clinical research basic terminology

Your Guide to Understanding Common Research Terms

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                              Demystifying Clinical Trials -- Part 2

The clinical research world can sometimes seem confusing. Research teams have many people in different roles, and they may use words that are unfamiliar to people outside of research work.

The guide below defines some commonly used words and phrases. Let us know in the comments below or on our Facebook , Twitter , or Instagram pages if you’d like definitions of other words or parts of the research process!

Accrual – the number of subjects who have completed or are actively in the process of completing a study. The accrual goal is how many subjects are needed to finish the study (2).

Adverse event (AE) – a negative symptom or experience encountered by an subject during the course of a clinical trial. Adverse events can be expected or unexpected.

Assent – a minor child’s affirmative agreement to participate in a clinical trial. Failure to object may not be taken as assent.

Clinical research coordinator – a study team member who manages the day-to-day study tasks as directed by the principal investigator. (3)

Consent form – a document explaining all relevant study information to assist the study subject in understanding the expectations and requirements of participating in the trial. This document is presented to and signed by the study subject.

Control arm/group – a comparison group of study subjects who are not treated with the investigational agent. The subjects in this group have the same disease or condition under study, but receive either a different treatment, no treatment, or a placebo.

Data – the objective information gathered during a research study that is used to determine the results of the study.

De-identification – the process of removing identifiers (personal names, dates, social security numbers, etc.) that directly or indirectly point to a person, and removing those identifiers from the data. De-identification of protected health information is essential for protecting patient privacy (4).

Enroll/Enrollment – the process of an eligible participant signing a consent form and voluntarily agreeing to participate in a research study (2).

Ethics committee – an independent group of both medical and non-medical professionals who are responsible for verifying the integrity of a study and ensuring the safety, integrity, and human rights of the study participants.

Food and Drug Administration (FDA) – the agency within the Department of Health and Human Services (DHHS) that enforces public health laws related to research conduct.

Greater than minimal risk – the research involves more than minimal risk to subjects (2).

Health Insurance Portability and Accountability Act of 1996 (HIPAA) – required the Department of Health & Human Services to develop regulations protecting the privacy and security of certain health information (5). The HIPAA Privacy Rule established the conditions under which health information may be used or disclosed by approved entities for research purposes (6).

Hypothesis – a specific, clear, and testable proposition or prediction about the possible outcome of a scientific research study (7).

Informed consent – the process of discussing a clinical trial that goes beyond signing the consent form. The discussion should provide sufficient information so that a subject can make an informed decision about whether or not to enroll in a study, or continue participation in a study. Informed consent is a voluntary agreement to participate in research, and should be an ongoing conversation throughout a subject’s entire time in the study (8).

Investigational New Drug Application (IND) – the process through which an investigator requests the FDA to allow human testing of a new drug.

Institutional Review Board (IRB) – an independent group of professionals designated to review and approve the clinical protocol, informed consent forms, study advertisements, and patient brochures to ensure that the study is safe for human participation. It is also the IRB’s responsibility to ensure that the study adheres to the FDA’s regulations.

Minimal risk – the probability that harm or discomfort anticipated in the research study are not greater than those encountered in daily life or during routine physical examinations (2).

National Institutes of Health (NIH) – agency within DHHS that provides funding for research, conducts studies, and funds multi-site national studies.

Protected Health Information (PHI) – individually identifiable health information. HIPAA provides federal protections for personal health information and gives patients more control over their health information. It also sets boundaries for how entities and institutions can use and release health records (9).

Placebo – an inactive substance designed to resemble the drug being tested. It is used as a control to rule out any psychological effects testing may present. Most advanced clinical trials include a control group that is unknowingly taking a placebo.

Principal Investigator – the primary individual responsible for conducting a clinical trial and adhering to federal regulations, institutional policies, and IRB regulations (2).

Protocol – a detailed plan that sets out the objectives, study design, and methodology for a clinical trial. A study protocol must be approved by an IRB before research may begin on human subjects.

Randomization – study participants are assigned to groups in such a way that each participant has an equal chance of being assigned to each treatment or control group. Since randomization ensures that no specific criteria are used to assign any patients to a particular group, all the groups will be equally comparable.

Research – systematic investigation designed to develop or contribute to generalizable knowledge.

Standard treatment/Standard of care – the currently accepted treatment or intervention considered to be effective in the treatment of a specific disease or condition.

Statistical significance – the probability that an event or difference was occurred by chance alone. In clinical trials, the level of statistical significance depends on the number or participants studied and the observations made, as well as the magnitude of differences observed.

Subject/Participant – a patient or healthy individual participating in a research study.

Treatment arm/group – a group of study subjects who are treated with the investigational agent.

Visit schedule/Test schedule – the number, frequency, and type of exams, tests, and procedures that research subjects will be expected to undergo during the study. Some visits may be the same as normal clinical care visits, while others may be required just for the purpose of collecting data for the research study.

Definitions taken from https://www.centerwatch.com/health-resources/glossary/ unless otherwise cited.

(2) https://www.mayo.edu/research/institutional-review-board/definition-terms

(3) https://acrpnet.org/2018/08/14/the-anatomy-of-a-great-clinical-research-coordinator/

(4) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5977668/

(5) https://www.hhs.gov/hipaa/for-professionals/privacy/index.html

(6) https://www.hhs.gov/hipaa/for-professionals/special-topics/research/index.html

(7) https://methods.sagepub.com/Reference//encyclopedia-of-survey-research-methods/n472.xml

(8) https://oprs.usc.edu/files/2017/04/Informed-Consent-Booklet-4.4.13.pdf

(9) https://www.hhs.gov/hipaa/for-individuals/faq/187/what-does-the-hipaa-privacy-rule-do/index.html

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Nih clinical research trials and you, glossary of common terms, clinical research.

Clinical research is medical research that involves people to test new treatments and therapies.

Clinical Trial

A research study in which one or more human subjects are prospectively assigned to one or more interventions (which may include placebo or other control) to evaluate the effects of those interventions on health-related biomedical or behavioral outcomes.

Healthy Volunteer

A Healthy volunteer is a person with no known significant health problems who participates in clinical research to test a new drug, device, or intervention.

Inclusion/Exclusion Criteria

Inclusion/Exclusion Criteria are factors that allow someone to participate in a clinical trial are inclusion criteria . Those that exclude or not allow participation are exclusion criteria .

Informed Consent

Informed consent explains risks and potential benefits about a clinical trial before someone decides whether to participate.

Patient Volunteer

A patient volunteer has a known health problem and participates in research to better understand, diagnose, treat, or cure that disease or condition.

Phases of Clinical Trials

Clinical trials are conducted in “phases.” The trials at each phase have a different purpose and help researchers answer different questions.

  • Phase I trials — An experimental drug or treatment in a small group of people (20–80) for the first time. The purpose is to evaluate its safety and identify side effects.
  • Phase II trials — The experimental drug or treatment is administered to a larger group of people (100–300) to determine its effectiveness and to further evaluate its safety.
  • Phase III trials — The experimental drug or treatment is administered to large groups of people (1,000–3,000) to confirm its effectiveness, monitor side effects, compare it with standard or equivalent treatments.
  • Phase IV trials — After a drug is licensed and approved by the FDA researchers track its safety, seeking more information about its risks, benefits, and optimal use.

A placebo is a pill or liquid that looks like the new treatment but does not have any treatment value from active ingredients.

A Protocol is a carefully designed plan to safeguard the participants’ health and answer specific research questions.

Principal Investigator

A Principal Investigator is a doctor who leads the clinical research team and, along with the other members of the research team, regularly monitors study participants’ health to determine the study’s safety and effectiveness.

Randomization

Randomization is the process by which two or more alternative treatments are assigned to volunteers by chance rather than by choice.

Single- or Double-Blind Studies

Single- or double-blind studies (also called single- or double-masked studies) are studies in which the participants do not know which medicine is being used, so they can describe what happens without bias. In single-blind ("single-masked") studies, you are not told what is being given, but the research team knows. In a double-blind study, neither you nor the research team are told what you are given; only the pharmacist knows. Members of the research team are not told which participants are receiving which treatment, in order to reduce bias. If medically necessary, however, it is always possible to find out which treatment you are receiving.

Types of Clinical Trials

  • Diagnostic trials determine better tests or procedures for diagnosing a particular disease or condition.
  • Natural history studies provide valuable information about how disease and health progress.
  • Prevention trials look for better ways to prevent a disease in people who have never had the disease or to prevent the disease from returning.
  • Quality of life trials (or supportive care trials) explore and measure ways to improve the comfort and quality of life of people with a chronic illness.
  • Screening trials test the best way to detect certain diseases or health conditions.
  • Treatment trials test new treatments, new combinations of drugs, or new approaches to surgery or radiation therapy.

This page last reviewed on April 20, 2023

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Helping you understand clinical research

The Clinical Research Glossary offers easy to understand clinical research definitions. 

All definitions are developed by the MRCT Center and a committed team of patient advocates and other professionals in medicine and research.  Before definitions are released, they are reviewed by members of the public.

The Clinical Research Glossary started as a pilot project in 2020 and is now a CDISC global standard for clear communication. This means that more and more groups are learning about and using this resource.

Welcome! We hope this resource is helpful to you.

clinical research basic terminology

The combined effect when two or more things are used together.

Following the study directions and requirements.

Any health problem that happens during the study.

A health problem that happens during the study and is reported as possibly caused by the study treatment.

To examine study data to answer a question and help reach conclusions.

Remove, change, or hide personal details to protect participant privacy.

A substance that causes the body's immune system to react.

A group of participants in a research study who all receive the same study treatment.

Willingness to take part in a research study by someone who is not able to give legal consent.

A document used to explain the details of a research study to children or people who are unable to give legal consent.

Information that is collected and analyzed from a study participant .

Information that is collected and analyzed from a study participant at the start of a study.

A research study that tests one study treatment for different diseases and conditions.

The ways a research study might help the participant and others.

Flaws in the way a study is designed, done, or analyzed that lead to one conclusion being favored over another.

Something in the body that is measured as an indicator of personal health or disease.

A way to prevent pregnancy.

Taking a sample of blood by using a needle.

A health change that researchers measure to show that the study treatment helps the study participants .

A controlled method of studying health and illness in people.

A research staff member who helps manage studies.

A research study that tests drugs, devices and treatments to see if they are safe and work in people.

A health care provider.

A group of study participants that are similar in some way.

A study comparing two or more treatments.

Following research requirements.

A way to take pictures of the inside of a person's body using a type of radiation and a computer.

To do a study or procedure.

The defined range of numbers used to describe where the results are expected to fall.

Protecting personal information from people who should not have access.

When the study outcome is influenced by outside conditions that were not expected by the study researchers.

A document used to explain the planned research before a person decides whether or not to join a study.

A group that is paid by the study sponsor to support research studies.

When things should not be used or done together because of possible harm.

The people in a study who do not receive the study treatment or do not have the condition being studied.

When two or more measures are linked.

Information collected from or about people taking part in a research study

An independent group of experts that reviews study data to make sure that patient safety is protected.

To remove a study participant from a study.

To stop a study treatment in a participant .

An illness getting worse over time.

The length of time after treatment that a person lives without the illness coming back.

Refusing to be part of a research study.

A kind of study where increasing amounts of a study treatment are given to different groups to find the best dose.

A study that is set up so that the study treatment that each participant receives is not known by the participants or the researchers.

An electronic version of an informed consent form .

How well a treatment works.

How well a study treatment works in the study.

The reasons a person can be included in, or excluded from, a study.

A process to make a treatment or vaccine available during a public health emergency, before all research is complete, and before full approval is granted.

A measure of the expected effect of the study treatment.

The action of a participant joining the study after providing informed consent.

A person who studies where, why, how often, and to what populations health concerns and diseases happen.

When two or more things in a study are about the same.

The same or almost the same result.

To examine, review, and understand.

A list of reasons a person cannot be included in a study.

A process for a doctor to request an unapproved treatment for a seriously ill patient.

Something that is being tested in research but not yet proven.

A process to find facts that can guide the design of future studies.

How often something happens over a period of time.

How research results can apply to people who were not part of the study.

A measure of risk that compares two treatments in the same study.

A study participant who does not have a disease or condition, including the one being studied.

A parent's features and traits being passed to their biological children before birth.

An idea that is tested in a research study.

Something that supports or encourages research participation .

Number of new cases or events during a period of time.

A list of requirements a person must meet to take part in a study.

The process of learning and discussing the details of a research study before deciding whether to take part.

A way to give a fluid to the study participant , usually through a vein.

A team of people who review studies to protect the rights and welfare of study participants .

Not regular or predictable.

A treatment or drug that is not yet approved for the condition being studied.

A drug, device, vaccine, or other treatment being tested in a study.

A person who leads a research study.

Research that collects data from the same participants over a long time.

A way to take pictures of the inside of a person’s body with a machine that uses strong magnets and radio waves.

The most or largest amount.

The average.

The middle number in a set of numbers when listed in order from lowest to highest.

Very small.

The smallest or least amount.

To observe , check, or evaluate something in a study over time.

The number of people who develop a disease or illness in a group over time.

The number of deaths in a group of people over time.

A study that takes place at more than one research center.

A test result that shows a person does not have what was tested for.

So small that it has little to no impact.

Not following research requirements.

A study to test if a study treatment works about as well as another treatment for the same condition.

A purpose or goal of a study.

A study that collects health information about study participants without giving a treatment.

To watch or see how participants are doing in a study.

Once in a while.

The chance of a health event happening in one group compared with the chance of the same event happening in another group.

The use of a treatment in a different way or for a condition other than what it is approved for.

A type of study where participants and research staff know which treatment participants are being given.

A description of the overall results of the study.

The way that a study endpoint is measured.

A number that researchers use to show that a result did not occur by chance.

To take part in a study.

The information that patients share about their own health or well-being to answer questions in a study.

Evaluation by independent experts.

At regular or expected times.

A study that measures the effects of a drug on the human body.

A study that measures what happens to a drug in a person’s body over time.

A process to detect, review, and make decisions about drug safety to protect patients.

A step in the overall clinical research process to test a new drug, device, or treatment.

Something that looks like the treatment being studied, but doesn't contain any medicine 

A study with two or more groups where one group is given a placebo .

A research study that tests and compares two or more study treatments for a disease or condition, with study treatment groups being added or removed during the study period.

A test result that shows a person has what was tested for.

When participants can still receive a study treatment after their participation has ended.

A study to test a treatment in the lab or in animals before testing it in people.

Number of known cases or events in a group.

A study measure that is used to answer the main research question.

The likelihood or chance that something might happen.

The length of time without a person's illness getting worse.

Research that uses new data collected from participants .

A complete description of the research plan and procedures.

A person who is legally allowed to make research decisions for someone else.

Replace personal details with a code so that data are protected.

What the study is testing.

How someone feels and functions day to day.

A list of questions for study participants to answer as part of the study.

A way to use chance to place study participants into different study treatment groups.

Research that uses chance to assign participants into study groups.

The reason why a study, or something in a study, is being done.

Health-related information collected from many different types of records and used for research purposes.

Findings from analyzing Real World Data .

An organized list of research information.

Pay money back to participants for their out-of-pocket study costs.

The chance of a harmful event happening in one study group compared with another.

Findings from the study.

Research that uses already existing data.

A comparison of the possible bad and potential good things that could happen if a participant joins a research study.

The possible harms of being in a research study.

The number of participants in a study or study group.

A chart that lists the study activities and when they will happen during a study.

Tests and questions to find out if a person can join a study.

A measure used to answer other important questions in the study that are not the main research question.

How well a medical test can accurately identify people who have a disease or trait.

Happening in a specific order.

A health change that is not the intended effect of the treatment and usually considered a problem.

A study that is set up so that the study treatment each participant receives is not known by the participants but is known by the researchers.

How well a medical test can accurately identify people who do not have a disease or trait.

The group that is in charge of, or pays for, a research study.

The usual treatment given to patients for an illness.

Results that are very unlikely to have occurred by chance.

The way a study is set up to answer the study question.

A treatment given to the participants in a study

The steps of a research study from beginning to end.

A person who joins a research study.

All the participants in a study.

A person who uses math to help design a study and interpret the data .

A study with a smaller group of participants already enrolled in the main study.

A study to test if a study treatment works better than another treatment for the same condition.

