1

Vector Biology Program, 

Division of Microbiology and Infectious Diseases

National Institute of Allergy and Infectious Diseases

National Institutes of Health

A Primer for the Design and 

Conduct of Clinical Trials for 

Vector Interventions 

 May 7-8, 2018

 Meeting Report
2

Table of Contents 

Executive Summary................................................................................................................. 3

Meeting Summary ................................................................................................................... 3

Session I. Generating Evidence for Decision Makers ........................................................................ 4

Session II. Planning a Field Study ..................................................................................................... 5

Session III. Regulatory Requirements ............................................................................................... 6

Session IV. Putting It All Together: Case Studies ............................................................................... 7

Session V. Team-Based Exercise and Next Steps............................................................................... 8

Appendix 1: Agenda ................................................................................................................ 9

Appendix 2: Participants....................................................................................................... 11

Appendix 3: Relevant Publications........................................................................................ 14

Appendix 4: Resources.......................................................................................................... 16
3

Executive Summary 

On May 7-8, 2018, the National Institute of Allergy and Infectious Diseases (NIAID) held a twoday workshop to discuss the development of clinical trials for vector control interventions. The 

intended outcomes of the workshop were to: 1) better understand how to develop rigorously 

designed, multidisciplinary clinical trials for vector interventions; 2) enable multidisciplinary 

collaborations; and 3) improve capacity of investigators to develop competitive applications for 

NIAID clinical trial funding opportunities. 

Attendees included investigators involved in vector control product development, experts from 

industry, representatives from regulatory agencies, other funders of vector control research, and 

NIAID staff. The first day included presentations and discussions on planning a field study, 

understanding regulatory requirements, and reviewing case studies. On the second day, 

participants worked in break-out groups to develop sample outlines of a hypothetical clinical 

study for an assigned vector intervention. Discussions included the identification of various 

challenges, gaps, and recommendations for designing and implementing vector control 

intervention trials. 

Meeting Summary 

Opening Remarks

Dr. Emily Erbelding, Director of the Division of Microbiology and Infectious Diseases (DMID) 

in NIAID, opened the workshop by contextualizing the importance of vector control research. 

She noted that a recent CDC report indicated that infectious diseases transmitted by vectors like 

mosquitos, fleas, and ticks more than doubled in the US between 2004 – and 2018 

(https://www.cdc.gov/ncezid/dvbd/vital-signs/index.html). Dr. Adriana Costero-Saint Denis, 

Vector Biology Program Officer in DMID’s Parasitology and International Programs Branch, 

stated that the purpose of the workshop was to discuss the development and planning of clinical 

trials for vector interventions that aim to generate evidence for decisionmakers. 

Keynote: The Need for Clinical Trials of Vector Interventions

Dr. Anne Wilson of Durham University emphasized the public health importance of vector 

control by highlighting that 80% of the world’s population is at risk of contracting at least one 

vector-borne disease. She provided examples of vector control successes as well as challenges to 

their sustained effectiveness and to the development of new tools. Dr. Wilson outlined two 

pathways for WHO prequalification of vector control products: 1) a product in a class with an 

existing WHO policy recommendation can proceed to prequalification; 2) a product in a class 

without a WHO policy recommendation requires a Vector Control Advisory Group (VCAG) 

review, a recommendation by the Strategic and Technical Advisory Group (STAG) or Malaria 

Policy Advisory Committee (MPAC), and a WHO policy recommendation to proceed to 
4

prequalification. For products that are first-in-class, the VCAG requires at least two randomizedcontrolled trials in different settings with epidemiological outcomes. Dr. Wilson also highlighted 

that there is a lack of evidence on the efficacy of vector control tools; therefore, there is a need to 

invest in rigorously designed field studies. In the discussion that followed, it was noted that it is

important to distinguish between efficacy (whether a tool works), effectiveness (whether it 

reduces disease), and compliance (whether people use it correctly). 

