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therapeutic potential Some health authorities provide accelerated
approval programs for new drugs, depending on their therapeutic
or innovative potential; for the FDA classification as  P (priority)
or  S (standard) does exist.
therapy management ’! see disease management.
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three-way crossover design ’! see crossover, design.
time-event schedule ’! see flow chart.
time trade-off (TTO) Technique for measuring utility or quality
of life; patients are asked about the number of years in their pres-
ent health state they would be willing to trade for a shorter life
span in full health.
time-treatment interaction ’! see carry-over effect.
TNM-staging Stands for tumour-node-metastasis; widely used clas-
sification system of the Unio Internationalis Contra Cancrum,
UICC (Union International contre le Cancer, Unio Internationalis
Contra Cancrum) which is based on the size of the primary tu-
mour T (To no evidence of primary tumour, T4-tumour invades
adjacent organs and vessels, TIS, Tx), degree of local spread to
lymphnodes N (No N3, N4 if applicable, Nx) and distant spread
of metastases M (Mo M1, Mx); histopathologic grading is also of
prognostic importance (Histopathologic Grade G: Gx  grade can-
not be assessed; G1  well differentiated; G2  moderately differen-
tiated; G3  poorly differentiated; G4  undifferentiated; ’! see also
tumour staging.
Table 4
AJCC/UICC Dukes
Stage 0 Tis N0 M0
Stage I T1 N0 M0 A
T2 N0 M0
Stage II T3 N0 M0 B
T4 N0 M0
Stage III any T N1 M0
any T N2 M0 C
any T N3 M0
thr
Stage IV any T any N M1 D
Dukes B, C is composed of better and worse prognostic groups;
tolerance Reduction in the response of a drug treatment in a particu-
lar patient, e.g. by induction of enzymes as in the case of barbitu-
rates; ’! see also tachyphylaxis.
total organ carbon (TOC) Analysis of the Total Organ Carbon is a
method used to test pure water and to validate it s quality or clean-
ing procedures.
total quality management (TQM) In clinical research, TQM is en-
sured by strict adherence to GCP, GLP, and GMP, including various
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additional standards such as e.g ISO 9000 and EN 45000; ’! see
also qality assurance.
toxic dose level (TDL) Lowest dose that produces haematological,
chemical or other drug induced changes in the animal such that
doubling the dose is not lethal; ’! see also noel.
toxicity tests Single dose t. (acute tests) are used to establish the
lethal dose of a compound in at least two different species by at
least two different routes of administration (incl. usually intrave-
nously and route planned for application in man); increasing dos-
es are administered till an end-point, usually death, is reached;
test animals are observed usually for a period of 14 but not less
than 7 days; in repeat-dose t. (sub-acute t./less than 1 months
duration, subchronic t. 1 3 months, chronic t./>3 months) the
top dose is chosen so that it produces some minimal adverse
effect (e.g. reduction in rate of body-weight gain) and dose/re-
sponse relationship can be examined (2 species of mammals,
one of which must be a non-rodent); for products to be admin-
istered once only to humans, a test lasting 2 to 4 weeks shall be
performed; reproductive toxicity t. investigate potential adverse
effects during production and fertilization of gametes; embryo/
foetal and perinatal t. investigates effects of a drug administered
to the female during pregnancy or embryogenesis resp. ( fetal
toxicity or  teratology ) or during birth and subsequent devel-
opment; mutagenicity t. reveal changes in the genetic material of
individuals or cells; carcinogenicity t. are normally required for
substances likely to be applied in man longer than 3 months; in-
tensive toxicity tests are especially important for products likely
to be administered regularly over a prolonged time of a patient s
life; as example for the correlation between planned duration of
human treatment and necessary toxicity testing the following
overview can be given:
Table 5
tox
Human treatment Toxicity studies (in two species, one
non-rodent)
one/several doses, 1 day 2 weeks
repeated doses up to 14 days 4 weeks
repeated doses up to 1 month 1 month
up to 3 months 3 months
>3 months up to 6 months 6 months
above 6 months 6 months
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the FDA still requests 12 months chronic toxicity tests for drugs
intended to be used for longer than 6 months; a complete toxicity
program costs about 5 to 10 million US$ and may use about 5,000
animals; ’! see also carcinogenicity tests, ecotoxicity, geno-
toxicity, immunotoxicity, ld-10, maximum tolerated dose,
minimal toxic dose, Mutagenicity test, no-toxic-effect-lev-
el, old substance, therapeutic index.
toxicokinetic Relates body drug concentrations and their kinetics to
toxicological findings.
trade name syn. proprietary name, brand name, invented name;
name used together with a trade mark or the name of the manu-
facturer (opp. international non-proprietary name, generic
name); relates to a finished product and identifies the manufac-
turer; for a commercially available medicinal product; within the
EC it is recommended to use the same t.n. throughout the Com-
munity, unless a justification to do otherwise is given; in most
countries the t.n. is liable to revocation after 3 5 years of non-use.
EMEA states  if there is a minimum of 3 distinguishing letters, it is
unlikely that it will be considered that there is a risk of confusion in
writing ( 3-letter rule ).
traditional herbal medicinal product EU: Medicinal product of
herbal origin that has been in medicinal use throughout a period
of at least 30 years preceding the date of application, including at
least 15 years within the European Community; claimed indica-
tions must be appropriate without the supervision of a medical
practitioner; ’! see also functional food, phytomedicines.
transdermal delivery system (TDDS) syn.: transdermal delivery de-
vice (TDD); ’! see transdermal patch, drug delivery.
transdermal patch Special formulation where the drug is absorbed
through the skin, e.g. nitroglycerin, nicotin a.s.o.; in passive patch-
es, the drug diffuses into the skin as a result of a gradient in either
the drug concentration or solubility; in active patches, external
forces are used; transdermal delivery is limited by the size of the
tox
drug (upper limit around 500 Dalton), the water and lipid solubil-
ity and the pharmacologically effective dose to be delivered; po-
tential irritation/sensitisation of the drug towards the skin must be
excluded; hair follicles can act also as an entry portal for both an-
tigens and DNA to the skin; penetration enhancer are: liposomes
and ethanol; physical methods are also used such as iontophore-
sis.
transgenic drug Drug (usually a protein) which is manufactured
from transgenic animals (e.g. by introducing a human gene such
as for antithrombin III in a cow which then excrets the drug with
the milk); ’! see biotechnology, gene therapy.
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transition matrix Frequently used format for presentation of e.g. labo-
ratory data (example given for a total of 170 subjects, x-axis: number
of subjects with observations as specified after treatment, y-axis:
number of observations before treatment); ’! see also shift table.
Table 6
Before After
lowered normal raised total
lowered 95014
normal 27291470
raised 0 454186
total 36 79 55 170
transplantation over 28.000 human-to-human organ transplants
were carried out in 2006 in the U.S (1994: 18.200); over 1 million
people worldwide has received allograft organs and some of them
have already survived more than 25 years; 5-years survival rates
for most organ transplant programmes are around 70%; demand
for organs outstrips supply; ’! see also allogenic, biological [ Pobierz caÅ‚ość w formacie PDF ]