The investigative site is responsible for recruiting and enrolling study subjects who meet the protocol’s criteria for inclusion and exclusion. Remember that this recruitment process is considered part of the informed consent process.
When approached about conducting a study, carefully assess whether your site can meet the enrollment goals in the time frame stipulated for the study. Sponsors would prefer that the investigator turn down a study rather than inflate their ability to meet enrollment goals.
The following are some reasons sites may not meet enrollment goals:
- Ineffective recruiting from available resources
- Ineffective forecasting of number of subjects during the planning stages of the study
- Diversion of potential subjects to competing studies
- Improper understanding of the enrollment criteria
- Overly restrictive enrollment criteria
- Higher percentage of dropouts or more concurrent illness than anticipated
Questions to Ask Before Accepting a Study
- What is the subject population? Do you have qualifying patients in your practice? If seasonal, is the enrollment period within the peak time?
- What is the enrollment timeline? If it is extremely tight, will you be able to enroll the number needed in the time frame required?
- Is the sponsor developing a central recruitment effort (central calling center, centralized materials)? If yes, what does that mean for the investigative site? If there is a centralized call center and two sites in the same area, how will the leads be distributed?
- Will the sponsor provide a budget for advertising materials? If yes, how much?
Establishing a plan for recruiting subjects is vital to meeting enrollment goals. The recruiting plan will vary based on the subject population to be enrolled, how the site will access those subjects, and the time frame for enrolling. During the process of selecting investigators, many sponsors will visit the potential site to assess the facilities and discuss the study with the investigator. Have a basic recruiting strategy outlined to discuss with the sponsor.
Subject Recruitment Sources
Patients in Your Practice
One of the more common places to find subjects is within the physician’s own private practice. If the subject is interested, the consent form must be signed before beginning procedures related to qualification requirements. If your site intends to expand its research capabilities, consider developing an authorization form asking the patient for their permission to enter their name in a research database at the site and permission to contact them if an appropriate research study becomes available (this is especially important when dealing with subjects recruited through advertising). Maintaining such a patient database can be a valuable asset in recruiting patients.
Subjects Referred from Other Physicians
Tapping into the medical community is another means of recruiting subjects for studies. Some physicians may be reluctant to refer their private patients to another private practice for participation in a clinical study. To overcome the more common concerns, a site may make the following assurances to physicians who have patients to refer:
- Participants who are referred and qualify will still be followed by the referring physician.
- The investigator will send information on study subjects’ responses to the investigational product to the referring physicians—after the completion of the study, if the study is blinded.
Open communication with referring physicians contributes to a good working relationship and opportunities for future referrals. Develop a template for letters to physicians who have referred their patients to the investigative site, informing them of the final enrollment numbers and thanking them for their assistance. If a referred patient is not enrolled as a subject, include the reason for exclusion, especially if the physical examination at screening revealed a medical problem.
You can find subjects through referrals from nonmedical sources. You can target advocacy groups for the particular disease state you are working with—such as the Arthritis Foundation, Lupus Foundation, Diabetes Association, or local senior centers. Mass research-oriented mailings for health care professionals and the community can educate the public while raising awareness of your research efforts.
FDA considers direct advertising (i.e., advertising intended to be seen or heard by prospective subjects) to be part of the informed consent process as well as the subject-selection process. Therefore, IRB review and approval is required to ensure that the information is not misleading and that the ad is not coercive.
If the sponsor or CRO anticipates difficulty in enrolling subjects, they may develop advertising materials for sites to use or implement a broad advertising campaign to enhance enrollment.
A site may also advertise for study subjects in its own community. All advertising, whether developed by the sponsor or the site, must have IRB approval.
In general, FDA believes that advertising to recruit research subjects should be limited to the information prospective subjects need to determine their eligibility and interest. Advertisements may include the following information, when appropriately worded. However, not all of this information is not required.
- The name and address of the clinical investigator or research facility
- The condition under study and the purpose of the research
- A summary of the eligibility criteria
- A brief list of the benefits of participation—such as a no-cost physical examination
- The time or other commitment required of the subjects
- The location of the research and the person or office to contact for more information
When discussing a study with a subject:
- Listen carefully to subject’s and family member’s concerns
- Provide your contact information to study subjects
- Spend as much time as the subject needs to become comfortable with the study
- Send a letter to the subject’s primary care provider to notify them of their subject’s study participation and regularly update them on their subject’s progress
Sites should initiate retention efforts during the screening phase. Minimizing retention loss starts with identifying subjects who meet the eligibility criteria, understand the purpose and timelines of the study, and recognize their responsibilities, length of commitment, and expectations as study subjects.
Education, communication, and support are key to keeping stud participants motivated, committed to the study, and involved through the end of the study.
Subjects who feel that they have been appropriately educated about a study are more likely to take ownership of their responsibilities while enrolled and remain in the study for the duration.
Once recruited, subjects may withdraw from a study for several reasons. Some major obstacles to retention can be:
- Misunderstanding about clinical study participation by the subject or family/friends
- Misunderstanding about placebo treatment group
- Concerns about the protocol complexity and treatments, especially when the study is long or there are numerous tests/procedures
- Transportation issues
- No improvement in the subject’s disease state
- Lack of customer service, including uninterested staff, long waits to be seen with no explanation or apology, difficulty in contacting research staff, or no contact between visits
- Lack of physician involvement or contact. In clinical research, the subject provides a service to the study. The physician should accord the subject the appropriate respect for that service
Overcoming These Obstacles
- Stay in contact with subjects at least monthly, if the study is long-term. Determine the subjects preferred method of communication. Provide a visit reminder the day before a scheduled visit.
- At each visit, briefly review the consent form and ask if subjects have any additional concerns or questions.
- Say thank you, but also thank them in other ways such as sending birthday cards, or a card on their study anniversary.
- Ensure that staff maintain patient confidentiality and are friendly, enthusiastic and professional in all patient encounters
- Pay attention to your subject population’s special. For example, in a study of the elderly, transportation may be an issue. Can the site pay for transportation such as taxis or pickup vans?
- Provide flexible clinic visits to accommodate after work or weekends.
- If a subject misses a study visit, contact the subject as soon as possible to determine the reason and reschedule.
Identify Potential Signs Leading to Study Withdrawal
Look for “red flags” of subject discontent such as
- Missed or frequently rescheduled visits
- Difficulty reaching the subject
- Missed study drug doses
- Complaints about study visits
- Changes in health
- Impatience during study visits
- Being quiet or withdrawn during study visits
Changes in study personnel can also affect subject retention, especially in a study with elderly subjects who have established a relationship with study staff.
If a subject appears to be considering withdrawal from a study
- Listen carefully to the subject’s concerns and restate the subject’s value to the study.
- Involve the principal investigator in conversations with the subject.
- Talk with the subject and try to identify issues or specific reason(s) they want to withdraw. Sometimes recent lifestyle changes or health issues create a temporary adherence problem.
- Determine if the reason(s) can be resolved. Some reasons may be related to study requirements that the subject perceives as burdensome.
- Do not try to coerce the subject to remain in the study; they may withdraw at any time for any reason.
- Depending on the protocol, ask if the subject would agree to phone calls to complete follow-up assessments.
- If contact with the subject becomes a problem, stress the importance of keeping in touch. It may be possible to arrange for the subject to contact the study site at a specified time, annually, or even at the “final visit” stage of the study.
In all cases, the PI should document a withdrawal of consent in the subject’s study records.