absorption- the process by which medications reach the blood stream when administered
other than intravenously, for example through nasal membranes.
ADME- absorption,
distribution, metabolism, excretion as it usually pertains to compounds and medicines
Adverse drug reaction (ADR)- in the pre-approval clinical experience with a new medicinal product or its
new usages, particularly as therapeutic dosages may not be established: all noxious and unintended responses to a medicinal
product related to any dose should be considered adverse drug reactions. The phrase “responses to a medicinal
product” means that a casual relationship between a medicinal product and an adverse event is at least a reasonable
possibility, ie: meaning the relationship can not be ruled out.
Regarding marketed products, a response to a drug which is noxious and unintended
and which occurs at doses normally used in man for prophylaxis, diagnosis or therapy of diseases or for modification of physiological
function.
adverse event (AE)- An untoward medical occurrence
in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a
casual relationship with this treatment. An adverse event can therefore be any unfavorable and unintended sign, symptom,
or disease temporarily associated with the use of a medicinal product, whether or not related to the medicinal product.
audit
report- a written evaluation by the sponsor’s auditor
of the results of the audit
audit trail- documentation that allows the reconstruction
of the course of events
Bayesian statistics- a statistical approach
named for Thomas Bayes (1701-1761) that has among its features, giving a subjective interpretation to probability, accepting
the idea that it is possible to talk about the probability of a hypothesis being true and of parameters having particular
values.
bioavailability- the rate and extent to which a drug is absorbed
or is otherwise available to the treatment site in the body.
bioequivalence-
scientific basis on which generic and brand name drugs are compared. To be considered bioequivalent, the bioavailability
of two products must not differ significantly when the two prodcust are given in the same studies at the same dosage under
the same conditions.
biostatistics- branch of statistics applied
to the analysis of biological phenomenon.
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.
COSTART- Coding Symbols for
Adverse Reaction Terms
data and safety monitoring board (DSMB)- researchers-
ideally independent of the trials they monitor-who periodically review data from blinded, placebo controlled trials.
A DSMB can stop a trial if toxicities are found or if treatment is proved beneficial.
data encryption standard (DES)- a widely used method of data encryption using a private key that the US government
judged so difficult to break that it was restricted for export to other countries. Each message uses one of 72 quadrillion
or more possible encryption keys that are chosen at random. The sender and receiver must both know and use the same
private key. DES applies a 56-bit key to each 64-bit block of data.
double blind study- a study in which neither the subjects nor the investigators know what treatment a subject is being given.
effectiveness- the desired measure of a drug’s influence on a disease condition
as proved by substantial evidence from adequate and well controlled investigations.
efficacy- a products availability to produce beneficial effects on the course or duration of a disease.
Food and Drug Administration
(FDA)-
GCP- Good Clinical Practices
Health Level 7 (HL7)- a clinical data interchange messaging system in which messages
are structured according to a predefined format and sent from one system to another. The sending system only needs to
know how to convert its data into an HL7 message, the receiving system needs to only know how to extract the data.
ICD 9- International Classification of Diseases, 9th Revision
Independent Data
Monitoring Committee (IDMC)- a 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 end points,
and to recommend to a sponsor whether to continue, modify or stop a trial.
Independent Ethics Committee (IEC)- an independent review board constituted of medical, scientific and non-scientific 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 trial protocol and of the methods and material
to be used in obtaining and documenting informed consent of the trial subjects.
informed consent- a process by which a subject voluntarily confirms his or her willingness to participate in a
trial after having been informed of all of the aspects of the trial that are relevant to the subjects decision to participate.
Informed consent is documented by means of a written, signed, dated informed consent form. Under 21 CFR 50.20 no informed
consent may include a “waiver” of any of the subjects legal rights, or releases or appears to release the investigator,
sponsor, institution, or its agents from liability for negligence.
ICF- informed
consent form
ICH- International Conference of Harmonization
Institutional Review
Board (IRB)- an independent review board constituted of medical,
scientific and non-scientific 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 continueing review
of trial protocol and of the methods and material to be used in obtaining and documenting informed consent of the trial subjects.
Sometimes referred to as Independent Review Board, Independent Ethics Committee.
IND- Investigational New Drug application
investigator-
the person responsible for the conduct of a clinical trial at a particular site. If the trial is conducted by a team
of individuals at a trial site, the investigator is the responsible leader of that team and may be called the principal investigator.
MedDRA- Medical Dictionary for Regulatory Activities, standard medical terminology
designed to supercede other terminologies used in the medical product development process including COSTART and ICD 9 and
others.
