Clinical Trial Terminology

Considering to participate in a clinical trial can raise a lot of to diseases such as cardiovascular disease, cancer,
questions for potential participants. You may be searching and stroke.2
for answers to your questions on the internet, by asking your
doctor, or through information obtained from clinical trial Despite the incredible power of pharmaceuticals and

personnel. A lot of information is available through a variety their historic role in changing our health and our lifespan,

of channels and choosing to be a part of a clinical trial should there are still many human ailments for which no known

be an educational process. treatments exist. Many scientists and doctors are focused
on fixing this issue, driving medicine forward, and
One key part of this process is learning to speak the discovering treatments that will further increase life
“clinical trial language.” This means becoming familiar expectancy and improve human quality of life.
with clinical trial terms that you may hear certain personnel
use and understanding clinical trial methods that you Running a clinical trial is one critical step in solving this

may be a part of. problem and identifying drugs that can help achieve this goal.

Before we get to the in-depth terminology used to describe A Clinical Trial Definition
the details of clinical trials, let’s clearly define what clinical A clinical trial is a research study involving human subjects
trials are and get a clearer understanding of their value. that test new treatment methods, new drugs, and methods
for measuring the effectiveness of a test treatment on a
Clinical Trials Explained: disease or medical condition. Often, human volunteers are
The Value of Research given one or more investigational therapies to test the effects
The life expectancy of humans has been rapidly on their health of behavior.3 In other words, clinical trials
increasing throughout history. Pharmaceuticals allow researchers to test whether or not an exploratory
are partly responsible.1 medication or medical method is safe for a certain
disease or condition.
For instance, before the early 20th century and the discovery
of antibiotics, human life expectancy was about 30 years Clinical trials allow scientists and doctors to answer
less than it was in 2016 (78.8 years).2 With the discovery questions like: “Does drug A work better than drug B?”
of antibiotics, the major contributors to non-age-related or “Do participants recover faster if they get this study
death changed from infectious and communicable diseases drug before or after cardiac surgery?” Scientists can
accurately evaluate medications by studying their effects
on healthy people and on those with the condition the Terms Related to the Risks and Benefits of a Clinical Trial
drug is designed to target. • Adverse Event: an unfavorable change in the health
of a participant, including abnormal laboratory findings,
As a potential clinical trial participant, you may be
that happens during a clinical study or within a certain
interested in understanding the various types of
amount of time after the study has ended.4
clinical trials, their different methodologies, and in
what instance each one is used. Below, we go beyond • Contraindication: a situation in which

a clinical trial definition and delve further into clinical a specific treatment should not be used because

trial terms, with more in-depth descriptions of the it may be harmful.5

methods used—placebo-controlled, randomized or • Efficacy and Effectiveness: efficacy is the

blinded—and the clear distinctions between them. performance of an intervention under ideal and
controlled circumstances, as in a clinical trial.
For more information on what a clinical trial is, see Effectiveness is the performance under
“What is a Clinical Trial?” “real-world” conditions.6

• Informed Consent: a process used by researchers

Understanding Clinical Trial Terms
to communicate the risks and potential benefits of
To conduct a clinical trial, scientists and doctors use
participating in a clinical study to potential and
intricate clinical trial methods designed to maintain
enrolled participants.4
the accuracy or integrity of the data collected during
a clinical trial. These methods may appear overly Terms Related to the Types of Clinical Trials
complicated to you as a participant, however; in addition and Methods Used
to maintaining data integrity, these methods are meant to
• Biologic: a class of drugs isolated from a variety of
keep you as safe as possible.
natural sources (human, animal, or microorganism),
may be produced by biotechnology methods, and
The discovery of an effective treatment for a disease
are composed of sugars, proteins, or nucleic acids
requires that several types of clinical trials be conducted
or complex combinations of these substances, or
before the investigational treatment can be approved
may be living entities such as cells and tissues.7
by a regulatory agency, such as the U.S. Food and Drug
Administration (FDA). The type of trial will determine how • Blinding: a method used in certain types of clinical
many participants are involved, the trial design, and trials that keeps study participants from knowing
many other factors. what study treatment they are receiving. This is
called single-blinding.8
To help decode some of the jargon that you may hear from
• Diagnostic Trials: a research study that evaluates
researchers or personnel while you are engaged in your
methods of detecting disease.9
clinical trial, let’s clearly define some of the more common
• Dose-Ranging Study: a type of clinical trial where
clinical trials names, acronyms, and terminology.
different doses of a drug are tested to determine

