An Adverse Event is unfavorable change in the health of a participant, including abnormal laboratory findings, that happens during a clinical study or within a certain time period after the study is over. This may or may not be caused by the intervention being studied.
In the U.S., the Food and Drug Administration (FDA) must approve a substance as a drug before it can be marketed. The approval process involves several steps including pre-clinical laboratory and animal studies, clinical trials for safety and efficacy, filing of a New Drug Application by the manufacturer of the drug, FDA review of the application, and FDA approval/rejection of application.
In regards to research, the term Arm signifies a group or subgroup of participants in a clinical trial who receives specific interventions, or no intervention, according to the study protocol. This is decided before the trial begins. Most randomized trials have two arms, but some have three arms, or even more.
Assent is the term for a child’s affirmative agreement to participate in a clinical investigation. Mere failure to object may not, absent affirmative agreement, be construed as assent.
Blinding or Masking is the process through which one or more parties to a clinical trial are unaware of the treatment assignments. Blinded studies are conducted to prevent the unintentional biases that can affect subject data when treatment assignments are known. Types of Blinding or masking include Single blind, Double blind, None/Open label.
- Single blind - A type of masking in which one party involved with the clinical trial, either the investigator or participant, does not know which participants have been assigned which interventions.
- Double blind - A type of masking in which two or more parties involved with the clinical trial do not know which participants have been assigned which interventions. Typically, this includes the investigator and participant.
- None/Open Label - Describes a clinical trial in which masking is not used. That means that all parties involved with the trial know which participants have been assigned which interventions.
Cardiology/Vascular Diseases are diseases having to do with the structure and function of the heart and blood vessels. Studies in these areas include: heart failure, coronary artery disease, high cholesterol, blood clots, circulation disorders, and others.
Clinical research is medical research that involves people to test new treatments and therapies.
A Clinical Study is research study using human subjects to evaluate the effect of interventions or exposures on biomedical or health-related outcomes. Two types of clinical studies are interventional studies (or clinical trials) and observational studies.
A Control Group is a comparison group of study subjects who are not treated with the investigational agent. The subjects in this group may receive no therapy, a different therapy, or a placebo.
Drug Safety and Monitoring Board (DSMB)
An independent committee, composed of community representatives and clinical research experts, that reviews data while a clinical trial is in progress to ensure that participants are not exposed to undue risk. A DSMB may recommend that a trial be stopped if there are safety concerns or if the trial objectives have been achieved.
The term effective dose is a product's ability to produce beneficial effects on the duration or course of a disease. Efficacy is measured by evaluating the clinical and statistical results of clinical tests.
Eligibility Criteria are the key standards that people who want to participate in a clinical study must meet or the characteristics that they must have. These include inclusion criteria and exclusion criteria. For example, a study might only accept participants who are above or below certain ages. Inclusion criteria are the factors (or reasons) that allow a person to participate in a clinical study. Exclusion criteria are the factors (or reasons) that prevent a person from participating in a clinical study.
The acronym FDA stands for the Food and Drug Administration. The FDA is an agency within the U.S. Department of Health and Human Services. FDA is responsible for protecting the public health by making sure that human and veterinary drugs, vaccines and other biological products, medical devices, the nation's food supply, cosmetics, dietary supplements, and products that give off radiation are safe, effective, and secure
Human Subjects Review Board
A Human Subjects Review Board is a group of people who review, approve, and monitor the clinical study protocol. Their role is to protect the rights and welfare of human research subjects participating in a study. The group typically includes people with varying backgrounds, including a community member, to make sure that research activities conducted by an organization are completely and adequately reviewed. Also known as an institutional review board (IRB) or ethics committee.
IRB (Institutional Review Board)
An Institutional Review Board (IRB) is 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 and effective for human participation. It is also the IRB's responsibility to ensure that the study adheres to the FDA's regulations.
