Adverse Event (AE) - An AE is any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during the study, having been absent at baseline, or if present at baseline, appears to worsen.
Approval (in relation to IRB/IEC) - The affirmative decision of the IRB that the clinical trial has been reviewed (i.e. protocol, informed consent(s), conflict of interests, etc.) and may be conducted at the institution site within the constraints set forth by the IRB, the institution, good clinical practice (GCP), and the applicable regulatory requirements.
Case Report Form (CRF) - A printed, optical, or electronic (known as an eCRF) document designed to record all of the protocol-required information to be captured as part of the study.
Clinical Coordinating Center (CCC) - A group organized to coordinate the clinical aspects of a multi-center trial. Most often, the CCC is headed by the Clinical Principal Investigator and is responsible for protocol development, clinical sites, and oversight of clinical study operations and facilities.
Clinical Research Coordinator (CRC) - Person who handles the administrative and day-to-day responsibilities of a clinical trial, acts as liaison for the clinical site, and reviews all data and records before a monitor's visit. On small studies, this may be the study investigator. In a multi-site study, the coordinator at the CCC oversees the clinical research coordinators at the clinical sites and is called the Project Coordinator.
Clinical trial - The NIH defines a clinical trial1 as a research study in which one or more human subjects2 are prospectively assigned3 to one or more interventions4 (which may include placebo or other control) to evaluate the effects of those interventions or health-related biomedical or behavioral outcomes.5 See NOT-OD-15-015.
Data Coordinating Center (DCC)/ Data Management Center (DMC) - A group that is organized to handle data management in a multi-center trial. Activities of a DMC generally include creating a Data Management Plan (DMP), case report forms (CRF), data quality control, data collection data from clinical sites, editing data, preparing administrative and management reports and either performing data analysis of sending the study data to the Statistical Analysis Center (SAC).
Data Management Plan (DMP)- A plan that documents the flow of participants and study forms through the study and the flow of data from the clinical sites to the DMC; defines the data handling and quality control procedures including error identification and resolution; identifies reports that describe study progress and status; and describes steps to derive an analytic data set from edited or "clean" records. Software and hardware systems along with quality control and validation of these systems are included along with documentation and quality control of analytic programs and tables.
Data and Safety Monitoring Board (DSMB) - please see Safety Monitoring Body (SMB).
Delegation of Authority (DOA) (Description of Responsibility)/Site Signature Log - This is a log that should provide a comprehensive list of study staff members and the duties that have been delegated to them by the PI. It is required for both observational and interventional clinical research studies. The purpose of the DOA is to: (a) serve as the site signature log and (b) ensure that the individuals performing study-related tasks and procedures are appropriately trained and authorized by the PI to perform them. The log should be completed prior to initiation of any study-related tasks and procedures. The original form should be maintained at each site in their regulatory/study binder. The form should be updated during the course of the study as needed
Drug/Device Plan - A plan that documents every aspect of study treatment involvement including procedures for verification that shipments are received, proper storage at site, dispensing instructions, return or destruction of intervention, and all necessary documentation. This also applies to any investigational device used in the study and would be referred to as the Device Plan.
Enrollment Log/Master Participant Log - an essential document that records the chronological enrollment of participants by personal identification number (PIN) as they are enrolled into a clinical study. The Enrollment Log contains the study participant name or initials, study PIN #, informed consent date, and number and dates of visits participated in by the study participant. This should be kept in a secured location with procedures in place regarding who has access to remove and under what conditions. With today's computer systems, this log may be an extension of an automated screening log or may be generated by the computer.
Essential Study Documents - Documents that individually and collectively permit evaluation of the conduct of a study and the quality of the data produced. These documents include those referred in ICH GCP 8.0 Essential Documents for the Conduct of a Clinical Trial. See also Study Files/Master Binder. Exclusion Criteria - A list of criteria, any one of which excludes a potential participant from enrolling in a study.
Federal Wide Assurance (FWA) - Institutions conducting clinical studies research (not otherwise exempt) supported by any agency of the U.S. Department of Health and Human Services (HHS), then the institution must have an OHRP-approved assurance of compliance with the HHS regulations (45 CFR 46.103) for the protection of human subjects.
Financial Disclosure/Conflict of Interest Documentation - Certification that no financial arrangements with an investigator have been made where study outcome could affect compensation; that the investigator has no proprietary interest in the intervention; that the investigator does not have a significant equity interest in the sponsor of the covered study; and that the investigator has not received significant payments of other sorts; and/or disclosure of specified financial arrangements and any steps taken to minimize the potential for bias.
Good Clinical Practices - 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. (http://www.fda.gov/oc/gcp/regulations.html)
Health Insurance Portability and Accountability Act (HIPAA) - Legislation adopted by Congress which took effect in 2003 that strictly dictates the parameters that identifiable private health information (PHI) can be shared outside of the research environment. (http://www.hhs.gov/ocr/hipaa/)
Inclusion Criteria - The criteria that prospective participants must meet to be eligible for participation in a study.