The following clinical trial terms have been organized which is the safest and most effective.10

into specific categories:

2
• Double-Blind Study: when both study participants the drug or study treatment being given to an
and clinical trial personnel are blinded from knowing individual participant.12
what study treatment the individual participants • Pilot Study: a small-scale test of the methods and
are receiving.8 procedures to be used on a larger scale for the
• Pre-Clinical Research: small studies designed to provide purpose of examining the feasibility of an approach.13
detailed information on dosing and toxicity levels. • Placebo and Placebo-Controlled: an inactive
These studies occur before clinical trials in substance or other intervention, called a placebo,
humans and can be in vitro, meaning in a test tube, that looks the same as, and is given the same way as,
and/or in vivo, meaning in animals.11 an active drug or treatment being tested. The effects
• Phase 1 Research: a phase of research that describes of the active drug or other intervention are compared
clinical trials that focus on the safety of a drug. They to the effects of the placebo. This is called a placebo-
are usually conducted with healthy volunteers, and controlled study.14
the goal is to determine the drug’s most frequent and • Principal Investigator (PI): the person who is responsible
serious adverse events and how the drug is broken for the scientific and technical direction of the entire
down and excreted by the body. These trials usually clinical study.4
involve a small number of participants. 4

• Protocol: the written description of a clinical study.

• Phase 2 Research: a phase of research that describes It includes the study’s objectives, design, and methods.
clinical trials that gather preliminary data on whether It may also include relevant scientific background
a drug works (that is, the drug’s effectiveness) in and statistical information.4
people who have a certain condition or disease. Safety
• Randomization: random, meaning by chance,
is evaluated, and short-term adverse events are studied.4
assignment of clinical trial participants to the
• Phase 3 Research: a phase of research that describes study treatments being tested in a clinical trial.4
clinical trials that gather more information about a
• Screening Trials: trials that test the best way
drug’s safety and effectiveness by studying different
to detect certain diseases or health conditions.3
populations and different dosages and by using the
drug in combination with other drugs. These trials • Sponsor: the organization or person who initiates the

typically involve larger numbers of participants than study and has authority and control over the study.4

phase 1 and phase 2 trials.4 • Study Coordinator: The study coordinator, also called

• Phase 4 Research: a phase of research that describes a clinical research coordinator (CRC), is responsible

clinical trials that occur after the FDA has approved a for carrying out many key operational procedures in the

drug for marketing. They include so-called postmarket management of clinical trials, including administrative,

requirement and commitment studies that are required feasibility analysis, regulatory compliance, recruiting,

of or agreed to by the study sponsor. These trials gather patient care, and evaluation of study data.15

additional information about a drug’s safety, efficacy, • Study Nurse: The Study Nurse, or Clinical Trial Nurse,
or optimal use. 4
interacts with patients participating in clinical trials by

• Open-Label Trial: a type of study in which both the ensuring the patient understands benefits and risks,

health providers and the participants are aware of informed consent, and other decisions pertaining to

3
 the pending trial, and once enrolled, can administer Terms Related to Analyzing Clinical Trial Data
medications or perform other critical procedures. 16
• Intent-To-Treat (ITT): a population of clinical trial
participants that includes all randomized participants
• Sub-Investigator (Sub-I): The Sub-investigator is a in the groups to which they were randomly assigned,
research fellow, resident investigator, or other member of regardless of their adherence with the entry criteria,
the team who assists the investigator in the conduct of regardless of the study treatment they actually received,
the clinical investigation. They may or may not perform and regardless of subsequent withdrawal from study
any significant clinical investigation-related duties at the treatment or deviation from the protocol.22
discretion of the Primary Investigator.17 • Modified Intent-To-Treat (mITT): a subset of the
• Toxicology: The study of poisons, including the Intent-to-Treat population that excludes randomized
source, effect, and treatment of poisoning. It is a subjects in a justified way, such as participants who
branch of pharmacology (the study of drugs). 18
were deemed ineligible after randomization or certain

