GCP compliance in medical practice deals with those things that are just
prudent to do in ones medical specialty and are driven by the specialty boards.
The documentation and time spent are a decision of how sick the patient is and
what billing code will be chosen.
GCP compliance in medical research requires strict adherence to a study
protocol. If the Pi veers from the protocol it should only be in the name of
protecting the subject from immediate harm. And ten the CRA and the IRB need to
be notified and possible the subject early terminated from the trial. Documentation
in the source documents and the CRF's (Case Report Forms) is immense compared
with regular medical practice.
GCP defines the Pi Principle Investigator) as an individual doctor who
is responsible for the conduct or actually conducts the experimental drug
study.
GCP defines the Sponsor as the drug company that is sponsoring the
experimental research protocol. By sponsoring is meant: funding, organizing,
initiating, managing and running.
Sponsor-Investigator is defined by GCP as the doctor that is both the Pi
and the sponsoring drug company.
GCP defines
Adverse Drug Reaction (ADR) in the pre-approval
clinical experience (IND) with a new medicinal product
or its new usages, particularly as the therapeutic dose(s) may not be
established, as all noxious and unintended responses to a medicinal product
related to any dose and should be considered adverse drug reactions. The phrase "responses to a medicinal product" means that a causal relationship between a
medicinal product and an adverse event is at least a reasonable possibility,
(i.e., the relationship cannot be ruled out). Regarding marketed medicinal
products: A response to a drug that is noxious and unintended and that occurs
at doses normally used in man for prophylaxis, diagnosis, or therapy of
diseases or for modification of physiological function.
GCP defines an
Adverse Event (AE) as any untoward medical occurrence in a patient or clinical
investigation subject administered a pharmaceutical product and that does not
necessarily have a causal relationship with this 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.
Applicable
Regulatory Requirement(s): Any law(s) and regulation(s) addressing the conduct
of clinical trials of investigational products of the jurisdiction where a
trial is conducted.
Approval (in
relation to Institutional Review Boards (IRB's)): The affirmative decision of
the IRB that the clinical trial has been reviewed 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.
Audit: 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 accurately reported
according to the protocol, sponsor's standard operating procedures (SOP's),
good clinical practice (GCP), and the applicable regulatory requirement(s).
Audit Certificate:
A declaration of confirmation by the auditor that an audit has taken place.
Audit Report: A
written evaluation by the sponsor's auditor of the results of the audit.
Audit Trail: Documentation
that allows reconstruction of the course of events.
Blinding/Masking:
A procedure in which one or more parties to the trial are kept unaware of the
treatment assignment(s). Single blinding usually refers to the subject(s) being
unaware, and double-blinding usually refers to the subject(s), investigator(s),
monitor, and, in some cases, data analyst(s) being unaware of the treatment assignment(s).
Case Report Form
(CRF) or Case Record Form: 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.
Causality
Assessment: An assessment made by an investigator that describes the
relationship between the test product and an adverse event.
Clinical Hold: An
order issued by the FDA to suspend or delay a clinical investigation.
Clinical Research
Associate (CRA): An associate, employee, or independent representative of a
sponsor or contract research organization (CRO) whose responsibilities include
monitoring of clinical study data at investigative sites.
Clinical Research
Coordinator (CRC): An associate, employee, or independent representative of an
investigator whose responsibilities include assisting a clinical investigator
with the conduct of a clinical trial.
Clinical
Trial/Study/Drug Study: Any investigation in human subjects intended to
discover or verify the clinical, pharmacological, and/or other pharmacodynamics
effects of an investigational product(s), and/or 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 object of ascertaining its safety and/or efficacy. The terms clinical trial,
clinical study and drug study are synonymous.
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.
Code of Federal
Regulations (CFR): The official location of federal law of the United States. Titles 21 and 45 of the CFR relate to
clinical trials.
Comparator
(Product): An investigational or marketed product (i.e., active control), or placebo,
used as a reference in a clinical trial. Trials using active comparator
products are often referred to as comparative trials. Trials using placebos are
commonly referred to as placebo controlled studies.
Compliance (in
relation to trials): Adherence to all the trial-related requirements, good
clinical practice (GCP) requirements, and the applicable regulatory
requirements.