When two or more things used together have a greater effect than each thing alone.

How much a study treatment changes a condition, symptom, or function.

A research study that tests and compares two or more study treatments for one disease or condition.

To confirm that a process or test works as planned, or results are true.

Choosing to participate in research without feeling pressured.

To choose to join a study.

A time before starting a study treatment when a person stops taking other medicines.

To stop being a participant in a study.

A way of taking pictures of the inside of a person's body using X-ray radiation.

Welcome to the SOM Clinical Research Glossary

Quickly look up the meaning of words, acronyms, or abbreviations commonly used in clinical research:

  • Narrow your search by typing the word you are looking for in the search box. Clear the search box to start a new search.
  • Use the alphabet bar for quick filtering of words by first letter or select a word category to explore words that are related. Remove the letter or word filters by clicking the respective ALL button.

Return to the glossary index page after each word search using the « Back to Glossary Index link.

  • Adverse Drug Reaction (ADR)
  • Adverse Event (AE)
  • Adverse Reaction (AR)
  • Age of majority
  • AIR (Activities Interests and Relationships)
  • ALCOA (Attributable, Legible, Contemporaneous, Original, Accurate)
  • ALCOA Plus, ALCOA+
  • Ancillary review
  • Applicable Clinical Trial (ACT)
  • Applicable regulatory requirements
  • Approved drug
  • Aspirational benefit
  • Association for Clinical and Translational Science (ACTS)
  • Association for the Accreditation of Human Research Protection Programs (AAHRPP)
  • Association of Clinical Research Professionals (ACRP)
  • Audit report
  • Audit trail
  • Baseline assessment
  • Billing Coverage Analysis (BCA)
  • Biological Product
  • Biological specimen
  • Biologics License Application (BLA)
  • Biomedical Research Imaging Center (BRIC)
  • Biospecimen
  • Biospecimen Processing Facility (BSP)
  • Breach of confidentiality
  • Budget justification
  • Budget period
  • Budget revision
  • Business Associate
  • Business Associate Agreement (BAA)
  • Carolina Data Warehouse for Health (CDW-H)
  • Case Report Form (CRF)
  • Ceded review
  • Centers for Disease Control and Prevention (CDC)
  • Centers for Medicare & Medicaid Services (CMS)
  • Centralized monitoring
  • Certificate of Confidentiality (CoC)
  • Certified copy
  • Clinical and Translational Research Center (CTRC)
  • Clinical and Translational Science Awards (CTSA) Program
  • Clinical development
  • Clinical investigation
  • Clinical monitor
  • Clinical research
  • Clinical Research Accountability Unit (CRAU)
  • Clinical Research Associate (CRA)
  • Clinical Research Coordinator (CRC)
  • Clinical Research Management System (CRMS)
  • Clinical Research Support Office (CRSO)
  • Clinical significance
  • Clinical study
  • Clinical trial
  • Clinical Trial Agreement (CTA)
  • ClinicalTrials.gov
  • Clinical Trials Quality Assurance (CTQA) Program
  • Code of Federal Regulations (CFR)
  • Co-investigator
  • Collaborative Institutional Training Initiative (CITI)
  • Collateral benefit
  • Commercial Institutional Review Board (IRB)
  • Common data model
  • Common Rule
  • Common Terminology Criteria for Adverse Events (CTCAE)
  • Compensation
  • Competitive Renewal
  • Computable Phenotype
  • Concomitant medication
  • Confidential Disclosure Agreement (CDA)
  • Confidentiality
  • Conflict of Interest (COI)
  • Conflict of Interest Office
  • Consent capacity
  • Continuing noncompliance
  • Continuing review
  • Contract Research Organization (CRO)
  • Control group
  • Coordinating Center (CC)
  • Corrective and Preventive Action (CAPA) Plan
  • Data acquisition
  • Data and Safety Monitoring Board (DSMB)
  • Data and Safety Monitoring Committee (DSMC)
  • Data and Safety Monitoring Plan (DSMP)
  • Database Management System (DBMS)
  • Data encryption
  • Data Integrity
  • Data management
  • Data Management and Sharing Plan (DMS Plan)
  • Data Management Plan (DMP)
  • Data Management System (DMS)
  • Data Monitoring Committee (DMC)
  • Data Use Agreement (DUA)
  • Delegation of Authority (DOA) Log
  • Demographic data
  • Department of Health and Human Services (DHHS)
  • Direct benefit
  • Direct cost
  • Disapproval
  • Discontinue
  • Disease registry
  • Dosage regimen
  • Dose Limiting Toxicity (DLT)
  • Double blinding
  • Drug toxicity
  • ECRT (Effort Certification and Reporting Technology)
  • Electronic Case Report Form (eCRF)
  • Electronic Data Capture (EDC)
  • Electronic Health Record (EHR)
  • Electronic Informed Consent (eIC)
  • Electronic Medical Record (EMR)
  • Elements of informed consent
  • Eligibility criteria
  • Embryonic Stem Cell Research Oversight (ESCRO) Committee
  • Encounter Level Data
  • Environment, Health and Safety (EHS)
  • Essential document
  • Exclusion criteria
  • Exculpatory language
  • Exempt review
  • Expanded access
  • Expedited review
  • Experimental drug
  • Experimental group
  • Export Compliance Office
  • Export control
  • Fabrication
  • Falsification
  • Family Educational Rights and Privacy Act (FERPA)
  • FDA Form 482
  • FDA Form 483
  • FDA Form 1571
  • FDA Form 1572
  • Feasibility assessment
  • Federalwide Assurance (FWA)
  • Food and Drug Administration (FDA)
  • Food, Drug and Cosmetics Act
  • Free text data
  • Full board review
  • Generalizability, Generalization
  • Good Clinical Practice (GCP)
  • Grant application
  • Grant Number
  • Greater than minimal risk
  • Health literacy
  • Healthy volunteer
  • HIPAA authorization
  • HIPAA covered entity
  • HIPAA (Health Insurance Portability and Accountability Act)
  • HIPAA Privacy Rule
  • Humanitarian Device Exemption (HDE)
  • Humanitarian Use Device (HUD)
  • Human Research Protection Program (HRPP)
  • Human subject
  • Human Subjects Research (HSR)
  • Identifiable biospecimen
  • Identifiable private information
  • Impartial witness
  • Inclusion criteria
  • Inclusion/Exclusion (I/E) criteria
  • Independent Ethics Committee (IEC)
  • Independent IRB
  • Indirect benefit
  • Indirect Facility & Administrative (F&A) costs
  • Individual Conflict of Interest (COI)
  • Industry Contracting (IC)
  • Industry sponsored study
  • Informed Consent Form (ICF)
  • Informed Consent (IC)
  • Institution
  • Institutional Biosafety Committee (IBC)
  • Institutional Conflict of Interest (COI)
  • Institutional Integrity and Risk Management (IIRM)
  • Institutional Official (IO)
  • Institutional Privacy Office (IPO)
  • Institutional Privacy Officer
  • Institutional Review Board Information System (IRBIS)
  • Institutional Review Board (IRB)
  • Interaction
  • International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9CM)
  • International Council for Harmonisation (ICH)
  • Intervention
  • Interventional study
  • Investigation
  • Investigational device
  • Investigational Device Exemption (IDE)
  • Investigational drug
  • Investigational Drug Service (IDS)
  • Investigational New Drug (IND)
  • Investigational New Drug (IND) safety report
  • Investigational plan
  • Investigational product (IP)
  • Investigator
  • Investigator agreement
  • Investigator-initiated study
  • Investigator's Brochure (IB)
  • IRB application
  • IRB approval
  • IRB Authorization Agreement (IAA)
  • IRB expiration
  • IRB of record
  • Just-in-Time (JIT)
  • Key information
  • Legally Authorized Representative (LAR)
  • Legally effective informed consent
  • Letter of intent
  • Life-threatening adverse event
  • Limited dataset
  • Lineberger Comprehensive Cancer Center (LCCC)
  • Local considerations
  • Longitudinal study
  • Long Term Follow-Up (LTFU)
  • Lost to Follow Up (LTFU)
  • Manual of procedures (MOP)
  • Material transfer agreement (MTA)
  • Medical device
  • Medical monitor
  • Medical record
  • Medical Record Number (MRN)
  • Memorandum of understanding (MOU)
  • Minimal risk
  • Monitoring plan
  • Monitoring report
  • Multicenter study
  • Multisite study
  • National Institutes of Health (NIH)
  • New Drug Application (NDA)
  • NIH National Library of Medicine (NLM)
  • NIH Public Access Policy
  • No Cost Extension (NCE)
  • Nonclinical study
  • Noncompliance
  • Nondisclosure agreement (NDA)
  • Nonsignificant Risk (NSR) medical device
  • Nonsignificant Risk (NSR) medical device study
  • North Carolina Translational and Clinical Sciences (NC TraCS) Institute
  • Not Human Subjects Research (NHSR)
  • Notice of Award (NOA)
  • Notice of privacy practices
  • Not reasonably available (as it applies to locating a parent)
  • Observational study
  • Observational Study Monitoring Board (OSMB)
  • Office for Human Research Protections (OHRP)
  • Office for Innovation, Entrepreneurship and Economic Development (IEED)
  • Office of Clinical Trials (OCT)
  • Office of Human Research Ethics (OHRE)
  • Office of Research Communications (ORC)
  • Office of Research Development (ORD)
  • Office of Research Information Systems (ORIS)
  • Office of Research (OoR)
  • Office of Research Support and Compliance (ORSC)
  • Office of Sponsored Research (OSR)
  • Office of Technology Commercialization (OTC)
  • Office of the Vice Chancellor for Research (OVCR)
  • Office of University Counsel (OUC)
  • Off-label use
  • On-site monitoring
  • Open-label trial
  • Organizational Conflict of Interest (COI)
  • Package insert
  • Parental permission
  • Participant
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Clinical Research Glossary

Expand your clinical research word power with the som clinical research glossary.

Clinical research has a highly specialized vocabulary with a vast number of acronyms and abbreviations that help facilitate scientific communication. Whether you are new to clinical research or an experienced member of the research team, understanding and remembering the nuances of clinical research vocabulary can be challenging.

To ensure a consistent and clear clinical research communication, the CRSO has created the SOM Clinical Research Glossary , a comprehensive clinical research glossary in clear and plain language that aligns with industry and regulatory standards. As the glossary is intended to be broadly applicable to various types of research and audiences, its definitions provide nuances of usage. If there are variations in how key agencies are defining a term, each definition is provided.

We need your feedback

The SOM Clinical Research Glossary is intended to be a living resource that will be periodically updated with new terms and clarifications. Please let us know, if there is a word, acronym, or abbreviation you see regularly in clinical research that is not included in the glossary or if you want to propose an alternative definition.

Clinical Trials

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Glossary of clinical trial terms

The glossary below will help you understand clinical research terms often used by researchers and other scientists.

Active, not recruiting

The clinical trial is happening, but researchers are not looking for more participants at this time.

Adverse event

A medical problem that happens or worsens during a clinical trial or within a certain time period after the trial is over. An adverse event may or may not be caused by the investigational treatment a person took.

Clinical trial (or research study)

A clinical trial is a research study designed to learn how our bodies respond to investigational medicines or other investigational treatments. During the clinical trial, participants are assigned to get a treatment or sometimes, no treatment. The purpose of a trial is usually to find ways to prevent, diagnose, or treat a disease or other health condition.

Clinical trial phases

Any treatment (vaccine, medicine, medical device, or procedure) must go through 3 phases of clinical trials. Each phase tests the treatment’s safety, how well it works, amount (dose), and side effects.

A disease, disorder, syndrome, illness, or injury that researchers are studying.

Controlled trial

A type of clinical trial that compares one treatment to another treatment. Often, a new investigational treatment is compared to a standard or usual treatment (called the control). The control may be a group of participants in the same trial or a group of participants from an earlier trial or study.

Eligibility criteria

A clinical trial’s requirements for people who want to join. These include inclusion criteria (factors that allow a person to join a trial) and exclusion criteria (factors that prevent a person from joining a trial). For example, a trial might only accept participants who are above or below certain ages.

The number of participants in a clinical trial. The “estimated enrollment” is the number of participants that the researchers need for the trial.

Exclusion criteria

The factors (or reasons) that prevent a person from joining a clinical trial.

Expanded access

A process regulated by the federal agencies that allows pharmaceutical companies to provide a new investigational treatment (before it’s approved) to patients with serious diseases or conditions who cannot take part in a clinical trial.

Inclusion criteria

The factors (or reasons) that allow a person to join a clinical trial.

Informed consent

Informed consent is the process in which researchers talk with people who are thinking about enrolling, or have enrolled, in a clinical trial. They will have you read an informed consent form (ICF) that describes the possible benefits and risks. It tells you that taking part in the trial is voluntary, and that you may leave the trial at any time.

The goal of the informed consent process is to protect the participants who enroll in clinical trials. The informed consent process starts when a possible participant first asks for information about a trial and continues until the trial ends.

Informed consent form (ICF)

The document used in the informed consent process.

Investigational medication

A drug or biological product that is used in a clinical trial but has not been approved by health authorities (the drug is either not available for a doctor to prescribe or is available but not approved by the health authority for the use being studied).

Institutional Review Board (IRB)

A committee of doctors, data experts, community advocates, and others who help ensure that a trial is done in an ethical manner and the rights of participants are protected. They review, approve, and check on the trial’s plan (protocol) that explains what researchers will do during the trial. For example, they will review the informed consent form. Also called an ethics committee.

Open studies

Studies that are enrolling participants now or in the future, or involve drugs that are available for expanded access (may be used by certain patients before federal agency approval).

A look-alike substance that does not contain an active drug or treatment. A placebo is made to look, taste, and be given like the actual drug being studied.

The written description of a clinical trial. It includes the trial’s goals, design, and methods. It may also include data and science-related background information.

The organization or person who starts the trial, pays for it, and has authority and control over it.

A treatment that helps provide protection to certain infections, usually given as a shot.

Still have questions?

Our FAQ section has answers to commonly asked questions and a glossary of words to know.

Frequently asked questions

clinical research basic terminology

clinical research basic terminology

Clinical Research Terminology 101: Language to Know

Any medications or procedures used today, as well as new data and discoveries, had to go through extensive clinical research and trials to ensure their safety and efficacy. Clinical research is a complex procedure, but understanding how it works should not be. Knowing the right clinical research terminology can go a long way toward helping you understand how the process works.

Clinical Research and Clinical Trials: Are They the Same?

You may come across both of these terms, so it is crucial that you know the difference. Clinical research is patient-oriented research conducted on human subjects or a sample that comes from humans (i.e., organs or tissue samples), in which the researcher interacts with the subjects directly.

The most common types of patient-oriented research include:

  • Investigations of how human diseases work
  • Design of therapeutic interventions
  • Development of new techniques or technologies
  • Operation of clinical trials

Clinical research also refers to behavioral and epidemiological studies as well as healthcare services research.

A clinical trial fits under the umbrella of clinical research. It is an experiment designed to answer specific questions about treatments, illnesses, medications, and more.

Volunteers: Healthy and Patient Volunteers

The volunteers chosen for the clinical research project are either healthy people who don’t have ties to the conditions related to the study or patient volunteers who are affected by the health issues being researched.

Phases of Clinical Research

Clinical research goes through many phases.

Phase I involves clinical trials with a small group of people, generally between 20 and 80, to evaluate everything from safe dosage ranges to the type of side effects that can be expected. This phase can include patient volunteers as well as healthy participants.

Phase II takes place with a larger group of volunteers, usually a few hundred, to continue establishing safety and efficacy. This phase involves people who have the condition being studied and can help determine risks and short-term side effects.

Phase III involves thousands of participants, comparing the intervention to other similar procedures while also keeping an eye on adverse effects. This is the phase where the most information is gathered to present for approval.

Phase IV takes place after the intervention has been marketed. It can help check effectiveness in the general population and provide information on side effects.

Differences Between Single-Blind and Double-Blind Studies

Clinical research terminology will include whether the trial was single-blind or double-blind.

Single-blind means that the researchers know whether a participant is receiving a placebo or the active treatment — while the participant does not know. A double-blind study is one in which neither the researcher nor the participant knows until after the trial is over.

