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What is a "Special Population"?
Initial estimates of clinical pharmacokinetic parameters are usually made under
standardized conditions in as homogeneous group of volunteers as is possible. After
an overnight fast, the test dosage form is administered with 240 mL [no more! No
less!] of room temperature tap water. Over the next 4 or 5 estimated half-lives,
10 to 20 blood samples are collected to measure the analytes of interest. The subjects
participating in the study are usually healthy male, nonsmoking volunteers, between
the ages of 18 and 45, weighing more than 50 kg, but usually within 15% of ideal
body weight, with all clinical laboratory and physical assessment within normal
limits. The subjects take no medications and have no unusual habits that would potentially
interfere with assessment of pharmacokinetic parameters. Clearly, these subjects
do not reflect most of the patients who will be taking the medications upon their
approval, and probably not even reflective of subjects with various diseases who
will be participate in phase 2 and 3 studies. ‘Special Populations’ is the catch
all reference to subjects and patients who differ in some way from the standard
healthy volunteers who make up the reference population. The most frequently studied
special populations are people with impaired renal function or impaired hepatic
function. Kidney and liver health and function are usually important to the elimination
of drugs and so an understanding of the impact of decreased elimination-organ function
is necessary to guide dosing for patients in clinical trials and for patients receiving
medications. Other special populations include children, from premature neonates
to teenagers, the elderly, including the very old, those above age 75 years, pregnant
or lactating women, and the obese. Differences in pharmacokinetics and pharmacodynamics
between women and men and among people of different ethnicity or race are also usually
included in Special Population discussions as well.
Why is there an AAPS Focus Group interested in Special Populations?
While the impact of renal impairment and hepatic impairment was understood to affect
drug elimination, the wide range of impairment, and the confounding effects of different
pathology that may or may not coexist with end organ failure make the study of these
patients challenging. Other special population studies were prompted by well known
therapeutic disasters, such as ‘gray baby syndrome’ that may be observed in infants
receiving chloramphenicol. Regulatory guidances have been developed for the study
of drugs in children, the elderly, as well as the conduct of pharmacokinetic studies
in subjects with impaired hepatic function, impaired renal function among others,
but important study issues remain. As assay technology and computer power have improved,
study design has become more sophisticated and in turn, more important research
questions identified. The need for efficient trial design necessitates careful planning
so that the appropriate special population studies are performed, without undue
risk to these sometimes very fragile subjects.
The Special Population Studies Focus Group is affiliated with both the CPTR and
the PPDM sections because the research questions arising about drug use in special
populations, issues of efficiently studying special populations, designing studies
to include them with other subjects, appropriate interpreting and ultimately arriving
at reasonable dosing recommendations for use of medications fall in both sections.
It is also not unreasonable, that the Special Population Studies Focus Group would
also work with other sections interested in excipients or formulations for example,
because of issues of common interest. One of the Hot Topics held at the 2008 Annual
Meeting on the topic of the new Pediatric Investigation Plan procedure recently
introduced in Europe was sponsored by the Special Population Studies Focus Group
with the support of the Regulatory Sciences Section.
Like all focus groups, the Special Populations Focus Group proposes programming
for the AAPS Annual Meeting and the National Biotechnology Conference, and members
are encouraged to submit posters to the national meetings and papers to AAPS Journal
on topics of interest to drug development in Special Populations.
The Special Population Studies focus group discusses topics such as:
- Pharmacokinetic and pharmacodynamic studies in populations such as the elderly,
women and children
- The effect of renal impairment on hepatic cirrhosis on the on the pharmacokinetics
of various drugs
- Pharmacokinetic studies in some disease catagories, e.g., diabetes, CHF, stable
coronary artery disease
The focus group chair will collect topics of interest and an attempt will be made
to cover these topics at the Annual Meetings. If you have an interest in becoming
part of this Focus Group please contact Dyal C. Garg, Ph.D.
JOIN THE SPECIAL POPULATION STUDIES FOCUS GROUP
To join the Special Population Studies Focus Group, click
here.
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