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trial in the particular way; methods/subjects/patients: description of
selection criteria, design, blinding, statistical methods etc; results:
with baseline comparison of treatment groups, number of subjects
randomized, analyses of efficacy and safety according to intent-
to-treat principle, number of subjects which might be excluded
from analyses and reasons, estimation of (group) differences, p-val-
ues, confidence intervals, evaluation of centre by treatment in-
teraction (for multicentre trials); discussion/conclusions: critical
comparison with published or other existing information; according
to EC guidelines of good clinical practice (III) r. of clinical trials have
to be archived 5 years beyond the life time of the product; ’! see
also development safety update report, expedited reporting,
final report, integrated report, imrad, parent-child/foetus
report, periodic safety update report, s-2 report.
reprocessing EC (IV): the reworking of all or part of a batch of
product of an unacceptable quality from a defined stage of produc-
rep
tion so that its quality may be rendered acceptable by one or more
additional operations
.
reproducibility Often used synonymously to precision and vari-
ability; extent to which the same result is obtained (or would have
been obtained) when a measurement is repeated; the better the r. of
measurements, the lower the standard deviation and therefore
the variance; ’! see also accuracy, measurement properties.
reproductive toxicity Toxic effects upon reproduction of mammals;
studies investigate possible adverse effects of substances on male
or female fertility and general reproductive performance ( seg-
ment I ), teratogenicity ( segment II ), and peri- or postnatal ef-
fects resp. such as physical and functional development in the off-
spring ( segment III ); ’! see also genotoxicity, toxicity tests,
labelling.
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rescue medication also called escape medication; medicines identi-
fied in a study protocol as those that may be administered to the
patients when the efficacy of the investigational medicinal product
(IMP) is not satisfactory, or the effect of the IMP is too great and
is likely to cause a hazard (adverse reaction) to the patient, or to
manage an emergency situation).
research and development (R&D) The average new chemical en-
tity (NCE) costs about 802 million US $ (2002) (estim. 1990: $ 231
million) and takes about 12 years, with little changes since 1987,
from synthesis to marketing approval (about 3 years in the 1960s);
this includes costs of failed projects and time costs (mean develop-
ment times: long-term animal studies 3.5 years, phase I 1.5 years,
phase II 2 years, phase III 3.5 years, new drug application review
by FDA 1.5 years); to bring 10 NCEs on the market, it is estimated
that researchers must evaluate 100,000 compounds of which com-
panies can put about 100 products into clinical trials but only
two of the 10 NCE will be profitable for the discovering company;
worldwide R&D expenses were about 49 billion US$ in 2004 (esti-
mate of the PhRMA) (after 15,000 million US $ in 1988, 24,500 mil-
lion in 1992 and 33,700 million in 1995), with about 15 20 NCEs
approved each year (35 in 1989); each additional week of clinical
development accounts for a loss of sales revenues in the order of
$ 1 10 million US $; worldwide ethical pharmaceutical sales were
in the order of $ 400,000 in 2002 (112.000 million in 1988); R&D ori-
ented companies expend about 10 20% of their revenues for R&D
and 20 30% for marketing; ’! see also development, health care
costs, life cycle management, new chemical entity, market-
ing authorisation, pharmaceutical market.
research coordinator ’! see clinical trial coordinator
research nurse ’! see study nurse.
res
response R. can be presented in different ways, e.g. as difference
(value before value after), as ratio (value after/value before), as
percentage change [(value after/value before 1) × 100], percentage
of patients with a defined value at a given moment, a.s.o.
response (cancer treatment) For reporting results of cancer treat-
ment the following definitions (WHO) of objective response are
used (separately!): (I) measurable disease: complete response (CR)
= disappearance of all known disease, determined by 2 observa-
tions not less than 4 weeks apart; partial r. (PR) = 50% or more
decrease in total tumour size of the lesions which have been mea-
sured to determine the effect of therapy by 2 observations not less
than 4 weeks apart (there can be no appearance of new lesions or
progression of any lesion); no change (NC) = 50% decrease in total
tumour size cannot be established nor has a 25% increase in the
162
size of one or more measurable lesions been demonstrated; pro-
gressive disease (PD) = 25% or more increase in the size of one or
more measurable lesions, or the appearance of new lesions; (II)
unmeasurable disease: complete r. (CR) = complete disappearance
of all known disease for at least 4 weeks; partial r. (PR) = estimated
decrease in tumour size of 50% or more for at least 4 weeks; no
change (NC) = no significant change for at least 4 weeks; this in-
cludes stable disease, estimated decrease of less than 50%, and
lesions with estimated increase of less than 25%; progressive dis-
ease (PD) = appearance of any new lesion not previously identified
or estimated increase of 25% or more in existent lesions; (III) re-
sponse criteria for bone metastases: complete r. (CR) = complete
disappearance of all lesions on X-ray or scan for at least 4 weeks;
partial r. (PR) = partial decrease in size of lytic lesions, recalcifica-
tion of lytic lesions, or decreased density of blastic lesions or ob-
servation of any progression for at least 4 weeks; no change (NC) =
because of the slow response of bone lesions the designation no
change should not be applied until at least 8 weeks have passed
from the start of therapy; progressive disease (PD) = increase in
size of existent lesions or appearance of new lesions; duration: CR
lasts from the date of its first record to the date of first observation
of progression; overall r. lasts from the first day of treatment to the
date of first observation of progression; ’! see also performance
status.
restricted marketing authorization ’! see conditional approval,
post-marketing surveillance.
retain samples In some countries (e.g. in Germany) national regula-
tions request that samples of drugs used in clinical trials are kept
for control purposes beyond termination of the trial.
retest date In clinical trials with new substances data on long term
res
stability are frequently not available; in these cases a provisional
expiry date is given that may be prolonged as soon as new stability
data become available; ’! see also expiry date.
retrospective study opposite: prospective study; ’! see prospective
study.
return EC (IV): sending back to the manufacturer or distributor
of a medicinal product which may or may not present a quality
defect
.
ribozyme Ribonucleic enzymes; class of new therapeutics planned
for the treatment of viral infections, autoimmune disease, endo-
crine disease and cancers; like antisense oligonucleotides they
suppress gene expression by binding to mRNA templates, thus
suppressing mRNA translation and therefore the production of
disease-causing proteins; ’! see, gene therapy, ribozyme.
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risk combination of probability of harm and severity of that harm
(Source: ISO Guide 51; ICH Q9step4, QRM); Absolute r. = r. of de-
veloping the condition (disease) or outcome/response (e.g. cure,
adverse effect) if the subject participates in/takes the putative
cause; in the control group this is the r. of developing the condi-
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