Study Setting
The study reported here analyses data collected during the informed consent discussions for an observational, cohort study that was designed to assess the incidence of TB in infants enrolled within 2 weeks of birth and followed up for a period of 2 years. The study was conducted in the Palamaner area of Chittoor district in Andhra Pradesh, and the study area included villages and towns. The area is largely rural and semi-urban, with the majority of the population being involved in agriculture or agriculture related activities. The study area was divided in to 594 population units of discrete villages and towns, with a minimum population of 200. These were classified as rural low development, rural high development, or semi-urban, on the basis of infrastructure and development indicators including electricity, road and transport, and presence of a school and health facility. Infants were included in the study if they were BCG-vaccinated and were available for follow up for 2 years after enrollment, and a parent or guardian provided informed consent. Infants were randomized to active surveillance (regular home visits every 2 months for 2 years, which included anthropometry and a brief questionnaire to detect signs and symptoms of TB) or passive surveillance (cases were recorded if reported at health care facilities). The study did not involve any investigational product, but included a standardized protocol of TB diagnostic procedures if infants were suspected of having TB. Of a total of 7,424 recorded births in the study area, 4,878 fulfilled inclusion criteria and 4,382 (89.8%) were enrolled as participants. The study was approved by the institutional ethical review board of the St John's National Academy of Health Sciences and the Ministry of Health Screening Committee of the Government of India, in addition to which it underwent ethical review by a contracted Ethical Review Board of the Aeras Global TB Vaccine Foundation.
Informed Consent Process
The field supervisors in the study team were responsible for obtaining informed consent. This team of 12 (with some replacements over the course of the study) was all male, each with a minimum of 12 years of school education. A minority of them had received a tertiary education. Study physicians and research nurses were not involved in the consent process, in case the power differential between health care providers and the study population influenced parents' decisions about whether to enrol their children in the study.
Study personnel were trained on ICH-GCP (International Conference on Harmonization - Good Clinical Practice) guidelines and on informed consent procedures as part of a professional development program. They were sensitized to the historical antecedents of current guidelines for the protection of human volunteers in clinical research. Specific to this research study, all personnel involved in obtaining consent were instructed to encourage questions from the parent providing consent and to note down the questions and comments at the back of the consent form if the questions went beyond simple clarifications of the contents of the informed consent form.
Parental consent was taken from any parent who was available at the home of potential participants. Initially a confidential setting was sought for the consent process. In practice, however, the discussions often took place in the presence of other family members or neighbours after the parent indicated his or her comfort with their presence. In this situation, the study team members were instructed to ensure that the decision to participate should be taken independently by the parent, without pressure from the other people present. Research coordinators and study managers would observe the informed consent process on supervisory visits and provide feedback to field supervisors to strengthen participatory consent practices.
The informed consent form was translated into colloquial Telugu, the local language. It was structured around questions, as the study team felt that this approach is more intuitive than a narrative consent form for both the study personnel and parents [8]. The main questions addressed in the consent form related to the identity of the sponsor; reasons for being selected for participation; study procedures including the TB diagnostic process; potential risks and benefits; confidentiality; research organizations' responsibilities; and, whom to contact for further information. After consent had been obtained, the socio-demographic characteristics of the parents were documented during a subsequent visit as part of the baseline information for each study subject.
Analysis
Once recruitment for the research study was completed, the questions asked during the informed consent were coded into a range of different categories, loosely corresponding with the structure of the informed consent document. As many of the questions did not correspond exactly to the questions posed in the informed consent sheet, new codes were also created. The informed consent data were entered into the larger database for the study, which included socio-economic household characteristics.
The data were analysed in Statistical Package for the Social Sciences v. 17.0 (SPSS). Frequencies for type of question asked were calculated first. Subsequently, cross-tabulations with chi squared tests were conducted to identify statistically significant associations between asking a question during the consent discussion and a range of household social, economic and demographic variables. These included level of development of settlement in which the household was situated (low rural, high rural, semi-urban); mother's age; religion (Hindu, Muslim or other); Caste (Dalit/Harijan or other; Dalits/Harijans are the lowest Hindu caste in India and are typically socially and economically disadvantaged); and, mother's and father's education and occupation. Household construction material and household cooking fuel use were also assessed as indicators of socio economic status (SES); stone and brick construction was considered higher SES and all other constructions lower SES, and liquid petroleum gas was considered higher SES and all other types of cooking fuel use were considered lower SES. Other variables that were examined were household exposure to TB (we thought this might increase questions asked); both parents being present during consenting; and, which parent - mother or father - signed the consent form. Finally, the relationship between the fieldworker taking the consent and participation in the informed consent discussion was explored.
In the next stage of analysis, a multivariate logistic regression model was constructed to examine the effect of socio-economic and demographic variables on participation in the informed consent discussion. The binary outcome variable was "Did either parent ask a question during the informed consent discussion?" All the variables from the bivariate analysis that had shown significant association were included, except for the identity of the fieldworker. The reason for excluding the fieldworker variable was that our focus in the multivariate analysis was to identify participant related factors affecting participation in informed consent.