Applicable Clinical Trial
Applicable clinical trial is the term used in Title VIII of the Food and Drug Administration Amendments Act (FDAAA) of 2007 (P.L. 110-85) to designate the scope of clinical trials that may be subject to the registration and results reporting requirements in FDAAA.
Basic Experimental Studies with Humans
Studies that prospectively assign human participants to conditions (i.e., experimentally manipulate independent variables) and that assess biomedical or behavioral outcomes in humans for the purpose of understanding the fundamental aspects of phenomena without specific application towards processes or products in mind.
Research with human subjects that is:
1) Patient-oriented research. Research conducted with human subjects (or on material of human origin such as tissues, specimens, and cognitive phenomena) for which an investigator (or colleague) directly interacts with human subjects. Excluded from this definition are in vitro studies that utilize human tissues that cannot be linked to a living individual. It includes: (a) mechanisms of human disease, (b), therapeutic interventions, (c) clinical trials, or (d) development of new technologies.
2) Epidemiological and behavioral studies.
3) Outcomes research and health services research
Studies falling under 45 CFR 46.101(b) (4) (Exemption 4) are not considered clinical research by this definition.
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.
See Common Rule definition of research at 45 CFR 46.102(d)
See Common Rule definition of human subject at 45 CFR 46.102(f)
The term "prospectively assigned" refers to 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.
An intervention is defined as a manipulation of the subject or subject's environment for the purpose of modifying one or more health-related processes and/or endpoints. Examples include, but are not limited, to: drugs/small molecules/compounds, biologics, devices; procedures (e.g., surgical techniques); delivery systems (e.g., telemedicine, face-to-face); strategies to change health-related behavior (e.g., diet, cognitive therapy, exercise, development of new habits); and, treatment, prevention, and diagnostic strategies.
A health-related biomedical or behavioral outcome is defined as the pre-specified effect of an intervention on the study subjects. Examples include positive or negative changes to physiological or biological parameters (e.g., improvement of lung capacity, gene expression); psychological or neurodevelopmental parameters (e.g., mood management intervention for smokers; reading comprehension and/or information retention); disease processes; health-related behavior; and, well-being or quality of life
Biomedical clinical trials of an experimental drug, treatment, device, or behavioral intervention may proceed through four phases:
Phase I. Tests a new biomedical intervention in a small group of people (e.g. 20-80) for the first time to determine efficacy and evaluate safety (e.g., determine a safe dosage range and identify side effects).
Phase II. Study the biomedical or behavioral intervention in a larger group of people (several hundred) to determine efficacy and further evaluate safety.
Phase III. Study to determine efficacy of the biomedical or behavioral intervention in large groups of people (from several hundred to several thousand) by comparing the intervention to other standard or experimental interventions as well as to monitor adverse effects, and to collect information that will allow the interventions to be used safely.
Phase IV. Studies conducted after the intervention has been marketed. These studies are designed to monitor the effectiveness of the approved intervention in the general population and to collect information about any adverse effects associated with widespread use.
Clinical Trial Research Experience
The involvement of a student, postdoctorate, or early career faculty member in a clinical trial led by their mentor or other investigator, with the goal of obtaining clinical trial experience relevant to their research interests and career goals. A clinical trial research experience is one in which the participant is supervised by a more experienced investigator and is intended to prepare the participant to potentially lead an independent clinical trial in the future. The applicant can be part of the clinical trial team and can use the data generated during the clinical trial research experience in his/her proposed research project. NIH expects the mentor to assume overall responsibility of the trial including registering and reporting in clinicaltrials.gov and obtaining IRB approval.
Data and Safety Monitoring Board (DSMB)
A formal, independent board of experts including investigators and biostatisticians that advise study investigators regarding the safety progression of a study. In general, NIH requires the establishment of DSMBs for multi-site clinical trials involving interventions that entail potential risk to the participants and for all Phase III clinical trials. As necessary, a DSMB may be appropriate for Phase I and Phase II or other clinical trials if the studies are blinded (masked), employ high-risk interventions, or involve vulnerable populations.