Serious Adverse Event

A serious adverse event is any adverse health issue that occurs in a participant during the clinical trial and:

  • Is life-threatening
  • Results in death
  • Requires hospitalization
  • Causes disability or incapacity
  • Results in birth defects

Serious adverse events are investigated and determined to be related or unrelated to the treatment being studied.

Intervention

An intervention can be a procedure or a treatment like a drug, supplement, vaccine, behavior modification, or device modification.

Inclusion and Exclusion Criteria

Inclusion and exclusion criteria refer to the screening requirements that a volunteer must meet to participate in the trial. Factors can be age, sex, medical history, and much more.

Good Clinical Practice

Good clinical practice is the standard for the performance, conduct, design, auditing, recording, reporting, and analysis of clinical trials. It helps ensure that the data provided is accurate and that all of the participants’ rights are respected.

Quality Assurance and Quality Control

Quality assurance is a clinical research term that means the systematic approach that makes certain data is gathered and recorded following good clinical practices and standard protocol. It refers to operational steps taken to ensure that the trial follows all quality-related activities. These operational steps can involve checking completed forms.

Informed Consent

Before a volunteer can participate in a clinical trial, they must be given all of the information on the trial, the schedules, expected treatments, and potential adverse reactions in writing. The volunteer must sign their consent.

Randomization

Researchers help eliminate bias by turning to randomization. This is the process of assigning treatments in a random fashion.

Stopping Rules

These are the rules that would prompt the stopping of the trial. The reasons a halt to the trial can occur involve everything from safety concerns to futility.

Placebos and Placebo-Controlled Studies

A placebo is an inactive liquid, pill, powder, or other intervention that provides no treatment value. During clinical trials, placebos provide a comparison against which to measure the effectiveness of treatment.

A placebo-controlled study is a trial in which a placebo is given to a group of participants while an active intervention is given to the other group.

Open-Label Trial

This type of trial is one in which all participants and investigators know about the intervention being tested.

Manual of Procedures

The manual of procedures provides the protocol for the trial. It helps to keep protocol implementation and data collection consistent throughout the length of the trial.

The Ins and Outs of Clinical Research

Clinical research terminology can seem overwhelming, but having the basics down can help you understand the research and results.

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Understanding Clinical Trials

Clinical research: what is it.

a man talking to a doctor

Your doctor may have said that you are eligible for a clinical trial, or you may have seen an ad for a clinical research study. What is clinical research, and is it right for you?

Clinical research is the comprehensive study of the safety and effectiveness of the most promising advances in patient care. Clinical research is different than laboratory research. It involves people who volunteer to help us better understand medicine and health. Lab research generally does not involve people — although it helps us learn which new ideas may help people.

Every drug, device, tool, diagnostic test, technique and technology used in medicine today was once tested in volunteers who took part in clinical research studies.

At Johns Hopkins Medicine, we believe that clinical research is key to improve care for people in our community and around the world. Once you understand more about clinical research, you may appreciate why it’s important to participate — for yourself and the community.

What Are the Types of Clinical Research?

There are two main kinds of clinical research:

Observational Studies

Observational studies are studies that aim to identify and analyze patterns in medical data or in biological samples, such as tissue or blood provided by study participants.

blue icons representing people

Clinical Trials

Clinical trials, which are also called interventional studies, test the safety and effectiveness of medical interventions — such as medications, procedures and tools — in living people.

microscope

Clinical research studies need people of every age, health status, race, gender, ethnicity and cultural background to participate. This will increase the chances that scientists and clinicians will develop treatments and procedures that are likely to be safe and work well in all people. Potential volunteers are carefully screened to ensure that they meet all of the requirements for any study before they begin. Most of the reasons people are not included in studies is because of concerns about safety.

Both healthy people and those with diagnosed medical conditions can take part in clinical research. Participation is always completely voluntary, and participants can leave a study at any time for any reason.

“The only way medical advancements can be made is if people volunteer to participate in clinical research. The research participant is just as necessary as the researcher in this partnership to advance health care.” Liz Martinez, Johns Hopkins Medicine Research Participant Advocate

Types of Research Studies

Within the two main kinds of clinical research, there are many types of studies. They vary based on the study goals, participants and other factors.

Biospecimen studies

Healthy volunteer studies.

Clinical trials study the safety and effectiveness of interventions and procedures on people’s health. Interventions may include medications, radiation, foods or behaviors, such as exercise. Usually, the treatments in clinical trials are studied in a laboratory and sometimes in animals before they are studied in humans. The goal of clinical trials is to find new and better ways of preventing, diagnosing and treating disease. They are used to test:

Drugs or medicines

clinical research basic terminology

New types of surgery

clinical research basic terminology

Medical devices

clinical research basic terminology

New ways of using current treatments

clinical research basic terminology

New ways of changing health behaviors

clinical research basic terminology

New ways to improve quality of life for sick patients

clinical research basic terminology

 Goals of Clinical Trials

Because every clinical trial is designed to answer one or more medical questions, different trials have different goals. Those goals include:

Treatment trials

Prevention trials, screening trials, phases of a clinical trial.

In general, a new drug needs to go through a series of four types of clinical trials. This helps researchers show that the medication is safe and effective. As a study moves through each phase, researchers learn more about a medication, including its risks and benefits.

Is the medication safe and what is the right dose?   Phase one trials involve small numbers of participants, often normal volunteers.

Does the new medication work and what are the side effects?   Phase two trials test the treatment or procedure on a larger number of participants. These participants usually have the condition or disease that the treatment is intended to remedy.

Is the new medication more effective than existing treatments?  Phase three trials have even more people enrolled. Some may get a placebo (a substance that has no medical effect) or an already approved treatment, so that the new medication can be compared to that treatment.

Is the new medication effective and safe over the long term?   Phase four happens after the treatment or procedure has been approved. Information about patients who are receiving the treatment is gathered and studied to see if any new information is seen when given to a large number of patients.

“Johns Hopkins has a comprehensive system overseeing research that is audited by the FDA and the Association for Accreditation of Human Research Protection Programs to make certain all research participants voluntarily agreed to join a study and their safety was maximized.” Gail Daumit, M.D., M.H.S., Vice Dean for Clinical Investigation, Johns Hopkins University School of Medicine

Is It Safe to Participate in Clinical Research?

There are several steps in place to protect volunteers who take part in clinical research studies. Clinical Research is regulated by the federal government. In addition, the institutional review board (IRB) and Human Subjects Research Protection Program at each study location have many safeguards built in to each study to protect the safety and privacy of participants.

Clinical researchers are required by law to follow the safety rules outlined by each study's protocol. A protocol is a detailed plan of what researchers will do in during the study.

In the U.S., every study site's IRB — which is made up of both medical experts and members of the general public — must approve all clinical research. IRB members also review plans for all clinical studies. And, they make sure that research participants are protected from as much risk as possible.

Earning Your Trust

This was not always the case. Many people of color are wary of joining clinical research because of previous poor treatment of underrepresented minorities throughout the U.S. This includes medical research performed on enslaved people without their consent, or not giving treatment to Black men who participated in the Tuskegee Study of Untreated Syphilis in the Negro Male. Since the 1970s, numerous regulations have been in place to protect the rights of study participants.

Many clinical research studies are also supervised by a data and safety monitoring committee. This is a group made up of experts in the area being studied. These biomedical professionals regularly monitor clinical studies as they progress. If they discover or suspect any problems with a study, they immediately stop the trial. In addition, Johns Hopkins Medicine’s Research Participant Advocacy Group focuses on improving the experience of people who participate in clinical research.

Clinical research participants with concerns about anything related to the study they are taking part in should contact Johns Hopkins Medicine’s IRB or our Research Participant Advocacy Group .

Learn More About Clinical Research at Johns Hopkins Medicine

For information about clinical trial opportunities at Johns Hopkins Medicine, visit our trials site.

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Clinical Trials and Clinical Research: A Comprehensive Review

Venkataramana kandi.

1 Clinical Microbiology, Prathima Institute of Medical Sciences, Karimnagar, IND

Sabitha Vadakedath

2 Biochemistry, Prathima Institute of Medical Sciences, Karimnagar, IND

Clinical research is an alternative terminology used to describe medical research. Clinical research involves people, and it is generally carried out to evaluate the efficacy of a therapeutic drug, a medical/surgical procedure, or a device as a part of treatment and patient management. Moreover, any research that evaluates the aspects of a disease like the symptoms, risk factors, and pathophysiology, among others may be termed clinical research. However, clinical trials are those studies that assess the potential of a therapeutic drug/device in the management, control, and prevention of disease. In view of the increasing incidences of both communicable and non-communicable diseases, and especially after the effects that Coronavirus Disease-19 (COVID-19) had on public health worldwide, the emphasis on clinical research assumes extremely essential. The knowledge of clinical research will facilitate the discovery of drugs, devices, and vaccines, thereby improving preparedness during public health emergencies. Therefore, in this review, we comprehensively describe the critical elements of clinical research that include clinical trial phases, types, and designs of clinical trials, operations of trial, audit, and management, and ethical concerns.

Introduction and background

A clinical trial is a systematic process that is intended to find out the safety and efficacy of a drug/device in treating/preventing/diagnosing a disease or a medical condition [ 1 , 2 ]. Clinical trial includes various phases that include phase 0 (micro-dosing studies), phase 1, phase 2, phase 3, and phase 4 [ 3 ]. Phase 0 and phase 2 are called exploratory trial phases, phase 1 is termed the non-therapeutic phase, phase 3 is known as the therapeutic confirmatory phase, and phase 4 is called the post-approval or the post-marketing surveillance phase. Phase 0, also called the micro-dosing phase, was previously done in animals but now it is carried out in human volunteers to understand the dose tolerability (pharmacokinetics) before being administered as a part of the phase 1 trial among healthy individuals. The details of the clinical trial phases are shown in Table ​ Table1 1 .

This table has been created by the authors.

MTD: maximum tolerated dose; SAD: single ascending dose; MAD: multiple ascending doses; NDA: new drug application; FDA: food and drug administration

Clinical research design has two major types that include non-interventional/observational and interventional/experimental studies. The non-interventional studies may have a comparator group (analytical studies like case-control and cohort studies), or without it (descriptive study). The experimental studies may be either randomized or non-randomized. Clinical trial designs are of several types that include parallel design, crossover design, factorial design, randomized withdrawal approach, adaptive design, superiority design, and non-inferiority design. The advantages and disadvantages of clinical trial designs are depicted in Table ​ Table2 2 .

There are different types of clinical trials that include those which are conducted for treatment, prevention, early detection/screening, and diagnosis. These studies address the activities of an investigational drug on a disease and its outcomes [ 4 ]. They assess whether the drug is able to prevent the disease/condition, the ability of a device to detect/screen the disease, and the efficacy of a medical test to diagnose the disease/condition. The pictorial representation of a disease diagnosis, treatment, and prevention is depicted in Figure ​ Figure1 1 .

An external file that holds a picture, illustration, etc.
Object name is cureus-0015-00000035077-i01.jpg

This figure has been created by the authors.

The clinical trial designs could be improvised to make sure that the study's validity is maintained/retained. The adaptive designs facilitate researchers to improvise during the clinical trial without interfering with the integrity and validity of the results. Moreover, it allows flexibility during the conduction of trials and the collection of data. Despite these advantages, adaptive designs have not been universally accepted among clinical researchers. This could be attributed to the low familiarity of such designs in the research community. The adaptive designs have been applied during various phases of clinical trials and for different clinical conditions [ 5 , 6 ]. The adaptive designs applied during different phases are depicted in Figure ​ Figure2 2 .

An external file that holds a picture, illustration, etc.
Object name is cureus-0015-00000035077-i02.jpg

The Bayesian adaptive trial design has gained popularity, especially during the Coronavirus Disease-19 (COVID-19) pandemic. Such designs could operate under a single master protocol. It operates as a platform trial wherein multiple treatments can be tested on different patient groups suffering from disease [ 7 ].

In this review, we comprehensively discuss the essential elements of clinical research that include the principles of clinical research, planning clinical trials, practical aspects of clinical trial operations, essentials of clinical trial applications, monitoring, and audit, clinical trial data analysis, regulatory audits, and project management, clinical trial operations at the investigation site, the essentials of clinical trial experiments involving epidemiological, and genetic studies, and ethical considerations in clinical research/trials.

A clinical trial involves the study of the effect of an investigational drug/any other intervention in a defined population/participant. The clinical research includes a treatment group and a placebo wherein each group is evaluated for the efficacy of the intervention (improved/not improved) [ 8 ].

Clinical trials are broadly classified into controlled and uncontrolled trials. The uncontrolled trials are potentially biased, and the results of such research are not considered as equally as the controlled studies. Randomized controlled trials (RCTs) are considered the most effective clinical trials wherein the bias is minimized, and the results are considered reliable. There are different types of randomizations and each one has clearly defined functions as elaborated in Table ​ Table3 3 .

Principles of clinical trial/research

Clinical trials or clinical research are conducted to improve the understanding of the unknown, test a hypothesis, and perform public health-related research [ 2 , 3 ]. This is majorly carried out by collecting the data and analyzing it to derive conclusions. There are various types of clinical trials that are majorly grouped as analytical, observational, and experimental research. Clinical research can also be classified into non-directed data capture, directed data capture, and drug trials. Clinical research could be prospective or retrospective. It may also be a case-control study or a cohort study. Clinical trials may be initiated to find treatment, prevent, observe, and diagnose a disease or a medical condition.

Among the various types of clinical research, observational research using a cross-sectional study design is the most frequently performed clinical research. This type of research is undertaken to analyze the presence or absence of a disease/condition, potential risk factors, and prevalence and incidence rates in a defined population. Clinical trials may be therapeutic or non-therapeutic type depending on the type of intervention. The therapeutic type of clinical trial uses a drug that may be beneficial to the patient. Whereas in a non-therapeutic clinical trial, the participant does not benefit from the drug. The non-therapeutic trials provide additional knowledge of the drug for future improvements. Different terminologies of clinical trials are delineated in Table ​ Table4 4 .

In view of the increased cost of the drug discovery process, developing, and low-income countries depend on the production of generic drugs. The generic drugs are similar in composition to the patented/branded drug. Once the patent period is expired generic drugs can be manufactured which have a similar quality, strength, and safety as the patented drug [ 9 ]. The regulatory requirements and the drug production process are almost the same for the branded and the generic drug according to the Food and Drug Administration (FDA), United States of America (USA).

The bioequivalence (BE) studies review the absorption, distribution, metabolism, and excretion (ADME) of the generic drug. These studies compare the concentration of the drug at the desired location in the human body, called the peak concentration of the drug (Cmax). The extent of absorption of the drug is measured using the area under the receiver operating characteristic curve (AUC), wherein the generic drug is supposed to demonstrate similar ADME activities as the branded drug. The BE studies may be undertaken in vitro (fasting, non-fasting, sprinkled fasting) or in vivo studies (clinical, bioanalytical, and statistical) [ 9 ].

Planning clinical trial/research

The clinical trial process involves protocol development, designing a case record/report form (CRF), and functioning of institutional review boards (IRBs). It also includes data management and the monitoring of clinical trial site activities. The CRF is the most significant document in a clinical study. It contains the information collected by the investigator about each subject participating in a clinical study/trial. According to the International Council for Harmonisation (ICH), the CRF can be printed, optical, or an electronic document that is used to record the safety and efficacy of the pharmaceutical drug/product in the test subjects. This information is intended for the sponsor who initiates the clinical study [ 10 ].

The CRF is designed as per the protocol and later it is thoroughly reviewed for its correctness (appropriate and structured questions) and finalized. The CRF then proceeds toward the print taking the language of the participating subjects into consideration. Once the CRF is printed, it is distributed to the investigation sites where it is filled with the details of the participating subjects by the investigator/nurse/subject/guardian of the subject/technician/consultant/monitors/pharmacist/pharmacokinetics/contract house staff. The filled CRFs are checked for their completeness and transported to the sponsor [ 11 ].

Effective planning and implementation of a clinical study/trial will influence its success. The clinical study majorly includes the collection and distribution of the trial data, which is done by the clinical data management section. The project manager is crucial to effectively plan, organize, and use the best processes to control and monitor the clinical study [ 10 , 11 ].

The clinical study is conducted by a sponsor or a clinical research organization (CRO). A perfect protocol, time limits, and regulatory requirements assume significance while planning a clinical trial. What, when, how, and who are clearly planned before the initiation of a study trial. Regular review of the project using the bar and Gantt charts, and maintaining the timelines assume increased significance for success with the product (study report, statistical report, database) [ 10 , 11 ].

