ONGOING RESEARCH PROJECTS
Vaccine Trial Design
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We consider general methods for innovative and adaptive vaccine trial designs tailored to the setting of emerging pathogens. Inspired by our work on the Ebola ring vaccination trial in Guinea, we consider responsive trials that follow an outbreak as it progresses. We also consider multi-outbreak trial designs for settings with unpredictable disease incidence.
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Dean NE, Halloran ME, Longini IM (2018). Design of Vaccine Trials during Outbreaks with and without a Delayed Vaccination Comparator. Annals of Applied Statistics 12(1): 330-347. doi.org/10.1214/17-AOAS1095
Dean NE, Gsell PS, Brookmeyer R, De Gruttola V, Donnelly CA, Halloran ME, Jasseh M, Nason M, Riveros X, Watson C, Henao-Restrepo AM, Longini IM (2019+). Considerations for the design of vaccine efficacy trials during public health emergencies. In press at Science Translational Medicine.
Dean NE, Gsell PS, Brookmeyer R, De Gruttola V, Donnelly CA, Halloran ME, Jasseh M, Nason M, Riveros X, Watson C, Henao-Restrepo AM, Longini IM (2019+). Considerations for the design of vaccine efficacy trials during public health emergencies. In press at Science Translational Medicine.
Test Negative Designs
We study the methodological properties of the test negative design, which is a recently developed epidemiological study design routinely used to evaluate influenza vaccine effectiveness. We consider the application of the test negative design to other diseases, focusing on the setting of outbreaks.
Dean NE (2019). RE: "Measurement of vaccine direct effects under the test-negative design." American Journal of Epidemiology 188(4): 806. https://doi.org/10.1093/aje/kwz019
Dean NE (2019). RE: "Measurement of vaccine direct effects under the test-negative design." American Journal of Epidemiology 188(4): 806. https://doi.org/10.1093/aje/kwz019
Outbreak Modeling
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In collaboration with our colleagues at MOBS Lab at Northeastern University, we model the spread of infectious diseases using the Global Epidemic and Mobility Model (GLEAM). We have previously applied this model to study Ebola and Zika outbreaks.
Zhang Q, Sun K, Chinazzi M, Pastore-Piontti A, Dean NE, Rojas DP, Merler S, Mistry D, Poletti P, Rossi L, Bray M, Halloran ME, Longini IM, Vespignani A (2017). Spread of Zika virus in the Americas. Proceedings of the National Academy of Sciences 114(22): E4334- E4343. https://doi.org/10.1073/pnas.1620161114 Dean NE, Vespignani A, Halloran ME, Longini IM (2016). Zika virus: only a few small outbreaks likely to occur in the continental US. The Conversation. |
COMPLETED RESEARCH PROJECTS
rVSV Ebola Vaccine Efficacy Trial
As part of the "Ebola ça Suffit" trial team, I supported the design and analysis of a Phase III Ebola vaccine trial in Guinea during the 2014-15 West African Ebola epidemic. The trial used an innovative ring vaccination design, in which clusters were formed from the contacts and contacts of contacts of confirmed Ebola cases. The interim and final results, published in The Lancet, demonstrated high efficacy of the vaccine. Over 100,000 doses of the vaccine have since been used in Ebola outbreaks since.
Ebola ça Suffit Ring Vaccination Trial Consortium (2015). The ring vaccination trial: a novel cluster randomised controlled trial design to evaluate vaccine efficacy and effectiveness during outbreaks, with special reference to Ebola. BMJ 351: h3740.
https://doi.org/10.1136/bmj.h3740
Henao-Restrepo A-M, Longini IM, Egger M, Dean NE, Edmunds WJ, Camacho A, Carroll MW, Doumbia M, Duraffour S, Enwere G, Grais R, Gunther S, Hossmann S, Kondé MK, Kone S, Kuisma E, Levine M, Mandal S, Norheim G, Riveros X, Soumah A, Trelle S, Vicari AS, Watson CH, Draguez B, Kéïta S, Røttingen J-A, Kieny M-P (2015). Efficacy and effectiveness of an rVSV-vectored vaccine expressing Ebola surface glycoprotein: interim results from the Guinea ring vaccination cluster-randomised trial. The Lancet 386(9996): 857-866.
https://doi.org/10.1016/S0140-6736(15)61117-5
Henao-Restrepo AM, Camacho A, Longini IM, Watson CH, Edmunds WJ, Egger M, Carroll MW, Dean NE, Doumbia M, Draguez B, Duraffour S, Enwere G, Grais R, Gunther S, Gsell PS, Hossmann S, Kondé MK, Kéïta S, Kone S, Kuisma E, Levine M, Mandal S, Mauget T, Norheim G, Rivreros X, Soumah A, Trelle S, Vicari AS, Røttingen J-A, Kieny MP (2017). Efficacy and effectiveness of an rVSV-vectored vaccine in preventing Ebola virus disease: final results from the Guinea ring vaccination, open-label, cluster-randomised trial (Ebola ça Suffit!). The Lancet 389(10068): 505-518.
https://doi.org/10.1016/S0140-6736(16)32621-6
Gsell P, Camacho A, Kucharski A, Watson CH, Bagayoko A, Danmadji S, Dean NE, Diallo A, Djidonou H, Doumbia M, Fallah M, Enwere G, Higgs ES, Mauget T, Mory D, Riveros X, Thierno Oumar F, Toure A, Vicari AS, Longini IM, Edmunds WJ, Henao-Restrepo AM, Kéïta S (2017). Ring vaccination of adults and children with rVSV-ZEBOV in response to an outbreak of Ebola virus disease in Guinea, 2016: an operational and vaccine safety report. Lancet Infectious Diseases 17(12): 1276-1284.