Session I. Generating Evidence for Decision Makers 

Speaker Presentations: 

1. New Tools for Vector Control: A Regional Perspective – 

Dr. Haroldo Bezerra of the Pan American Health Organization (PAHO) outlined the goals of 

the Public Health Entomology and Vector Control Program at PAHO, which include 

strengthening the application of entomology in vector control, implementing Integrated 

Vector Management (IVM), and establishing a surveillance and management system for 

insecticide resistance. He also provided examples of current pilot studies of novel techniques 

in the Americas, including several studies of Wolbachia and gene drive methods. 

2. Observational Studies for Vector Interventions – 

Dr. Ben Beard of the Centers for Disease Control and Prevention (CDC) illustrated the utility 

of observational studies in assessing the effectiveness of new vector control tools. He 

defined an observational study as observing the effect of exposure on the study subjects 

without assigning the exposure to the participants. He reviewed the strengths and weaknesses 

of different types of observation study designs, including case-control studies, cohort studies, 

cross-sectional studies, and other controlled designs. 

3. Clinical Trial Designs to Address Different Questions/Settings – 

Dr. Immo Kleinschmidt of the London School of Hygiene and Tropical Medicine made the 

case that clustered randomized controlled trials (cRCTs) are the best way to evaluate vector 

control interventions. He reviewed several examples of cRCTs and noted that it is important 

to consider the community setting when designing a trial. 

Panel Discussion: 

A panel of ten experts, five from disease-endemic countries and five representing major funders, 

took questions from participants on study design, the regulatory environment, country-specific 

context, and vector-specific considerations. Key takeaways were: 

• There is a need for funders and regulatory decisionmakers to establish standards for the

minimum level of protective benefit required for an intervention to be viable. 
5

• In terms of efficacy versus effectiveness, it was suggested that local program officials 

typically care more about effectiveness (i.e. reduction of disease). 

• The VCAG process is seen by some as overly rigorous and inflexible. The requirement 

for two randomized controlled trials in different settings was discussed as being too 

onerous, particularly during an outbreak when an intervention is needed urgently. 

• It was suggested that including entomological data in a study design can help explain 

conflicting results for the same intervention in different settings. 

• There is a consensus that the evidence base for vector control interventions needs to be 

expanded, but there are varying viewpoints on how much evidence is needed and how to 

obtain it.

Session II. Planning a Field Study 

Speaker Presentations: 

1. Risk Assessment – 

Dr. Fred Gould of North Carolina State University reviewed the three components of risk 

assessment – risk analysis, risk characterization, and risk management – and illustrated the 

importance of appropriate risk consideration when designing a clinical trial. 

2. Bioethics/Community Engagement – 

Dr. James Lavery of Emory University discussed that while community and stakeholder 

engagement (CSE) is recognized by funders and as a valuable part of research programming, 

the limited evidence base for CSE is hurting its funding allocations. He suggested that 

research funders can improve the evidence base for CSE by: 1) encouraging better reporting 

and scrutinizing already funded CSE strategies; 2) recognizing the asymmetry in evidence 

required for CSE compared to other aspects of research programs; 3) recognizing CSE as a 

critical part of program performance; and 4) experimenting with flexibility in protocols and 

budgets that adapt to stakeholder insights and studying the implications on program 

performance. 

3. Field Site Selection – 

Dr. Thomas Scott of the University of California-Davis explained that there are few 

published guidelines on site selection for vector control trials. He outlined various site 

selection criteria, including presence of the vector, sufficient incidence of the disease, and 

adequate local political and regulatory support. 

4. Challenges and Successes – 
6

Dr. Simon Warner of Oxitec, a company that develops insect control technology, described 

the company’s OX513A gene drive technology. Oxitec injects male Aedes mosquitos with 

the self-limiting gene OX513A. The males then mate with wild female Aedes and pass the 

gene to their offspring. The males die within days, and the offspring do not survive to 

adulthood. Oxitec has conducted successful field trials of this technology in Brazil, Panama, 

and the Cayman Islands. 

