Participants, Patients, Subjects, Volunteers, What to Use?

For people who participate in clinical trials, what should we call them? Subject, volunteer (healthy volunteer), participant, or patient? This seems like an easy question, but there are actually a lot of disagreements. Here are some of the articles and blogs discussing this:

Subject, Volunteer, Participant, or Patient?	The author clearly disliked the use of ‘subject’ for clinical trial participants. “In spite of its official sanctioned use, I’ve always objected to the term ‘subject’ to describe a person who donates time, effort and bodily fluids to further clinical research.  It has a negative connotation for me, conjuring up the image of a cold scientific investigation.  I wonder if people considering participating in clinical research studies are dissuaded by this term?  Do they feel they will be ‘subject’ ed to tests and procedures?   Acted upon, rather than participating in their health care?”
Revisiting What to Call People Who Participate in Clinical Research	The author prefers the term ‘participants’ to be used and even used the survey data to support the use of ‘participants’. “The New England Journal of Medicine, American Journal of Public Health, and International Committee of Medical Journal Editors all use the term participant exclusively. NIH Director Francis Collins is quoted as saying, “Medical advances would not be possible without participants in clinical trials.”
People are “participants” in research: Further suggestions for other terms to describe “participants” are needed	As the title suggested, “People are participants in research, not subjects”. Suggesting that the word “subject” should be banned from reports of research on humans. The word “subject” is demeaning.
When to use subjects, participants or volunteers to describe your research subjects	The author seems to be open to all of these terms that may be best used in different situations. Also provided are the definitions for each of these terms: Participants A participant is a person that voluntarily participates in a study. This is perhaps the most accepted terms and is generally recommended when in doubt (provided the subject of the investigation is human). Subjects The term subject describes the person or thing that is the topic of study.  Patients A patient is a participant with a medical condition which is the interest of the investigation.  Volunteers A volunteer is someone that freely offers to participate in a study. A volunteer is very similar to the participant and implies that the person as a whole is actively involved in the study. It also infers that they are free from any particular factor of interest, such as a medical condition.

The term ‘patient’ cannot cover all people who participate in clinical trials. While the clinical trials will ultimately be conducted in the patients who have a medical condition which is the interest of the investigation, clinical trial participants can also be volunteers or healthy volunteers, not patients. Here are some situations that the clinical trial participants are volunteers or healthy volunteers:

• Phase I clinical trials including first-in-human trials. The majority of phase I studies are conducted in healthy volunteers at a dedicated clinical research unit. Only in rare situations (such as oncology studies, studies using human-plasma derived products), are phase I studies conducted in patients.
• Vaccine clinical trials. In vaccine clinical trials, volunteers (or the participants who do not have the disease) are recruited.  The purpose of these clinical trials is to test if the vaccine will safe and effective against developing a disease.
• Preventive clinical trials. If the purpose of a clinical trial is to test if any therapeutic agent (not necessarily the vaccine) can prevent a disease, the participants will be volunteers and should not be called ‘patients’.
• Clinical trials in pregnant women. Pregnancy women are not patients.

People can get confused about using the term ‘volunteers’. In a co-ed by professors Emanuel and Offit, “Could Trump Turn a Vaccine Into a Campaign Stunt?”, the authors mistakenly used the term ‘patients’ for the planned vaccine clinical trials. For Covid-19 vaccine clinical trials, volunteers, healthy volunteers, or healthy volunteers with potential exposure to Covid-19 are recruited to participate in clinical trials. The term 'patient' should not be used. The term 'patient' can be used in therapeutical clinical trials where the purpose is to test if a drug/therapy (such as remdesivir, antibody cocktail,...) is effective in treating Covid-19 infected patients.

"Pfizer is planning to give its vaccine to approximately 8,000 patients. The N.I.H. is planning to enroll 30,000 participants — 20,000 getting a candidate vaccine and 10,000 research controls."

"Researchers are expecting that it will be likely to take at least another eight to 12 months to determine whether these coronavirus vaccines are effective. Scientists have to wait until a sufficient number of patients are exposed to coronavirus to see if the vaccine really reduces the infection rate, as well as how many people develop uncommon side effects. For comparison, the effectiveness trial for the rotavirus vaccines took about four years and the human papillomavirus vaccine studies to prevent cervical cancer took seven years."

“Scientists have to wait until a sufficient number of patients are exposed to coronavirus to see if the vaccine really reduces the infection rate, as well as how many people develop uncommon side effects. “

For years, we have been using the term ‘subject’ to describe clinical trial participants. The term ‘subject’ can cover all different types of clinical trial participants including patients and healthy volunteers. The term ‘subject’ reflects the facts (whether we like it or not) that the participants are subjects in clinical trials.

Many regulatory guidelines used the term ‘subject’ or ‘human subject’. As mentioned in an article “Comparison of FDA and HHS Human Subject Protection Regulations”:

"Human subject" means an individual who is or becomes a participant in research, either as a recipient of the test article or as a control. A subject may be either a healthy individual or a patient.

Human subject" means a living individual about whom an investigator (whether professional or student) conducting research obtains (1) data through intervention or interaction with the individual, or (2) identifiable private information.

There is a trend that the term ‘participant’ is commonly used to replace the term ‘subject’. For example, in Transcelerate Biopharma’s Common Protocol Template and NIH/FDA’s “Final “Phase 2 and 3 Clinical Trial” Template Documents”, the term ‘participant’ or ‘participants’ is used and the term ‘subject’ or ‘subjects’ is only used in special places. ‘Number of subjects’ is now called the ‘number of participants’.  

The term ‘patient’ may be preferred by doctors and study coordinators in investigational sites but is not usually used in clinical trial protocols. The term ‘patient’ may still be used in some special cases such as patient-reported outcome (PRO) and patient medical record. The term 'patient' is commonly used in publications for clinical trials conducted in patients. 

Even though the term ‘participant’ may be preferred in clinical trial protocols, the term ‘subject’ may be used in other clinical trial documents. For example, in case report form and database set up, the term 'subject' will continue to be used. The term ‘subject’ is the primary term used in CDISC documents such as CDASH (Clinical Data Acquisition Standards Harmonization) and SDTM (Study Data Tabulation Model) that we are following as the data standards. The variable Subjid is used for the subject identifier; the variable Usubjid is used for the unique subject identifier, …

In journal publications, we continue to see that different terms are used depending on the nature of the participants in a specific clinical trial. In the New England Journal of Medicine, the term ‘patient’ or ‘patients’ is used in clinical trials conducted in patients and the ‘participant’ or ‘participants’ is used in clinical trials conducted in volunteers or healthy volunteers. The term ‘subject’ is gradually phased out in publication. 

• in Jackson et al "An mRNA Vaccine against SARS-CoV-2 —Preliminary Report", the term 'participant' or 'participants' is used to describe the volunteers who participated in this vaccine trial. 
• in Beigel et al "Remdesivir for the Treatment of Covid-19 — Preliminary Report", the term 'patient' or 'patients' is used to describe the participants who are patients with Covid-19 infections.