Reaching Adolescents in Clinical Research

Donald P. Orr, M.D., Professor of Pediatrics, Nursing Research, and Dietetics and Nutrition, Director of Adolescent Medicine, Indiana University School of Medicine, Indianapolis, Indiana

Dr. Donald Orr began his presentation by describing the issues that investigators face when they target adolescents as research subjects. Adolescents are at the highest risk for sexually transmitted infections (STIs); therefore, they often are the target population for research. They are difficult to deal with because both society and their parents do not want to contend with sexually active adolescents. Dr. Orr reported on recruitment and retention in the Indianapolis Young Women's Project.

Adolescents as Research Subjects

As research subjects, children are a special population. Under NIH guidelines, children are considered a vulnerable population needing additional protection, according to the Code of Federal Regulations (CFR). Special guidelines for research involving children call for defining minimal risk in the context of the lives of children instead of in the context of the population. If the research does not benefit them, doing greater than minimal risk research is very difficult. One must define the benefits of participating in the research.

The informed consent process presents specific, special issues for vulnerable populations. Does a 16-year-old, sexually active adolescent have the capacity to consent? Does an adolescent who is not sexually active have the capacity to consent? Who can consent when enrolled in a clinical trial? Is it the parent? What if the research involves a sensitive topic and the adolescent-the minor-does not want his or her parents to know he or she is sexually active, but divulging the participation in a clinical trial would reveal that? How does one obtain parental permission when the research involves a sensitive topic? Can active consent or permission or passive consent or permission be used? Should a guardian ad litem be assigned to enroll minors in projects?

Using adolescents as research subjects also raises questions about protection, compensation for participation, and access to subjects:

• Protection. Adolescents must be protected from harm, but what level of harm is justifiable? Adolescents' confidentiality also must be protected, but to what extent? In addition, adolescents deserve "distributive justice," or fairness, but what about targeting specific populations and offering equal access to potential benefits in research?
• Compensation for participation. What is fair compensation for participation? The amount should be noncoercive, but how is that defined for a minor? What form should the compensation take? Money? Vouchers? Prizes? Raffle tickets? Who should be the recipient of the compensation? The adolescent? The parent?
• Access to subjects. How can researchers gain access to a population of minors?

Mid-America Adolescent Cooperative STD Research Center

Dr. Orr described the Mid-America Adolescent Cooperative STD Research Center, which is engaged in research on adolescent STIs. Based at Indiana University with co-operations at the University of Iowa, Northwestern University, and Louisiana State University, it is one of the seven NIAID-funded cooperative research centers on STIs and the only one devoted entirely to adolescents.
Indianapolis is a medium-sized Midwest city with a population of approximately 750,000. About 20 percent of the population within greater Indianapolis is African American, and less than 5 percent is Latino. There are essentially no other minority populations within the greater Indianapolis area. Because this community is very conservative, doing research about sexuality is very difficult. In fact, many legislators in the area have attempted to close down many of the projects. The researchers work within primary care adolescent clinics that are part of the urban health system. About 60 to 70 percent of the patients are African Americans.

Young Women's Project

This longitudinal study attempts to look at behavioral, psychosocial, and biological risk and protective factors for lower-tract STIs in 300 14- to 17-year-old women from 3 adjacent adolescent clinics. Adolescents are enrolled in the study without regard to sexual experience or infection status. This facet of the study design creates problems for parents who are concerned that in some way the researchers are deceiving them. Because it is a study of STIs and risk factors, parents perceive that their daughters are considered sexually active or that being in the project will encourage them to become sexually active. This perception is one of the major difficulties in recruitment.

Dr. Orr stated that the Young Women's Project is a very intrusive study. It collects quarterly clinical and biological specimens involving pelvic examinations in addition to very personal behavioral data. For 6 months of the year, the researchers collect daily diaries and weekly biologic samples (self-obtained vaginal swabs). Some cervical biopsies are collected on a very limited basis with the older patients. The study includes a questionnaire, interviews, a whole host of specimens, and a parent questionnaire at enrollment, at 12 months, at 24 months, and beyond.

Issues Involved in the Young Women's Project

Dr. Orr described the issues involved in the project:

• The researchers needed to obtain both parental permission and adolescent consent.
• The researchers acknowledged the sensitive nature of the topic with the parents and subjects and called for shared trust involving the parent, the adolescent, the clinics, the community, and the researchers. The researchers also announced their resolve to protect the participants' confidentiality. In addition, the researchers knew they might have to handle the potentially negative impact of the study being discussed or misrepresented in the media.
• There was a large subject burden. The study was demanding, intrusive, and invasive in many ways, both personally and physically.
• The longitudinal study is in its fifth year, with hopes of being extended for another 5 years. The study has collected over 30,000 days of diary entries and other forms over the 5 years of study.

Progress, Retention, and Data Collection

The project has enrolled 220 adolescents, the majority of whom (192) are African American. That number basically represents the composition of the clinics. A total of 25 of the enrolled adolescents are white, and 3 are Hispanic. Twenty-one adolescents dropped out of the study because of the time involved or because they moved or were no longer interested. Most of them withdrew within the first 3 months of the study. The retention is approximately 85 percent at 3 years, which is quite good considering it is a difficult population.