Dr. Stephen Dobson of MosquitoMate described the use of Wolbachia to suppress mosquito 

populations. Wolbachia is a bacterium found in insect species that is inherited and interferes 

with sexual reproduction. Wolbachia can be used in two different strategies: population 

replacement and population suppression. In population replacement, Wolbachia-infected

females are released into an area to interfere with virus transmission. In suppression, 

infected males are released with the goal of reducing the mosquito population. 

Discussion: 

• Participants noted the need to expand the evidence base for CSE but acknowledged that 

some things worth doing are not easily measurable or quantifiable. 

• Layering is an important strategy in designing an intervention trial. Layering refers to 

determining the most appropriate time for various aspects of a project. In gene drive, for 

example, community engagement is critical at the outset because without community 

support an intervention may not move forward.

• Participants noted that sometimes it is impossible to predict whether a site will have 

sufficient incidence rates during the site selection phase. In those cases, selecting multiple 

sites can mitigate risk. Multiple sites may also be required to assess an intervention in 

different contexts. 

Session III. Regulatory Requirements 

Speaker Presentations: 

1. Environmental Protection Agency (EPA): Vector Control Pesticides – 

Dr. Susan Jennings of the EPA described the EPA’s pesticide registration process. Pesticide 

registration data requirements depend on which category the pesticide falls into –

conventional chemical pesticides, biopesticides, or antimicrobial pesticides. There are also 

different types of registrations beyond commercial use such as experimental use permits 

(EUP). Dr. Jennings noted that a current challenge for regulators is determining how to 

categorize and register new interventions such as Wolbachia and gene drive methods which 

do not fall neatly under existing categories. Dr. Jennings also noted the importance of risk 

assessment and risk management in the evaluation of a pesticide. 

2. Food and Drug Administration (FDA): New Animal Drugs and Vector Control – 
7

Dr. Heather Lombardi of the FDA explained various vector control methods that target 

animals, including drugs directly administered to livestock to reduce transmission and 

genetic engineering of animals to reduce disease or transmission. She stated that new animal 

drugs are regulated under the United States Federal Food, Drug, and Cosmetics Act (FD&C 

Act). The Act defines a new animal drug as “any drug intended for use for animals other than 

man.” She explained that in the 2017 “Guidance for Industry 236” document, the FDA 

clarified that mosquito-related products that function as pesticides for population control are 

not drugs and are therefore regulated by the EPA. Mosquito-related products for lowering 

viral loads or preventing disease transmission are drugs and are regulated by the FDA. Dr. 

Lombardi outlined the steps involved in reviewing/approving new animal drugs. She 

recommended that sponsors involve the FDA early in product development, especially for 

novel products which pose a regulatory challenge. 

3. NIAID Funding Opportunities for Clinical Research and Resources 

Dr. Greg Deye of NIAID’s Division of Microbiology and Infectious Diseases reviewed the 

definition and aspects of a clinical trial according to NIH. He explained that the defining 

components of clinical trials are that participants are prospectively assigned to an 

intervention and that the intervention is evaluated for biomedical or behavioral outcomes. A 

study with only an entomological endpoint would not be considered a clinical trial. Dr. Deye 

outlined NIH funding mechanisms for clinical trials and provided links to further resources 

and funding announcements. 

Session IV. Putting It All Together: Case Studies 

Investigators involved in planning or executing ongoing vector control intervention trials 

presented their trial designs, planning considerations, challenges and lessons learned. The 

presenters included:

• Dr. Mauro Teixeira of Universidade Federal de Minas Gerais, who is planning a Phase III 

parallel-design, cluster-randomized trial to evaluate OX513A genetically engineered 

mosquitos to reduce the burden of arboviruses in Brazil. 

• Dr. Mark Mulligan of Emory University’s NIAID-funded Vaccine and Treatment 

Evaluation Unit (VTEU), who gave an overview of the vaccine discovery and 

development process. 

• Dr. Katie Anders of Monash University and Dr. Nicholas Jewell of the University of 

California-Berkley, who described the Applying Wolbachia to Eliminate Dengue 

(AWED) trial in Indonesia that showed Wolbachia-infected mosquito deployments

reduced incidence of Dengue in the study population. 

