Research

RESEARCH PROJECTS

Ongoing Research Projects

Observational Vaccine Studies

We study the methodological properties of observational vaccine studies with a focus on the test negative design. The test negative design is a recently developed epidemiological study design routinely used to evaluate influenza vaccine effectiveness and now applied to COVID-19. We consider the application of the test negative design to these and other diseases, considering the unique challenges of infectious disease outbreaks and how these work in conjunction with traditional randomized trials.

Related Publications

Dean NE*, Hogan JW*, Schnitzer ME* (2021). Covid-19 vaccine effectiveness and the test-negative design. New England Journal of Medicine. 385: 1431-1433. 

Dean NE (2021). COVID vaccination studies: plan now to pool data, or be bogged down in confusion. Nature. 591(7849): 179.

Dean NE (2021). Hospital admissions due to COVID-19 in Scotland after one dose of vaccine. The Lancet. 397(10285): 1601-1603.

Lewnard JA, Patel MM, Jewell NP, Verani JR, Kobayashi M, Tenforde M, Dean NE, Cowling BJ, Lopman BA (2021). Theoretical framework for retrospective studies of the effectiveness of SARS-CoV-2 vaccines. Epidemiology 32(4): 508-517. 

Lipsitch M, Dean NE (2020). Understanding COVID-19 vaccine efficacy (2020). Science. 370 (6518): 763-765.

Dean NE, Halloran ME, Longini IM (2020). Temporal Confounding in the Test Negative Design. American Journal of Epidemiology. 189 (11): 1402-1407.

Dean NE (2019). RE: “Measurement of vaccine direct effects under the test-negative design.” American Journal of Epidemiology 188(4): 806. 

Vaccine Trial Design

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

Related Publications

Madewell ZJ, Dean NE, Berlin JA, Coplan PM, Davis KJ, Struchiner CJ, Halloran ME (2021). Challenges of evaluating and modeling vaccination in emerging infectious diseases. Epidemics. 37: 100506.

Madewell ZJ, Pastore y Piontti A, Zhang Q, Burton N, Yang Y, Longini IM, Halloran ME, Vespignani A, Dean NE (2021). Using simulated infectious disease outbreaks to guide the design of individually randomized vaccine trials. Clinical Trials. 18(5): 630-638.

Krause P, Fleming TR, Longini I, Henao-Restrepo A, Peto R, for the World Health Organization Solidarity Vaccines Trial Expert Group (Dean NE, Halloran ME, Huang Y, Gilbert PB, De Gruttola V, Gsell P, Janes HE, Nason MC, Riveros X, Smith P) (2020). COVID-19 vaccine trials should seek worthwhile efficacy. The Lancet 396 (10253): 741-743.

Dean NE, Pastore y Piontti A, Madewell ZJ, Cummings DAT, Hitchings MDT, Joshi K, Kahn R, Vespignani A, Halloran ME, Longini IM (2020). Ensemble forecast modeling for the design of COVID-19 vaccine efficacy trials. Vaccine 38 (46): 7213-7216.

Ogburn EL, Bierer BE, Brookmeyer R, Choirat C, Dean NE, De Gruttola V, Ellenberg SS, Halloran ME, Hanley DF, Lee JK, Wang R, Scharfstein DO (2020). Aggregating data from COVID-19 trials. Science Jun 12;368(6496): 1198-1199.

Kimmel SE, Califf RM, Dean NE, Goodman SN, Ogburn EL (2020). COVID-19 clinical trials: a teachable moment for improving our research infrastructure and relevance. Annals of Internal Medicine 173 (8): 652-653.

Dean NE, Gsell PS, Brookmeyer R, Crawford F, Donnelly C, Ellenberg S, Fleming T, Halloran ME, Horby P, Jaki T, Krause P, Longini I, Mulangu S, Muyembe-Tamfum JJ, Nason M, Smith PG, Wang R, Henao-Restrepo AM, De Gruttola V (2020). Accumulating evidence from randomized clinical trials across outbreaks. New England Journal of Medicine.

Bellan SE, Eggo RM, Gsell PS, Kucharski A, Dean NE, Donohue R, Zook M, Odhiambo F, Longini I, Brisson M, Mahon B, Edmunds WJ, Henao-Restrepo AM (2019). An online decision tree for vaccine trial design during infectious disease epidemics: The InterVax-Tool. Vaccine 37(31): 4376-4381.

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. Science Translational Medicine 11(499): eaat0360.

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.

Wilder-Smith A, Longini I, Zuber P, Bärnighausen T, Edmunds WJ, Dean NE, Masseray-Spicher V, Benissa MR, Gessner BG (2017). The public health value of vaccines beyond efficacy: methods, measures and outcomes. BMC Medicine 15: 138.

COVID-19 Epidemiology and Modeling

Our group has been active during the COVID-19 pandemic, with work on epidemiological analysis of household studies and modeling the disease dynamic. Modeling work is done in collaboration with our colleagues at MOBS Lab at Northeastern University using the Global Epidemic and Mobility (GLEAM) Model.

