What is a Clinical Trial?
Adverse Event (AE)
An AE is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product; an AE does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.
Any of the treatment groups in a randomized trial. Most r.andomized trials have two "arms," but some have three "arms," or more.
A systematic and independent examination of trial-related activities and documents to determine whether the evaluated trial-related activities were conducted, and the data were recorded, analyzed, and reported according to the protocol, sponsor’s standard operating procedures (SOPs), good clinical practice (GCP), and the applicable regulatory requirement(s).
A secure, computer generated, time-stamped electronic record that allows reconstruction of the course of events relating to the creation, modification, and deletion of an electronic record. An audit trail can also exist as a written record.
1. Information gathered at the beginning of a study from which variations found in the study are measured. 2. A known value or quantity with which an unknown is compared when measured or assessed. 3. The initial time point in a clinical trial, just before a participant starts to receive the experimental treatment which is being tested. Safety and efficacy of a drug are often determined by monitoring changes from the baseline values.
Bias occurs when a point of view prevents impartial judgment on issues relating to the subject of that point of view. In clinical studies, bias is controlled by blinding and randomization.
A randomized trial is "blinded" if the participant is not told which arm of the trial he is on. This is also called masked.
A procedure in which one or more parties involved with the trial are kept unaware of the treatment assignment(s). Single blinding usually indicates that knowledge of treatment assignments is withheld from the study subject(s). Double or triple blinding indicates that knowledge of treatment assignments is withheld from study subject(s), investigator(s), monitor, and, in some cases, data analyst(s).
Case Report Form (CRF)
A printed, optical, or electronic document designed to record all of the protocol-required information to be reported to the sponsor on each trial subject.
Pertaining to or founded on observation and treatment of participants, as distinguished from theoretical or basic science.
A clinical researcher in charge of carrying out the protocol of a clinical trial.
Study of a drug, biologic, or device in human subjects.
A clinical trial is a research study to answer specific questions about new therapies or new ways of using known treatments. Clinical trials (also called medical research and research studies) are used to determine whether new drugs or treatments are safe and effective. Carefully conducted clinical trials are the fastest and safest way to find treatments that work in people. Trials are conducted in four phases: Phase I tests a new drug or treatment in a small group of participants; Phase II expands the study to a larger group; Phase III expands the study to an even larger group of people; and Phase IV takes place after the drug or treatment has been licensed and marketed.
Any investigation in human subjects intended to discover or verify the clinical, pharmacological and/or other pharmaco-dynamic effects of an investigational product(s). In addition these studies are used to identify any adverse reactions to an investigational product(s), and/or to study absorption, distribution, metabolism, and excretion of an investigational product(s) with the goal of ascertaining safety and/or efficacy of the product.
Clinical Trial/Study Report
A written description of a trial/study of any therapeutic, prophylactic, or diagnostic agent conducted in human subjects, in which the clinical and statistical description, presentations, and analyses are fully integrated into a single report.
Any member of the clinical trial team designated and supervised by the investigator at a trial site to perform critical trial-related procedures and/or to make important trial-related decisions (e.g., associates, residents, research fellows).
In epidemiology, a group of individuals who have specific characteristics in common.
Compliance (in relation to trials)
Adherence to all the trial-related requirements, good clinical practice (GCP) requirements, and the applicable regulatory requirements.
Prevention of disclosure, to other than authorized individuals, of a sponsor’s proprietary information or of a subject’s identity.
Confidentiality Regarding Trial Participants
This topic refers to maintenance of the confidentiality of trial participants including their personal identity and all personal medical information. The trial participants' consent to the use of records for data verification purposes should be obtained prior to the trial. Assurance that confidentiality will be maintained must be given to the study participant.
A written, dated, and signed agreement between two or more involved parties that sets out any arrangements on delegation and distribution of tasks and obligations and, if appropriate, on financial matters. The protocol may serve as the basis of a contract.
Contract Research Organization (CRO)
A person or an organization (commercial, academic, or other) contracted by the sponsor to perform one or more of a sponsor’s trial-related duties and functions.
In many clinical trials, one group of patients will be given an experimental drug or treatment, while the control group is given either a standard treatment for the illness/condition or a placebo, with the purpose of comparing the two groups. This is the standard by which experimental observations are evaluated.
A controlled trial is one in which there is at least one experimental group and one control group.