Presentations were followed by a discussion of general trial issues as well as issues specific to 

the case studies. A major discussion point was the need to better explain conflicting results from 
8

trials of the same intervention, particularly to decisionmakers who may misinterpret discrepant

results. There are varying environmental, ecological, and social factors that may cause different 

results for the same intervention in different settings. It was suggested that modeling could be 

useful in explaining and anticipating variability in results from different settings. 

Session V. Team-Based Exercise and Next Steps 

Participants were organized into 10 groups focused on a specific vector species (Aedes, 

Anopheles, Culex, Sabethes, Ixodes, Lutzomyia, Glossina, Xenopsylla, Simulium, and Triatoma) 

and vector control intervention. Each group designed a mock clinical trial to test their 

intervention and presented it the larger group. 

Challenges & Gaps

During the meeting, participants noted various challenges and gaps for designing and 

implementing clinical trials for vector control, including the following: 

• New tools are needed to control vector-borne diseases. 

• There is insufficient evidence on the effectiveness of many vector control interventions, 

particularly for Aedes. More evidence is needed, but there is no consensus on how much 

or what type of evidence is needed. 

• Vector-borne disease control programs are often under-resourced and cannot support 

proper surveillance to monitor the effectiveness of the interventions. 

• New methods are needed to monitor the efficacy or effectiveness of a vector control 

intervention where the disease is declining but is still endemic, and where there is 

potential for resurgence when public health interventions end. 
9

Appendix 1: Agenda

DAY 1: 

5/7/2018

Knowledge Base Presentations

7:15 – 8:15am Registration

8:15 – 8:30am

Welcome Emily Erbelding, NIAID

Purpose/Format/Expectations Adriana Costero-Saint Denis, NIAID

8:30 – 9:00am Keynote: The Need for Clinical Trials of 

Vector Interventions Anne Wilson, Durham University

Generating Evidence (data) For Decision-Makers, Thomas Scott, Chair

9:00 – 9:20am New Tools for Vector Control: A Regional 

Perspective 

Haroldo Bezerra, Pan American 

Health Organization

9:20 – 9:40am Observational Studies for Vector 

Interventions

Ben Beard, CDC

9:40 – 10:00am Clinical Trial Designs to Address Different 

Questions/Settings

Immo Kleinschmidt, London School 

of Hygiene and Tropical Medicine

10:00 – 10:15am BREAK

10:15 – 11:20am Panel Discussion: Generating Evidence, Gaps and Challenges

Participants:

Kate Kolaczinski, The Global Fund to Fight AIDS, TB and Malaria 

Haroldo Bezerra, Pan American Health Organization

Immo Kleinschmidt, Vector Control Advisory Group 

Steven Kern, Bill and Melinda Gates Foundation

Jennifer Armistead, US Agency for International Development

Amy Morrison, Peru

Mauro Teixeira, Brazil 

Ulrike Fillinger, Kenya

Seydou Doumbia, Mali

Planning a Field Study, Ulrike Fillinger, Chair

11:20 – 11:40am Risk Assessment

Fred Gould, North Carolina State 

University

11:40 – 12:00pm Bioethics/Community Engagement James Lavery, Emory University

12:00 – 1:00pm LUNCH

1:00 – 1:20pm Field Site Selection

Thomas Scott, University of 

California, Davis

1:20 – 2:00pm Challenges and Successes Simon Warner, Oxitec

Stephen Dobson, MosquitoMate
10

Regulatory Requirements, Steve Huang, Chair

2:00 – 2:15pm Environmental Protection Agency (EPA) Susan Jennings, EPA

2:15 – 2:30pm Food and Drug Administration (FDA) Heather Lombardi, FDA

2:30 – 3:00pm NIAID Funding Opportunities for Clinical 

Research and Resources Gregory Deye, NIAID

3:00 – 3:30pm BREAK

Putting It All Together - Case Studies, Gregory Deye, Chair

3:30 – 4:00pm Vector Population Suppression Mauro Teixeira, Universidade 

Federal de Minas Gerais 

Mark Mulligan, VTEU

4:00 – 4:30pm Vector Population Replacement Katie Anders, Monash University 

Nicholas Jewell, University of 

California, Berkley

4:30 – 5:00pm Discussion

5:00 – 5:30pm Conclusions for Day 1 and Preparation for 

Day 2

DAY 2: 