The steps critical to planning a clinical trial include the idea, review of the available literature, identifying a problem, formulating the hypothesis, writing a synopsis, identifying the investigators, writing a protocol, finding a source of funding, designing a patient consent form, forming ethics boards, identifying an organization, preparing manuals for procedures, quality assurance, investigator training and initiation of the trial by recruiting the participants [ 10 ].

The two most important points to consider before the initiation of the clinical trial include whether there is a need for a clinical trial, if there is a need, then one must make sure that the study design and methodology are strong for the results to be reliable to the people [ 11 ].

For clinical research to envisage high-quality results, the study design, implementation of the study, quality assurance in data collection, and alleviation of bias and confounding factors must be robust [ 12 ]. Another important aspect of conducting a clinical trial is improved management of various elements of clinical research that include human and financial resources. The role of a trial manager to make a successful clinical trial was previously reported. The trial manager could play a key role in planning, coordinating, and successfully executing the trial. Some qualities of a trial manager include better communication and motivation, leadership, and strategic, tactical, and operational skills [ 13 ].

Practical aspects of a clinical trial operations

There are different types of clinical research. Research in the development of a novel drug could be initiated by nationally funded research, industry-sponsored research, and clinical research initiated by individuals/investigators. According to the documents 21 code of federal regulations (CFR) 312.3 and ICH E-6 Good Clinical Practice (GCP) 1.54, an investigator is an individual who initiates and conducts clinical research [ 14 ]. The investigator plan, design, conduct, monitor, manage data, compile reports, and supervise research-related regulatory and ethical issues. To manage a successful clinical trial project, it is essential for an investigator to give the letter of intent, write a proposal, set a timeline, develop a protocol and related documents like the case record forms, define the budget, and identify the funding sources.

Other major steps of clinical research include the approval of IRBs, conduction and supervision of the research, data review, and analysis. Successful clinical research includes various essential elements like a letter of intent which is the evidence that supports the interest of the researcher to conduct drug research, timeline, funding source, supplier, and participant characters.

Quality assurance, according to the ICH and GCP guidelines, is necessary to be implemented during clinical research to generate quality and accurate data. Each element of the clinical research must have been carried out according to the standard operating procedure (SOP), which is written/determined before the initiation of the study and during the preparation of the protocol [ 15 ].

The audit team (quality assurance group) is instrumental in determining the authenticity of the clinical research. The audit, according to the ICH and GCP, is an independent and external team that examines the process (recording the CRF, analysis of data, and interpretation of data) of clinical research. The quality assurance personnel are adequately trained, become trainers if needed, should be good communicators, and must handle any kind of situation. The audits can be at the investigator sites evaluating the CRF data, the protocol, and the personnel involved in clinical research (source data verification, monitors) [ 16 ].

Clinical trial operations are governed by legal and regulatory requirements, based on GCPs, and the application of science, technology, and interpersonal skills [ 17 ]. Clinical trial operations are complex, time and resource-specific that requires extensive planning and coordination, especially for the research which is conducted at multiple trial centers [ 18 ].

Recruiting the clinical trial participants/subjects is the most significant aspect of clinical trial operations. Previous research had noted that most clinical trials do not meet the participant numbers as decided in the protocol. Therefore, it is important to identify the potential barriers to patient recruitment [ 19 ].

Most clinical trials demand huge costs, increased timelines, and resources. Randomized clinical trial studies from Switzerland were analyzed for their costs which revealed approximately 72000 USD for a clinical trial to be completed. This study emphasized the need for increased transparency with respect to the costs associated with the clinical trial and improved collaboration between collaborators and stakeholders [ 20 ].

Clinical trial applications, monitoring, and audit

Among the most significant aspects of a clinical trial is the audit. An audit is a systematic process of evaluating the clinical trial operations at the site. The audit ensures that the clinical trial process is conducted according to the protocol, and predefined quality system procedures, following GCP guidelines, and according to the requirements of regulatory authorities [ 21 ].

The auditors are supposed to be independent and work without the involvement of the sponsors, CROs, or personnel at the trial site. The auditors ensure that the trial is conducted by designated professionally qualified, adequately trained personnel, with predefined responsibilities. The auditors also ensure the validity of the investigational drug, and the composition, and functioning of institutional review/ethics committees. The availability and correctness of the documents like the investigational broacher, informed consent forms, CRFs, approval letters of the regulatory authorities, and accreditation of the trial labs/sites [ 21 ].

The data management systems, the data collection software, data backup, recovery, and contingency plans, alternative data recording methods, security of the data, personnel training in data entry, and the statistical methods used to analyze the results of the trial are other important responsibilities of the auditor [ 21 , 22 ].

According to the ICH-GCP Sec 1.29 guidelines the inspection may be described as an act by the regulatory authorities to conduct an official review of the clinical trial-related documents, personnel (sponsor, investigator), and the trial site [ 21 , 22 ]. The summary report of the observations of the inspectors is performed using various forms as listed in Table ​ Table5 5 .

FDA: Food and Drug Administration; IND: investigational new drug; NDA: new drug application; IRB: institutional review board; CFR: code of federal regulations

Because protecting data integrity, the rights, safety, and well-being of the study participants are more significant while conducting a clinical trial, regular monitoring and audit of the process appear crucial. Also, the quality of the clinical trial greatly depends on the approach of the trial personnel which includes the sponsors and investigators [ 21 ].

The responsibility of monitoring lies in different hands, and it depends on the clinical trial site. When the trial is initiated by a pharmaceutical industry, the responsibility of trial monitoring depends on the company or the sponsor, and when the trial is conducted by an academic organization, the responsibility lies with the principal investigator [ 21 ].

An audit is a process conducted by an independent body to ensure the quality of the study. Basically, an audit is a quality assurance process that determines if a study is carried out by following the SPOs, in compliance with the GCPs recommended by regulatory bodies like the ICH, FDA, and other local bodies [ 21 ].

An audit is performed to review all the available documents related to the IRB approval, investigational drug, and the documents related to the patient care/case record forms. Other documents that are audited include the protocol (date, sign, treatment, compliance), informed consent form, treatment response/outcome, toxic response/adverse event recording, and the accuracy of data entry [ 22 ].

Clinical trial data analysis, regulatory audits, and project management

The essential elements of clinical trial management systems (CDMS) include the management of the study, the site, staff, subject, contracts, data, and document management, patient diary integration, medical coding, monitoring, adverse event reporting, supplier management, lab data, external interfaces, and randomization. The CDMS involves setting a defined start and finishing time, defining study objectives, setting enrolment and termination criteria, commenting, and managing the study design [ 23 ].

Among the various key application areas of clinical trial systems, the data analysis assumes increased significance. The clinical trial data collected at the site in the form of case record form is stored in the CDMS ensuring the errors with respect to the double data entry are minimized.

Clinical trial data management uses medical coding, which uses terminologies with respect to the medications and adverse events/serious adverse events that need to be entered into the CDMS. The project undertaken to conduct the clinical trial must be predetermined with timelines and milestones. Timelines are usually set for the preparation of protocol, designing the CRF, planning the project, identifying the first subject, and timelines for recording the patient’s data for the first visit.

The timelines also are set for the last subject to be recruited in the study, the CRF of the last subject, and the locked period after the last subject entry. The planning of the project also includes the modes of collection of the data, the methods of the transport of the CRFs, patient diaries, and records of severe adverse events, to the central data management sites (fax, scan, courier, etc.) [ 24 ].

The preparation of SOPs and the type and timing of the quality control (QC) procedures are also included in the project planning before the start of a clinical study. Review (budget, resources, quality of process, assessment), measure (turnaround times, training issues), and control (CRF collection and delivery, incentives, revising the process) are the three important aspects of the implementation of a clinical research project.

In view of the increasing complexity related to the conduct of clinical trials, it is important to perform a clinical quality assurance (CQA) audit. The CQA audit process consists of a detailed plan for conducting audits, points of improvement, generating meaningful audit results, verifying SOP, and regulatory compliance, and promoting improvement in clinical trial research [ 25 ]. All the components of a CQA audit are delineated in Table ​ Table6 6 .

CRF: case report form; CSR: clinical study report; IC: informed consent; PV: pharmacovigilance; SAE: serious adverse event

Clinical trial operations at the investigator's site

The selection of an investigation site is important before starting a clinical trial. It is essential that the individuals recruited for the study meet the inclusion criteria of the trial, and the investigator's and patient's willingness to accept the protocol design and the timelines set by the regulatory authorities including the IRBs.

Before conducting clinical research, it is important for an investigator to agree to the terms and conditions of the agreement and maintain the confidentiality of the protocol. Evaluation of the protocol for the feasibility of its practices with respect to the resources, infrastructure, qualified and trained personnel available, availability of the study subjects, and benefit to the institution and the investigator is done by the sponsor during the site selection visit.

The standards of a clinical research trial are ensured by the Council for International Organizations of Medical Sciences (CIOMS), National Bioethics Advisory Commission (NBAC), United Nations Programme on Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome (HIV/AIDS) (UNAIDS), and World Medical Association (WMA) [ 26 ].

Recommendations for conducting clinical research based on the WMA support the slogan that says, “The health of my patient will be my first consideration.” According to the International Code of Medical Ethics (ICME), no human should be physically or mentally harmed during the clinical trial, and the study should be conducted in the best interest of the person [ 26 ].

Basic principles recommended by the Helsinki declaration include the conduction of clinical research only after the prior proof of the safety of the drug in animal and lab experiments. The clinical trials must be performed by scientifically, and medically qualified and well-trained personnel. Also, it is important to analyze the benefit of research over harm to the participants before initiating the drug trials.

The doctors may prescribe a drug to alleviate the suffering of the patient, save the patient from death, and gain additional knowledge of the drug only after obtaining informed consent. Under the equipoise principle, the investigators must be able to justify the treatment provided as a part of the clinical trial, wherein the patient in the placebo arm may be harmed due to the unavailability of the therapeutic/trial drug.

Clinical trial operations greatly depend on the environmental conditions and geographical attributes of the trial site. It may influence the costs and targets defined by the project before the initiation. It was noted that one-fourth of the clinical trial project proposals/applications submit critical data on the investigational drug from outside the country. Also, it was noted that almost 35% of delays in clinical trials owing to patient recruitment with one-third of studies enrolling only 5% of the participants [ 27 ].

It was suggested that clinical trial feasibility assessment in a defined geographical region may be undertaken for improved chances of success. Points to be considered under the feasibility assessment program include if the disease under the study is related to the population of the geographical region, appropriateness of the study design, patient, and comparator group, visit intervals, potential regulatory and ethical challenges, and commitments of the study partners, CROs in respective countries (multi-centric studies) [ 27 ].

Feasibility assessments may be undertaken at the program level (ethics, regulatory, and medical preparedness), study level (clinical, regulatory, technical, and operational aspects), and at the investigation site (investigational drug, competency of personnel, participant recruitment, and retention, quality systems, and infrastructural aspects) [ 27 ].

Clinical trials: true experiments

In accordance with the revised schedule "Y" of the Drugs and Cosmetics Act (DCA) (2005), a drug trial may be defined as a systematic study of a novel drug component. The clinical trials aim to evaluate the pharmacodynamic, and pharmacokinetic properties including ADME, efficacy, and safety of new drugs.

According to the drug and cosmetic rules (DCR), 1945, a new chemical entity (NCE) may be defined as a novel drug approved for a disease/condition, in a specified route, and at a particular dosage. It also may be a new drug combination, of previously approved drugs.

A clinical trial may be performed in three types; one that is done to find the efficacy of an NCE, a comparison study of two drugs against a medical condition, and the clinical research of approved drugs on a disease/condition. Also, studies of the bioavailability and BE studies of the generic drugs, and the drugs already approved in other countries are done to establish the efficacy of new drugs [ 28 ].

Apart from the discovery of a novel drug, clinical trials are also conducted to approve novel medical devices for public use. A medical device is defined as any instrument, apparatus, appliance, software, and any other material used for diagnostic/therapeutic purposes. The medical devices may be divided into three classes wherein class I uses general controls; class II uses general and special controls, and class III uses general, special controls, and premarket approvals [ 28 ].

The premarket approval applications ensure the safety and effectiveness, and confirmation of the activities from bench to animal to human clinical studies. The FDA approval for investigational device exemption (IDE) for a device not approved for a new indication/disease/condition. There are two types of IDE studies that include the feasibility study (basic safety and potential effectiveness) and the pivotal study (trial endpoints, randomization, monitoring, and statistical analysis plan) [ 28 ].

As evidenced by the available literature, there are two types of research that include observational and experimental research. Experimental research is alternatively known as the true type of research wherein the research is conducted by the intervention of a new drug/device/method (educational research). Most true experiments use randomized control trials that remove bias and neutralize the confounding variables that may interfere with the results of research [ 28 ].

The variables that may interfere with the study results are independent variables also called prediction variables (the intervention), dependent variables (the outcome), and extraneous variables (other confounding factors that could influence the outside). True experiments have three basic elements that include manipulation (that influence independent variables), control (over extraneous influencers), and randomization (unbiased grouping) [ 29 ].

Experiments can also be grouped as true, quasi-experimental, and non-experimental studies depending on the presence of specific characteristic features. True experiments have all three elements of study design (manipulation, control, randomization), and prospective, and have great scientific validity. Quasi-experiments generally have two elements of design (manipulation and control), are prospective, and have moderate scientific validity. The non-experimental studies lack manipulation, control, and randomization, are generally retrospective, and have low scientific validity [ 29 ].

Clinical trials: epidemiological and human genetics study

Epidemiological studies are intended to control health issues by understanding the distribution, determinants, incidence, prevalence, and impact on health among a defined population. Such studies are attempted to perceive the status of infectious diseases as well as non-communicable diseases [ 30 ].

Experimental studies are of two types that include observational (cross-sectional studies (surveys), case-control studies, and cohort studies) and experimental studies (randomized control studies) [ 3 , 31 ]. Such research may pose challenges related to ethics in relation to the social and cultural milieu.

Biomedical research related to human genetics and transplantation research poses an increased threat to ethical concerns, especially after the success of the human genome project (HGP) in the year 2000. The benefits of human genetic studies are innumerable that include the identification of genetic diseases, in vitro fertilization, and regeneration therapy. Research related to human genetics poses ethical, legal, and social issues (ELSI) that need to be appropriately addressed. Most importantly, these genetic research studies use advanced technologies which should be equally available to both economically well-placed and financially deprived people [ 32 ].

Gene therapy and genetic manipulations may potentially precipitate conflict of interest among the family members. The research on genetics may be of various types that include pedigree studies (identifying abnormal gene carriers), genetic screening (for diseases that may be heritable by the children), gene therapeutics (gene replacement therapy, gene construct administration), HGP (sequencing the whole human genome/deoxyribonucleic acid (DNA) fingerprinting), and DNA, cell-line banking/repository [ 33 ]. The biobanks are established to collect and store human tissue samples like umbilical tissue, cord blood, and others [ 34 ].

Epidemiological studies on genetics are attempts to understand the prevalence of diseases that may be transmitted among families. The classical epidemiological studies may include single case observations (one individual), case series (< 10 individuals), ecological studies (population/large group of people), cross-sectional studies (defined number of individuals), case-control studies (defined number of individuals), cohort (defined number of individuals), and interventional studies (defined number of individuals) [ 35 ].

Genetic studies are of different types that include familial aggregation (case-parent, case-parent-grandparent), heritability (study of twins), segregation (pedigree study), linkage study (case-control), association, linkage, disequilibrium, cohort case-only studies (related case-control, unrelated case-control, exposure, non-exposure group, case group), cross-sectional studies, association cohort (related case-control, familial cohort), and experimental retrospective cohort (clinical trial, exposure, and non-exposure group) [ 35 ].