Memorandum of Understanding (MOU)- a memorandum between FDA
and a regulatory agency in another country that allows mutual recognition of inspections
monitoring- the act of overseeing the progress of a clinical trial and ensuring that it is conducted in accordance
with the protocol, standard operating procedures (SOP’s), good clinical practices (GCP’s), and all applicable
regulatory requirements.
New Drug Application (NDA)- an application to
the FDA to market a new drug in the United States
pharmacodynamics (PD)- the
branch of pharmacology that studies reactions between drugs and living structures including the processes of bodily responses
to pharmacological, biochemical, physiological, and therapeutic effects.
pharmacoeconomics- branch of economics the applies cost-benefit, cost-utility, cost-minimization, and cost-effectiveness analyses to
compare the economics of different pharmaceutical products or to compare drug therapy to other treatments.
pharmacogenetics- the study of how a drug reacts with genetic makeup or the genetic response
to a drug.
pharmacokinetics (PK)- the study of the process of bodily
absorption, distribution, metabolism, excretion (ADME) of compounds and medicines.
pharmacology- the science that deals with the characteristics, effect and uses of drugs and their interactions
with living organisms.
pharmacovigilance- term used for adverse event
monitoring and reporting in some countries.
Phase I Trials- initial safety
trails on a new medicine in which investigators attempt to establish the dose range tolerated by about 20-80 healthy volunteers
for single and multiple doses. Although usually conducted with healthy volunteers, sometime severely ill patients for
example those with AIDS or cancer are used. When pharmacokinetic issues are being addressed (example; metabolism
of a new antiepileptic medicine in stable epileptic patients whose microsomal liver enzymes have been induced by other epileptic
medicines) less ill patients may be used.
Phase IIa Trials- Pilot clinical
trials to evaluate safety and efficacy of selected populations of about 100-300 patients who have the disease or condition
to be treated, diagnosed or prevented. Often involve hospitalized patients who can be closely monitored. Objectives
may focus on dose response, type of patient, frequency of dosing or any number of other issues involving safety and efficacy.
Phase
IIb Trials- Well-controlled trials to evaluate safety and efficacy
in patients who have the disease or condition to be treated, diagnosed or prevented. These trials usually present the
most rigorous tests of a medicine’s efficacy.
Phase III Trials- Multi center
studies involving populations of perhaps 1000-3000 patients for whom the medicine is eventually intended. Phase III
trials generate additional safety and efficacy data from relatively large numbers of patients in both controlled and uncontrolled
designs and are used to support a Product License Application (PLA). Trials are conducted under special conditions are
in special groups of patients which is dictated byu the nature of a particular medicine or disease.
Phase IIIb Trials- trials conducted after submission of a new drug application (NDA) but
before the products approval and market launch. These trials may supplement or complete earlier trials, or they may
seek different kinds of information (ie: quality of life, marketing).
Phase IV Trials- After a medicine is marketed, Phase IV trials provide additional details about a producst safety and efficacy.
They may be used to evaluate formulations, dosages, durations of treatment, medicine interactions, and other factors.
Patients from various demographic groups may be studied. An important part of these studies in detecting and defining
previously unknown or inadequately quantified adverse reactions and related risks. Phase IV studies that are primarily
observational or nonexperimental are often referred to as postmarketing surveillance.
Phase V Trials- Postmarketing surveillance is commonly referred to as Phase V
PLA- Product License Application which is submitted to the FDA
protocol- a document that describes the objectives, design, methodology, statistical considerations,
and organization of a trial
Serious Adverse Event (SAE)- any untoward medical
occurrence that at any dose, results in death, is life threatening, requires inpatient hospitalization or prolongation of
existing hospitalization, results in persistent or significant disability or is a congenial anomaly/birth defect.
single blind study- a study in which the subjects do not know if they are receiving the active
drug or a placebo
sponsor- an individual, institution, company
or organization who takes responsibility for the initiation
standard deviation- indicator of the relative variability of a variable around its mean, the square root of the variance
SOP- standard operating procedures
statistical significance- level at which an investigator can conclude that observed differences are not due to chance alone, for
example a p value of .05 (also called significance at the .05 level) indicates that there is about a 1 in 20 chance that the
difference observed occurred by chance alone
triple blind study- a
study in which neither the organizers and analysts of the study nor the subjects and
investigators have knowledge of the treatment
variance- a measure by which
an amount differs from the mean
