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The following message was posted to: PharmPK
Hello,
I have one question regarding the terms of "safety" and
"tolerability" of
one drug. I think the terms are not the same meaning. Can you kindly
explain
further to me.
Can you give which online source I can find more information about that?
Thanks in advance and Best Regards,
Thanh Huyen
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Dear Thanh,
[Although this may be a little off topic]
According to the glossay in ICH E9 (i.e. Statistical Principles for
Clinical Trials,
c.f. http://www.ich.org/LOB/media/MEDIA485.pdf)
"The safety of a medical product concerns the medical risk to the
subject, usually
assessed in a clinical trial by laboratory tests (including clinical
chemistry and
haematology), vital signs, clinical adverse events (diseases, signs
and symptoms),
and other special safety tests (e.g. ECGs, ophthalmology).
The tolerability of the medical product represents the degree to
which overt adverse
effects can be tolerated by the subject."
Kind regards,
Jan Hartstra
Sr. Biometrician
Pharma Bio-Research Group B.V.
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The following message was posted to: PharmPK
Huyen,
Here some definitions:
Safety is a relative concept referring to the freedom from harm or
damage resulting from adverse reactions or physical, psychological,
or behavioral abnormalities that occur as a result of medicine use.
Safety is usually measured with one or more of the following:
physical examination (e.g., vital signs, neurological,
opthalmological, general physical), laboratory evaluations of
biological samples (e.g., hematology, clinical chemistry,
urinalysis), special tests and procedures (e.g., electrocardiogram,
pulmonary function tests), psychiatric tests and evaluations, and
determination of clinical signs and symptoms. It refers also to the
long term occurrence of harm.
Tolerability represents the degree to which overt adverse effect can
be tolerated by the subject. Tolerability is usually measured by the
rate of dropouts and is much different depending on the therapeutic
class. For example the adverse effects that can be tolerated by
subjects receiving cancer chemotherapy are much more severe than
those of patients receiving treatment for a benign condition such as
a simple headache. In fact, the formers are willing to endure serious
side affects in exchange for a prolongation of survival or chance of
a cure (I am willing to suffer from severe nausea and fatigue if this
will give me a chance of cure).
The latter will balance the analgesic effect with any other unwanted
effects and refuse to continue treatment unless the balance is
extremely favourable (my headache went away but my stomach was upset,
so what is the use of this medication?).
Safety is a general term whereas tolerability depends on the
therapeutic class and gives you an idea of the drug effectiveness
rather than efficacy i.e. a drug can be effective on the course of a
disease but in real life (in well-controlled investigations) too many
patient refuse treatment due to side effects (poor tolerability) and
as a results of this the drug has limited clinical therapeutic value.
References:
Clinical Research Glossary version 4.0
Applied Clinical Trial actmagazine.com
EMEA CPMP/ICH/363/96. March 1998
Guidance on statistical principle for clinical trials
Page 35
Best regards,
Stefano Persiani, PhD
Director,
Drug Metabolism, Pharmacokinetics and Dynamics
Rotta Research Laboratorium
The R&D Division of Rottapharm SpA
Via Valosa di Sopra, 9
20052 Monza (MI)
ITALY
T +39 039 7390396
F +39 039 7390371
E-mail: stefano.persiani.-at-.rotta.com
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Thanh,
A European definition can be found in the following guideline: http://
www.emea.eu.int/pdfs/human/ich/036396en.pdf
"The safety of a medical product concerns the medical risk to the
subject...
The tolerability of the medical product represents the degree to
which overt adverse effects can be tolerated by the subject"
The FDA opinion on that is basically the same.
Best regards,
Michael Beckert, MD
Executive VP & COO
LifeCycle Pharma A/S
Kogle Alle 4
DK-2970 Horsholm
Denmark
Phone: +45.36130381
Fax: +45.36130319
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