• Treatment Regimen: a structured treatment plan participants who never started study treatment.22

designed to improve or maintain health.19 • Per-Protocol Analysis: interpretation of randomized

• Pharmacokinetics: the activity of drugs in the body clinical trial results that removes data from participants

over a period of time, including the processes by who didn’t comply with a clinical trial protocol.23

which drugs are absorbed, distributed in the body, • Statistical Significance: describes a mathematical
localized in the tissues, and excreted. 20
measure of difference between groups. The difference
is said to be statistically significant if it is greater than
Terms Related to Recruiting Participants to Clinical Trials what might be expected to happen by chance alone.24
• Clinical Trial Registry: a collection of information • Study Endpoint: in clinical trials, an event or outcome
about individuals with a specific diagnosis or condition that can be measured objectively to determine whether
that may be used to seek out people who are good the intervention being studied is beneficial.25
candidates to participate in clinical trials.21

• Inclusion/Exclusion Criteria: the specific characteristics Terms Related to Regulatory Review and Approval

that determine whether a person is allowed or not • Good Clinical Practice (GCP): a set of principles that
allowed to participate in a clinical trial. Together, these helps ensure the safety, integrity, and quality of
make up the eligibility criteria.4 clinical trials by addressing elements related to the

• Healthy Volunteer: a person with no known significant design, conduct, and reporting of clinical trials.26

health problems who participates in clinical research • New Drug Application (NDA): an application by which
to test a new drug, device, or intervention.3 drug sponsors formally propose that the FDA approve

• Patient Volunteer: a person who has a known health a new pharmaceutical for sale and marketing in the

problem and participates in research to better United States.27

understand, diagnose, treat, or cure that disease • Off-label Use: use of an FDA-approved drug
or condition.3 as treatment for an unapproved condition.28

4
• On-label Use: use of an FDA-approved drug • PICO Framework: a framework for building and
as treatment for an approved condition. 28
answering a clinical or health care related question.

• Peer Review: a quality control measure in research, PICO is an acronym for:30

- Patient population or problem: how would you describe
where professionals review each other’s work to
a group of patients in the study?
make sure it is accurate, relevant, and significant.29
- Intervention (i.e., a cause, prognostic factor, treatment,
etc.): which main intervention is of interest in the study?
- Comparison intervention (if necessary): is the study
including placebo or standard to compare to the
exploratory intervention?
- Outcomes: what is the hope for the intervention and what
will it accomplish?

References:
1. Life Expectancy. Our World in Data website: https://ourworldindata.org/life-expectancy. Accessed April 26, 2018.

2. Adedeji WA. The treasure called antibiotics. Ann Ib Postgrad Med. 2016;14(2):56-57.

3. NIH Clinical Research Trials and You. NIH website: https://www.nih.gov/health-information/nih-clinical-research-trials-you/glossary-common-terms. Published February 2016. Accessed April 26, 2018.

4. Glossary of Common Site Terms. ClinicalTrials.gov website: https://clinicaltrials.gov/ct2/about-studies/glossary. Published April 2018. Accessed April 26, 2018.

5. Contraindication. MedlinePlus website: https://medlineplus.gov/ency/article/002314.htm. Published April 2018. Accessed April 26, 2018.

6. Singal AG, Higgins PDR, Waljee AK. A Primer on Effectiveness and Efficacy Trials. Clin Transl Gastroenterol. 2014;5(1):e45.

7. What Are “Biologics” Questions and Answers. U.S. Food & Drug Administration website: https://www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CBER/ucm133077.htm.
Published February 2018. Accessed April 26, 2018.

8. Day SJ, Altman DG. Blinding in clinical trials and other studies. BMJ. 2000; 321:504.

9. NCI Dictionary of Cancer Terms. NCI website: https://www.cancer.gov/publications/dictionaries/cancer-terms/def/diagnostic-trial. Accessed April 26, 2018.

