• Prabhat Jha, Vendhan Gajalakshmi, Prakash C Gupta, Rajesh Kumar, Prem Mony, Neeraj Dhingra, Richard Peto, and RGI-CGHR Prospective Study Collaborators.
• Centre for Global Health Research, Public Health Sciences, St Michael's Hospital, McLaughlin Centre for Molecular Medicine, University of Toronto, Toronto, Canada. prabhat.jha@utoronto.ca
• PLoS Med. 2006 Feb 1; 3 (2): e18.

BackgroundOver 75% of the annual estimated 9.5 million deaths in India occur in the home, and the large majority of these do not have a certified cause. India and other developing countries urgently need reliable quantification of the causes of death. They also need better epidemiological evidence about the relevance of physical (such as blood pressure and obesity), behavioral (such as smoking, alcohol, HIV-1 risk taking, and immunization history), and biological (such as blood lipids and gene polymorphisms) measurements to the development of disease in individuals or disease rates in populations. We report here on the rationale, design, and implementation of the world's largest prospective study of the causes and correlates of mortality.Methods And FindingsWe will monitor nearly 14 million people in 2.4 million nationally representative Indian households (6.3 million people in 1.1 million households in the 1998-2003 sample frame and 7.6 million people in 1.3 million households in the 2004-2014 sample frame) for vital status and, if dead, the causes of death through a well-validated verbal autopsy (VA) instrument. About 300,000 deaths from 1998-2003 and some 700,000 deaths from 2004-2014 are expected; of these about 850,000 will be coded by two physicians to provide causes of death by gender, age, socioeconomic status, and geographical region. Pilot studies will evaluate the addition of physical and biological measurements, specifically dried blood spots. Preliminary results from over 35,000 deaths suggest that VA can ascertain the leading causes of death, reduce the misclassification of causes, and derive the probable underlying cause of death when it has not been reported. VA yields broad classification of the underlying causes in about 90% of deaths before age 70. In old age, however, the proportion of classifiable deaths is lower. By tracking underlying demographic denominators, the study permits quantification of absolute mortality rates. Household case-control, proportional mortality, and nested case-control methods permit quantification of risk factors.ConclusionsThis study will reliably document not only the underlying cause of child and adult deaths but also key risk factors (behavioral, physical, environmental, and eventually, genetic). It offers a globally replicable model for reliably estimating cause-specific mortality using VA and strengthens India's flagship mortality monitoring system. Despite the misclassification that is still expected, the new cause-of-death data will be substantially better than that available previously.

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