Transcript “Emerging Regions” (ERs)

Critical Considerations for
Clinical Research in
“Emerging Regions” (ERs)
Craig A. Metz, PhD
Vice President, Regulatory
GlaxoSmithKline
Key Points to Consider
Data Integrity
Generalizability
Ethics
What’s Being Said About
Studies in ERs
Notable Quotes
In addition to manufacturing challenges, Dr. Woodcock
explained that FDA has to interpret and extrapolate
data from clinical trials conducted overseas. “We
have to figure out how to deal with...intensified in recent
years...extrapolating findings from one population, maybe
a Third World-type of population, to our population and
making sure the drug could still be safe and
effective...under the conditions of the United States.”
Notable Quotes
John Jenkins
Jenkins, who spoke on the audience-submitted question
with CDER associate director for medical policy Robert
Temple, said the trend has also caused FDA to have
“concerns about the local standards of medical
practice and how that may influence the ability to
extrapolate and interpret the data that are brought back
for consideration for the U.S. population.”
Notable Quotes
Robert Temple
“I’m more worried about depression studies. We’ve had some
fairly stunning examples of at least one drug that looked
pretty good in studies in South America and Eastern
Europe, and we’re finding them not replicable in Western
Europe and the U.S. We have no idea what that means. We
have no reason to think anybody cheated.”
“it’s extremely common to accept data that’s collected from a
wide variety of places in the world. Usually there’s fair
consistency and it’s not a particular problem. I have to say
we’ve not seen studies from India yet. We’ve seen a couple
of giant Chinese studies that could very well figure in favorable
actions — but not India yet, although we all know people who
are moving there. When you talk to companies about what
they encounter, they’re well aware that there are differences
in delving through protocols that are different by region ...”
Notable Quotes
Senator Grassley
According to an FDA official interviewed by HHS OIG,
about 20% to 25% of the trials for products that FDA
oversees occur outside the U.S., and this number is
growing. Because FDA’s regulations generally do not
apply to trials conducted outside of the U.S., the agency’s
oversight of foreign trials is limited. What steps, if any,
is FDA taking to ensure the quality and integrity of
data from foreign clinical trials, and what is FDA
doing to improve its monitoring of such trials?
Notable Quotes
EMEA Reflection Paper
Clinical trials are now increasingly being conducted in
countries outside the EU and the relevance of the data
for EU patients is not always clear. In addition, there
are now also examples of results of trials conducted
globally, for which interpretation of the data for the EU
was difficult.
Data Integrity
Each FDA Division may have a different philosophy
regarding data from ERs
Are appropriate sensitivity analyses being conducted to
evaluate the potential for regional effects?
– How/when do you obtain regulatory authority concurrence with
your analytical plan?
When are the regulatory authorities apprised of your
proposed enrollment balance across regions for the
primary efficacy studies?
Data Generalizability
Potential for unknown/poorly understood regional
differences in medical practices/standard of care
Potential impact of culture/language on the effective
deployment of PROs in ERs
Placebo response rates may be higher in ERs for certain
disease settings which could decrease study power and
lead to failed trials
The more subjective the primary registration endpoint is
the more regulatory risk is invoked with a development
program involving significant recruitment from ERs
Ultimate Goal
APPROVAL
NOT
submission