10. Dose-Ranging Trial. AIDSinfo website: https://aidsinfo.nih.gov/understanding-hiv-aids/glossary/1560/dose-ranging-trial. Published April 2018. Accessed April 26, 2018.

11. Step 2: Preclinical Research. U.S. Food & Drug Administration website: https://www.fda.gov/ForPatients/Approvals/Drugs/ucm405658.htm. Published January 2018. Accessed April 30, 2018.

12. NCI Dictionary of Cancer Terms. NCI website: https://www.cancer.gov/publications/dictionaries/cancer-terms/def/open-label-study. Accessed April 30, 2018.

13. Leon AC, Davis LL, Kraemer HC. The Role and Interpretation of Pilot Studies in Clinical Research. J Psychiatr Res. 2011;45(5):626-629.

14. NCI Dictionary of Cancer Terms. NCI website: https://www.cancer.gov/publications/dictionaries/cancer-terms/search?contains=false&q=placebo. Accessed April 30, 2018.

15. The Anatomy of a Great Clinical Research Coordinator. Association of Clinical Research Professionals (ACRP) Website: https://acrpnet.org/2018/08/14/the-anatomy-of-a-great-clinical-research-coordinator/
Published August 14, 2018. Accessed March 4, 2019.

16. What is a research nurse and what do they do? Clinfield Limited website: https://clinfield.com/what-is-a-research-nurse-and-what-do-they-do/ Published February 11, 2013. Accessed March 5, 2019.

17. Information Sheet Guidance for Sponsors, Clinical Investigators, and IRBs. U.S. Food & Drug Administration website: https://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM214282.pdf
Published May 2010. Accessed March 4, 2019.

18. NCI Dictionary of Cancer Terms. NCI website: https://www.cancer.gov/publications/dictionaries/cancer-terms/def/toxicology. Accessed April 30, 2018.

19. HIV/AIDS Glossary. AIDSinfo website: https://aidsinfo.nih.gov/understanding-hiv-aids/glossary/1641/treatment-regimen. Accessed April 30, 2018.

20. NCI Dictionary of Cancer Terms. NCI website: https://www.cancer.gov/publications/dictionaries/cancer-terms/def/pharmacokinetics. Accessed April 30, 2018.

21. List of Registries. NIH website: https://www.nih.gov/health-information/nih-clinical-research-trials-you/list-registries. Published March 2018. Accessed April 26, 2018.

22. Gupta SK. Intention-to-treat concept: A review. Perspect Clin Res. 2011;2(3):109-112.

23. Ranganathan P, Pramesh CS, Aggarwal R. Common pitfalls in statistical analysis: Intention-to-treat versus per-protocol analysis. Perspect Clin Res. 2016;7(3):144-146.

24. NCI Dictionary of Cancer Terms. NCI website: https://www.cancer.gov/publications/dictionaries/cancer-terms/def/statistically-significant. Accessed April 30, 2018.

25. NCI Dictionary of Cancer Terms. NCI website: https://www.cancer.gov/publications/dictionaries/cancer-terms/def/endpoint. Accessed April 30, 2018.

26. Good Clinical Practice Training. NIH website: https://grants.nih.gov/policy/clinical-trials/good-clinical-training.htm. Published December 2017. Accessed April 26, 2018.

27. New Drug Application (NDA). U.S. Food & Drug Administration website: https://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/
NewDrugApplicationNDA/default.htm. Published March 2016. Accessed April 30, 2018.

28. Understanding Unapproved Use of Approved Drugs “Off Label.” U.S. Food & Drug Administration website: https://www.fda.gov/ForPatients/Other/OffLabel/ucm20041767.htm. Published February 2018.
Accessed April 30, 2018.

29. Peer review: what is it and why do we do it? MedicalNewsToday website: https://www.medicalnewstoday.com/articles/281528.php. Published August 2017. Accessed April 30, 2018.

30. PICO Framework. PubMed Health website: https://www.ncbi.nlm.nih.gov/pubmedhealth/PMHT0029906/. Accessed April 30, 2018.