Data Safety and Monitoring Board (DSMB)
The DSMB is an independent committee composed of community representatives and clinical research experts that reviews data while a clinical trial is in progress. This board ensures that participants are not exposed to undue risk. A DSMB may recommend that a trial be discontinued if there are safety concerns or if the trial objectives have been achieved.
Diagnostic trials are conducted to find better tests or procedures for diagnosing a particular disease or condition. These trials usually include participants who have signs or symptoms of the disease or condition being studied.
Permission to examine, analyze, verify, and reproduce any records and reports that are important to evaluation of a clinical trial is termed direct access. Any party (e.g., domestic and foreign regulatory authorities, sponsors, monitors, and auditors) with direct access should take all reasonable precautions within the constraints of the applicable regulatory requirement(s) to maintain the confidentiality of subjects’ identities and sponsor’s proprietary information.
Direct entry refers to recording data where an electronic record is utilized in the original capture of the data. Examples are the keying by an individual of original observations into the system, or automatic recording by the system of the output of a balance that measures subject’s body weight etc. In these cases, the electronic document is the source document.
The process of killing most pathogenic organisms or rendering them inert is termed disinfection.
All records, in any form (including, but not limited to, written, electronic, magnetic, and optical records; and scans, x-rays, and electrocardiograms) that describe or record the methods, conduct, and/or results of a trial, the factors affecting a trial, and the actions taken.
A clinical trial in which two or more doses of an agent (such as a drug) are tested against each other to determine which dose works best and is least harmful.
A clinical trial design in which neither the participating individuals nor the study staff know which participants are receiving the experimental drug and which are receiving a placebo (or another therapy). Double-blind trials are thought to produce objective results because the expectations of the doctor and the participant about the experimental drug do not affect the outcome; also called double-masked study.
A modification of the effect of a drug when administered with another drug is termed drug-drug interaction. The effect may be an increase or a decrease in the action of either substance, or it may be an adverse effect that is not normally associated with either drug.
Efficacy of a drug or treatment refers to the maximum ability of a drug or treatment to produce a result regardless of dosage. A drug passes efficacy trials if it is effective at the dose tested and against the illness for which it is prescribed. In the procedure mandated by the FDA, Phase II clinical trials gauge efficacy and Phase III trials confirm it.
Electronic Case Report Form (e-CRF)
An auditable electronic record designed to record information required by the clinical trial protocol to be reported to the sponsor on each trial subject.
Electronic Patient Diary
An electronic record into which a clinical study participant directly enters observations or directly responds to an evaluation checklist.
Any combination of text, graphics, data, audio, pictorial, or other information representation in digital form that is created, modified, maintained, archived, retrieved, or distributed by a computer system.
These guidelines summarize the characteristics that participants must possess to take part in a clinical study or trial; these include inclusion and exclusion criteria.
Overall outcome that the protocol is designed to evaluate.
Documents that individually and collectively permit evaluation of the conduct of a study and the quality of the data produced.
A drug that is not FDA licensed for use in humans, or as a treatment for a specific condition.
Food and Drug Administration (FDA)
The U.S. Department of Health and Human Services agency responsible for ensuring the safety and effectiveness of all drugs, biologics, vaccines, and medical devices, including those used in the diagnosis, treatment, and prevention of HIV infection, AIDS, and AIDS-related opportunistic infections. The FDA also works with the blood banking industry to safeguard the nation's blood supply.
Internet address: https://www.fda.gov
Guidelines of Good Clinical Practice
These guidelines represent quality standards (ethical and scientific) for conducting clinical trials under FDA regulations.
Internet address: https://www.fda.gov/oc/gcp/guidance.html
A testable, proposed explanation advanced as a basis to guide experimental investigation.
The International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use.
Internet address: https://www.ich.org
The medical or social standards used to determine whether a person may or may not be allowed to participate in a specific clinical trial. These criteria are based on such factors as age, gender, type and stage of a disease, previous treatment history, and other medical conditions. It is important to note that inclusion and exclusion criteria are not used to reject people personally, but rather to identify appropriate participants and keep them safe.
Informed Consent Process
The process of learning about all of the pertinent facts about a specific clinical trial before deciding whether or not to participate. Informed consent may include provision of information to study participants throughout the duration of the study. To help someone decide whether or not to participate, the doctors and nurses involved in the trial explain the details of the study. Once a participant has understood all pertinent elements of a trial and agrees to participate, the participant is said to have given "informed consent".
