A multi-country cluster randomized controlled effectiveness evaluation to accelerate the introduction of Vi polysaccharide typhoid vaccine in developing countries in Asia: rationale and design


Camilo J. Acosta (corresponding author), Claudia M. Galindo, Mohammad Ali, R. Leon Ochiai, M. Carolina Danovaro-Holliday, Anne-Laure Page, Jin Kyung Park, Hyejon Lee, Mahesh K. Puri, Bernard Ivanoff, John D. Clemens and Zhi-Yi Xu, International Vaccine Institute, Research Park, San 4-8 Bongcheon-7-Dong, Kwanak-gu, Seoul, South Korea 151-818. Tel: +1-610-7873112; Fax: 1-610-7877057; E-mail: camilo_acosta2003@yahoo.com
Remon Abu Elyazeed, Epidemiology Unit, Enteric Disease Research Program, US NAMRU 3, Cairo, Egypt.
Vu Dinh Thiem, Do Gia Canh, Dang Duc Anh and Dang Duc Trach, National Institute of Hygiene and Epidemiology, Hanoi, Vietnam.
Yang Jin, Yang Honghui and Dong Bai-qing, Guangxi Center for Disease Prevention and Control, Nanning, Guangxi, China.
Magdarina D Agtin, Rooswanti Soeharno and Cyrus H. Simanjuntak, National Institute of Health Research and Development, Ministry of Health Republic of Indonesia, Indonesia.
Narain H. Punjabi, NAMRU-2, Jakarta, Indonesia.
Dipika Sur, Byomkesh Manna and Sujit Kumar Bhattacharya, National Institute of Cholera and Enteric Diseases, Kolkata, India.
Qamaruddin Nizami and Zulfikar Bhutta, Aga Khan University, Karachi, Pakistan.
Tikki Pang, Research Policy and Cooperation, World Health Organization, Geneva, Switzerland.
Allan Donner, University of Western Ontario, Ont., Canada.


Phase-III vaccine efficacy trials typically employ individually randomized designs intended to ensure that measurements of vaccine protective efficacy reflect only direct vaccine effects. As a result, decisions about introducing newly licensed vaccines into public health programmes often fail to consider the substantially greater protection that may occur when a vaccine is deployed in public health programmes, due to the combination of direct plus indirect vaccine protective effects. Vaccine total protection can be better evaluated with cluster randomized trials. Such a design was considered to generate policy relevant data to accelerate the rationale introduction of the licensed typhoid fever Vi polysaccharide (PS) vaccine in Asia by the Diseases of the Most Impoverished (DOMI) typhoid fever programme. The DOMI's programme multi-country study is one of the largest cluster randomized vaccine trials ever mounted in Asia, which includes approximately 200 000 individuals. Its main objective is to determine the effectiveness of a licensed Vi PS vaccine. The rationale and design of this study are discussed. Preliminary results are presented that determined the final planning of the trial before immunization. Important methodological and practical issues regarding vaccine cluster randomized designs are illustrated.