Informed Consent - A process by which a participant or legal guardian voluntarily confirms his or her willingness to participate in a particular trial, after having been informed of all aspects of the trial that are relevant to the participant's decision to take part in the clinical trial. Informed consent is documented by means of a written, signed, and dated informed consent form, which has been approved by an IRB/IEC.
Institutional Review Board (IRB)/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, of protocols and amendments, and of the methods and material to be used in obtaining and documenting informed consent of the trial participant. Investigational Device Exemption (IDE) - An IDE is a request for authorization from the Food and Drug Administration (FDA) to administer an investigational device to humans. Such authorization must be secured prior to interstate shipment and administration of any new device that is not the subject of an approved Pre-Market Approval Application (PMA) (21 CFR 812).
Investigational New Drug Application (IND) - An IND is a request for authorization from the Food and Drug Administration (FDA) to administer an investigational drug or biological product to humans. Such authorization must be secured prior to interstate shipment and administration of any new drug or biological product that is not the subject of an approved New Drug Application or Biologics/Product License Application (21 CFR 312).
Investigator Meeting/Site Initiation Visit - A meeting or visit held prior to participant enrollment at a site(s). The purpose is to acquaint all site personnel with the relevant aspects of the study prior to any participant enrollment and involves the review/discussion of the following: protocol, case report form completion, missed visits, IRB/IEC reporting requirements, adverse event reporting, etc.
Lost to follow-up: refers to subjects who at one point were actively participating in the clinical research but have become lost (either by error or by being unreachable) at the point of follow-up in the study.
Manual of Procedures (MOP) - The MOP is developed to facilitate consistency in protocol implementation and data collection across study participants and clinical sites. Further, the MOP provides reassurance to all participants that scientific integrity and study participant safety are closely monitored and increases the likelihood that the results of the study will be scientifically credible. The MOP is analogous to a toolkit in that it contains information needed for the conduct and operations of a clinical trial and can be used as a training document.
Masking/Blinding - A procedure in which one or more parties in the 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).
Master Study Files - File or binder that contains copies of the documents that are generally known as essential documents or regulatory documents. In a multi-site trial, the Master Study Files will include copies of essential documents from each of the study sites and is typically maintained by the CCC. Please see Study Files/Regulatory Binder.
Medical Safety Monitor (MSM) - Appointed by the Principal Investigator (PI) to oversee a clinical research project if there is more than minimal risk to the study participants. The NINDS requires that each DSMB-monitored trial have an assigned MSM, independent of the study investigators with no apparent conflict of interest, who is responsible for review of individual serious adverse events (SAEs) as they occur, and regular reporting of SAEs to the DSMB and others, as appropriate. Some SMC's may also identify a MSM to review SAEs. The NINDS Program Director must approve of the MSM and specific monitoring procedures she/he will follow. The Medical Safety Monitor will prepare regular reports concerning SAEs (not segregated by treatment group) for submission to the PI, the DSMB and, as appropriate, the FDA.
Monitoring Reports - A document that records the monitoring site visits conducted during the study and includes the name and signature of the person conducting the site visit, date(s) and purpose of the visit.
Monitoring Plan - A monitoring plan then describes the type of monitoring that will take place (e.g. sample or all participants within a site; key data or all data), the schedule of when these activities are to take place, how they are reported, and a timeframe to resolve any issues found.
New Drug Application (NDA) - The NDA application is the vehicle through which drug sponsors formally propose that the FDA approve a new pharmaceutical for sale and marketing in the U.S. The data gathered during the animal studies and human clinical trials of an Investigational New Drug (IND) become part of the NDA (21 CFR 314). (http://www.fda.gov/cder/regulatory/applications/nda.htm#Introduction)
Organizational Plan - The plan that describes the purpose and roles of each study staff member in each of the participating study organizations.
Pre-screening and Screening Process - Potential study participants' medical history and background are reviewed to determine if eligible for study enrollment. Processes must be in place for that document how individuals are identified and contacted, questions to be asked at pre-screening and screening, how are responses recorded, and how are people tracked for further follow-up.
Process Site Visit (PSV) - The purpose of the visit is to review the general processes and operations of a clinical trial and obtain an overview of the study status.
Progress Assessment Visit (PAV) - The purpose of the visit is to assure that the safety and rights of clinical participants are upheld. Activities may include reviewing essential documents, ensuring protocol compliance, verifying that the study is properly conducted, assuring that adverse events are identified, and verifying data quality.
Protocol - 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.
Protocol Amendments - A written description of a change(s) to or formal clarification of a protocol. These should be version controlled with dates and stored with the protocol.
Protocols Deviations Report - Internal documents created for the ongoing quality control with respect to protocol compliance and determination of protocol deviations and/or violations.
Protocol Deviations - Failure to conduct all aspects of the 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:
Quality Assurance (QA) - The externally 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 requirement(s), i.e. site or center audits, external monitoring, etc..
Quality Control (QC) - 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, i.e. data and form checks, monitoring by study staff, routine reports, and correction procedures.