Confidentiality: Prevention
of disclosure, to other than authorized individuals, of a sponsor's proprietary
information or of a subject's identity.
Contract: 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.
Control Group: A
group of subjects in a clinical trial used to provide a basis for comparison to
a test drug. In clinical trials, a control group may receive no treatment,
placebo or a different active drug.
Controlled Study:
A clinical study that includes at least one control group.
Crossover Trial: A
type of clinical trial design during which subjects receive one treatment and
then change to another treatment. This design allows each subject to serve as
his/her own control in a statistical analysis.
Concomitant
Medication: Medications used by subjects in a clinical trial that are in
addition to the protocol specified treatments.
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.
Coordinating
Committee: A committee that a sponsor may organize to coordinate the conduct of
a multicenter trial. The committee may be allowed to be unblinded to monitor
subject safety and make decisions regarding stopping or continuing the study
during its conduct.
Coordinating
Investigator: An investigator assigned the responsibility for the coordination
of investigators at different centers participating in a multicenter trial.
Curriculum Vitae
(CV): A description of the education, training, and experience of a person.
Dose Form: The
form in which a drug is administered (e.g., tablet, capsule, liquid,
injectable, topical, or inhalant).
DoseRange: The range of doses administered or
tolerated in a clinical trial. In early phase research, multiple doses are
often administered to determine the most effective dose and the best tolerated
dose.
Dose Regimen: The
amount and interval between doses, or frequency per day, of a drug administered
to a subject.
Dose Response: The
relative therapeutic responses across a range of drug doses. A dose response study
evaluates subject responses across a range of doses of the test drug.
Documentation: 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.
Double-blind: A
study in which medication identity is unknown to study subjects and either the investigator
or study evaluator.
Drop-out: A
subject who leaves a study prior to completion.
Drug
Accountability: The process of accounting for the amount of drug sent to an
investigator, the amount reported as taken by study subjects, and the amount of
drug returned to the sponsor at the end of a trial.
Drug Development:
The process of developing a drug, which may include both pre-clinical and
clinical research studies necessary to submit a marketing application for
approval to a regulatory authority.
Drug Disposition:
The process of documenting the amount of drug administered to or provided to
clinical research study subjects.
Efficacy: The
ability of a drug to produce beneficial therapeutic effects in an illness.
Effectiveness: A
quantified or measured therapeutic benefit of a drug, usually measured in a
controlled clinical trial.
Essential
Documents: Documents that individually and collectively permit evaluation of
the conduct of a study and the quality of the data produced.
Ethics Committee:
An independent body of persons whose responsibility is to evaluate the ethics
of a proposed clinical trial, prior to its start. An ethics committee may also
be an IRB.
Exclusion
Criteria: Criteria defined in a clinical study protocol that prevent a subject
from enrolling in the study.
Federal Register:
A daily US government publication that documents, among other things, proposed and
final regulations.
Food and Drug
Administration (FDA): The US federal agency that governs drug research and
approval in the United States.
FDA Advisory
Committee: An appointed committee of medical experts and/or public
representatives, each with limited tenure, who may be called upon by the FDA to
provide input regarding approval of products or other significant medical
issues related to health care.
FDA Guidelines: Guidance
documents issued by the FDA that provide additional detail, clarification, and interpretation
of the FDA regulations. Numerous guidelines exist and may be obtained on the
FDA website www.fda.gov.
FDA Form 1571: The
FDA form for an Investigational New Drug (IND) application. The form is used by
sponsors to submit the original IND as well as provide voluntary, or required
subsequent information or updates.
FDA Form 1572: The
FDA Statement of Investigator Form. This form must be signed by all clinical investigators
prior to commencing a clinical study conducted under the US IND regulations.
FDA Form 356h: The
FDA New Drug Application Form. This form is used by sponsors to submit a new drug
application (NDA) to the FDA, as well as update previously submitted
applications.
Good Clinical
Practice (GCP): 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 subjects are
protected.
Impartial Witness:
A person, who is independent of the trial, who cannot be unfairly influenced by
people involved with the trial, who attends the informed consent process if the
subject or the subject's legally acceptable representative cannot read, and
attests that the informed consent form was read to the subject and or legal
representative of the subject.