Ethics and concerns in clinical trial/research

Because clinical research involves animals and human participants, adhering to ethics and ethical practices assumes increased significance [ 36 ]. In view of the unethical research conducted on war soldiers after the Second World War, the Nuremberg code was introduced in 1947, which promulgated rules for permissible medical experiments on humans. The Nuremberg code suggests that informed consent is mandatory for all the participants in a clinical trial, and the study subjects must be made aware of the nature, duration, and purpose of the study, and potential health hazards (foreseen and unforeseen). The study subjects should have the liberty to withdraw at any time during the trial and to choose a physician upon medical emergency. The other essential principles of clinical research involving human subjects as suggested by the Nuremberg code included benefit to the society, justification of study as noted by the results of the drug experiments on animals, avoiding even minimal suffering to the study participants, and making sure that the participants don’t have life risk, humanity first, improved medical facilities for participants, and suitably qualified investigators [ 37 ].

During the 18th world medical assembly meeting in the year 1964, in Helsinki, Finland, ethical principles for doctors practicing research were proposed. Declaration of Helsinki, as it is known made sure that the interests and concerns of the human participants will always prevail over the interests of the society. Later in 1974, the National Research Act was proposed which made sure that the research proposals are thoroughly screened by the Institutional ethics/Review Board. In 1979, the April 18th Belmont report was proposed by the national commission for the protection of human rights during biomedical and behavioral research. The Belmont report proposed three core principles during research involving human participants that include respect for persons, beneficence, and justice. The ICH laid down GCP guidelines [ 38 ]. These guidelines are universally followed throughout the world during the conduction of clinical research involving human participants.

ICH was first founded in 1991, in Brussels, under the umbrella of the USA, Japan, and European countries. The ICH conference is conducted once every two years with the participation from the member countries, observers from the regulatory agencies, like the World Health Organization (WHO), European Free Trade Association (EFTA), and the Canadian Health Protection Branch, and other interested stakeholders from the academia and the industry. The expert working groups of the ICH ensure the quality, efficacy, and safety of the medicinal product (drug/device). Despite the availability of the Nuremberg code, the Belmont Report, and the ICH-GCP guidelines, in the year 1982, International Ethical Guidelines for Biomedical Research Involving Human Subjects was proposed by the CIOMS in association with WHO [ 39 ]. The CIOMS protects the rights of the vulnerable population, and ensures ethical practices during clinical research, especially in underdeveloped countries [ 40 ]. In India, the ethical principles for biomedical research involving human subjects were introduced by the Indian Council of Medical Research (ICMR) in the year 2000 and were later amended in the year 2006 [ 41 ]. Clinical trial approvals can only be done by the IRB approved by the Drug Controller General of India (DGCI) as proposed in the year 2013 [ 42 ].

Current perspectives and future implications

A recent study attempted to evaluate the efficacy of adaptive clinical trials in predicting the success of a clinical trial drug that entered phase 3 and minimizing the time and cost of drug development. This study highlighted the drawbacks of such clinical trial designs that include the possibility of type 1 (false positive) and type 2 (false negative) errors [ 43 ].

The usefulness of animal studies during the preclinical phases of a clinical trial was evaluated in a previous study which concluded that animal studies may not completely guarantee the safety of the investigational drug. This is noted by the fact that many drugs which passed toxicity tests in animals produced adverse reactions in humans [ 44 ].

The significance of BE studies to compare branded and generic drugs was reported previously. The pharmacokinetic BE studies of Amoxycillin comparing branded and generic drugs were carried out among a group of healthy participants. The study results have demonstrated that the generic drug had lower Cmax as compared to the branded drug [ 45 ].

To establish the BE of the generic drugs, randomized crossover trials are carried out to assess the Cmax and the AUC. The ratio of each pharmacokinetic characteristic must match the ratio of AUC and/or Cmax, 1:1=1 for a generic drug to be considered as a bioequivalent to a branded drug [ 46 ].

Although the generic drug development is comparatively more beneficial than the branded drugs, synthesis of extended-release formulations of the generic drug appears to be complex. Since the extended-release formulations remain for longer periods in the stomach, they may be influenced by gastric acidity and interact with the food. A recent study suggested the use of bio-relevant dissolution tests to increase the successful production of generic extended-release drug formulations [ 47 ].

Although RCTs are considered the best designs, which rule out bias and the data/results obtained from such clinical research are the most reliable, RCTs may be plagued by miscalculation of the treatment outcomes/bias, problems of cointerventions, and contaminations [ 48 ].

The perception of healthcare providers regarding branded drugs and their view about the generic equivalents was recently analyzed and reported. It was noted that such a perception may be attributed to the flexible regulatory requirements for the approval of a generic drug as compared to a branded drug. Also, could be because a switch from a branded drug to a generic drug in patients may precipitate adverse events as evidenced by previous reports [ 49 ].

Because the vulnerable population like drug/alcohol addicts, mentally challenged people, children, geriatric age people, military persons, ethnic minorities, people suffering from incurable diseases, students, employees, and pregnant women cannot make decisions with respect to participating in a clinical trial, ethical concerns, and legal issues may prop up, that may be appropriately addressed before drug trials which include such groups [ 50 ].

Conclusions

Clinical research and clinical trials are important from the public health perspective. Clinical research facilitates scientists, public health administrations, and people to increase their understanding and improve preparedness with reference to the diseases prevalent in different geographical regions of the world. Moreover, clinical research helps in mitigating health-related problems as evidenced by the current Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) pandemic and other emerging and re-emerging microbial infections. Clinical trials are crucial to the development of drugs, devices, and vaccines. Therefore, scientists are required to be up to date with the process and procedures of clinical research and trials as discussed comprehensively in this review.

The content published in Cureus is the result of clinical experience and/or research by independent individuals or organizations. Cureus is not responsible for the scientific accuracy or reliability of data or conclusions published herein. All content published within Cureus is intended only for educational, research and reference purposes. Additionally, articles published within Cureus should not be deemed a suitable substitute for the advice of a qualified health care professional. Do not disregard or avoid professional medical advice due to content published within Cureus.

The authors have declared that no competing interests exist.

Dana-Farber Cancer Institute

Research Types Explained: Basic, Clinical, Translational

“Research” is a broad stroke of a word, the verbal equivalent of painting a wall instead of a masterpiece. There are important distinctions among the three principal types of medical research — basic, clinical and translational.

Whereas basic research is looking at questions related to how nature works, translational research aims to take what’s learned in basic research and apply that in the development of solutions to medical problems. Clinical research, then, takes those solutions and studies them in clinical trials. Together, they form a continuous research loop that transforms ideas into action in the form of new treatments and tests, and advances cutting-edge developments from the lab bench to the patient’s bedside and back again.

Basic Research

When it comes to science, the “basic” in basic research describes something that’s an essential starting point. “If you think of it in terms of construction, you can’t put up a beautiful, elegant house without first putting in a foundation,” says David Frank, MD , Associate Professor of Medicine, Medical Oncology, at Dana-Farber Cancer Institute. “In science, if you don’t first understand the basic research, then you can’t move on to advanced applications.”

David Frank, MD.

Basic medical research is usually conducted by scientists with a PhD in such fields as biology and chemistry, among many others. They study the core building blocks of life — DNA, cells, proteins, molecules, etc. — to answer fundamental questions about their structures and how they work.

For example, oncologists now know that mutations in DNA enable the unchecked growth of cells in cancer. A scientist conducting basic research might ask: How does DNA work in a healthy cell? How do mutations occur? Where along the DNA sequence do mutations happen? And why?

“Basic research is fundamentally curiosity-driven research,” says Milka Kostic, Program Director, Chemical Biology at Dana-Farber Cancer Institute. “Think of that moment when an apple fell on Isaac Newton’s head. He thought to himself, ‘Why did that happen?’ and then went on to try to find the answer. That’s basic research.”

Dan Stover, MD, and Heather Parsons, MD, conduct basic research in metastatic breast cancer.

Clinical Research

Clinical research explores whether new treatments, medications and diagnostic techniques are safe and effective in patients. Physicians administer these to patients in rigorously controlled clinical trials, so that they can accurately and precisely monitor patients’ progress and evaluate the treatment’s efficacy, or measurable benefit.

“In clinical research, we’re trying to define the best treatment for a patient with a given condition,” Frank says. “We’re asking such questions as: Will this new treatment extend the life of a patient with a given type of cancer? Could this supportive medication diminish nausea, diarrhea or other side effects? Could this diagnostic test help physicians detect cancer earlier or distinguish between fast- and slow-growing cancers?”

Successful clinical researchers must draw on not only their medical training but also their knowledge of such areas as statistics, controls and regulatory compliance.

Translational Research

It’s neither practical nor safe to transition directly from studying individual cells to testing on patients. Translational research provides that crucial pivot point. It bridges the gap between basic and clinical research by bringing together a number of specialists to refine and advance the application of a discovery. “Biomedical science is so complex, and there’s so much knowledge available.” Frank says. “It’s through collaboration that advances are made.”

For example, let’s say a basic researcher has identified a gene that looks like a promising candidate for targeted therapy. Translational researchers would then evaluate thousands, if not millions, of potential compounds for the ideal combination that could be developed into a medicine to achieve the desired effect. They’d refine and test the compound on intermediate models, in laboratory and animal models. Then they would analyze those test results to determine proper dosage, side effects and other safety considerations before moving to first-in-human clinical trials. It’s the complex interplay of chemistry, biology, oncology, biostatistics, genomics, pharmacology and other specialties that makes such a translational study a success.

Collaboration and technology have been the twin drivers of recent quantum leaps in the quality and quantity of translational research. “Now, using modern molecular techniques,” Frank says, “we can learn so much from a tissue sample from a patient that we couldn’t before.”

Translational research provides a crucial pivot point after clinical trials as well. Investigators explore how the trial’s resulting treatment or guidelines can be implemented by physicians in their practice. And the clinical outcomes might also motivate basic researchers to reevaluate their original assumptions.

“Translational research is a two-way street,” Kostic says. “There is always conversation flowing in both directions. It’s a loop, a continuous cycle, with one research result inspiring another.”

Learn more about research at Dana-Farber .

clinical research basic terminology

The glossary below will assist you in understanding the words and phrases that frequently appear on ClinicalResearch.com. Although people involved in clinical research will often use these words and phrases, the definitions here describe the words and phrases only in the context of how they appear on ClinicalResearch.com.

Adverse event/effect

Unwanted effect of a drug, device, or procedure. Sometimes an adverse event may be due to something other than the drug, device, or procedure.

Advocacy and support groups

Organizations that assist specific patient populations and their families, and provide them with useful support tools.

Approved medications

In each region/country, the local authority must review and approve a new medication so that it can be sold/prescribed. For example, the Food and Drug Administration completes this review in the United States, and the European Medicines Agency completes this review in Europe.

A group of participants in a clinical trial in which everyone in the group is receiving the same treatment at the same dose. Clinical trials comparing different treatments (comparative clinical trials) have at least 2 arms.

The point at the start of a clinical trial right before a participant receives an investigational treatment. Data collected at baseline is compared with data gathered later in the trial. The differences measured can help to determine the safety and efficacy of an investigational treatment.

Any medical product manufactured from a living organism or its products.

Blinded trial

A clinical trial is blinded if the participants and/or investigators do not know which arm the participants are assigned to.

Clinical development

The scientific activities that take an investigational drug, device, or procedure from Phase 1 through to Phase 4.

Clinical research

The study of health and illness in people. Clinical research is how we develop new treatments and gather knowledge for better health and medical care.

Clinical Research Associate (CRA)

Performs all the necessary checks to help ensure the rights and safety of participants are guaranteed and the trial follows the protocol closely. Click here to see the people you might meet as a clinical trial participant.

Clinical Research Coordinator (CRC)

Involved in monitoring trial-related activities and making sure they are done properly. Click here to see the people you might meet as a clinical trial participant.

Clinical trial

A research study involving human participants that tests and evaluates an investigational drug, device, or procedure to find out how safe it is and how well it works.

Clinical Trial Protocol

A clinical trial’s blueprint, describing in detail the steps of the trial.

A group of participants recognized as having at least one shared characteristic.

Comparator (product)

The drug, device, or procedure (approved or investigational), or placebo, that the investigational drug, device, or procedure is compared with in a clinical trial.

Complying with all trial-related requirements, including adhering to the Good Clinical Practice guidelines and ethical and legal obligations.

Contract research organization (CRO)

An organization (commercial, academic, or other) that the sponsor hires to take over one or more of the tasks and responsibilities related to the running of a clinical trial.

Control arm

One or more arms of participants will receive the investigational drug, device, or procedure, and the control arm will receive either the current standard drug, device, or procedure for the condition being investigated, or a placebo. The control arm will be compared with the investigational arm(s) in a clinical trial to see if the investigational drug, device, or procedure is effective.

Data Coordinator

Works with the trial team to collect and organize all relevant clinical research data according to the protocol. Click here to see the people you might meet as a clinical trial participant.

Declaration of Helsinki

A series of ethical principles concerning medical research involving human beings, first published by the World Medical Association in 1964 in Helsinki, Finland. These principles include processes that need to be followed to make sure patients are safe taking part in clinical trials.

Demographic data

Clinical trial participants’ individual characteristics, such as sex, age, medical history, relatives’ medical history, and traits, that are applicable to the clinical trial.

Dosage regimen

Refers to how much medicine is given in one dose, how often a dose of medicine is given per day, and the time that passes between each dose.

Double-blind

In double-blind clinical trials, neither the trial doctor nor the participant knows which treatment arm the participant is assigned to.

The effectiveness of the drug, device, or procedure being investigated.

Eligibility criteria

The inclusion and exclusion criteria, which investigators use to select participants for the trial.

An outcome that the trial is intended to assess.

Enrolling/Enrollment

The overall process by which a potential participant joins a clinical trial.

Ethics committee (EC)

An ethics committee is a body of medical and non-medical specialists who are responsible for confirming the safety, integrity, and human rights of the trial participants.

European Medicines Agency (EMA)

Regulatory agency responsible for issuing rules and regulations in Europe regarding the conduct of clinical trials. The European Medicines Agency is also responsible for reviewing and approving new medicines in Europe so that they can be sold/prescribed.

Exclusion criteria

Part of the eligibility criteria. The exclusion criteria are used to determine if a person should be excluded from taking part in a clinical trial. The exclusion criteria vary by trial.

Expanded access

The US Food and Drug Administration processes that supply investigational medications to participants who are not able to take part in clinical trials and are not responding well to available medications.

Food and Drug Administration (FDA)

The federal agency of the US Department of Health and Human Services that enforces the Food, Drug and Cosmetics Act. The Food, Drug and Cosmetics Act is a collection of laws approved by the US federal government, which gives authority to the Food and Drug Administration (FDA) to supervise the safety of food, drugs, and cosmetics in the United States. In the context of clinical research, the FDA is responsible for reviewing and approving new medicines in the United States so that they can be sold/prescribed.

Generic drug

An approved drug with the same active ingredient and intended use as a brand-name drug, but not the same inactive characteristics, such as color and taste. Only after the brand-name drug’s patent has expired can a generic drug be marketed.

Good Clinical Practice (GCP)

An international set of ethical and scientific quality standards that all aspects of clinical research must meet.

In vitro testing

Testing that takes place outside the body in an artificial setting, such as a test tube.

In vivo testing

Testing that takes place in humans and animals.

Incident rate

The number of new occurrences of a disease in a group of people during a specific period of time.

Inclusion criteria

Part of the eligibility criteria. The inclusion criteria are used to determine if a person may be able to participate in a clinical trial. The inclusion criteria vary by trial.

Informed Assent Form

For people who are under the age of consent in their country, their parents/legal guardian will need to sign an Informed Assent Form to enable their child to take part in the trial.

Informed consent

Clinical trial regulation requires researchers to give potential participants complete written information about the clinical trial before they agree to participate. This is called informed consent. The information provided must be written in a manner that allows the potential participant to understand all the trial details.

Informed Consent Form (ICF)

Before joining a clinical trial, participants need to sign the Informed Consent Form (ICF) to show they have been given information about the clinical trial and that they agree to take part in it. Even after they sign the ICF, participants can leave the clinical trial at any time and for any reason without penalty.

Institutional review board (IRB)

A group of people who review elements of a clinical trial, such as the protocol and patient recruitment materials, to make sure that the trial is safe and has the potential to be effective for participants. The institutional review board also checks that all the US Food and Drug Administration’s rules and regulations are followed.

International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH)

A project to unite regulatory authorities and pharmaceutical companies, so together they can make the scientific and technical aspects of developing and registering new medicinal products more efficient.

Intervention

A process at the core of a clinical trial. This can include any product, investigational or approved, given to participants in a clinical trial, and non-invasive tactics, such as changes to diet and exercise.

