Prospective harmonisation of four international randomised controlled trials in Canada, China, India and South Africa: the Healthy Life Trajectories Initiative

Objectives: the Healthy Life Trajectories Initiative (HeLTI) is an international multistudy consortium that supports the development and integration of four randomised controlled trials (RCTs) conducted in South Africa, India, China and Canada. HeLTI aims to evaluate interventions to improve the health and well-being of mothers and children, starting from preconception through pregnancy and early childhood until age 5 years. This paper describes the process by which we prospectively harmonised the participating studies and provides a descriptive analysis of the study-specific harmonisation potential.Design: prospective harmonisation of four international RCTs.Methods: a list of core variables to be collected across ten waves of data collection was defined. Taking this list into consideration, investigators developed country-specific questionnaires that were then assessed and adjusted to optimise the harmonisation potential across countries. As questionnaires were not identical, where required, processing scripts were generated to help transform the collected data into the core variable format.Setting: the four RCTs are conducted in Canada, China, India and South Africa. The prospective harmonisation was led by the Maelstrom Research team in Canada.Participants: between 4500 and 6000 women planning to get pregnant are recruited in each RCT. Women remain in the study if they become pregnant inside the planned interval of 1–3 years, depending on the country.Results: a total of 1962 variables from questionnaires, physical measurements and biospecimen analyses were defined across 10 timepoints of data collection and 3 subpopulations (mothers, partners and children). These variables cover 47 different domains of information. For the preconception phase, following the development of questionnaires and their implementation in the data collection software, 77.2% of the core variables defined can be created across the four studies.Conclusion: the HeLTI harmonisation process was successful, and the datasets generated represent a valuable resource allowing researchers to address a wide range of research questions on the impact of behaviour change interventions on maternal and child health indicators in different populations

Long term renal function in Asian HIV-1 infected adults receiving tenofovir disoproxil fumarate without protease inhibitors

Objectives: The risk of kidney dysfunction on the WHO recommended first line regimens containing tenofovir disoproxil fumarate (TDF) without protease inhibitors (PI) remains unclear in Asian patients, especially those with low body weight. Methods: Using data collected in a multicenter clinical trial in Thailand and proportional hazard regression models, we compared the risk of a >25% estimated glomerular filtration rate (eGFR) reduction in HIV naive patients initiating TDF or zidovudine (AZT) containing non-PI regimen. Results: Of 640 patients included in the analysis, 461 (72%) received a TDF-containing regimen for a median 6.7 years and 179 (28%) an AZT-containing regimen for 6.5 years. The risk of a >25% eGFR reduction was not associated with treatment (HR 1.11, 95% CI 0.84-1.47, P = 0.46). In multivariate analysis, the risk of >25% eGFR reduction form baseline was associated with body weight at baseline (HR 2.12, 95% CI 1.48-3.02 for 60 kg, P 25% eGFR reduction did not significantly vary with treatment (P = 0.27). Conclusions: The risk of eGFR reduction was not higher on TDF- versus AZT-based non-PI regimens. Although the risk of eGFR reduction was greater for patients of lower body weight, this risk was not significantly increased by TDF

Prospective harmonisation of four international randomised controlled trials in Canada, China, India and South Africa: the Healthy Life Trajectories Initiative

Objectives The Healthy Life Trajectories Initiative (HeLTI) is an international multistudy consortium that supports the development and integration of four randomised controlled trials (RCTs) conducted in South Africa, India, China and Canada. HeLTI aims to evaluate interventions to improve the health and well-being of mothers and children, starting from preconception through pregnancy and early childhood until age 5 years. This paper describes the process by which we prospectively harmonised the participating studies and provides a descriptive analysis of the study-specific harmonisation potential.Design Prospective harmonisation of four international RCTs.Methods A list of core variables to be collected across ten waves of data collection was defined. Taking this list into consideration, investigators developed country-specific questionnaires that were then assessed and adjusted to optimise the harmonisation potential across countries. As questionnaires were not identical, where required, processing scripts were generated to help transform the collected data into the core variable format.Setting The four RCTs are conducted in Canada, China, India and South Africa. The prospective harmonisation was led by the Maelstrom Research team in Canada.Participants Between 4500 and 6000 women planning to get pregnant are recruited in each RCT. Women remain in the study if they become pregnant inside the planned interval of 1–3 years, depending on the country.Results A total of 1962 variables from questionnaires, physical measurements and biospecimen analyses were defined across 10 timepoints of data collection and 3 subpopulations (mothers, partners and children). These variables cover 47 different domains of information. For the preconception phase, following the development of questionnaires and their implementation in the data collection software, 77.2% of the core variables defined can be created across the four studies.Conclusion The HeLTI harmonisation process was successful, and the datasets generated represent a valuable resource allowing researchers to address a wide range of research questions on the impact of behaviour change interventions on maternal and child health indicators in different populations