Inclusion
criteria: Criteria defined in a protocol that subjects must meet to be eligible
for participation in a clinical trial.
Indemnification: A
commitment made from one party to another (in clinical trials usually from the
sponsor to an investigator, institution, or institutional review board (IRB) to
hold the indemnified party harmless from financial loss due to the effects of a
drug used in a trial.
Indication: In
drug therapy, the purpose for which a drug is being used.
Independent Data
Monitoring Committee (IDMC) (Data and Safety Monitoring Board, Monitoring
Committee, Data Monitoring Committee): An independent data monitoring committee
that may be established by the sponsor to assess at intervals the progress of a
clinical trial, the safety data, and the critical efficacy endpoints, and to
recommend to the sponsor whether to continue, modify, or stop a trial. May be
synonymous with coordinating committee.
Independent
Ethics Committee (IEC): An independent body (a review board or a committee,
institutional, regional, national, or supranational), constituted of
medical/scientific professionals and nonmedical/nonscientific members, whose
responsibility it is to ensure the protection of the rights, safety, and
well-being of human subjects involved in a trial and to provide public
assurance of that protection, by, among other things, reviewing and approving/providing
favorable opinion on the trial protocol, the suitability of the investigator(s),
facilities, and the methods and material to be used in obtaining and documenting
informed consent of the trial subjects. The legal status, composition,
function, operations, and regulatory requirements pertaining to Independent
Ethics Committees may differ among countries, but should allow the Independent
Ethics Committee to act in agreement with GCP as described in the ICH GCP
Guideline. Also known as an IRB.
Informed Consent:
A process by which a subject 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 subject's decision to participate. Informed
consent is documented by means of a written, signed, and dated informed consent
form.
Inspection: 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 sponsor's and/or contract research organization's
(CRO's) facilities, or at other establishments deemed appropriate by the
regulatory authority(ies).
Institution
(medical): Any public or private entity or agency or medical or dental facility
where clinical trials are conducted.
Institutional
Review Board (IRB): 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 subjects. Also known
as an IEC.
Investigational
New Drug (IND): A drug not yet approved for marketing by
regulatory authorities.
Investigational
Product: 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.
Investigator: 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: A compilation of the clinical and non-clinical data on the
investigational product(s) that is relevant to the study of the investigational
product(s) in human subjects. May also be referred to as an Investigator's Drug
Brochure.
Labeling: The
written information that describes the contents within a container or package
of a drug, or written information that accompanies a drug that describes the
known scientific information about the drug, or provides information on how to
use the drug.
Legally
Acceptable Representative: An individual or juridical or other body authorized
under applicable law to consent, on behalf of a prospective subject, to the
subject's participation in the clinical trial.
MedWatch Form: A
form used by the FDA to record adverse events in clinical trials, or those
which are spontaneously reported by health care practitioners.
Monitoring: 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 (SOP's), GCP, and the applicable regulatory
requirement(s).
Monitoring Report:
A written report from the monitor to the sponsor after each site visit and/or
other trial related communication according to the sponsor's standard operating
procedures.
Multicenter Trial:
A clinical trial conducted according to a single protocol but at more than one
site, and, therefore, carried out by more than one investigator.
Non-clinical
Study: Biomedical studies not performed on human subjects.
Open-label Study:
A study in which the identity of the medication is known to all parties,
including both the subject and investigator.
Opinion (in
relation to Independent Ethics Committee): The judgment and/or the advice
provided by an Independent Ethics Committee (IEC).
Original Medical
Record: See Source Documents.
Package Insert: The
labeling information that accompanies an approved, marketed drug.
Parallel Groups
Study: A study in which subjects receive one of two or more treatments for a
defined period of time.
Patient: A human
being with a defined medical condition. (see subject or research subject
volunteer).
Pharmacodynamics:
The evaluation of the pharmacologic effects of a product on physiologic
function in a biological system.
Pharmacoeconomics:
The evaluation of the economic effects associated with the use of
pharmaceutical products.
Pharmacokinetics:
The quantitative measurement of the absorption, distribution, metabolism, and
excretion of a drug in a biological system.
Pharmacology: The
study of the effects of a drug in a biological system.
Phases of
Clinical Trials: The sequential generation of information about a drug through
clinical research studies. Phases of clinical research include phase I, II,
III, and IV.