Dr. Orr stated that the study collects diary data for 84 days every 6 months. The diaries tell about social and sexual contacts, sexual behaviors, substance use, mood, and symptoms. The subjects also provide weekly vaginal swabs, which are analyzed for a multitude of infectious agents. The swabs are collected at the homes by field assistants.

Steps Involved in Conducting the Study

Dr. Orr described the steps that the researchers took to engage the community, including the clinics in which they were working. The clinics are a major player in the health care of the youth in Indianapolis.

• The researchers met with the community leaders and organizations, including the head of the public health department, parents who were identified by the community and various other individuals as being important key players, the health center advisory boards, youth-serving organizations, and the police department. The study addressed the important problem of adolescent sexuality and STIs. The areas under study have the highest prevalence of STIs in the country; in fact, a square mile area north of the study area was identified as having the highest rate of syphilis in the United States. When that fact reached the media, it helped raise the level of awareness within the community regarding the importance of the topic.
• The researchers attempt to be honest and up front about the objectives of the study and to show how the study is built on experience with earlier studies. They conduct exit interviews and have discussions with the adolescents and their parents about their participation in the study. The study also provides regular feedback to the clinics and the advisory boards.
• The research staff joined the clinical staff to create a team. Everyone who works in the three clinics is regarded as part of the team. As providers, the researchers are all very visible in the community and the clinics. The clinics are reimbursed for the use of their rooms.
• The team is well trained and supervised. The researchers attempt to identify people who are caring and sincere. The team is made up of an ethnically diverse population. Weekly team meetings are run by a project manager who has a high school education-not by the PIs. The researchers attempt to make adjustments based on the feedback from the team and the clinics. They give positive feedback to the clinics and to the team itself.
• The researchers enroll parents and adolescents and obtain written informed consent and permission from both. The researchers are up front about the study purpose and explicit about confidentiality. They announced that they would give confidential information about the adolescent to the parent if it happened that the child had an STI or became sexually active. Researchers explained that if they found anything that they believed was dangerous about a child or something that might jeopardize a child in any way, they would talk with the adolescent and then inform the parents.
• The researchers reimburse the participants at the level of unskilled workers. The participants also get free treatment and intensive screening for infections. The incidence rates within 3 months showed that 30 percent of the young women had a second sexually transmitted infection.
• The researchers maintained frequent contact with the adolescents. They were seen weekly during intensive data collection. The subjects made quarterly clinic visits, and contact information was updated regularly. The subjects do not move a great deal, but their phone numbers change frequently, so the researchers attempt to have multiple contact points and send the subjects reminders for visits. They also send the participants birthday cards and holiday cards.

Subjects' Willingness To Participate in the Study

Dr. Orr discussed the study's use of exit interviews, which asked salient questions about the reasons for participating in the study; they also asked the parents similar questions. Their candid responses included (1) the researchers' honesty with parents and adolescents about the study, (2) the researchers' ability to inspire trust, that is, to know what to say and how much to probe without appearing too intrusive, (3) the caring quality of the staff, including their respect, openness, and willingness to accept the adolescents' beliefs, attitudes, and behaviors without being judgmental, (4) the adolescents' ability to be themselves and use their own language, (5) the staff's encouraging the adolescents to achieve their personal goals, (6) the staff's willingness to listen to the subjects and to communicate with them as friends, and (7) the team's ability to establish a rapport with the subjects and the parents.

In addition, the young people liked the reminders they received by telephone or by mail as an incentive to keep their appointments. As a couple of the young women said, "This is a talented team who cares about what adolescents do." They did not mention the money, although it clearly helped them.

Dr. Orr concluded his presentation by offering the following suggestions about recruitment for clinical studies:

• Ensure that the project has scientific importance.
• Know the community.
• Ensure that the study is relevant to the community by accurately assessing the community's needs.
• Engage the community.
• Build a skilled research staff.
• Develop a rapport with the participants.
• Provide ongoing feedback.

Discussion

Dr. Orr's presentation prompted the following questions:

• A participant who is an applied anthropologist and an ethnomarketer asked whether the researchers had to deal with aspects of extended family because of the fictive kin aspect of family integration and cohesion in the African American community either in terms of recruitment or ability to assent. Dr. Orr responded that the researchers viewed the family as whoever came and spoke to them. To participate, a young woman had to first indicate she was interested, and then her guardian, usually her mother, had to agree to allow her to be in the study. Next, the researchers asked the mothers if they would participate in a parent capacity.
• Another participant asked whether in the hypersegregated communities of the clinics, the data reflected same partners. Dr. Orr responded that same partners were found anecdotally in the study through the diaries.
• An attendee asked Dr. Orr to elaborate on the interview. Dr. Orr explained that the enrollment interview was a semistructured interview after consent combined with one-page daily diary entries. The diaries were collected each week. Then 3 months later, a structured interview was conducted to ascertain behavioral collection data in the interval. With trained interviewers or research personnel, adolescents can be easily engaged in this type of interview.
• Another attendee asked about the resources in terms of effort, time, and planning and the knowledge needed to generate a budget for a proposal that adequately reflects what it costs to do what has been described. Dr. Orr replied that the budget must estimate recruitment, reimbursement, and staff salaries. An attendee mentioned that the biggest cost-eaters in a budget involve tracking time.