Related Publications

Davis JT, Chinazzi M, Perra N, Mu K, Pastore y Piontti A, Ajelli M, Dean NE, Gioannini C, Litvinova M, Merler S, Rossi L, Sun K, Xiong X, Halloran ME, Longini IM, Viboud C, Vespignani A (2021). Estimating the establishment of local transmission and the cryptic phase of the COVID-19 pandemic in the USA. Cryptic transmission of SARS-CoV-2 and the first COVID-19 wave. Nature 600, 127-132.

Madewell ZJ, Yang Y, Longini IM, Halloran ME, Dean NE (2021). Factors Associated With Household Transmission of SARS-CoV-2: An Updated Systematic Review and Meta-analysis. JAMA Network Open 4(8) e2122240-e2122240.

Hitchings MDT, Dean NE, Garcia-Carreras B, Hladish TJ, Huang AT, Yang B, Cummings DAT (2021). The usefulness of SARS-CoV-2 test positive proportion as a surveillance tool. American Journal of Epidemiology 190(7): 1396-1405.

Giovanetti M, Cella E, Benedetti F, Magalis BR, Fonseca V, Fabris S, Campisi G, Ciccozzi A, Angeletti S, Borsetti A, Tambone V, Sagnelli C, Pascarella S, Riva A, Ceccarelli G, Marcello A, Azarian T, Wilkinson E, de Oliveira T, Alcantara LCJ, Cauda R, Caruso R, Dean NE, Browne C, Lourenco J, Salemi M, Zella D, Ciccozzi M (2021). SARS-CoV-2 shifting transmission dynamics and hidden reservoirs potentially limit efficacy of public health interventions in Italy. Communications Biology 4(489) doi: 10.1038/s42003-021-02025-0.

Li F, Li Y-Y, Liu M-J, Fang L-Q, Dean NE, Wong GWK, Yang X-B, Longini I, Halloran ME, Wang H-J, Liu P-L, Pang Y-H, Yan Y-Q, Liu S, Xia W, Lu, X-X, Liu Q, Yang Y, Xu S-Q (2021). Household transmission of SARS-CoV-2 and risk factors for susceptibility and infectivity in Wuhan: a retrospective observational study. Lancet Infectious Diseases.

Madewell ZJ, Yang Y, Longini IM, Halloran ME, Dean NE (2020). Household transmission of SARS-CoV-2: a systematic review and meta-analysis of secondary attack rate. JAMA Network Open 3(12) e2031756-e2031756.

Jing QL, Liu MJ, Yuan J, Zhang ZB, Zhang AR, Dean NE, Luo L, Ma MM, Longini IM, Kenah E, Lu Y, Ma Y, Jalali N, Fang LQ, Yang ZC, Yang Y (2020). Household secondary attack rate of COVID-19 and associated determinants in Guangzhou, China: a retrospective cohort study. Lancet Infectious Diseases 20 (10): 1141-1150.

Aleta A, Martin-Corral D, Pastore y Piontti A, Ajelli M, Litvinova M, Chinazzi M, Dean NE, Halloran ME, Longini I, Merler S, Pentland A, Vespignani A, Moro E, Moreno Y (2020). Modeling the impact of testing, contact tracing and household quarantine on second waves of COVID-19. Nature Human Behaviour 4: 964-971.

Cluster Randomized Trial for Preventing Mosquito-Borne Disease

In conjunction with our collaborators, we are conducting a two-arm, parallel, unblinded, cluster randomized controlled trial in Mérida, Yucatán State, Mexico, to quantify the overall efficacy of targeted indoor residual spraying in reducing the burden of laboratory-confirmed arbovirus clinical disease. Targeted indoor residual spraying (TIRS) refers to the selective application of residuals insecticides on indoor Aedes aegypti resting locations. This project is led by Dr. Gonzalo Vaqzuez-Prokopec at Emory University and is currently underway.

Related Publications

Manrique-Saide P, Dean NE, Halloran ME, Longini IM, Collins MH, Waller LA, Gomez-Dantes H, Lenhart A, Hladish TJ, Che-Mendoza A, Kirstein OD, Romer Y, Correa-Morales F, Palacio-Vargas J, Mendez-Vales R, Pérez PG, Pavia-Ruz N, Ayora-Talavera G, Vazquez- Prokopec GM (2020). The TIRS trial: protocol for a cluster randomized controlled trial assessing the efficacy of preventive targeted indoor residual spraying to reduce Aedes-borne viral illnesses in Merida, Mexico. Trials 21: 839.

Completed Research Projects

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 rVSV-ZEBOV vaccine. Hundreds of thousands of doses of the vaccine have since been used in Ebola outbreaks since.

Related Publications

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.

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, Riveros 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.

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.

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.

Ebola Epidemiology and Modeling

In addition to our work on the Guinea Ebola vaccine trial, we conducted epidemiological and modeling analyses to study the disease dynamic and the potential impact of different vaccination strategies.