Data and Safety Monitoring Plan
Prior to award, this plan must be approved by the applicant’s IRB and the NIH awarding IC prior to the accrual of human subjects. The reporting of Adverse Events must be reported to the IRB, the DSMB (if applicable) or other monitoring entity, the NIH funding Institute or Center, and other required entities. This policy requirement is in addition to any monitoring requirements imposed by 45 CFR part 46.
Research plans can be described at time of application, but research will not immediately begin (will occur later in the funding period)
Provides race and ethnicity data for the cumulative number of human subjects enrolled in an NIH-funded clinical research study since the protocol began. This data is provided in competing continuation applications and annual progress reports.
Hispanic or Latino: A person of Cuban, Mexican, Puerto Rican, South or Central American, or other Spanish culture or origin, regardless of race. The term, “Spanish origin,” can be used in addition to “Hispanic or Latino.”
Not Hispanic or Latino
In addition to OMB ethnic and racial categories, each ethnic/racial group contains subpopulations that are delimited by geographic origins, national origins, and/or cultural differences. It is recognized that there are different ways of defining and reporting racial and ethnic subpopulation data. The subpopulation to which an individual is assigned depends on self-reporting of specific origins and/or cultural heritage. Attention to subpopulations also applies to individuals who self-identify with more than one race. These ethnic/racial combinations may have biomedical, behavioral, and/or socio-cultural implications related to the scientific question under study.
An existing dataset may be constructed of different types of data including but not limited to survey data, demographic information, health information, genomic information, etc. Also included would be data to be derived from existing samples of cells, tissues, or other types of materials that may have been previously collected for a different purpose or research question but will now be used to answer a new research question. In general, these will be studies meeting the NIH definition for clinical research with a prospective plan to analyze existing data and/or derive data from an existing resource and where no ongoing or future contact with participants is anticipated.
Research studies in the early and conceptual stages of development. Exploratory studies may differ substantially from current thinking or practice and may not yet be supported by substantial preliminary data.
Health-Related Biomedical or Behavioral Outcome
As related to the definition of a clinical trial, the pre-specified goal(s) or condition(s) that reflect the effect of one or more interventions on human subjects' biomedical or behavioral status or quality of life. Examples include: positive or negative changes to physiological or biological parameters (e.g., improvement of lung capacity, gene expression); positive or negative changes to psychological or neurodevelopmental parameters (e.g., mood management intervention for smokers; reading comprehension and /or information retention); positive or negative changes to disease processes; positive or negative changes to health-related behaviors; and, positive or negative changes to quality of life.
A living individual about whom an investigator (whether professional or student) conducting research obtains data through intervention or interaction with the individual or obtains identifiable private information. Regulations governing the use of human subjects in research extend to use of human organs, tissues, and body fluids from identifiable individuals as human subjects and to graphic, written, or recorded information derived from such individuals. (See Public Policy Requirements and Objectives-Human Subjects Protections).
Human Subjects Assurance
A document filed by an institution conducting research on human subjects with the Office for Human Research Protections--HHS which formalizes its commitment to protect the human subjects prior to receiving any HHS grant funding.
Independent Clinical Trial
An independent clinical trial is one for which the researcher proposing the study has primary or lead responsibility for conducting and executing the trial. NIH policy permits individual career development awardees and individuals appointed to institutional career development awards to be involved in a range of clinical trial activities, including leading independent clinical trials. For NRSA trainees or fellows, however, NIH policy precludes leading an independent clinical trial as part of their training experience. Instead, NRSA trainees and fellows interested in clinical trials may gain clinical trial research experience by working on a trial led by their mentor or another investigator.
Person's voluntary agreement, based upon adequate knowledge and understanding, to participate in human subjects research or undergo a medical procedure.
In giving informed consent, people may not waive legal rights or release or appear to release an investigator or sponsor from liability for negligence. Go to 21 CFR 50.20 and 50.25
Institutional Review Board (IRB)
An administrative body established to protect the rights and welfare of human research subjects recruited to participate in research activities conducted under the auspices of the organization with which it is affiliated. The Institutional Review Board has the authority to approve, require modifications in, or disapprove all research activities that fall within its jurisdiction.