Interventional study

A clinical trial that aims to test a potential new drug, medical device, or surgical procedure (referred to as the “intervention”).

Investigational medication

A potential new drug that is undergoing clinical research.

Longitudinal study

An observational study in which data are measured two or more times from the same population of patients over a period of time.

A member of the trial team who is appointed by the sponsor to perform all the necessary checks to make sure the trial follows the protocol closely and the rights and safety of participants are assured.

National Institutes of Health (NIH)

An agency of the US Department of Health and Human Services that focuses on funding health and medical research.

New Drug Application (NDA)

All data (non-clinical, clinical, pharmacological, and pharmacokinetic) related to a drug that are compiled and presented to the US Food and Drug Administration so the drug can be approved for marketing in the United States.

Observational study

A type of clinical research study that aims to learn more about approved medications through observation. For people who take part, the treatment and medical care they receive is what they are currently receiving, i.e. they are not prescribed anything by and do not receive medical care from the people involved in the study.

Off-label use

When a drug approved by the US Food and Drug Administration is used for a condition it has not been approved for.

Open-label trial

A clinical trial is open-label if the participants and doctors know which treatment arm patients are assigned to.

Outcome measure (primary and secondary)

In a clinical trial, the safety and efficacy of an investigational drug, device, or procedure are measured by outcomes. These outcomes are related to patients, such as patient survival or health-related quality of life.

Over-the-counter (OTC)

Refers to a medicine that is available for purchase in a pharmacy without a prescription.

Participant Information Sheet (PIS)

This document has ethical approval and contains details about the trial rationale and aim, the intervention being tested, potential risks and benefits, and trial-related procedures. The Participant Information Sheet covers the information that needs to be explained and discussed with potential participants and their legal representatives or parents, if applicable, before signing the Informed Consent Form.

Pharmacodynamics

The study of the relationship between the amount of a drug used and its effects on the body.

Pharmacoeconomics

The review of the relationship of cost versus benefit for a given drug, device, or procedure compared with other similar treatment options.

Pharmacokinetics

The examination of the way the human body takes in, circulates, and excretes a drug.

A placebo is a “dummy treatment,” which looks like the genuine medicine but contains no active ingredient.

Prescreening

Prescreening of potential participants over the telephone, on a clinical trial website, or in person to work out their potential eligibility and suitability for a clinical trial is often a first step for recruiting people into clinical trials.

Prevention trial

A clinical trial that aims to discover improved methods to prevent participants who have never had a particular disease from developing it, or to stop a disease coming back.

Principal Investigator

Responsible for running the clinical trial according to the protocol, keeping accurate records of how the trial procedures are carried out, and reporting any side effects of the trial medication. Click here to see the people you might meet as a clinical trial participant.

Quality assurance

Processes that make sure a clinical trial is being managed as per the Good Clinical Practice (GCP) guidelines and that all data produced are correct.

Randomization

Randomization in a clinical trial is when participants are randomly put into groups and each group is assigned by chance to receive a different treatment.

Recruitment

The period of a clinical trial when the trial team is identifying and enrolling participants.

Regulatory Affairs

Each pharmaceutical company has a Regulatory Affairs division. This division is involved in the whole drug development process, and part of its role is being responsible for making sure that each clinical trial complies with government regulations.

Regulatory agencies

Government agencies that are responsible for issuing rules and regulations regarding the conduct of clinical trials in their respective countries (e.g. the US Food and Drug Administration, the European Medicines Agency).

Regulatory Coordinator

Makes sure the trial is compliant with regulations and ethical standards. Click here to see the people you might meet as a clinical trial participant.

Research Nurse

Involved in the screening of potential participants, participant consent, participant randomization, data collection, reporting of adverse events, and preparing trial documents and reports. Click here to see the people you might meet as a clinical trial participant.

Research Pharmacist

Provides trial medication at certain visits and documents the return of trial medication. Click here to see the people you might meet as a clinical trial participant.  

Research team

The clinical research team are the people involved in running the trial. A clinical research team may include the following people: Principal Investigator, Sub-Investigator, Clinical Research Coordinator, Clinical Research Associate, Regulatory Coordinator, Data Coordinator, Research Nurse, Research Pharmacist, and Trial Assistant. Click here to see the people you might meet as a clinical trial participant.  

Serious adverse event (SAE)

Any unwanted effect of a drug, device, or procedure that is deadly, is life-threatening, causes permanent disability, or leads to hospitalization.

Single-blind

In single-blind clinical trials, the investigator knows which treatment the participant is receiving, but the participant does not know. Occasionally, it is the other way around and the participant knows which treatment they are receiving, but the investigator does not.

Company or organization starting, managing, and funding a clinical trial.

Standard operating procedure (SOP)

Official instructions for the organization of clinical trials to make sure that all elements of a clinical trial are carried out in a well-organized and consistent way.

Standard of care

A treatment approach that most healthcare professionals recognize as suitable.

Study completion date

The final date in a clinical trial when data are collected from participants.

Sub-Investigator

Medical doctors that work in a trial under the supervision of the Principal Investigator. Click here to see the people you might meet as a clinical trial participant.

Participant in a clinical trial.

Trial Assistant

Provides support to the Principal Investigator for trial monitoring and reporting, data management, and audits. Click here to see the people you might meet as a clinical trial participant.

A person’s psychological and physical welfare.

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The Research Glossary

The free online glossary for key terms and concepts used in clinical research.

Clinical Research Fast Track

Statement of the Investigator form that must be filed by an investigator running a clinical trial to study a new drug or agent. The investigator agrees to follow the U.S. Food and Drug Administration (FDA) Code of Federal Regulations for the clinical trial. The investigator verifies that he or she has the experience and background needed to conduct the trial and that it will be done in a way that is ethical and scientifically sound.

The portion of the Code of Federal Regulations that governs food and drugs within the United States for the Food and Drug Administration (FDA).

Electronic Records and Electronic Signatures-Provides guidance for companies using paperless record-keeping systems and ensures the use of electronic record-keeping systems are documented securely, authenticity, and are adequately maintained.

regulations pertaining to INDs

Protection of Human Subjects. Compliance with these parts is intended to protect the rights and safety of subjects involved in investigations filed with the Food and Drug Administration.

Financial Disclosure by Clinical Investigators.This section and conforming regulations require an applicant whose submission relies in part on clinical data to disclose certain financial arrangements between sponsor(s) of the covered studies and the clinical investigators and certain interests of the clinical investigators in the product under study or in the sponsor of the covered studies.

Institutional Review Boards. Ensures initial and continuing review of research. Regulates reportings, changes, approvals, and eliminates apparent immediate hazards to the human subjects. .

regulations pertaining to devices.

A value that is outside of the normal range value, both low or high.

Error free data, any changes or amendments should be accompanied by documentation to support the changes.

A list or disclosure of any known/potential costs that could accrue beyond the trial procedures

An unintended reaction to a drug taken at a normal dose.

any untoward medical occurrence in a study subject administered a pharmaceutical product; it does not necessarily have a causal relationship with the treatment.

clinical research basic terminology

a notice or announcement in a public medium promoting clinical trial.

Principles by which Good Documentation of data: Attributable, Legible, Contemporaneous, Original, Accurate, and Complete

Other available treatments or no treatment at all.

A professional group that publishes research to advance public health and advocates for the interests of registered physician-members

Used to express willingness to participate in research by persons who are by definition too young to give informed consent but are old enough to understand the proposed research in general, its expected risks and possible benefits, and the activities expected of them as subjects.

credentialing organization recognizing professionals involved in all aspects of clinical studies/trials who have demonstrated the knowledge, skills, and abilities to perform ethical and responsible clinical research by passing proctored exams.

This means that the evidence or data collected is attributable to the person collecting it. This ensures accountability. This contains a record of who performed an action and when.

The initial time point in a clinical trial that provides a basis for assessing changes in subsequent assessments or observations. At this reference point, measurable values such as physical exam, laboratory tests, and outcome assessments are recorded.

The potential positive outcomes that should be disclosed to the participants.

A point of view or preference which prevents impartial judgment in the way in which a measurement, assessment, procedure, or analysis is carried out or reported.

A sample of material, such as urine, blood, tissue, that may be used for a laboratory test or stored in a biorepository to be used for research.

The financial plan for clinical trials, including cost and expenses.

a record of the information collected from a subject during a trial. The information that is collected is based on what the protocol specifies.

is a division of the U.S. Food and Drug Administration (FDA) that monitors drugs.

A credential award for those who has met eligibility requirements, demonstrated proficiency of specific knowledge and job‐related skills, and passed the standardized certification exam.

An abnormal value with a result where a course of treatment has had genuine and quantifiable effects

Clinical trials are a kind of clinical research designed to evaluate and test new interventions such as a device or medications. Clinical trials are often conducted in four phases. The trials at each phase have a different purpose and help scientists answer different questions.

typically work for CROs. They are responsible for monitoring the study at study sites. They visit sites and look at the data collected and make sure the site is following the protocol. They work closely with the clinical research coordinators at the study sites.

An individual that handles the administrative and day-to-day responsibilities of a clinical trial and acts as a liaison for the clinical site. This person may collect the data or review it before it is entered into a study database.

NIH defines a clinical trial as a research study in which one or more human subjects are prospectively assigned to one or more interventions (which may include placebo or other control) to evaluate the effects of those interventions on health-related biomedical or behavioral outcomes. Clinical trials are used to determine whether new biomedical or behavioral interventions are safe, efficacious, and effective. Behavioral clinical trials involving an intervention to modify behavior (diet, physical activity, cognitive therapy, etc.) fit this definition of a clinical trial.

CTA serve as a legally binding contract between a sponsor and site. It outlines each party's responsibilities and obligations for the clinical trial.

clinical research basic terminology

A software system used to manage clinical trials in clinical research. This CTMS will serve as a single, centralized, web-based enterprise resource to support clinical research studies conducted

clinical research basic terminology

This is a visit in which the sponsor of the research study ensure that all of the necessary aspects of the study closure have been completed

The Code of Federal Regulations is the codification of the general and permanent rules published in the Federal Register by the executive departments and agencies of the Federal Government.

an overt or implicit threat of harm is intentionally presented by one person to another in order to obtain compliance or consent

Any form of reimbursement or monies for time/ or travel. This can be in many forms, checks, on a loaded payment card, gift card, or transportation card. Other compensations may include hotel, travel, and food.

Are there blank spaces in the data collection points? Even if there is an N/A you must write “N/A” in order to satisfy this element of ALCOA-C!

Prescription and over-the-counter drugs and supplements a study participant has taken along with the study intervention. This information may be collected as a history item as well as during the study_assignment. Some studies may collect only those medications that may interact with the study or intervention or that may exclude an individual from participating in a study_assignment.

Ensurance of the participants' private information being in compliance with HIPAA and all privacy laws.

A conflict of interest occurs when individuals involved with the conduct, reporting, oversight, or review of research also have financial or other interests, from which they can benefit, depending on the results of the research.

Potential issues that could result from a subject withdrawing prior to completion date.

Site information, including address, email address and phone numbers for study staff. Contacts may also include IRB and Sponsor information.

Is the documentation happening in real time vs. retroactively documenting an occurrence.

this is when the IRB re-reviews the study to determine if it is appropriate for the study to continue, as is or with modifications.

This is the Clinical Trial Agreement (CTA) of Clinical Research Agreement (CRA). This is an agreement with a for-profit company providing funding or a drug/device for a Clinical Trial. This can be a Sponsor-initiated or Investigator-Initial-Clinical Trial

The group of individuals in a clinical trial assigned to a comparison intervention.

The regimen is being compared to a control; the control being a placebo (medically ineffectual treatment) or a standard treatment.

A clinical trial in which at least one group of participants is given a test intervention, while at least one other group concurrently receives a control intervention.

A group organized to coordinate the planning and operational aspects of a multi-center clinical trial. CCs may also be referred to as Data Coordinating Centers (DCCs) or Data Management Centers (DMCs).

A CAPA Plan is a series of actions taken to resolve a compliance issue, and most importantly, to prevent further recurrence. A CAPA plan will focus on the immediate noncompliance and the broader scope of the problem.

The communication between site and sponsor, CRO, or any other important person(s).

a company that provides clinical trial management services for the pharmaceutical, biotech, and medical device industries.

A curriculum vitae is a document that showcases a persons’ academic and professional accomplishments. It is used to apply for positions within areas where a person's specific knowledge or expertise is required.

A software system to manage relationships with customers

a committe of experts reviewing clinical trial data on an ongoing basis to ensure the safety of study subjects and validity and integrity of the data.

Plan included with the grant application for clinical trials which establishes the overall framework for data and safety monitoring, how adverse events will be reported to the IRB and the NIH and, when appropriate, how the NIH Guidelines and FDA regulations for INDs and IDEs will be satisfied.

This is the process of locking a clinical trial database. This action is taken to prevent any further changes to the database. The database is locked after review, query resolution and determination that it is ready for analysis.

The processes of handling the data collected during a clinical trial from development of the study forms/CRFs through the database locking process and transmission to statistician for final analysis.

A plan that documents the processes for handling the flow of data from collection through analysis. Software and hardware systems along with quality control and validation of these systems, as relevant are described.

Trials executed through telemedicine and mobile/local healthcare providers, using processes and technologies that differ from the traditional clinical trial model

clinical research basic terminology

studies executed virtually through telemedicine with our without a “site”, using processes and technologies differing from the traditional clinical trial model.

is a set of ethical principles regarding human experimentation developed originally in 1964 for the medical community by the World Medical Association (WMA). It is widely regarded as the cornerstone document on human research ethics

a list of who is authorized to do certain tasks on a trial.

refers to the practice of looking for better ways to identify a particular disorder or condition.

A trial design in which neither the investigator or the subject knows which treatment the subject is receiving.

Indication that the clinical trial intervention produces a desired therapeutic effect on the disease or condition under investigation.

A test used to check a heart’s rhythm and electrical activity

an electronic record of the information collected from a subject during a trial. The information that is collected is based on what the protocol specifies.

A digital version of a COA (Clinical Outcome Assessment), which measures and records how a patient is feeling or functioning

is a web-based software application used to collect, clean, transfer, and process data in clinical trials.

is an electronic version of a patients medical history, that is maintained by the provider over time, including demographics, progress notes, problems, medications, ect.

an alternative to the conventional paper consent form, this must be desinged compliant with 21 CFR Part 11.

An electronic investigator site file (eISF) is a technology solution designed to organize, collect, store, track, and archive required and essential study documents for an individual site involved in a particular research study

Electronic patient-reported outcomes (ePRO) are patient-provided information about symptoms, side effects, drug timing and other questions recorded on an electronic device during a clinical trial

An electronic version of regulatory at the CRO and Sponsor level. Tells the story of how the trial ran across all sites told by the official documents maintained.

List of criteria guiding enrollment of participants into a study_assignment. The criteria describe both inclusionary and exclusionary factors, (e.g. inclusion criterion - participants must be between 55 and 85 years old; exclusion criterion

The process of registering or entering a patient into a clinical trial. Once a patient has been enrolled, the participant would then follow the clinical trial protocol

an electronic version of the story of how a trial ran, told by the official documents maintained. Referred to as a “reg binder” or “ISF” at the site level.

When correcting data, it should meet the ALCOAC GDP with one line crossing out the error, then initial, date, and short explanation of the correction.

A type of eligibility criteria. These are reasons that a person is not allowed to participate in a clinical study

clinical research basic terminology

This is also known as the “Inspectional Observations”. This is a list of conditions or practices that indicate the potential violation of the FDA’s requirements. The observations on the FDA Form 483 are listed in descending order of importance. This is not an all inclusive list but more of a snapshot of possible issues noted at the site. This form is a public document that is available only by request.

Is the process of evaluating the particular site for the possibility of conducting the clinical trial or study. This process is to ensure that the site is able to to conduct the trial, within the budget and the timeline as well as maintain the integrity of the data and participant safety

clinical research basic terminology

When a clinical investigator or staff member has disclosable financial interests and arrangements, the disclosure statement submitted to FDA is required to include a description of any steps taken to minimize the potential for bias resulting from any of the disclosed financial interests and arrangements.

