1

William Jordan

Senior Policy Advisor

Office of Pesticide Programs

OPP Policy Decisions Regarding 

Insect Repellent Efficacy Testing
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Policy Issues

 Objective of repellent efficacy testing

 Choice of endpoint for repellent efficacy studies

 Statistics & handling of censored data

General Considerations

 Consistency of approach

 History of testing methods/implementation
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Issue 1: Objective of Repellent Testing

 Preferred objective is to measure 

duration of complete protection 

 Consistent with market research by 

both EPA and registrants: Repellent 

users expect and demand complete 

protection
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Issue 2: Choice of Endpoint

 Preferred study endpoint is first confirmed 

failure event

 Failure events vary depending on species:

 Landing (or bite) for mosquitoes and flies

 Crossing for ticks and chiggers

 Choice of confirmed events as endpoints 

reduces variability
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Issue #3: Statistics & Data Censoring

 Preferred summary statistic is Kaplan-Meier 

median Complete Protection Time with 95% c.i.

 If K-M median is not calculable, mean CPT with 

95% c.i. is acceptable

 Underestimates of mean and variance resulting 

from treating censored data points as confirmed 

failure events are acceptable for regulatory 

purposes
6

John M. Carley

Office of Pesticide Programs

Product Performance Test Guidelines 

OPPTS 810.3700: Insect Repellents 

to be Applied to Human Skin
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Role of Guidelines

 Data requirements

 Defined by regulation

 Interpreted and applied case-by-case

 Test guidelines

 Advisory, not mandatory

 If a particular data requirement is imposed, here’s how we 

recommend you address it

 Standard Evaluation Procedures (SEPs)

 Labeling standards
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Assumptions Underlying Guideline

 OPP will continue to require laboratory and 

field tests of topical repellent efficacy

 Guideline should include standard methods 

for commonly required types of repellent 

efficacy testing

 Guideline should serve as a single source 

for all guidance directly relevant to 

sponsors and investigators conducting 

repellent efficacy tests
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Events Since October 2008

 HSRB Comments

 On guideline draft of September 2008

 On subsequently reviewed protocols and 

completed studies

 Other Comments

 WHO Repellent Testing Guidelines

 Consumer Research
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EPA Response

 Compile all HSRB and other comments

 Use multidisciplinary internal workgroup to 

analyze comments by topic and issue

 Consult with repellent scientists from USDA

 Identify and resolve policy questions

 Revise guideline within policy framework in 

response to comments
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Scope of This Guideline

 Guideline includes 

 Technical guidance for commonly required standard performance 

tests for skin-applied repellents

 What investigators need to know about the Human Studies Rule 

to prepare protocols and conduct studies likely to be reviewed 

favorably by EPA and the HSRB

 Guideline does not include technical guidance for 

 Non-standard or rarely performed tests 

 Tests of repellency of impregnated fabrics or clothing

 Tests of products intended to repel insects from indoor or 

outdoor spaces
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Overall Structure of Guideline

 Introduction and Definitions

 General guidance applying to all repellent studies

 Developing a protocol

 Review of protocols

 Changes to approved protocols

 Execution

 Reporting

 Records retention

 Guidance applying to commonly required tests

 References and Appendices
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Commonly Required Standard Tests

 Lab tests to determine typical 

consumer dose

 Lab tests with mosquitoes

 Lab tests with biting flies

 Field tests with mosquitoes

 Field tests with biting flies

 Lab tests with ticks or chiggers
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Changes in this Revision

 Reflection of policy decisions

 Streamlined organization

 Changes in general guidance

 Study design

 Statistics

 Ethics

 Changes in specific guidance
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General Guidance: Study Design

 Clarify limited appropriateness of multiple treatments 

per subject 

 Recommend treated subjects not also serve as 

untreated controls

 Recommend positive controls in all studies (20% deet 

in ethanol at standard 1 g/600 cm2rate)

 Emphasize importance of representative samples 

 Recommend testing attractiveness to target pests to 

qualify subjects
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General Guidance: Statistics

 Recommend longer test duration and 

earliest practical treatment to reduce 

potential for data censorship

 Revise discussion of sample size

 Revise discussion of analysis plan
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General Guidance: Ethics

 Clarify—

 Prerequisite research

 Risks of concern are only those associated with participation in 

research (vice background risks)

 Regulations require benefits discussion and assessment of relation 

of benefits to risks

 Subjects from potentially vulnerable populations should not be 

arbitrarily excluded if special care would provide adequate 

protection of their safety and welfare

 Rationale for discouraging distant travel

 Cite Flesch-Kincaid Grade Level as measure of readability

 Call for specifying how investigators will confirm candidate 

understanding
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Specific Guidance: Dose Determination

 Clarify methods—

 For measuring subject skin area

 For calculating standard dose

 Identify additional reporting elements
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Specific Guidance: Mosquitoes & Flies

 Lab tests: Clarify rearing techniques, cage size, insect 

density

 Field tests: Clarify subject placement and behavior; 

revise site-selection criterion for pre-test absence of WNV

 Recommend standard positive control

 Discourage use of treated subjects as untreated controls 

 Identify additional reporting elements

 Merge and harmonize M & F guidance
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Specific Guidance: Ticks & Chiggers

 Clarify description of recommended method

 Recommend refining definition of “crossing” 

to suit species and life stage used in testing

 Accept concurrent testing with 2 species

 Clarify rearing techniques, number of ticks, 

test conditions, subject preparation

 Recommend standard positive controls
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Next Steps

 Publish this guideline for immediate use

 Further refine this guideline in response to 

comments and new developments 

 Continue development of additional 

guidelines:

 Impregnated materials and space repellents

 Exposure studies