Placebo: An agent
administered in a study that does not include any known therapeutic
ingredients.
Post Marketing
Surveillance Studies (PMSS): Studies conducted by sponsors after a product has
been approved and marketed. These are usually conducted to collect additional
safety information about the marketed drug. Also, spontaneously reported
adverse events, after marketing.
Pre-clinical
Study: Studies done in animals or laboratory settings prior to study in humans.
Proscribed
Medication: A medication not allowed to be taken by subjects participating in a
clinical trial.
Prospective Study:
A study planned and designed, prior to its initiation, to answer predefined
questions.
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
Amendment: A written description of a change(s) to or formal clarification of a
protocol.
Quality Assurance
(QA): 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
requirement(s).
Quality Control
(QC). The operational techniques and activities undertaken within the quality
assurance system to verify that the requirements for quality of the
trial-related activities have been fulfilled.
Randomization: The
process of assigning trial subjects to treatment or control groups using an
element of chance to determine the treatment assignments in order to reduce
bias.
Regulatory
Authorities: Government bodies having the power to regulate the development and
registration of pharmaceuticals, biologics, diagnostics and devices. In the ICH
GCP guideline, the expression "Regulatory Authorities" includes the authorities
that review submitted clinical data and those that conduct inspections. These
bodies are sometimes referred to as competent authorities.
Serious Adverse
Event (SAE) or Serious Adverse Drug Reaction (Serious ADR) Any untoward
medical occurrence that at any dose:
Results in
death
Is life-threatening
Requires
in-patient hospitalization or prolongation of existing hospitalization
Results in
persistent or significant disability/incapacity
Is a
congenital anomaly/birth defect.
Single-blind
Study: A study design in which only one entity (usually the subject) does not
know the identity of the medication.
Source Data: 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).
Source Documents:
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, laboratory data, subject files, and records kept at the
pharmacy, at the laboratories, and at medico-technical departments) involved in
the clinical trial.
Sponsor: An
individual, company, institution, or organization that takes responsibility for
the initiation, management, and/or financing of a clinical trial. The entity
that files and maintains an Investigational New Drug application in the USA.
Sponsor-Investigator:
An individual who both initiates and conducts, alone or with others, a clinical
trial, and under whose immediate direction the investigational product is
administered to, dispensed to, or used by a subject. The term does not include
any person other than an individual (e.g., it does not include a corporation or
an agency). The obligations of a sponsor-investigator include both those of a
sponsor and those of an investigator.
Standard
Operating Procedures (SOP's): Detailed, written instructions to achieve
uniformity of the performance of a specific function.
Stratification: A
study design technique used to control the effects of a variable known to
effect a disease or treatment.
Sub-investigator:
Any individual 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).
Subject/Trial
Subject: An individual who has given informed consent to participate in a
clinical trial, either as a recipient of the investigational product(s) or as a
control.
Subject
Identification Code: A unique identifier assigned by the investigator to each
trial subject to protect the subject's identity and used in lieu of the
subject's name when the investigator reports adverse events and/or other
trial-related data.
Test article: An
investigational drug, or other entity undergoing research.
Trial Master File:
A file maintained by a sponsor for each clinical investigation that includes
all documentation related to the trial.
Trial Site: The
location(s) where trial-related activities are actually conducted.
Unexpected
Adverse Drug Reaction: An adverse reaction, the nature or severity of which is
not consistent with the applicable product information (e.g., Investigator's
Brochure for an unapproved investigational product or package insert/summary of
product characteristics for an approved product).
Vulnerable
Subjects: Individuals whose willingness to volunteer in a clinical trial may be
unduly influenced by the expectation, whether justified or not, of benefits
associated with participation, or of a retaliatory response from senior members
of a hierarchy in case of refusal to participate. Examples are members of a
group with a hierarchical structure, such as medical, pharmacy, dental and
nursing students, subordinate hospital and laboratory personnel, employees of
the pharmaceutical industry, members of the armed forces, and persons kept in
detention. Other vulnerable subjects include patients with incurable diseases, persons
in nursing homes, unemployed or impoverished persons, and patients in emergency
situations, ethnic minority groups, homeless persons, nomads, refugees, minors,
and those incapable of giving consent.