The United States Food and Drug Administration is a federal agency of the Department of Health and Human Services. The Food and Drug Administration is responsible for protecting the public health by ensuring the safety, efficacy, and security of human and veterinary drugs, biological products, and medical devices; and by ensuring the safety of our nation's food supply, cosmetics, and products that emit radiation.

A standard for the design, conduct, performance, monitoring, auditing, recording, analyses, and reporting of clinical trials that provides assurance that the data and reported results are credible and accurate, and that the rights, integrity, and confidentiality of trial participants are protected.

The guideline that outlines requirements for designing, conducting, recording and reporting trials that involve the participation of human subjects

The term that describes the standard by which documents are created and maintained.

is a system for ensuring that products are consistently produced and controlled according to quality standards. It is designed to minimize the risks involved in any pharmaceutical production that cannot be eliminated through testing the final product.

A government agency that provide health services to Americans.

The Health Insurance Portability and Accountability Act of 1996 (HIPAA) is a federal law that required the creation of national standards to protect sensitive patient health information from being disclosed without the patient's consent or knowledge.

The first comprehensive Federal protection for the privacy of personal health information. The Privacy Rule regulates the way certain health care groups, organizations, or businesses, called covered entities under the Rule, handle the individually identifiable health information known as protected health information (PHI).

A patient or healthy individual who is or becomes a participant in research, either as a recipient of the intervention or as a control.

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

A type of eligibility criteria. These are the reasons that a person is allowed to participate in a clinical study

The protocol will specify the inclusion/exclusion criteria for enrollment into a clinical trial. This is colloquially referred to as I/E ("I" "E") in the field. The inclusion criteria must be present and the exclusion criteria absent for a subject to be eligible for the trial.

An informed consent document is typically used to provide subjects with the information they need to make a decision to volunteer for a research study. Federal regulations (45 CFR 46.116 ) provide the framework for the type of information that must be included as part of the consent process.

An informed consent form is a document used in clinical research that outlines important information about the study to potential participants. It is a legal document that provides prospective participants with an explanation of the purpose, procedures, and risks associated with the research study, as well as the potential benefits and alternatives. The informed consent form also explains the participant's rights and obligations during the study, including their ability to withdraw at any time without penalty. The form is usually written in lay language and must be signed by the participant or their legally authorized representative before they can participate in the study. The informed consent process is an essential part of ethical research, ensuring that participants fully understand the risks and benefits of the study before they decide to participate. It is also a legal requirement in most countries and is necessary to protect both the participants and the researchers.

A document that describes the rights of a study participant and provides details about the study, such as its purpose, duration, required procedures, and key contacts. Risks and potential benefits are explained in the informed consent document.

In accordance with FDA regulations, an IRB has the authority to approve, require modifications in (to secure approval), or disapprove research. This group review serves an important role in the protection of the rights and welfare of human research subjects. Sometimes called an Independent Ethics Committee(IEC)

An independent body constituted of medical, scientific, and nonscientific members whose responsibility it is to ensure the protection of the rights, safety, and well-being of human subjects involved in a trial by, among other things, reviewing, approving, and providing continuing review of trials, protocols and amendments, and of the methods and material to be used to obtaining and documenting informed consent of the trial participant.

Helps clinical trial sponsors and sites manage the patient and drug supply logistics throughout a clinical trial.

are the technologies that research sites use to enroll patients into clinical trials, randomize patients, and manage study drug supplies. Othernames: Interactive Web Response System (IWRS)/Interactive Voice Response System (IVRS)

This visit is conducted by the CRA to review source documents and study related materials to ensure protocol and regulatory compliance. This visit is completed during the conduct of the study

supports aviation with global standards for airline safety, security, efficiency and sustainability.

an organization that brings together the regulatory authorities and pharmaceutical industry to discuss scientific and technical aspects of drug registration.

A procedure or treatment such as a drug, nutritional supplement, gene transfer, vaccine, behavior or device modification that is performed for clinical research purposes.

a request from a study sponsor to obtain FDA approval to administer investigational drug to humans.

The IP may be a drug, biologic, medical device, or combination product that has not received a marketing approval.

clinical research basic terminology

(sometimes called Clinical Investigator or more often Principal Investigator (PI)) is an individual responsible for the preparation, conduct, and administration of a clinical trial.

This is a meeting where everyone involved with the new clinical trial to meet and become familiar with the study, including learning about the roles of the study

The Investigator’s Brochure is a comprehensive compilation of clinical and nonclinical data on the investigational product (drug, supplement, device or other product) maintained by a drug developer or investigator that contains the body of information about the investigational product obtained before and during a drug trial.

This is the process in accordance with FDA regulations, to which the IRB must review and approve all research involving humans prior to any research activities may begin. The IRB has the authority to approve, require modification in or disapprove the research.

Documentation after it has happened and notating it as “late entry”.

Is the documentation able to be read easily and clearly.

The long form embodies all the elements of informed consent as required under 21 CFR 50.25. When the long form is used, a copy must be provided to the person signing the form, that is, the subject or the subject's legally authorized representative.

A set of procedures describing study conduct. A MOP is developed to facilitate consistency in protocol implementation and data collection across study participants and clinical sites.

A procedure in which the investigator administering the assessments and intervention as well as the participants in a clinical trial are kept unaware of the treatment assignment(s). Single blinding usually refers to the study participant(s) being unaware, and double blinding usually refers to the study participant(s) and any of the following being unaware of the treatment assignment(s): investigator(s), monitor, and data analyst(s).

The primary Federal agency for conducting and supporting medical research.

A unique identification code given to each clinical study record registered on ClinicalTrials.gov. The format is "NCT" followed by an 8-digit number (for example, NCT00000419). Also called the ClinicalTrials.gov identifier

An application submitted by the manufacturer of a drug to the FDA, after the clinical trial has been completed, for a license to market the drug for a specified indication.

Also know as a confidently agreement. This is a contract that establishes a confidential relationship. The party or parties signing the agreement agree that sensitive information they may obtain will not be made available to any others.

A abnormal value that does not have a genuine effect.

The total amount of subjects the sponsor wants to enroll into participation in the study.

A ten point code that describes the basic principles of ethical behavior in the conduct of human experimentation.

The safety and data monitoring body for observational studies with large or vulnerable populations or risks associated with tests or standard of care.

A federal government agency within the Department of Health and Human Services (DHHS) charged with the protection of human subjects participating in government funded research. It issues assurances and oversees compliance of regulatory guidelines by research institutions.

Provides leadership in the protection of the rights, welfare, and wellbeing of subjects involved in research conducted or supported by the U.S. Department of Health and Human Services.

A study in which the subjects and the investigator are aware of the drug and/or dose that is being administered.

A clinical trial in which investigators and participants know which intervention is being administered.

Is the documentation the first pen to paper? Fun fact- if you take your measurements down on a napkin- that napkin is now SOURCE! Original records should be preserved, meaning the material used should be durable, in the case of duplicates, the creator of the original records should confirm the authenticity of the copies.

Refers to a medicine that can be bought without a prescription.

Subject, Sponsor, and/or Site has the right to terminate their participation at any point during the trial.

not inclusive ● Study Title- This is meant to explain the key features of the study purpose, design, population , procedures, timeline, and participant safety. ● Study Name ● Title Page ● Summary ● Flow Chart/Study Schema/Schedule of Events ● Baseline -An initial measurement that is taken at an early time point and used for comparison over time to look for changes. ● Introduction ● Study Objectives ● Study Design ○ Is it controlled? If so, what is the control? ○ Is it randomized? ○ Is it blinded? ● Randomization procedures ● Blinding ● Unblinding (breaking the blind) procedures ● IP ○ Name ○ Storage ○ Dosage ○ Formulation ○ Route of administration ○ Regimen ● Subject Selection ● I/E ● Enrollment Procedures ● Pre-Screening ● Screening ● Concomitant Medications (“Conmeds”) ○ Prescription ○ OTC ○ Herbal Supplements ○ Vitamins ● Exclusionary Medications ● AEs ● SAEs ● Data Recording ● Data Quality Assurance ● Data Analysis/Statistics

A type of observational study that collects information about patients' medical conditions and/or treatments to better understand how a condition or treatment affects patients in the real world

The process (in a living organism) of absorption, distribution, metabolism, and excretion of a drug or vaccine.

Researchers test an experimental drug or treatment in a small group of people for the first time. The researchers evaluate the treatment’s safety, determine a safe dosage range, and identify side effects.

The experimental drug or treatment is given to a larger group of people to see if it is effective and to further evaluate its safety.

The experimental study drug or treatment is given to large groups of people. Researchers confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the experimental drug or treatment to be used safely.

Post-marketing studies, which are conducted after a treatment is approved for use by the FDA, provide additional information including the treatment or drug’s risks, benefits, and best use.

A placebo is an inactive treatment. In fact, a placebo may be in a pill or tablet form, or it may be an injection or a medical device. Whatever the form, placebos often look like the real medical treatment that is being studied except they do not contain the active medication.

A method of investigation in which an inactive substance/treatment (the placebo) is given to one group of participants, while the test article is given to another group. The results obtained in the two groups are then compared to see if the investigational treatment is more effective in treating the condition.

The aim of a preclinical study is to collect data in support of the safety of the new treatment. Preclinical studies are required before clinical trials in humans can be started.

Activities before obtaining informed consent to determine initial eligibility for and interest in a study. Pre-screening may be performed over the telephone, in-person or on-line and may not include any research procedures

A visit to ensure pre-qualification of a site and eliminate sites that do not possess adequate qualities to conduct the trial.

This is to ensure pre qualification of the site and eliminates sites that do not meet the qualifications to conduct the clinical trial or study. This visit must take place to determine if additional resources should be used in order to perform a Site initiation Visit

Looks for better ways to prevent disorders from developing or returning. Different kinds of prevention research may study medicines, vitamins, vaccines, minerals, or lifestyle changes.

The person in charge and responsible for a clinical trial.

clinical research basic terminology

A pre-defined process (e.g., randomization) specified in an approved protocol that stipulates the assignment of research subjects (individually or in clusters) to one or more arms (e.g., intervention, placebo or other control) of the clinical trial.

A person's health information including but not limited to demographics, medical history, test/lab results, insurance information, ect.

Directions for how to run a particular trial.

A written description of a change(s) to or formal clarification of a protocol.

Failure to conduct a study as described in the protocol. The failure may be accidental or due to negligence and in either case, the protocol deviation should be documented. This also includes failure to comply with federal laws and regulations, the institution's commitments and policies, and standards of professional conduct and practice. Examples of noncompliance include:

Internal document created as part of the ongoing quality control process summarizing compliance with the protocol and listing protocol deviations and/or violations.

The reasoning behind a trial being conducted- what is the end goal? What is the desired outcome?

All those planned and systematic actions that are established to ensure that the trial is performed and the data are generated, documented (recorded) and reported in compliance with GCP and the applicable regulatory requirements.

The internal operational techniques and activities undertaken within the quality assurance system to verify that the requirements for quality of trial related activities have been fulfilled (e.g., data and form checks, monitoring by study staff, routine reports, correction actions, etc.).

explores ways to improve comfort and the quality of life for individuals with a chronic illness.

The process of assigning clinical trial participants to treatment or control groups using an element of chance to determine the assignments in order to reduce bias.

The patient population is randomly allocated to treatment groups. This helps reduce bias by ensuring there isn’t a pattern in assigning treatment to the subjects.

The act of trying to find the right patients for a clinical trial.

The targeted number of patients to screen or enroll in a clinical trial.

Advertisements and other items used to help find participants in the study.

The plan that outlines how individuals will be recruited for the study and how the study will reach the recruitment goal.

The story of how a trial ran is told by the essential documents maintained. Referred to as “reg binder” or “ISF” at the site level.

A systematic investigation including research development, testing and evaluation, designed to develop or contribute to generalizable knowledge.

the process of keeping patients/subjects in the study or engaged to participate in the study.

The strategy and tactics designed to keep patients enrolled in clinical trials, and from discontinuing participation and “dropping out.”

the targeted number of patients to keep in the tria after enrollment. Should be as close to 100% as possible.

The site’s plan to keep patients in the study long-term.

The potential negative outcomes that need to be disclosed to the participants.

an adaptive approach that directs monitoring focus and activities to the evolving areas of greatest need which have the most potential to impact patient safety and data quality.

A plan that outlines the oversight of a clinical trial.

An independent individual, often a clinician who is appointed by the NIA and performs data and safety monitoring activities in low-risk, single site clinical studies. The SO advises the NIA regarding participant safety, scientific integrity, and ethical conduct of a study_assignment. The SO is advisory to the Institute Director.

the process by which activities are evaluated to determine whether they are eligible for enrollment in a clinical trial.

An essential document that records all individuals who entered the screening process. The screening log demonstrates the investigator’s attempt to enroll a representative sample of participants.

A process designed to determine individual’s eligibility for participation in a clinical research study_assignment.

aims to find the best ways to detect certain disorders or health conditions

This is any untoward medical occurrence at any dose that results in death, is life-threatening, requires hospitalization (or prolongation of hospitalization), results in persistent or significant disability, or is a birth defect.

An IRB approved short form may be used in appropriate situations where the elements of the consent form are presented to the subject or subject’s legal authorized representative. It is a written summary of the information to be presented orally which is signed by the subject or subject’s LAR.

A study that is set up so that participants do not know which study treatment they are getting.

This is a visit conducted to evaluate the sites and it’s investigators, resources and the sites capabilities to conduct study terms. Infrastructure, adequacy and availability of the site facilities

The site initiation visit is a required visit to prepare and set up a research site to conduct a study and must occur prior to patient recruitment.

This is a critical visit that’s completed by the Sponsor prior to the start of the study. During this visit the Sponsor ensures that the investigators team has all of the necessary resources and is ready to conduct the human subjects research conducted under the Investigational New Drug (IND) or Investigational Device Exemption Application (IDE). The SIV ensures that the Investigator and team is aware of the responsibilities with the Study Protocol and are familiar with the study documentation, investigational product management and administrative procedures.

This is a meeting with a sponsor representative in order to ensure that the institution is fully capable and equipped to run the clinical study or trial. This visit may also be referred to as the Site Selection Visit (SSV) or Pre Study Qualification Visit (PSQV)

Record of the monitor (CRA) visiting the site. They are required to sign in and sign out.

an organization established to support global clinical research communities

Original documents, data, and records (e.g., hospital records, clinical and office charts, laboratory notes, memoranda, participant diaries, recorded data from automated instruments, x-rays, etc.) that are used in a clinical trial.

documents in which data collected for a clinical trial is first recorded. The data is usually later entered in an electronic data capturing system (EDC).

This is the process by which the data within the CRF or other data that has been collected is compared against the original source of information

The company, institution or organization that takes on legal responsibility for the initiation, management and/or financing of the research.

Treatment that is accepted by medical experts as a proper treatment for a certain type of disease and that is widely used by healthcare professionals.

Detailed written instructions to achieve uniformity of the performance of a specific function across studies and patients at an individual site.

Established safety criteria that would either pause or halt a study due to reasons including but not limited to futility or risk(s) to the participants.

Separation of a study cohort into subgroups or strata according to specific characteristics such as age, gender, etc., so that factors which might affect the outcome of the study, can be taken into account.

This is also known as the Feasibility Award, when a site is chosen by the sponsor to conduct a trial based on their feasibility.

in a clinical trial, the participants make up the study population.

A delegated member of the research tream that helps back up the PI and preform study related procedures.

Any unfavourable occurrence in a trial participant that is judged to have a major impact on their health and was not anticipated and could potentially be due to the intervention under investigation.

The Belmont Report summarizes ethical principles and guidelines for research involving human subjects. Three core principles are identified: respect for persons, beneficence, and justice.

Regulatory at the CRO and Sponsor level. Tells the story of how the trial ran across all sites told by the official documents maintained.

a list of who is trained to do what on a trial.

looks for better ways to treat disorders from developing or returning. Different kinds of prevention research may study medicines, vitamins, vaccines, minerals, or lifestyle changes.

The trial master file (TMF) is the collection of essential documents which allows the conduct of a clinical trial to be reconstructed and evaluated

clinical research basic terminology

Any serious adverse effect on health or safety or any life-threatening problem or death caused by, or associated with, a device, if that effect, problem, or death was not previously identified in a nature, severity, or degree of incidence in the investigational plan or application (including a supplementary plan or application) or any other unanticipated serious problem associated with a device that relates to the rights, safety, or welfare of subjects.

