2005).

6. E. Steinke, "Research, Ethics, Informed Consent, and Participant Recruitment," Clinical Nurse Specialist: The Journal for Advanced Nursing Practice, 18 (2) 88–97 (2004).

7. D. Wendler, R. Kington, J. Madans et al., "Are Racial and Ethnic Minorities Less Willing to Participate in Health Research?" PloS Medicine, 3 (2) (February 2006).

8. Women and Health Research: Ethical and Legal Issues of Including Women and Minorities in Clinical Studies, Vol. 1, A. Mastroianni, R. Faden, D. Federman, eds. (National Academy Press, Washington, DC, 1994).

9. Women and Health Research: Ethical and Legal Issues of Including Women and Minorities in Clinical Studies, Vol. 1, A. Mastroianni, R. Faden, D. Federman, eds. (National Academy Press, Washington, DC, 1994).

10. U.S. Census Bureau, Census 2000 Summary File 1, Matrices P7 and P9.

11. W.B. Sateren, E.L. Trimble, J. Abrams, "How Sociodemographics, Presence of Oncology Specialists, and Hospital Cancer Programs Affect Accrual to Cancer Treatment Trials," Journal of Clinical Oncology, 20 (8) 2109–2117 (2002).

12. Women and Health Research: Ethical and Legal Issues of Including Women and Minorities in Clinical Studies, Vol. 1, A. Mastroianni, R. Faden, D. Federman, eds. (National Academy Press, Washington, DC, 1994).

13. Women and Health Research: Ethical and Legal Issues of Including Women and Minorities in Clinical Studies, Vol. 1, A. Mastroianni, R. Faden, D. Federman, eds. (National Academy Press, Washington, DC, 1994).

14. Sources: Arbitron; Newspaper Association of America; American Demographics.

15. U.S. Census Bureau, Census 2000 Summary File 1, Matrices P7 and P9.

16. American Heart Association Web site, www.americanheart.org.