PHARMACOLOGY
PHARMACOLOGY
PHARMACOLOGY
AHMAD MURTAZA
Roll no:
70115960
Semester:
6B
Subject:
PHARMACOLOGY
Assignment:
The U.S. Food and Drug Administration (FDA) can significantly reduce the risk and
uncertainty that discourages drug developers from pursuing new antibiotics by
applying their unique access to data. A large hurdle in the approval of new
antibiotics is the determination of just how great the clinical effect must be. The
availability of robust and uniform historical controls to measure treatment effects
against would greatly increase the feasibility of completing trial enrollment and
remove some of the uncertainty that drug developers face in establishing
endpoints. The FDA has accumulated numerous and varied data sets on clinical
outcomes of infections under different treatment scenarios, including those with
pharmacometric data. These data are available to drug developers only in
fragmented, often proprietary records. The FDA should make these data useful to
current drug development efforts by conducting and publishing a meta-analysis
deriving historical control outcomes of different infections and under different
conditions.
The FDA should continue to build on the progress it has made in the last few years
toward using this analysis to establish clear, feasible, and uniform expectations of
clinical effectiveness across the field of antibiotic indications. While likely to be
imperfect, definition provided by a wide-reaching base of historical control data
would have three important benefits. It would significantly reduce the uncertainty
antibiotic developers face in trying to establish primary outcome expectations in
clinical trials to meet regulatory acceptance. It will also increase the feasibility of
completing trial enrollment. Acceptable historical controls will allow direction of all
enrollable patients to investigational therapy. In the many cases of studies reliant
on a limited enrollable population, this could make the difference between a study
being feasible or not.
The U.S. Department of Agriculture (USDA) can catalyze market forces that will
reduce the prolific agricultural use of antibiotics. The USDA has instituted
certification of consumer products to set standards specific to industry practices
and enable these to be recognized by consumers. Certifications such as “USDA
Prime” for beef products (4) and “Organic” and “Biobased” on a wide range of
commodities (5, 6) have as a side effect created labels with market value. The
USDA should exercise this certification authority and create a “No Feed-
Antibiotics” label to provide consumers with the same ability to discriminate food
products that have been produced without growth-promoting antibiotics.
Antibiotic use in agriculture is recognized as a contributor to increasing antibiotic
resistance (7). Public awareness of this problem is sufficient to strengthen market
incentives against the still prolific use of antibiotics in agriculture when combined
with a widely recognized certification. This, and the next proposed action, will have
incremental effects in reducing antibiotic use for animal growth promotion—the
next best alternative to a ban such as Europe's, which has been unachievable in
the U.S.
In December 2013, the FDA released Guidance for Industry number 213, which
seems unlikely to reduce the impact of using antibiotics as growth promoters in
farm animal production on the development of resistance. Although almost all of
the producers of antibiotics affected by the guidance signaled their intent to
request withdrawal of their approvals for feed use (14), many withdrawal requests
are stated to be because the, “products are no longer manufactured or marketed”
(15). The guidance focuses on eliminating the growth-promoting use of just
“medically important” antibiotics (16). This does not appear to be removing
antibiotics from use that are currently marketed and used for animal growth
promotion. Further, it will not close the gate on collateral selection for resistance
against medically important antibiotics, when genetically linked resistance
elements to other antibiotics remain under selection.