Phase III studies require the world-wide recruitment of a large number of patients.
Typically, thousands of patients are recruited through hospitals and local physicians.
Patients may be exposed for long periods, which may continue indefinitely if
the treatment provides a relief from symptoms.
Animal programmes must be enhanced to include chronic dosing studies of 6 to12
months duration. Further reproductive toxicology studies investigating damage
to the developing foetus and effects on male and female fertility must also
be performed. The portfolio of absorption, metabolism, distribution and excretion
(ADME) studies must be completed and additional immunotoxicology studies should
be considered. Due to the increased dosing period the cancer causing potential
of a drug must be evaluated. Rodent carcinogenicity studies are conducted for
the lifetime of the animals (18-24 months). The appearance of tumours and cancerous
lesions are reported after regular observations throughout the study and at
the terminal histopathology examination.
Again, exposures must be quantified through pharmacokinetic analysis with a
bioanalytical method validated to the requirements of Good Laboratory Practice
(GLP).
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