DISCUSSION QUESTIONS FOR MOSQUITO REPELLENT STUDIES

The Human Studies Review Board (HSRB or Board) has discussed and
provided advice to EPA on scientific and ethical issues related to the
conduct of field studies to evaluate the efficacy of mosquito repellent
products.  The HSRB has reviewed both proposals for new field studies
and the results of completed studies.  The HSRB has noted that, although
there are many similarities across studies, not all studies employ the
same study design.  The HSRB has identified several methodological
issues for which additional background information would assist the
Board in its evaluation of such studies.  

BACKGROUND	

Currently, EPA requires all pesticide products that claim to repel
mosquitoes to provide data on the duration of efficacy under field
conditions at two biologically distinct sites.  These data are derived
from human research with subjects who have been treated with the
repellent formulations in the field.  The Agency evaluates the duration
of repellent efficacy for a subject by calculating the time from
application of the repellent to the occurrence of an event indicating an
efficacy failure.  Historically, for field studies of mosquito
repellency, EPA has used the “first confirmed bite” as an indication
of efficacy failure on a test subject.  Several recent studies have
shifted to the “first confirmed landing with intent to bite;” EPA
has accepted this alternative endpoint.  A “confirmed landing” on a
test subject is a mosquito landing followed by a second landing on the
same subject within a specified period of time (usually 30 minutes)
after the initial landing.  

Field studies typically involve 6 – 10 subjects who have been treated
with a defined amount of the test material.  Each subject is then
regularly and repeatedly exposed to ambient mosquito populations for a
fixed interval of time until the subject experiences an efficacy failure
followed by a confirmation with the specified period of time. Mosquito
landing pressure (representing intent to bite) at a site is monitored by
concurrently exposing untreated subjects to mosquito landings.  A study
is considered valid only if there are at least a specified minimum
number of mosquito landings on untreated subjects during each exposure
interval. 

On October 25, 2007, the HSRB will discuss scientific aspects of the
design of field studies to assess the efficacy of mosquito repellents. 
For this meeting the Board has requested consultants to provide
specialized information or assistance to the Board.   The Board is
particularly interested in the frequency, duration and timing of
exposure of subjects to potential mosquito landings.  The Board requests
each consultant to respond briefly to the series of questions below. 
Please send the responses to the HSRB Chair and Designated Federal
Official (DFO) at least one week before the meeting—i.e., by no later
than October 18.  All responses will subsequently be provided to the
other consultants, the HSRB members, and EPA staff for their review, and
will be posted on   HYPERLINK "http://www.regulations.gov/" 
www.regulations.gov  under docket ID number, EPA-HQ-ORD-2007-0942.  HSRB
consultants will be available at the meeting to discuss their responses
and address questions from the Board.  The questions for Board
consultant consideration are provided below: 



DISCUSSION QUESTIONS

·	What do data show about the variability of the time intervals between
first and subsequent landings in mosquito repellent field trials?

The literature indicates that the time intervals between first and
subsequent bites/landing is quite variable and depends on several
factors such as skin temperature, blood content and circulation, hairs
on skin surface, and density of mosquito population.  Normally first
5-15 minutes is sufficient for a mosquito to find the host and land/bite


·	What is the current scientific understanding of how factors other
than repellent efficacy could affect the likelihood that an initial
event—a mosquito landing or mosquito bite—would be “confirmed”
by another similar event within 30 minutes?  Please address at least
these factors:

Characteristics of mosquito populations

The mosquito population densities vary widely and there is a lack of
coordination and agreement among investigators on mosquito population
sizes or landing/biting rates.  It has been shown that insect
populations of different density do not provide equivalent estimates of
protection time when the test method used depends on fixed endpoint for
protection time such as first (or second) observed bite.  This may be
because the first (or second) insect bite in a small test population
represents a less extreme position in the tolerance distribution than
the first (or second) bite in a large population. 

o	Characteristics of test sites

Weather conditions, test site terrain, vegetation, and proximity to
human dwellings probably can affect the mosquito host seeking and
landing/biting behavior.  It has been shown that temperature plays an
important role on the effectiveness and persistence of repellents. 
Protection periods of the repellents tested decreased by an average of
7.6 minutes for each increase of 1° C in ambient temperature.  

o	Characteristics of test subjects

Dr Strickman has adequately address the test subject characteristics in
his response 

o	Characteristics of test methods

In bioassay test methods the responses of the mosquito population to the
test material are determined over time/application.  Test method design
and observation/collection techniques have the potential of
significantly impacting the study results.  Factors such as test
exposure skin surface between control and treated subjects, restricting
exposure of control subject to beginning and end of the test, by
preventing actual bites and counting landings instead, and selective
application of treatments or selection of control subjects.  Such
shortcuts or substitutions inevitably lead to ambiguity in the data
obtained because the biting activity of a mosquito population is in a
constant state of flux in course of any repellent field test.

It is suggested that the ideal test methods incorporating or simulating
activities of the end user application/protection from mosquito
landing/bites may provide beneficial and relevant information.    

·	Can the impact of such factors on the likelihood or timing of an
initial and confirming event be predicted?  Can it be quantified?   

In repellent studies, procedures for recoding landing/bites may be
either continuous recording, meaning that the observer records the
occurrence and time of each landing/bite from the beginning to the end
of the method, or time sampling, meaning that the observer records the
occurrence of landing/biting periodically during the method.  In
repellent studies the initial and confirming event (landing/bites)
cannot be predicted.    

 

10/04/07	

	Col. Raj Gupta’s Responses to Discussion Questions