Informed Consent Document
A document that describes the rights of the study participants, and includes details about the study including: purpose, duration, required procedures, and key contacts. Risks and potential benefits are explained in the informed consent document. The participant then decides whether or not to sign the document. Informed consent is not a contract; the participant may withdraw from the trial at any time.
The act by a regulatory authority(ies) of conducting an official review of documents, facilities, records, and any other resources that are deemed by the authority(ies) to be related to the clinical trial and that may be located at the site of the trial, at the facilities of the sponsor and/or contract research organization (CRO), or at other establishments deemed appropriate by the regulatory authority(ies).
Institutional Review Board (IRB)
A committee of physicians, statisticians, researchers, community advocates, and others that ensures that a clinical trial is ethical and that the rights of study participants are protected. All clinical trials in the U.S. must be approved by an IRB before they begin. Every institution that conducts or supports biomedical or behavioral research involving human participants must, by federal regulation, have an IRB that initially approves and periodically reviews the research in order to protect the rights of human participants.
The generic name of the specific intervention being studied.
A process or action that is the main focus of the clinical study. This can include the use of a drug, gene transfer, vaccine, device, or procedure. It can also include less-invasive activities such as the use of a survey, education, or behavioral therapy.
Investigational New Drug
A new drug, antibiotic drug, or biological drug that is used in a clinical investigation. It also includes a biological product used in vitro for diagnostic purposes.
Refers to any drug (including a biological product for human use), medical device for human use, human food additive, color additive, electronic product, or any other article subject to regulation. This includes a pharmaceutical form of an active ingredient or placebo being tested or used as a reference in a clinical trial, including a product with a marketing authorization when used or assembled (formulated or packaged) in a way different from the approved form, or when used for an unapproved indication, or when used to gain further information about an approved use.
A person responsible for the conduct of the clinical trial at a trial site. If a trial is conducted by a team of individuals at a trial site, the investigator is the responsible leader of the team and may be called the principal investigator.
Investigator's Brochure (IB)
A compilation of the clinical and nonclinical data on the investigational product(s) that is relevant to the study of the investigational product(s) in human subjects.
The act of overseeing the progress of a clinical trial, and of ensuring that it is conducted, recorded, and reported in accordance with the protocol, standard operating procedures (SOPs), GCP, and the applicable regulatory requirement(s).
New Drug Application (NDA)
An application submitted by the manufacturer of a drug to the FDA - after clinical trials have been completed - for a license to market the drug for a specified indication.
A drug prescribed for conditions other than those approved by the FDA.
A clinical trial in which doctors and participants know which drug or vaccine is being administered.
An FDA category that refers to medications used to treat diseases and conditions that occur rarely. There is little financial incentive for the pharmaceutical industry to develop medications for these diseases or conditions. Orphan drug status, however, gives a manufacturer specific development incentives (through the Orphan Drug Act) to develop and provide such medications.
Review of a clinical trial by experts chosen by the study sponsor. These experts review the trial for scientific merit, participant safety, and ethical considerations.
The processes (in a living organism) of absorption, distribution, metabolism, and excretion of a drug.
A clinical study to test a new biomedical intervention in a small group of people (e.g. 20-80) for the first time to evaluate safety and to determine a safe dosage range and identify side effects.
Phase II includes the early controlled clinical studies conducted to obtain some preliminary data on the effectiveness of the drug for a specific indication or indications in patients with the disease or condition. This phase of testing also helps determine the common short-term side effects and risks associated with the drug. Phase II studies are typically well-controlled, closely monitored, and conducted in a relatively small number of patients, usually involving several hundred people.
Phase III studies are expanded controlled and uncontrolled trials. They are performed after preliminary evidence for effectiveness of the drug has been obtained in Phase II, and are intended to gather the additional information about effectiveness and safety that is needed to evaluate the overall benefit-risk relationship of the drug. Phase III studies also provide an adequate basis for extrapolating the results to the general population and transmitting that information in the physician labeling. Phase III studies usually include several hundred to several thousand people.
Post-marketing studies to gather additional information about the drug's risks, benefits, and optimal use. Phase IV studies usually include several hundred to several thousand people.