Unanticipated problems involving risks to subjects or others, which meet all of the following criteria:

Any problem or event that in the opinion of the local investigator meets all three of these criteria: Serious, Unanticipated (Not already described as a potential risk in the approved materials), and Related.

A procedure in which one or more parties to the trial are made aware of the treatment assignment(s).

A response to the Tuskegee Syphilis Study. Signed into law in 1974 and created the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. Identifies the basic principles of research conduct and oversees human experimentation in medicine

Third party companies to help with services and ancillary procedures of the clinical trial. Some examples may be payment services, central readers for procedures or imaging, and/or recruitment companies.

Ensuring patients agree completely unforced or uncoerced to be a subject in the study trial. Giving the patient alternatives, risk/benefits, and ample time to consent.

Includes children, pregnant women, prisoners, handicapped persons, the mentally disabled, people with acute or chronic severe mental illness, economically disadvantaged, and educationally disadvantaged. When some or all of the subjects are likely to be vulnerable to coercion or undue influence additional safeguards should be included in the study to protect the rights and welfare of these subjects.

Principles of Clinical Research

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  • Richard N. Puzzitiello 5 , 6 ,
  • Avinesh Agarwalla 5 , 6 ,
  • Brian Forsythe 5 , 6 &
  • Natalie L. Leong 5 , 6  

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A general understanding of clinical research is necessary both to thoughtfully read orthopedic literature and to contribute to literature by conducting research. This chapter addresses the different types of clinical research, as well as the definitions of the various levels of evidence. Then, a brief history of regulatory guidelines pertaining to human research is provided, along with an overview of current regulatory mechanisms. Other general considerations such as funding sources and challenges of conducting research are also addressed. Finally, a primer of basic statistical principles and calculations frequently used in clinical research is included at the end of the chapter.

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History of Research

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Clinical Trials: Ensuring Quality and Standardization

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Steps of a Research Study: From Research Question to Publication

Weller SC. A meta-analysis of condom effectiveness in reducing sexually transmitted HIV. Soc Sci Med. 1993;36(12):1635–44.

Article   CAS   Google Scholar  

Hurley SF, Jolley DJ, Kaldor JM. Effectiveness of needle-exchange programmes for prevention of HIV infection. Lancet. 1997;349(9068):1797–800.

Moyer VA. Force* USPST. Screening for HIV: U.S. preventive services task force recommendation statement. Ann Intern Med. 2013;159(1):51–60.

Article   Google Scholar  

Service USPH, Infectious Diseases Society of A, Group UIPoOIW. 2001 USPHS/IDSA guidelines for the prevention of opportunistic infections in persons infected with human immunodeficiency virus. HIV Clin Trials. 2001;2(6):493–554.

Ebell MH, Siwek J, Weiss BD, et al. Strength of recommendation taxonomy (SORT): a patient-centered approach to grading evidence in the medical literature. J Am Board Fam Pract. 2004;17(1):59–67.

Shea BJ, Hamel C, Wells GA, et al. AMSTAR is a reliable and valid measurement tool to assess the methodological quality of systematic reviews. J Clin Epidemiol. 2009;62(10):1013–20.

Cole MP, Jones CT, Todd ID. A new anti-oestrogenic agent in late breast cancer. An early clinical appraisal of ICI46474. Br J Cancer. 1971;25(2):270–5.

Ballentine C. Sulfanilamide disaster. In: Administration USFaD, ed. FDA Consumer Magazine, 1981.

Google Scholar  

Moses H, Matheson DH, Cairns-Smith S, George BP, Palisch C, Dorsey ER. The anatomy of medical research: US and international comparisons. JAMA. 2015;313(2):174–89.

Campbell MJ. Medical statistics. Chester: Wiley; 1990. p. 393.

Greenfield ML, Kuhn JE, Wojtys EM. A statistics primer: descriptive measures for continuous data. Am J Sports Med. 1997;25(5):720–3.

Kuhn JE, Greenfield ML, Wojtys EM. A statistics primer. Prevalence, incidence, relative risks, and odds ratios: some epidemiologic concepts in the sports medicine literature. Am J Sports Med. 1997;25(3):414–6.

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Puzzitiello, R.N., Agarwalla, A., Forsythe, B., Leong, N.L. (2019). Principles of Clinical Research. In: Makhni, E., Makhni, M., Swart, E., Bush-Joseph, C. (eds) Orthopedic Practice Management. Springer, Cham. https://doi.org/10.1007/978-3-319-96938-1_15

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How to … define clinical education research terminology: A glossary

Affiliations.

  • 1 Division of Medical Education, University of Manchester, Manchester, UK.
  • 2 Ophthalmology Department, Sunderland Eye Infirmary, South Tyneside and Sunderland NHS Foundation Trust, Sunderland, UK.
  • 3 School of Medical Education, Newcastle University, Newcastle upon Tyne, UK.
  • 4 Division of Surgery and Interventional Science, University College London, London, UK.
  • 5 Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK.
  • 6 CAMERa, Peninsula Medical School, University of Plymouth, Plymouth, UK.
  • 7 Medical Education Innovation and Research Centre, Imperial College London, London, UK.
  • PMID: 37503773
  • DOI: 10.1111/tct.13605

Clinical education research (ClinEdR) utilises diverse terminology, which can lead to confusion. A common language is essential for enhancing impact. An expert panel drawn from various workstreams within the National Institute for Health and Care Research (NIHR) Incubator for Clinical Education Research was tasked with reviewing an initial list of terms for the development of a glossary of terms in the field of ClinEdR. The glossary was populated with terms, definitions and foundational papers by the authors and peer-reviewed for accuracy. The glossary of terms developed for ClinEdR should enable researchers to use a common language, promoting consistency and improving communication. We anticipate this will be useful for ClinEdR students and early career researchers. The glossary could be integrated into educational research methods courses in ClinEdR, and through critical and reflective use, enhance the quality and subsequent impact of ClinEdR.

© 2023 The Authors. The Clinical Teacher published by Association for the Study of Medical Education and John Wiley & Sons Ltd.

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Su ZT , Hammadeh Z , Cheaib JG , Jing Y , Trock BJ , Han M. Trends in Industry-Sponsored Research Payments to Physician Principal Investigators. JAMA Netw Open. 2024;7(5):e2412432. doi:10.1001/jamanetworkopen.2024.12432

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Trends in Industry-Sponsored Research Payments to Physician Principal Investigators

  • 1 James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland

After passage of the Physician Payments Sunshine Act (PPSA), the Open Payments program (OPP) was launched in 2013 to increase transparency of physician-industry financial relationships. 1 Because research payments constitute the largest payment category in the OPP, 2 , 3 we characterized trends in industry-sponsored research payments (ISRPs).

This cohort study follows the Strengthening the Reporting of Observational Studies in Epidemiology ( STROBE ) reporting guideline. We used OPP data 4 to identify ISRPs inflation-adjusted to 2022 US $ values during 2015 to 2022. In the OPP, covered recipients include teaching hospitals, physicians, and advanced practice practitioners not employed by applicable organizations reporting payments. Noncovered entities (NCEs) are organizations that do not meet the OPP definition of covered recipients. ISRPs to NCEs are reportable if a covered physician is a principal investigator (PI). 4 We analyzed ISPRs to NCEs with physician PIs because these constituted most ISRPs by value (>70%). Where multiple (up to 5 could be listed per ISRP) PIs were listed for an ISRP, we attributed the full amount of that ISRP to the primary PI given a lack of disclosure requirements about fund allocations within an ISRP. This attribution avoided double counting of the same ISRP. We tested trends in total values using linear regression and trends in per-physician ISRPs using generalized linear models with a γ distribution to account for physician effects, with a 2-sided α < .05 applied. We used Stata statistical software version 18.0 (StataCorp).

Overall, ISRPs increased 20.0%, from $6.32 billion in 2015 to $7.58 billion in 2022 ( P  = .01). ISRPs to NCEs increased 19.1%, from $4.98 billion in 2015 to $5.93 billion in 2022 ( P  = .06), and the trend was not statistically significant; the total in 2022 accounted for 47.1% of all Open Payments ($12.58 billion) that year. In contrast, ISRPs paid directly to covered physicians decreased 61.7%, from $179.5 million to $68.8 million ( P  < .001) ( Table 1 ).

ISRPs to NCEs with a physician PI increased 23.0%, from $4.52 billion in 2015 to $5.55 billion in 2022 ( P  = .03), accounting for 44.1% of all Open Payments. General internists had the highest annual median ISRPs per PI ( Table 2 ). In 2022, ISRPs were made to NCEs with 21 518 physicians as primary PIs, accounting for 2.0% of US physicians. The maximum ISRP received by an NCE with a physician PI was $89.5 million.

This cohort study found that between 2015 and 2022, ISRPs increased by 20.0% to reach $7.58 billion by 2022. In comparison, National Institutes of Health research grants increased by 24% over this period, to $31.3 billion by 2022. 5 Most ISRPs were directed to NCEs rather than teaching hospitals or physicians. While direct ISRPs to physicians steadily declined over time, ISRPs to NCEs with physician PIs increased to $5.55 billion by 2022, accounting for almost half of all Open Payments. General internists had the highest ISRPs per PI, potentially reflecting their access to patients with chronic diseases of interest for industry-sponsored pharmaceutical research.

Reporting rules in the PPSA specify that only the research entity, affiliated physician PIs, and total amount of the research payment are mandated for disclosure. 6 Consequently, the industry is not obligated to divulge specific research payment amounts allocated to individual physicians within NCEs vs payments for direct research expenses. It becomes imperative to disclose ISRPs to individual physicians in NCEs to promote transparency and accountability within the health care system, as intended by the PPSA.

Our study has several limitations, including potential data reporting errors to the OPP, attribution of an ISRP exclusively to the primary PI, and unmeasured confounding. Despite these limitations, our study reveals a substantial increase in ISRPs to NCEs, comprising nearly half of overall Open Payments. Further research is needed to investigate factors associated with these payments to NCEs and their association with regulatory oversight and financial conflicts of interest.

Accepted for Publication: March 20, 2024.

Published: May 16, 2024. doi:10.1001/jamanetworkopen.2024.12432

Open Access: This is an open access article distributed under the terms of the CC-BY License . © 2024 Su ZT et al. JAMA Network Open .

Corresponding Author: Misop Han, MD, MS, James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, 600 N Wolfe St, Marburg 146, Baltimore, MD 21287 ( [email protected] ).

Author Contributions: Dr Hammadeh and Mr Jing had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Su, Hammadeh, Han.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Su, Hammadeh, Cheaib, Han.

Critical review of the manuscript for important intellectual content: All authors.

Statistical analysis: Su, Hammadeh, Jing, Trock.

Obtained funding: Han.

Administrative, technical, or material support: Hammadeh, Han.

Supervision: Trock, Han.

Conflict of Interest Disclosures: None reported.

Funding/Support: This study was supported by the Boucher Family Foundation.

Role of the Funder/Sponsor: The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Data Sharing Statement: See Supplement 2 .

Additional Contributions: We would like to thank Gerard Anderson, PhD (Johns Hopkins Bloomberg School of Public Health), for his careful review of and suggestions for the manuscript. We have obtained permission to include the name of the individual in the acknowledgment section of the manuscript. Dr Anderson was not compensated for this contribution.

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To avoid the pitfalls that inconsistent use of terms can lead to, NIH and FDA developed a glossary of terms related to clinical research that could be used to assist the research community in effectively communicating about clinical trials. NIH and FDA are most interested in hearing community feedback on the utility of the glossary in its goal of promoting effective communications. Comments will be accepted until June 24, 2024.

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    Basic research Basic research aims to improve knowledge and understanding, rather than finding a solution to a practical problem. It usually involves work in a laboratory - for example to find a gene linked to a disease or to understand how cancer cells grow. This kind of research can sometimes provide clues

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    The assignment of a group or subgroup of participants in a clinical trial to receive interventions, or no interventions, as specified in the study protocol. Assessment. A procedure (e.g. a blood test, scan, etc.) used to generate data required by the trial. Background therapy.

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    Welcome to the SOM Clinical Research Glossary Quickly look up the meaning of words, acronyms, or abbreviations commonly used in clinical research: Narrow your search by typing the word you are looking for in the search box. Clear the search box to start a new search. Use the alphabet bar for quick filtering of words […]

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    A case series in which the patients receive treatment in a clinic or other medical facility. (NCI) Clinical study or Clinical trial. A type of research study that tests how well new medical approaches work in people. These studies test new methods of screening, prevention, diagnosis, or treatment of a disease.

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    Probably, most people are familiar with basic (laboratory) research, clinical research, healthcare (services) research, health systems (policy) research, and educational research. Clinical research in this review refers to scientific research related to clinical practices. ... Other terms that are used for reliability include reproducibility ...

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    Clinical research is the comprehensive study of the safety and effectiveness of the most promising advances in patient care. Clinical research is different than laboratory research. It involves people who volunteer to help us better understand medicine and health. Lab research generally does not involve people — although it helps us learn ...

  16. Clinical Trials and Clinical Research: A Comprehensive Review

    Clinical research is an alternative terminology used to describe medical research. Clinical research involves people, and it is generally carried out to evaluate the efficacy of a therapeutic drug, a medical/surgical procedure, or a device as a part of treatment and patient management. ... True experiments have three basic elements that include ...

  17. Research Types Explained: Basic, Clinical, Translational

    Basic medical research is usually conducted by scientists with a PhD in such fields as biology and chemistry, among many others. They study the core building blocks of life — DNA, cells, proteins, molecules, etc. — to answer fundamental questions about their structures and how they work. For example, oncologists now know that mutations in ...

  18. Glossary

    A series of ethical principles concerning medical research involving human beings, first published by the World Medical Association in 1964 in Helsinki, Finland. These principles include processes that need to be followed to make sure patients are safe taking part in clinical trials.

  19. The Research Glossary

    The free online glossary for key terms and concepts used in clinical research. ... Identifies the basic principles of research conduct and oversees human experimentation in medicine. Vendor. Third party companies to help with services and ancillary procedures of the clinical trial. Some examples may be payment services, central readers for ...

  20. Principles of Clinical Research

    Outcomes are then measured in terms of absolute risk reduction (ARR), relative risk reduction (RRR), and the number needed to treat (NNT) ... The interdependence of basic science research and clinical research (Fig. 15.4) has led to improved clinical outcomes in a myriad of diseases. For example, in the 1970s, basic science studies showed that ...

  21. PDF A Glossary of Research Terminology

    A Glossary of Research Terminology Find Create Share Use Research knowledge . ... In clinical research this might span four ... 909-11): • the translation of basic research into a clinical application. • efficacy studies where new interventions are trialled. • effectiveness studies, where phase 2 interventions are trialled in real

  22. How to … define clinical education research terminology: A glossary

    The development of this glossary was a fundamental activity of the Incubator for ClinEdR, a National Institute for Health Research (NIHR) initiative in the United Kingdom to develop ClinEdR as an academic field and enhance the impact of the work done within the field. 1 The Incubator has a critical mass of researchers who work in the field of ...

  23. Introduction to Good Clinical Practice

    During this course, you will explore the essential elements of Good Clinical Practice and gain insights into its significance in the global clinical research arena. By the end of the course, you will have a solid understanding of the principles of GCP and its role in ensuring the integrity and reliability of clinical trial data.

  24. How to … define clinical education research terminology: A glossary

    Abstract. Clinical education research (ClinEdR) utilises diverse terminology, which can lead to confusion. A common language is essential for enhancing impact. An expert panel drawn from various workstreams within the National Institute for Health and Care Research (NIHR) Incubator for Clinical Education Research was tasked with reviewing an ...

  25. Trends in Industry-Sponsored Research Payments to Physician Principal

    This cohort study investigates trends in total and per-physician industry-sponsored research payments to physician principal investigators from 2015 to ... Clinical Implications of Basic Neuroscience; Clinical Pharmacy and Pharmacology; Complementary and Alternative Medicine ... This is an open access article distributed under the terms of the ...

  26. May 2024

    To avoid the pitfalls that inconsistent use of terms can lead to, NIH and FDA developed a glossary of terms related to clinical research that could be used to assist the research community in effectively communicating about clinical trials. NIH and FDA are most interested in hearing community feedback on the utility of the glossary in its goal ...