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 explains risks and potential benefits about a clinical trial before someone decides whether to participate. It is a process in which researchers communicate with potential and enrolled participants about a clinical study. This is when researchers:
- provide all the important information about the study, so that potential participants can decide whether to enroll (or if enrolled, to continue participating);
- ensure that potential participants understand the risks and potential benefits of participating in the study, and the alternatives to the research being conducted; and
- stress that enrolling in (and staying in) a clinical study is completely voluntary. Because giving consent to participate in research is not a contract, participants can leave a study at any time.
The goal of the informed consent process is to protect participants. It begins when a potential participant first asks for information about a study and continues throughout the study until the study ends. The researcher and potential participant have discussions that include answering the participant's questions about the research. All the important information about the study must also be given to the potential participant in a written document that is clear and easy to understand. This informed consent document is reviewed and approved by the human subjects review board for a study before it is given to potential participants. Generally, a person must sign an informed consent document to enroll in a study.
An intervention is a process or action that is the focus of a clinical study. This can include giving participants drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches such as surveys, education, and interviews. An intervention type is the general category for the intervention being studied. Intervention types include Drug, Device, Biological, and Procedure.
An Interventional Study is a clinical study in which participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. The assignments are determined by the study protocol. Participants may receive diagnostic, therapeutic, or other types of interventions.
An Investigational drug is a drug, or biological product that is used in a clinical trial but has not been approved by the FDA (the drug is either not available for a doctor to prescribe or, is available, but not approved by the FDA for the use being studied).
Investigational Medical Device
An investigational medical device is on that is the subject of a clinical study designed to evaluate the effectiveness and/or safety of the device.
Investigational Medical Device Classifications
Investigational medical devices have two possible classifications, a) significant risk (SR) and b) non-significant risk (NSR).
a) A SR device poses a potential for serious risk to the health, safety, or welfare or a subject. Such devices may only be studied under an Investigational Device Exemption (IDE) granted by the Federal Drug Administration. A device is SR (and requires an IDE) if it:
- Is intended as an implant, or
- Is purported to represented to be for a use in supporting or sustaining human life, or
- Is for a use of substantial importance in diagnosing, curing, mitigating, or treating disease, or otherwise preventing impairment to human health; or
- Otherwise presents a potential for serious risk to the health, safety, or welfare of a subject.
b) A NSR devise does not meet the above definition. The assessment of whether or not a device study represents a NSR is initially made by the sponsor/investigator. The IRB will then determine if the NSR designation is appropriate. If the IRB disagrees with the NSR claim, it will require the sponsor/investigator to submit an IDE application to the FDA.
A medical device is any health care product that does not achieve its primary intended purposes by chemical action or being metabolized. Medical devices can include:
- Surgical laser
- Vascular stents or balloons
- Interocular lenses
- Orthopedic pins
An Observational Study is a clinical study in which participants identified as belonging to study groups are assessed for biomedical or health outcomes. Participants may receive diagnostic, therapeutic, or other types of interventions, but the investigator does not assign participants to specific interventions (as in an interventional study).
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.
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. A principal investigator is responsible for the overall conduct of the clinical trial at his/her site.
Randomization is the process by which two or more alternative treatments are assigned to volunteers by chance rather than by choice.
A Serious Adverse Event is a adverse event that results in death, is life-threatening, requires inpatient hospitalization or extends a current hospital stay, results in an ongoing or significant incapacity or interferes substantially with normal life functions, or causes a congenital anomaly or birth defect. Medical events that do not result in death, are not life-threatening, or do not require hospitalization may be considered serious adverse events if they put the participant in danger or require medical or surgical intervention to prevent one of the results listed above
A side effect is 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.
The organization or person who oversees the clinical study and is responsible for analyzing the study data. A sponsor-investigator is the person who both initiates and conducts the clinical study. Sponsors can be government agencies such as the National Institutes of Health (NIH), pharmaceutical companies, individual doctors, health care centers, and organizations that develop medical devices or equipment.
Standard of Care Treatment
Standard of care treatment refers to the currently accepted treatment or intervention considered to be effective in the treatment of a specific disease or condition.
- Diagnostic trials determine better tests or procedures for diagnosing a particular disease or condition. Diagnostic trials usually include people who have signs or symptoms of the disease or condition being studied.
- 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.