Protocol Design - Recruitment

Recruitment procedures are the means by which the purposes of subject selection are actualized. Therefore, the number of subjects to be recruited must be based upon the number of subjects that are needed for the research study to achieve adequate statistical power. With this in mind, investigators may plan to recruit 10 to 15 percent more subjects than the number needed, so as to make up for those subjects who withdraw from the study.

When initially developing the study, investigators must select the method(s) of recruitment based on its potential to reach potential subjects in sufficient numbers (feasibility) and its appropriateness to the study population. Investigators should assess whether there are adequate numbers of subjects to recruit with regard to their intended study population (at their institution) by reviewing deidentified or identified electronic databases, paper records, or imaging studies. (This is considered an activity preparatory to research. If this review will involve protected health information, then investigators must complete a “Request for Access to Protected Health Information for a Research Purpose” form.)

But no matter the method of recruitment, the Institutional Review Board (IRB) must review the recruitment methodology and content and approve them prior to their use in recruiting subjects. The research protocol should clearly explain how potential subjects will be identified, the method of contact, and who will be contacting them. According to the Health Insurance Portability and Accountability Act (HIPAA) regulations, an investigator may contact a potential subject through any of the following approved methods: (1) discussing with his/her own patients the option of enrolling in a study, (2) obtaining written authorization from the patient for referral into a study, (3) providing background information in the form of recruitment materials about the study to the patient or the patient’s health care provider so that the potential subject can initiate contact with the investigator, and (4) accessing the individual’s personal health information (e.g., through medical records or databases) without subject authorization when the researcher has obtained an IRB-approved HIPAA waiver of authorization for recruitment purposes. Additional information on HIPAA is available in module 4.

Some of the more commonly used types of recruitment materials include direct advertising (flyers, posters, brochures), media advertisements (newspaper, television, radio, press releases, websites), recruitment letters, phone calls, and in-person recruitment (presentations and word-of-mouth to subjects). Each method presents different ethical issues for IRB approval and practical considerations for the investigator, and each is discussed separately in the Specific Guidance on Special Issues section of this module. All recruitment materials should, at a minimum, meet the following criteria: (1) state that the project is research, (2) offer a balanced presentation of the risks and benefits, (3) avoid claims of “superior treatment” and phrases like “new treatment,” (4) avoid using the term “free” with regard to study procedures, (5) minimize the focus on monetary awards, and (6) be approved by all applicable groups to post, send, or distribute recruitment materials.

Payment to Research Subjects

While the federal regulations governing human subjects research (45 CFR 46 or Common Rule) do not specifically mention the payment of research subjects, guidance is provided with regard to seeking informed consent under circumstances that minimize the possibility of undue influence. The Food and Drug Administration (FDA) guidance is more specific, because it states that the amount, method, timing, and reason for payment must be reviewed by the IRB so as to ensure that the payment does not unduly influence the subject. Furthermore, the FDA regulations state that this payment is not to be considered a benefit, but a recruitment incentive. This payment to subjects should be included in the Economic Considerations section of the protocol and the consent form and not in the Benefit section of either document. The FDA Information Sheets on this topic are available on their website. The most definitive guidance with regard to subject payment may be found in the Council for International Organizations of Medical Sciences (CIOMS). In summary, this guidance states that subjects may receive payment or reimbursements for inconvenience, time spent, and expenses incurred, as well as free medical care. However, these payments or the provision of medical services should not be so large as to influence subjects to participate against their better judgment. In addition, institutional policies must be followed for subject payments.

Payments to subjects are considered to be taxable income. Subjects should be informed that payments made to them will be reported to the IRS if the payments meet the federal reporting level.

When conducting research with prisoners, restrictions on payments may apply.

Although the U.S. Department of Health and Human Services (HHS), Office for Human Research Protections (OHRP) IRB Guidebook acknowledges differing opinions regarding the ethics and appropriateness of payment, several models of payment are proposed, including payment according to the following: (a) an established fee schedule, (b) the complexity of the study, (c) type and number of procedures to be performed, (d) the time involved, (e) the anticipated discomfort or inconvenience, or (f) an hourly rate depending upon the duration of the study or whether the subject is required to be admitted to a research inpatient unit. In addition, some investigators may pay “healthy” controls for their participation, whereas they may not pay, or may pay less, to subjects with a disease or condition. It is thought that the subjects (with a condition) are receiving benefit by contributing to knowledge about their disease or condition, and there is sometimes the possibility of direct benefit to the subject.

While various other models of payment have been proposed in the literature, prorating payments to subjects based on the duration of subject participation is endorsed by the FDA. Investigators should outline in both the protocol and the consent documents the prorating of payment based upon voluntary or involuntary withdrawal and/or the number of interventions, visits, or procedures completed. Subjects who withdraw for a reason such as a drug reaction are usually penalized less than those who withdraw from the study for an arbitrary reason. Care must be taken to ensure that the subject is not induced to continue with study procedures based upon the monetary award. However, the FDA does allow incentives for study completion to be specified, provided that such incentive is not perceived as undue influence.

For protocols in which proxy consent is necessary, the material rewards in the form of a payment for service should go to the subject, while the person providing the proxy consent receives reimbursement for “out-of-pocket” expenses, e.g., parking, meals, and travel. Therefore, in the case of pediatric research, some combination of reimbursement to the parent for expenses as related to the child’s participation could be combined with an age-appropriate incentive for participation for the child; e.g., gift certificates or toys. As stated earlier, this payment would be noted, as appropriate, in the Economic Considerations section of the parental permission form and the child’s assent form. No payment may be provided to a woman who donates an aborted fetus for research purposes.