Comparative effect sizes in randomised trials from less developed and more developed countries: meta-epidemiological assessment

Abstract

Objective: To compare treatment effects from randomised trials conducted in more developed versus less developed countries.

Design: Meta-epidemiological study.

Data sources: Cochrane Database of Systematic Reviews (August 2012).

Data extraction: Meta-analyses with mortality outcomes including data from at least one randomised trial conducted in a less developed country and one in a more developed country. Relative risk estimates of more versus less developed countries were compared by calculating the relative relative risks for each topic and the summary relative relative risks across all topics. Similar analyses were performed for the primary binary outcome of each topic.

Results: 139 meta-analyses with mortality outcomes were eligible. No nominally significant differences between more developed and less developed countries were found for 128 (92%) meta-analyses. However, differences were beyond chance in 11 (8%) cases, always showing more favourable treatment effects in trials from less developed countries. The summary relative relative risk was 1.12 (95% confidence interval 1.06 to 1.18; P<0.001; I(2)=0%), suggesting significantly more favourable mortality effects in trials from less developed countries. Results were similar for meta-analyses with nominally significant treatment effects for mortality (1.15), meta-analyses with recent trials (1.14), and when excluding trials from less developed countries that subsequently became more developed (1.12). For the primary binary outcomes (127 meta-analyses), 20 topics had differences in treatment effects beyond chance (more favourable in less developed countries in 15/20 cases).

Conclusions: Trials from less developed countries in a few cases show significantly more favourable treatment effects than trials in more developed countries and, on average, treatment effects are more favourable in less developed countries. These discrepancies may reflect biases in reporting or study design as well as genuine differences in baseline risk or treatment implementation and should be considers when generalising evidence across different settings.

Fig 1 Fetal and neonatal deaths with antenatal corticosteroids in women at risk of preterm birth

Fig 2 All cause mortality at 28 days with corticosteroids for treating sepsis and septic shock

Fig 3 Mortality with systemic antifungals in non-neutropenic critically ill patients

Fig 4 Case fatality with calcium antagonists in aneurysmal subarachnoid haemorrhage

Fig 5 All cause mortality with intravenous immunoglobulin for preventing infection in preterm or low birthweight infants

Fig 6 All cause mortality with transarterial embolisation in unresectable hepatocellular carcinoma. Only the effect estimates from each trial were retrievable for the corresponding meta-analysis

Fig 7 Mortality with antioxidants for preventing various diseases

Fig 8 Mortality with antioxidants for preventing gastrointestinal cancers

Fig 9 Mortality after postoperative radiotherapy for non-small cell lung cancer

Fig 10 Perinatal deaths with admission to hospital for bed rest for women with multiple pregnancy

Fig 11 Total mortality with altered fractionation radiotherapy for oral cavity and oropharyngeal cancer. Only the effect estimates from each trial were retrievable for the corresponding meta-analysis

Fig 12 Relative relative risks and 95% confidence intervals for mortality outcomes between more developed and less developed countries in meta-analyses with nominally significant effects. Relative relative risk estimates and 95% confidence intervals are shown for the 36 topics for which the respective meta-analyses had found nominally significant effects overall per fixed effects synthesis