https://doi.org/10.1016/S1473-3099(17)30541-8
https://doi.org/10.1136/bmj.h3740
Henao-Restrepo A-M, Longini IM, Egger M, Dean NE, Edmunds WJ, Camacho A, Carroll MW, Doumbia M, Duraffour S, Enwere G, Grais R, Gunther S, Hossmann S, Kondé MK, Kone S, Kuisma E, Levine M, Mandal S, Norheim G, Riveros X, Soumah A, Trelle S, Vicari AS, Watson CH, Draguez B, Kéïta S, Røttingen J-A, Kieny M-P (2015). Efficacy and effectiveness of an rVSV-vectored vaccine expressing Ebola surface glycoprotein: interim results from the Guinea ring vaccination cluster-randomised trial. The Lancet 386(9996): 857-866.
https://doi.org/10.1016/S0140-6736(15)61117-5
Henao-Restrepo AM, Camacho A, Longini IM, Watson CH, Edmunds WJ, Egger M, Carroll MW, Dean NE, Doumbia M, Draguez B, Duraffour S, Enwere G, Grais R, Gunther S, Gsell PS, Hossmann S, Kondé MK, Kéïta S, Kone S, Kuisma E, Levine M, Mandal S, Mauget T, Norheim G, Rivreros X, Soumah A, Trelle S, Vicari AS, Røttingen J-A, Kieny MP (2017). Efficacy and effectiveness of an rVSV-vectored vaccine in preventing Ebola virus disease: final results from the Guinea ring vaccination, open-label, cluster-randomised trial (Ebola ça Suffit!). The Lancet 389(10068): 505-518.
https://doi.org/10.1016/S0140-6736(16)32621-6
Gsell P, Camacho A, Kucharski A, Watson CH, Bagayoko A, Danmadji S, Dean NE, Diallo A, Djidonou H, Doumbia M, Fallah M, Enwere G, Higgs ES, Mauget T, Mory D, Riveros X, Thierno Oumar F, Toure A, Vicari AS, Longini IM, Edmunds WJ, Henao-Restrepo AM, Kéïta S (2017). Ring vaccination of adults and children with rVSV-ZEBOV in response to an outbreak of Ebola virus disease in Guinea, 2016: an operational and vaccine safety report. Lancet Infectious Diseases 17(12): 1276-1284.
https://doi.org/10.1016/S1473-3099(17)30541-8
Dengue SerosurveillanceI led a World Health Organization working group on the design and conduct of dengue seroprevalence surveys. We recommend a stratified multi-stage cluster sampling strategy targeting school-aged children. These serosurveys were designed to support WHO Strategic Advisory Group of Experts (SAGE) policy on dengue vaccination.
World Health Organization (2017). Informing Vaccination Programs: A Guide to the Design and Conduct of Dengue Serosurveys. Geneva, Switzerland. http://www.who.int/immunization/research/development/dengue serosurveys/en/ |
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HIV Drug Resistance Surveillance
As part of the World Health Organization's HIV Department drug resistance team, I provided guidance on the design and analysis of surveys of patients receiving antiretroviral therapy. The purpose of these surveys was to produce nationally representative estimates of HIV drug resistance to inform treatment policy in low- and middle-income countries. We considered pre-treatment resistance, acquired resistance, and resistance in infant and pediatric populations. I consulted with over 30 countries representing all global regions on the design and analysis of their surveys. I created user-friendly Excel-based sample size calculators and provided directions for data analysis using the Stata SVY command. I also supported the global analysis of data on routine clinic-level functioning ("Early Warning Indicators" of HIV drug resistance) from over 60 countries.
World Health Organization (2014). HIV Drug Resistance Concept Note – Surveillance of HIV drug resistance in adults initiating antiretroviral therapy (pretreatment HIV drug resistance). Geneva, Switzerland.
www.who.int/hiv/topics/drugresistance/protocols/en/
World Health Organization (2014). HIV Drug Resistance Concept Note – Surveillance of HIV drug resistance in adults receiving antiretroviral therapy (acquired HIV drug resistance). Geneva, Switzerland.
www.who.int/hiv/topics/drugresistance/protocols/en/
World Health Organization (2016). Global report on early warning indicators of HIV drug resistance: Technical report. Geneva, Switzerland.
www.who.int/hiv/pub/drugresistance/ ewi-hivdr-2016/en/
World Health Organization (2017). Surveillance of HIV drug resistance in children newly diagnosed with HIV by early infant diagnosis - Concept note. Geneva, Switzerland.
www.who.int/hiv/pub/drugresistance/hivdr-concept-note-2017/en/
World Health Organization (2014). HIV Drug Resistance Concept Note – Surveillance of HIV drug resistance in adults initiating antiretroviral therapy (pretreatment HIV drug resistance). Geneva, Switzerland.
www.who.int/hiv/topics/drugresistance/protocols/en/
World Health Organization (2014). HIV Drug Resistance Concept Note – Surveillance of HIV drug resistance in adults receiving antiretroviral therapy (acquired HIV drug resistance). Geneva, Switzerland.
www.who.int/hiv/topics/drugresistance/protocols/en/
World Health Organization (2016). Global report on early warning indicators of HIV drug resistance: Technical report. Geneva, Switzerland.
www.who.int/hiv/pub/drugresistance/ ewi-hivdr-2016/en/
World Health Organization (2017). Surveillance of HIV drug resistance in children newly diagnosed with HIV by early infant diagnosis - Concept note. Geneva, Switzerland.
www.who.int/hiv/pub/drugresistance/hivdr-concept-note-2017/en/
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