Randomization - The process of assigning trial participants to treatment or control groups using an element of chance to determine the assignments in order to reduce bias.
Randomization Code - The codes that decipher the randomization assignment numbers. The randomization codes and corresponding randomization assignments are kept under "lock and key" by the study statistician or designated staff member to protect the study blind. It is a good idea to generate more randomization assignment numbers than will be needed. The format for assigning treatment groups through randomization should prevent the investigators from accurately guessing to which treatment group a patient will be assigned. Randomization Plan- The statistician or data management group details the procedures that sites must follow to randomize a patient and ensures that randomization is applied consecutively. Randomization and blinding/unblinding procedures should be determined prior to the enrollment of the first subject.
Recruitment Plan - The plan that outlines how individuals will be recruited for the study and how the study will reach the recruitment goal. Recruitment plans should ideally describe each site's catchment area, potent sources of participants, and methods to reach referring physicians and patients, in addition to communication, community outreach strategies and tactics, as well as partnerships with condition specific advocacy groups. Evaluation plans for monitoring recruitment strategies and tactics to allow for any necessary course corrections should be included in the recruitment plan.
Retention Plan - The plan that details the methods in which the study will use in order to maintain study participation in the clinical trial, i.e. follow-up phone calls, send reminder letters, etc., and how efforts will be evaluated over the course of the study to ensure they are achieving the intended goals and outcomes
Safety Monitoring Body (SMB) - For trials that require independent oversight, a SMB can be appointed or recruited depending on study size and associated risk. A study SMB is one of the following entities:
Safety Monitoring Plan - A plan that outlines the independent oversight and communication structure of a Safety Monitoring Body (SMB) or Medical Safety Monitor (MSM), procedures for documenting and reporting of adverse events, serious adverse events and unexpected adverse events, procedures for ensuring human subject protection, and criterion for pausing or stopping the study due to safety concerns.
Screening Log - An essential document that records all individuals who entered pre- screening or screening and details the reasons why an individual was not enrolled or the enrollment date. The screening log demonstrates the lack of bias in the selection of participants and the investigator's attempt to enroll a representative sample of participants.
Serious Adverse Event (SAE) - Any untoward medical occurrence that:
Site Monitoring Report - A written report from the monitor to the investigator after each site visit and/or other trial-related communication according to the study's SOPs. The report outlines the overall status of the clinical site, study-related issues and suggestions for resolutions of issues.
Site Signature Log/Delegation of Authority - Documents the delegation of authority by the principal investigator through signatures and initials of persons authorized to execute specific study functions, i.e. informed consent process, physical exams, CRF completion, etc.
Source Document - Original documents, data, and records (e.g., hospital records, clinical and office charts, laboratory notes, memoranda, participant 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, participant files, and records kept at the pharmacy, at the laboratories, and at medico-technical departments involved in the clinical trial).
Standard Operating Procedures (SOPs) - Detailed written instructions to achieve uniformity of the performance of a specific function across studies and patients at an individual site.
Statistical Analysis Center (SAC) - A group organized to handle the statistical reporting and analysis of a multi-center trial. Activities include development of the Statistical Analysis Plan, presentation of data in listings and tables for the SMB, and statistical analysis of the data.
Statistical Analysis Plan- A plan developed by the study statistician that describes the study from an analytical standpoint, study endpoints, primary and secondary analysis including definitions of data to be used in these analyses, and proposed stopping rules.
Stopping Rules - Established safety criterion that would either pause or halt the study because of futility or risk(s) to the participants in or to be enrolled in the study.
Study Communications Plan - A plan that summarize and describes the communication flow between study centers, investigators, committees, etc. It also describes the handling of inquiries and emergency situations.
Study Files/Study Binder - General study records commonly known as essential study documents. They are usually kept in a Master Study Binder (or Regulatory Binder). Also known as Master Study Files, Administrative Binder, Investigator Binder, and Investigator Study File.
Training Plan - A plan that details what training and certifications are required of study staff in order to participate in the clinical trial and plans for continuous training as necessary in the event of modifications to the study, i.e. good clinical practice, HIPAA, human subject protection, protocol specific training, data collection, etc.
Treatment Accountability - A record that documents the study intervention (i.e. drug, device, etc.) receipt, dispensing, and returns. Accountability logs generally document the quantity and date intervention received from CCC or other source. Individual patient accountability logs document the participant identification number, quantity dispensed, lot or device number, amount of intervention remaining, quantity and date of intervention destruction/return, etc.
Unexpected Adverse Event - Any adverse event that has not been previously observed or such experience that is not anticipated and not indicated in either the protocol or Investigator's Brochure.
Unmasking/Unblinding - A procedure in which one or more parties to the trial are made aware of the treatment assignment(s).
Withdrawals: the decision by a study subject or an investigator to discontinue participation in the research study. Withdrawals may be from the entire study or from specific components and documentation of how the withdrawal should be recorded and reported should be determined by both the investigator and the IRB.
 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 a 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 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.
 Health-related biomedical or behavioral outcome is defined as 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.
Last Modified November 17, 2014