A placebo is an inactive pill, liquid, or powder that has no treatment value. In clinical trials, experimental treatments are often compared with placebos to assess the treatment's effectiveness.
Placebo Controlled Study
A method of investigation of drugs in which an inactive substance (the placebo) is given to one group of participants, while the drug being tested is given to another group. The results obtained in the two groups are then compared to see if the investigational treatment is more effective than the placebo in treating the condition.
A physical or emotional change, occurring after a substance is taken or administered, that is not the result of any special property of the substance. The change may be beneficial, reflecting the expectations of the participant and, often, the expectations of the person giving the substance.
Refers to the testing of experimental drugs in the test tube or in animals. This testing is undertaken before trials in humans may be carried out.
This FDA regulation requires submission to and/or inspection by the FDA, of certain data and information relevant to FDA-regulated investigational and/or marketed products. Examples include clinical trial data to support a New Drug Application or device Premarket Approval application.
Refers to trials that seek to find better ways to prevent disease in people who have never had the disease or to prevent a disease from returning. These approaches may include medicines, vitamins, vaccines, minerals, or lifestyle changes.
A document that describes the objective(s), design, methodology, statistical considerations, and organization of a trial. The protocol usually also gives the background and rationale for the trial, but these could be provided in other protocol referenced documents.
A written description of a change(s) to or formal clarification of a protocol.
Quality Assurance (QA)
All planned and systematic actions that are established to ensure that the trial is performed and that data are generated, documented (recorded), and reported in compliance with GCP and the applicable regulatory requirement(s).
Quality of Life Trials (or Supportive Care trials)
Refers to trials that explore ways to improve comfort and quality of life for people with a chronic illness.
The process of assigning trial subjects to treatment or control groups using an element of chance to determine the assignments in order to reduce bias.
A study in which participants are randomly (i.e., by chance) assigned to one of two or more treatment arms of a clinical trial. Occasionally placebos are utilized.
The risk to individual participants versus the potential benefits. The risk/benefit ratio may differ depending on the condition being treated and the medication/device being tested.
Refers to trials which test the best way to detect certain diseases or health conditions.
Any undesired actions or effects of a drug or treatment. Negative or adverse effects may include headache, nausea, hair loss, skin irritation, or other physical problems. Experimental drugs must be evaluated for both immediate and long-term side effects.
All information in original records and certified copies of original records of clinical findings, observations, or other activities in a clinical trial necessary for the reconstruction and evaluation of the trial. Source data are contained in source documents (original records or certified copies).
Original documents, data, and records (e.g., hospital records, clinical and office charts, laboratory notes, memoranda, subjects’ diaries or evaluation checklists, pharmacy dispensing records, recorded data from automated instruments, copies or transcriptions certified after verification as being accurate and complete, microfiches, photographic negatives, microfilm or magnetic media, x-rays, subject files, and records kept at the pharmacy, at the laboratories, and at medico-technical departments involved in the clinical trial).
An individual, company, institution, or organization that takes responsibility for the initiation, management, and/or financing of a clinical trial.
Standard Operating Procedures (SOPs)
Detailed, written instructions to achieve uniformity in the performance of a specific function.
A treatment currently in wide use and approved by the FDA, considered to be effective in the treatment of a specific disease or condition.
Standards of Care
Treatment regimen or medical management based on widely accepted patient care standards.
The probability that an event or difference occurred by chance alone. In clinical trials, the level of statistical significance depends on the number of participants studied and the observations made, as well as the magnitude of differences observed.
A technique that eliminates or kills all forms of life including microorganisms, spores, and viruses using heat, chemicals, gases etc.
A primary or secondary outcome used to judge the effectiveness of a treatment.
An adverse effect produced by a drug that is detrimental to the participant's health. The level of toxicity associated with a drug will vary depending on the medical condition the drug is used to treat.
IND stands for Investigational New Drug application, which is part of the process to get approval from the FDA for marketing a new prescription drug in the U.S. It makes promising new drugs available to desperately ill participants as early in the drug development process as possible. Treatment INDs are made available to participants before general marketing begins, typically during Phase III studies. To be considered for a Treatment IND a participant cannot be eligible to be in the definitive clinical trial.
An individual who participates in a clinical trial, either as a recipient of the investigational product(s) or as a control.
Well-being (of the trial subjects)
The physical and mental integrity of the subjects participating in a clinical trial.