The Importance of Healthy Volunteers in Clinical Trials
Healthy volunteers are individuals with no known significant health problems who willingly volunteer to participate in a clinical trial. Generally speaking, healthy volunteers can be needed for any type of clinical trial; it simply depends on the particular trial and the research question it seeks to answer. However, for clinical trials that evaluate new drug treatments (including Phase I, Phase II, Phase III, and Phase IV trials), healthy volunteers are typically only involved in the early-phase (Phase I) trials.
These trials are very small in scope, short in duration, and designed to test the safety, tolerability, and metabolism of drugs in healthy individuals. Phase II, III, and IV studies are generally designed to continue those evaluations in individuals who have a particular disease or condition. One exception to this is case-control studies. Case-control studies compare individuals who have a particular disease or condition with a group of individuals who do not have the disease.
These trials frequently match patients (cases) with healthy volunteers (controls) who share similar characteristics such as age, weight, gender, and marital status. During such trials, the healthy volunteers receive the same drug, test, or medical procedure that the patients receive. The researchers then compare the findings in the healthy volunteers to those in the patient group to help learn about the disease or treatment being studied.
What Do Healthy Volunteers Stand to Gain by Taking Part in a Clinical Trial?
The reasons why healthy people decide to volunteer to participate in a clinical trial are individual in nature. Some people may be motivated by the fact that a specific trial provides compensation for their time and efforts, whereas others may simply have the desire to participate in research in the hope that the findings will benefit other people in the future.
Beyond the altruistic and financial benefits of participation, clinical trials often provide access to free health screenings, blood tests, imaging procedures, and medications that are not available to the general public. This can be beneficial to healthy people who do not have health insurance, or who have limited access to medical care due to other reasons.
How Do Healthy Volunteers Qualify to Participate in Clinical Trials?
Just like patients, healthy volunteers must meet certain eligibility criteria in order to participate in a particular clinical trial. These eligibility criteria will be clearly stated in both the study protocol and any screening materials, and will list specific conditions or diseases (i.e., “significant health problems”) that a potential volunteer must not currently have (or have had in the past) in order to qualify for participation.
Eligibility criteria will vary between trials. Some clinical trials will require that healthy volunteers have no history of significant health problems such as heart disease, diabetes, cancer, or depression, whereas other trials may allow currently healthy volunteers to participate even if they have had one of these conditions in the past. The following are a few specific examples:
For some studies, body weight may be a limiting factor that would potentially impact the study’s outcome. As a result, overweight/obesity might be considered a “significant health problem” of relevance to the trial, and thus listed as an exclusion criteria.
However, a clinical trial that is designed to determine the effects of exercise and weight loss on measures of heart health would require the participation of individuals who need to lose weight, but who are otherwise healthy. In that case, an individual who is overweight could be considered a healthy volunteer.
Existing Medication Use
Often, the use of non-study-related medications during a clinical trial is not allowed. This is especially common in studies that are testing new drugs, as the use of other medications might impact the way in which the new drug is used by the body, or make it difficult to determine which drug caused any side effects that occurred.
The eligibility criteria for healthy volunteers in a specific clinical trial will clearly describe if the use of any medication, such as anti-anxiety medications or antidepressants, is permitted.
History of Cancer, Heart Disease, or other Serious Conditions
While some trials may require that healthy volunteers have no history at all of serious diseases (such as cancer), the eligibility criteria of other trials may not be as strict. For example, a clinical trial might seek to determine the long-term effects of prior radiation therapy to the brain on the memory of individuals who are currently healthy.
As such, this trial would need volunteers who are currently healthy but who have previously had radiation treatment to the brain. Such individuals might include those who received radiation treatment for brain cancer. Regardless, the specific eligibility criteria for a particular trial will detail whether a prior history of serious illness is or is not permitted.
Important Considerations for Healthy Volunteers During the Screening Process
During the screening process, the study recruiter will ask healthy volunteers to provide certain information regarding their personal health history. This information is used to determine if the healthy volunteer meets the eligibility criteria for the clinical trial.
Therefore, it is important to be completely honest on the screening form. Healthy volunteers should report any known health condition, even if they think it is minor and insignificant. Such honesty protects not only the integrity of the research being conducted, but also protects the volunteer from potential harm.