As related to the definition of a clinical trial, a manipulation of the subject or subject's environment for the purpose of modifying one or more health-related biomedical or behavioral processes and/or endpoints. Examples include: drugs/small molecules/compounds; biologics; devices; procedures (e.g., surgical techniques); delivery systems (e.g., telemedicine, face-to-face interviews); strategies to change health-related behavior (e.g., diet, cognitive therapy, exercise, development of new habits); treatment strategies; prevention strategies; and, diagnostic strategies.
Investigational New Drug (IND)
A new drug or biological drug that is used in a clinical investigation.
Investigational New Drug Application
Under regulation 21 CFR 312, application filed by a drug sponsor with FDA on Form FDA 1571 to conduct clinical trials, including detailed descriptions of all phases, protocols, IRB members, and investigators. Once clinical evaluation is completed, a new drug application must be submitted to FDA to obtain approval to market the drug.
IRB Reliance (Authorization) Agreement
A formal, written document that details an agreement for an institution engaged in nonexempt human subjects research to rely on the institutional review board (IRB) of another institution.
A mechanistic study is designed to understand a biological or behavioral process, the pathophysiology of a disease, or the mechanism of action of an intervention. A mechanistic study may be classified as a clinical trial if the study meets the NIH definition of a clinical trial.
NIH-Defined Phase III Clinical Trial
An NIH-defined Phase III clinical trial is a broadly based prospective Phase III clinical investigation, usually involving several hundred or more human subjects, for the purpose of evaluating an experimental intervention in comparison with a standard or controlled intervention or comparing two or more existing treatments. Often the aim of such investigation is to provide evidence leading to a scientific basis for consideration of a change in health policy or standard of care. The definition includes pharmacologic, non-pharmacologic, and behavioral interventions given for disease prevention, prophylaxis, diagnosis, or therapy. Community trials and other population-based intervention trials are also included.
Office for Human Research Protections (OHRP)
HHS office overseeing human subject protection for HHS-supported research. Go to OHRP.
Planned Enrollment Report
The Planned Enrollment Report is used when you are planning to conduct a study that meets the NIH definition for clinical research. It provides a breakdown of the planned sample by sex/gender, race, and ethnicity.
Prospective Basic Science Studies Involving Human Participants
As related to the definition of a clinical trial, 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 a clinical trial.
Formal description and design for a specific research project. A protocol involving human subject research must be reviewed and approved by an Institutional Review Board (IRB) if the research is not exempt, and by an IRB or other designated institutional process for exempt research.
American Indian or Alaska Native: A person having origins in any of the original peoples of North, Central, or South America, and who maintains tribal affiliation or community attachment.
Asian: A person having origins in any of the original peoples of the Far East, Southeast Asia, or the Indian subcontinent including, for example, Cambodia, China, India, Japan, Korea, Malaysia, Pakistan, the Philippine Islands, Thailand, and Vietnam. (Note: Individuals from the Philippine Islands have been recorded as Pacific Islanders in previous data collection strategies.)
Black or African American: A person having origins in any of the black racial groups of Africa. Terms such as “Haitian” or “Negro” can be used in addition to “Black or African American.”
Native Hawaiian or Other Pacific Islander: A person having origins in any of the original peoples of Hawaii, Guam, Samoa, or other Pacific Islands.
White: A person having origins in any of the original peoples of Europe, the Middle East, or North Africa.
Responsible party is the term used in Title VIII of the Food and Drug Administration Amendments Act (FDAAA) of 2007 (P.L. 110-85) to refer to the entity or individual who is responsible under FDAAA for registering a clinical trial and submitting clinical trial information to ClinicalTrials.gov.
A research protocol or set of experiments designed to investigate a scientific question.
The definition of a clinical study for the purposes of registering and reporting in ClinicalTrials.gov, can be found here.
A set of data elements about a research investigation involving human subjects that describes a proposed or on-going study, most commonly used in the context of the PHS Human Subjects and Clinical Trials Information form.
Note that for the purposes of initial application, NIH supports grouping studies that use the same human subjects population and same research protocols , the same research procedures, and the same human subjects population into a single study record, to the extent that the information provided is accurate and understandable to NIH staff and reviewers.