Related Publications

Ajelli M, Merler S, Fumanelli L, Pastore Y Piontti A, Dean NE, Longini IM, Halloran ME, Vespignani A (2016). Spatiotemporal dynamics of the Ebola epidemic in Guinea and implications for vaccination and disease elimination: a computational modeling analysis. BMC Medicine 14: 130.

Merler S, Ajelli M, Fumanelli L, Parlamento S, Pastore Y Piontti, Dean NE, Putoto G, Carraro D, Longini IM, Halloran ME, Vespignani A (2016). Containing Ebola at the source with ring vaccination. PLoS Neglected Tropical Diseases 10(11): e0005093.

Fang LQ, Yang Y, Jiang JF, Yao H, Kargbo D, Li X, Jiang BG, Kargbo B, Tong YG, Wang YW, Liu K, Kamara A, Dafae F, Kanu A, Jiang RR, Sun Y, Sun RX, Chen WJ, Ma M, Dean NE, Thomas H, Longini IM, Halloran ME, Cao WC (2016). Transmission Dynamics of Ebola Virus Disease and Intervention Effectiveness in Sierra Leone. Proceedings of the National Academy of Sciences 113(16): 4488-4493. 

Dean NE, Halloran ME, Yang Y, Longini IM (2016). Transmissibility and Pathogenicity of Ebola Virus: A Systematic Review and Meta-analysis of Household Secondary Attack Rate and Asymptomatic Infection. Clinical Infectious Diseases 62(10): 1277-1286.

Zika Epidemiology and Modeling

During the 2015-2016 Zika virus epidemic in the Americas, our group performed epidemiological analyses of outbreak data from Colombia, and we used computational modeling to study its introduction into the region and its potential for future spread.

Related Publications

Sun K, Zhang Q, Pastore-Piontti A, Chinazzi M, Mistry D, Dean NE, Rojas DP, Merler S, Poletti P, Rossi L, Halloran ME, Longini IM, Vespignani A (2018). Quantifying the risk of local Zika virus transmission in the contiguous US during the 2015–2016 ZIKV epidemic. BMC Medicine 16: 195.

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.

Rojas DP, Dean NE*, Yang Y*, Kenah E, Quintero J, Tomasi S, Ramirez EL, Kelly Y, Castro C, Carrasquilla G, Halloran ME, Longini IM (2016). The epidemiology and transmissibility of Zika virus in Girardot and San Andres Island, Colombia, September 2015 to January 2016. Eurosurveillance 21(28): pii=30283. 

HIV Drug Resistance Surveillance

As part of the World Health Organization’s HIV Department drug resistance team, Dr. Dean 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. Dr. Dean consulted with over 30 countries representing all global regions on the design and analysis of their surveys. Dr. Dean created user-friendly Excel-based sample size calculators and provided directions for data analysis using the Stata SVY command. Dr. Dean also supported the global analysis of data on routine clinic-level functioning (“Early Warning Indicators” of HIV drug resistance) from over 60 countries.

Related Publications

Dat VQ, Anh NTL, Van Nghia K, Linh NT, Thu HHK, Tam TTM, Ton T, Anh LQ, Phuc ND, Huong PTT, Nhan DT, Hai NH, Bertagnolio S, Crisp AM, Inzaule S, Dean NE, Jordan MR, Nguyen VTT (2022). The prevalence of pre-treatment and acquired HIV drug resistance in Vietnam: a nationally representative survey, 2017–2018. Journal of the International AIDS Society, 25: e25857.

Jordan MR, Hamunime N, Bikinesi L, Sawadogo S, Agolory S, Shiningavamwe AN, Negussie T, Fischer Walker CL, Raizes EG, Mutenda M, Hunter CJ, Dean NE, Steegen K, Kana V, Carmona S, Yang C, Tang AM, Parkin N, Hong SY (2020). High levels of HIV drug resistance among adults failing second-line antiretroviral therapy in Namibia. Medicine 99 (37): e21661. 

Hunt GM, Ledwaba J, Kalimashe M, Salimo A, Cibane S, Singh B, Puren A, Dean NE, Morris L, Jordan MR (2019). Provincial and national prevalence estimates of HIV-1 drug resistance in South Africa measured using two WHO-recommended methods. Antiviral Therapy 24, 203-210.

World Health Organization (2017). Surveillance of HIV drug resistance in children newly diagnosed with HIV by early infant diagnosis – Concept note. Geneva, Switzerland.

Mutenda N, Bukowski A, Nitschke AM, Nakanyala T, Hamunime N, Mekonen T, Tjituka F, Mwinga S, Mazibuko G, Mabirizi D, Sagwa E, Dean N, Jordan MR, Hong SY (2016). HIV Drug Resistance Early Warning Indicators in Main and Decentralized Outreach Antiretroviral Therapy Sites in Namibia. PLoS ONE 11(12): e0166649.

World Health Organization (2016). Global report on early warning indicators of HIV drug resistance: Technical report. Geneva, Switzerland.

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.

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.

Dengue Serosurveillance

Dr. Dean 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.

Related Publication

World Health Organization (2017). Informing Vaccination Programs: A Guide to the Design and Conduct of Dengue Serosurveys. Geneva, Switzerland.