Apart from determining eligibility, many of the screening questions are asked in order to identify individuals who might be adversely affected by the drug or treatment being used in the clinical trial. Therefore, it is in the volunteer’s best interest to be as forthright and honest when answering the study question.
Below are several commonly-asked questions pertaining to the screening process and disclosure of personal health information:
Q: “What if I have a condition I prefer to keep private, such as a sexually transmitted disease (STD)? Would this exclude me from participating as a healthy volunteer?”
A: If an individual’s STD status (or other condition they wish to keep private) is required to be known as part of the eligibility criteria for a clinical trial, the volunteer would be required to undergo testing or to provide documentation that confirms their STD status (or other private health information). In such cases, the presence of an STD would exclude the volunteer from participating.
From a privacy standpoint, the need to undergo STD testing (or state/provide information regarding STD status) would be clearly communicated to the potential volunteer during the recruitment process, as well as stated in the informed consent document.
Therefore, if an individual did not want their STD status (or other private health information) known, they could simply choose not to volunteer for the clinical trial. In such cases, the desire to keep certain personal health information private, such as STD status, is not an exclusion criteria per se, but it might cause a potential study volunteer to decide not to volunteer for a trial that requires that information.
Q: “Will a potential volunteer have to provide their medical records? Or will the recruiter go by the screening questionnaire and medical screening tests?”
A: This depends on the specific nature of the trial. Some trials may indicate that health information provided directly by the volunteer is sufficient to meet the eligibility criteria. In other instances, the researchers may require documentation confirming a prior diagnosis or other medical information.
Q: “Will the recruiters screen for alcohol, tobacco, and drug use?”
A: This depends on the specific eligibility of the particular clinical trial. If alcohol, tobacco, and/or drug use are restricted as per the eligibility criteria, then yes, screening for these activities would be performed by the recruiter.
Q: “Will the recruiters screen for HIV/AIDS?”
A: Currently, the US Food and Drug Administration (FDA) does not have a policy with regard to HIV testing in clinical trials; therefore, the decision to allow such testing is left up to the Institutional Review Boards (IRBs) that approve and monitor clinical trials on a local level.
In many early-phase studies (such as Phase I clinical trials), testing to determine HIV status is often a required eligibility criterion. This is due to several factors. First, it is a basic way to protect the health of the volunteers. Individuals who are HIV-positive have an increased risk for serious side effects to many medications, therefore knowing HIV status up-front helps to protect the health of potential volunteers.
Second, knowing the HIV status of participants helps to maintain the integrity of the research that is conducted. For example, if a particular drug or other therapy is found to have different effectiveness in HIV-positive volunteers versus HIV-negative volunteers, that impacts the ability to generalize the study findings.
When the researchers publish the results of their trial, it will be in the best interest of public health for them to note that different results were obtained between HIV-positive and HIV-negative participants.
Finally, certain drug therapies used as part of a clinical trial might interfere with HIV-specific treatments; therefore, it is in the interest of both research integrity and participant health to know if a volunteer is HIV-positive.
Q: “If the HIV test result is positive, how are the test results handled and reported by the research staff?”
A: Studies that require HIV testing will always inform volunteers of the results of their tests, as well as provide counseling to help them understand the significance of those results.
In addition, most states have laws that require positive test results (for HIV, Hepatitis, and many other communicable diseases) be reported to the state’s Board of Health or other state health agency. When doing so, however, the test results are kept as confidential as possible to the extent permissible under the applicable laws.
The need for HIV testing – and the process by which test results are reported to both the volunteer and any governmental/health agencies – will be clearly stated in the informed consent document.
Q: “If a volunteer forgets to list a condition on their initial screening form, and the condition is discovered during the trial, what will happen? Will they be asked to discontinue their participation on the clinical trial? If it is a paid trial, will they be required to forfeit their compensation?”
A: This depends on the specific nature of the trial. In many instances, the individual will no longer be allowed to participate in the trial, either because the newly discovered condition poses a health risk to the individual or interferes with the drug or treatment being investigated in the clinical trial.
Reasons why healthy volunteers (and patients) could be disqualified from participating in a trial once they have enrolled will always be listed in the informed consent document.
Whether or not the individual would still receive any scheduled study-related compensation would also depend on the payment schedule and restrictions as described in the informed consent document.