5/8/2018

Breakout Groups

9:00 - 9:15am Instructions for Day 2 Adriana Costero-Saint Denis, NIAID

Gregory Deye, NIAID

9:15 – 11:45am Team-Based Exercise

Team Aedes

Team Anopheles

Team Culex

Team Sabethes

Team Ixodes

Team Lutzomyia

Team Glossina

Team Xenopsylla

Team Simulium

Team Triatoma

11:45 – 12:45pm LUNCH

12:45 – 2:45pm Report Back from Each Team and 

Discussion (12 minutes per team)

2:45 – 3:00pm Next Steps Adriana Costero-Saint Denis, NIAID

Gregory Deye, NIAID

3:00pm ADJOURN
11

Appendix 2: Participants

Name Affiliation Email

Nicole Achee University of Notre Dame nachee@nd.edu

Giovanni Coelho PAHO coelhogio@paho.org

Katie Anders World Mosquito Program katie.anders@worldmosquito.org

Matthew Collins Emory University - Hope Clinic matthew.collins@emory.edu

Jae Arega NIAID/NIH aregaj@niaid.nih.gov

Adriana Costero-Saint Denis NIAID/NIH acostero@niaid.nih.gov

Jennifer Armistead USAID/PMI jarmistead@usaid.gov

Roberto Barrera CDC amz9@cdc.gov

Ben Beard CDC cbeard@cdc.gov

Brinda Dass Foundation for NIH bdass@fnih.org

Kable Davis US Environmental Protection 

Agency

davis.kable@epa.gov

Liza Dawson NIAID/NIH dawsonl@niaid.nih.gov

John Beigel NIAID/NIH jbeigel@niaid.nih.gov

Gregory Deye NIAID/NIH gregory.deye@nih.gov

Uli Bernier USDA-ARS Uli.Bernier@ARS.USDA.GOV

Stephen Dobson University of Kentucky / 

MosquitoMate Inc.

sdobson@mosquitomate.com

Haroldo Sergio da Silva 

Bezerra

PAHO/WHO bezerrha@paho.org

Sarah Burnett PATH sburnett@path.org

Luis Castellanos PAHO castellanosl@paho.org

Seydou Doumbia University Clinical Research 

Center University of BamakoUSTTB

sdoumbi@gmail.com

Sally Eatmon NIAID/NIH sally.eatmon@nih.gov

Lars Eisen CDC evp4@cdc.gov

Lee Hall NIAID/NIH lhall@niaid.nih.gov

Noel Elman GearJump Technologies noel@gearjumptech.com

Emily Erbelding NIAID/NIH emily.erbelding@nih.gov

Kacey Ernst University of Arizona kernst@email.arizona.edu

Kristine Evers Technical Resources 

International (TR) Inc.

kevers@tech-res.com

Rick Fairhurst NIAID/NIH rfairhurst@niaid.nih.gov

Jody Ference WRAIR Jody.L.Ference.civ@mail.mil

Ulrike Fillinger ICIPE ufillinger@icipe.org

Ghiorghis Ghenbot NIAID/NIH ghiorghis.ghenbot@nih.gov

Fred Gould NCSU Fred_Gould@ncsu.edu

Christopher Gregory CDC hgk4@CDC.GOV
12

Name Affiliation Email

M Elizabeth (Betz) Halloran Center for Inference and 

Dynamics of Infectious 

Diseases (CIDID)

betz@fhcrc.org

Gabriel Hamer Texas A&M University ghamer@tamu.edu

Mary Hayden National Center for 

Atmospheric Research

mhayden@ucar.edu

Alison Hinckley CDC ahinckley@cdc.gov

Steve Huang NIAID/NIH steve.huang2@nih.gov

Helen Hull-Sanders EPA hull-sanders.helen@epa.gov

Maliha Ilias NIAID/NIH maliha.ilias@nih.gov

Marcelo Jacobs-Lorena Johns Hopkins School of 

Public Health

ljacob13@jhu.edu

Stephanie James Foundation for NIH sjames@fnih.org

Susan Jennings EPA Office of Pesticide 

Programs

jennings.susan@epa.gov

Nicholas Jewell University of California 

Berkeley

jewell@berkeley.edu

Deirdre Joy NIAID/NIH djoy@mail.nih.gov

Jim Kazura Case Western Reserve 

University

jxk14@case.edu

Steven Kern Bill & Melinda Gates 

Foundation

steven.kern@gatesfoundation.org

John Keven Michigan State University kevenjoh@msu.edu

Randall Kincaid NIAID/NIH randall.kincaid@nih.gov

Immo Kleinschmidt London School of Hygiene 

and Tropical Medicine

Immo.Kleinschmidt@lshtm.ac.uk

Kate Kolaczinski The Global Fund to fight AIDS 

TB & Malaria

kate.kolaczinski@theglobalfund.org

Jim Lavery Emory University jlavery@emory.edu

Stella Lee FDA stella.lee@fda.hhs.gov

Lisa M Lee WRAIR Lisa.M.Le58.civ@mail.mil

Megan Littrell PATH mlittrell@path.org

Heather Lombardi FDA heather.lombardi@fda.hhs.gov

Brian Lovett University of Maryland lovettbr@umd.edu

Enca Martin-Rendon Oxitec Ltd enca.martin-rendon@oxitec.com

Rex Mbewe Michigan State University mbewerex@msu.edu

Christina McCormick NIAID/NIH christina.mccormick@nih.gov

Steve Meshnick UNC Gillings School of Global 

Public Health

meshnick@email.unc.edu

Joseph Millum CC/NIH millumj@cc.nih.gov

Amy Morrison University of California Davis amy.aegypti@gmail.com

Mark Mulligan Emory University mark.mulligan@emory.edu

Seema Nayak NIAID/NIH seema.nayak@nih.gov
13

Name Affiliation Email

Alan Reynolds EPA reynolds.alan@epa.gov

Effie Nomicos NIAID/NIH enomicos@mail.nih.gov

Jason Richardson IVCC Jason.Richardson@ivcc.com

Laura Norris Bill & Melinda Gates 

Foundation

laura.norris@gatesfoundation.org

Molly Robertson PATH mrobertson@path.org

David O'Brochta Foundation for NIH dobrochta@fnih.org

Thomas Scott UC Davis twscott@ucdavis.edu 

Sunil Parikh Yale University sunil.parikh@yale.edu

Angus Spiers Innovation 2 Impact angus.spiers@innovation2impact.org

Aisha Patel Technical Resources 

International Inc.

apatel@tech-res.com

Raymond St. Leger University of Maryland stleger@umd.edu

Freddy Perez PAHO perezf@paho.org

Dan Strickman Bill & Melinda Gates 

Foundation

dan.strickman@gatesfoundation.org

Alex Perkins University of Notre Dame taperkins@nd.edu

Bruce Swihart NIAID/NIH Bruce.swihart@nih.gov

Jetsumon Prachumsri Mahidol University jetsumon.pra@mahidol.edu

Mauro Teixeira Universidade Federal de 

Minas Gerais

mmtex.ufmg@gmail.com

Malla Rao NIAID/NIH mrao@niaid.nih.gov

Matt Thomas Penn State mbt1965@gmail.com

Bobby Reiner University of Washington bcreiner@uw.edu

Cecilia Toledo UFMG cecilia.a.marques@gmail.com

Karen Tountas Foundation for NIH ktountas@fnih.org

Tom Unnasch University of South Florida tunnasch@health.usf.edu

Gonzalo Vazquez-Prokopec Emory University gmvazqu@emory.edu

Ned Walker Michigan State University walker@msu.edu

Joyce Wanga Technical Resources 

International

jwanga@tech-res.com

Simon Warner Oxitec Ltd simon.warner@oxitec.com

Stephen Waterman CDC shw2@CDC.GOV

Anne Wilson Durham University anne.wilson@durham.ac.uk

Guiyun Yan University of California Irvine guiyuny@uci.edu

Gaby Zollner AFPMB gabriela.z.romero.civ@mail.mil
14

Appendix 3: Relevant Publications 

Background Documents on Trials for Vectors:

1. Evidence-based vector control? Improving the quality of vector control trials. (2015)

2. Randomized controlled trials and changing public health practice (2017)

3. Guidance Framework for Testing of Genetically Modified Mosquitoes. (2014)

4. How to design Vector Control efficacy trials (WHO) (2017)

5. Framework for rapid assessment and adoption of new vector control tools. (2014)

6. Design of epidemiological trials for vector control products (WHO). (2017)

7. Assessing the effects of interventions for Aedes aegypti control: systematic review and meta-analysis of 

cluster randomized controlled trials (2017)

8. Quantifying the epidemiological impact of vector control on dengue. (2016)

9. Considerations in the design of clinical trials to test novel entomological approaches to dengue control. 

(2012)

10. Cluster Randomized Test-Negative Design (CR-TND) Trials: A Novel and Efficient Method to Assess the 

Efficacy of Community Level Dengue Interventions. (2018)

11. Parachute use to prevent death and major trauma related to gravitational challenge: systemic review of 

randomized controlled trials. (2003)

Related Articles of Interest: 

1. Broadening the application of evolutionarily based genetic pest management. (2007)

2. Terms of reference for the external evaluation group on New Technologies for controlling Aedes spp 

(PAHO). (2017)

3. A critical assessment of vector control for dengue prevention. (2015)

Vector Control Approaches:

1. Insecticide-treated bed nets and curtains for preventing malaria (review). (2004)

2. Female Adult Aedes albopictus Suppression by Wolbachia-Infected Male Mosquitoes. (2016)

3. Male mosquitoes as vehicles for insecticide. (2015)

4. Oxitec’s Vector Control Solution. (2016)

5. House screening with insecticide-treated netting provides sustained reductions in domestic populations of 

Aedes aegypti in Merida, Mexico. (2018)

6. Efficacy of Aedes aegypti control by indoor Ultra Low Volume (ULV) insecticide spraying in Iquitos, Peru. 

(2018)

7. Impact of autocidal gravid ovitraps on Chikungunya virus incidence in Aedes aegypti (Diptera: Culicidae) in 

Areas with and without traps. (2016)

8. Design and testing of novel lethal ovitrap to reduce populations of Aedes mosquitoes: community-based 

participatory research between industry, academia, and communities in Peru and Thailand. (2016)

9. Modification of arthropod vector competence via symbiotic bacteria. (1993)

Clinical Trial Examples:

1. Efficacy of topical mosquito repellent (picaridin) plus long-lasting insecticidal nets versus long-lasting 

insecticidal nets alone for control of malaria: cluster-randomized controlled trial. 

2. Efficacy of indoor residual spraying with dichlorodiphenyltrichloroethane against malaria in Gambian 

communities with high usage of long-lasting insecticidal mosquito nets: a cluster-randomized controlled 

trial. 

3. Indoor residual spraying in combination with insecticide-treated nets compared to insecticide-treated 

nets alone for protection against malaria: a cluster-randomized trial in Tanzania. 
15

4. Effectiveness of residual acaricides to prevent Lyme Disease and other tick-borne diseases in humans.

5. Camino Verde (The Green Way): evidence-based community mobilization for dengue control in Nicaragua 

and Mexico: feasibility study and study protocol for a randomized controlled trial.

6. Effectiveness of a long-lasting piperonyl butoxide-treated insecticidal net and indoor residual spray 

interventions, separately and together, against malaria transmitted by pyrethroid-resistant mosquitoes: a 

cluster, randomized controlled, two-by-two fact. (2018)

7. Study protocol for cluster randomized controlled factorial design trial to assess the effectiveness and 

feasibility of reactive focal mass drug administration and vector control to reduce malaria transmission in 

the low endemic setting of Namibia. (2017)

8. Reduced incidence of Chikungunya virus infection in communities with ongoing Aedes aegypti mosquito 

trap intervention studies – Salinas and Guayama, Puerto Rico, November 2015-February 2016. (2016)

9. The additional benefit of residual spraying and insecticide-treated curtains for dengue control over 

current best practice in Cuba: evaluation of disease incidence in a cluster randomized trial in a low burden 

setting with intensive routine control. (2017)

10. Mitigating diseases transmitted by Aedes mosquitoes: a cluster randomized trial of permethrinimpregnated school uniforms. (2017)

11. The AWED trial (Applying Wolbachia to Eliminate Dengue) to assess the efficacy of Wolbachia-infected 

mosquito deployment to reduce dengue incidence in Yogyakarta, Indonesia: study protocol for a cluster 

randomized controlled trial. (in press, 2018)

Bioethics:

1. Ethical, social, and cultural considerations for site selection for research with genetically modified 

mosquitoes (2008)

2. Informed consent in field trials of gene-drive mosquitoes (2017)

3. Community engagement and the human infrastructure of global health research (2014)

4. What makes community engagement effective? Lessons from the Eliminate Dengue program in 

Queensland, Australia (2015)

Field Site Selection:

1. Criteria for identifying and evaluating candidate sites for open-field trials of genetically engineered 

mosquitoes (2014)

Risk Assessment/Management:

1. Expert risk perceptions and the social amplification of risk: a case study in invasive tree pests and diseases

(2017)

2. Maintaining quality of candidate strains of transgenic mosquitoes for studies in containment facilities in 

disease endemic countries (2018)

3. Understanding Risk: Informing Decisions in a Democratic Society (1996)
16

Appendix 4: Resources

U. S. REGULATORY AGENCY INFORMATION

Modernizing the Regulatory System for Biotechnology Products: Final Version of the 2017 Update to the 

Coordinated Framework for the Regulation of Biotechnology: 2017_coordinated_framework_update

Food and Drug Administration (FDA)

• Regulation of Mosquito-Related Products (GFI #236) (January 2017)

• Regulation of Intentionally Altered Genomic DNA in Animals (GFI #187) (January 2017)

Environmental Protection Agency (EPA)

Registration Issues

• https://www.epa.gov/ingredients-used-pesticide-products https://www.epa.gov/pesticideregistration/registration-requirements-and-guidance https://www.epa.gov/pesticideregistration

• Pesticide Registration Manual: Chapter 12 - Applying for an Experimental Use Permit (EUP)

Pesticides and Biotechnology:

• https://www.epa.gov/regulation-biotechnology-under-tsca-and-fifra/epas-regulationbiotechnology-use-pest-management

• https://www.epa.gov/regulation-biotechnology-under-tsca-and-fifra/modernizing-regulatorysystem-biotechnology-products

Environmental Assessment Explained

• EPA: Testing Requirements to Assess Risks to Human Health and the Environment

• FDA CVM Environmental Impact Consideration

• EFSA: Guidance on the environmental risk assessment of genetically modified animals

NIAID Clinical Resources

Guidance for Investigators:

• Clinical Trial Research at NIH: https://www.niaid.nih.gov/grants-contracts/clinical-trial-research

• Investigator-initiated Clinical Trials resources: https://www.niaid.nih.gov/grantscontracts/investigator-initiated-clinical-trial-resources

Clinical Resources:

• Vaccine and Treatment Evaluation Units: https://www.niaid.nih.gov/research/vaccinetreatment-evaluation-units-intro

• Infectious Diseases Clinical Research Consortium: https://www.niaid.nih.gov/research/idcrc

• Resources for Investigators: https://www.niaid.nih.gov/research/microbiology-and-infectiousdiseases-resources 
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Pan-American Health Organization

• http://www.who.int/neglected_diseases/vector_ecology/resources/WHO_HTM_NTD_VEM_201

7.03/en/ 

• https://www.who.int/neglected_diseases/vector_ecology/resources/WHO_HTM_NTD_VEM_20

17.05/en/