Assignment: Find any article using clustered data and describe: the unit of clustering; the hypothesized effects and the level at which the exposure is measured (is it a characteristic of the cluster or the observation within the cluster); and the statistical model used to estimate the effect. Describe whether there are any other statistical models that might be appropriate and whether they would be preferable (e.g., GEE vs mixed).
Article: Cissé, Badara, et al. "Effectiveness of Seasonal Malaria Chemoprevention in Children under Ten Years of Age in Senegal: A Stepped-Wedge Cluster-Randomised Trial." PLoS medicine 13.11 (2016): e1002175.
Study design: stepped-wedge, cluster randomized trial
Study setting: 3 districts of high malaria transmission in Mali
Trial duration: 3 years
Intervention: Seasonal malaria chemoprophylaxis (SMC) with sulphadoxine-pyrimethamine plus amodiaquine (SP-AQ), further classified into 3 arms:
- Control: No SMC
- SMC among children 3-59 months of age (in year 1)
- SMC among children 3 months to 10 years of age (year 2 and 3)
Unit of randomization: 54 health posts () were randomized to receive different combination of arms, according to the stepped-wedge design.
Hypothesized effects: SMC among children 3-59 months of age may reduce all-cause mortality
among children during the high malaria transmission season, and when extending SMC to children up to ten years of age may further prevent mortality.
Level at which exposure was measured: at the cluster level.
Level at which outcomes were measured: Primary endpoints, all-cause mortality and malaria incidence were measured at the cluster level.
- Parasite prevalence and prevalence of anemia was also considered an endpoint and can be construed as a measurement at the individual level (binary level data 0/1).
Statistical model used to estimate the effect: Effectiveness of SMC was estimated by fitting a Poisson regression model to the data on the number of deaths and the number of RDT-confirmed malaria cases in each health post occurring in the period starting from the date of the first round of SMC and ending one month after the last round of SMC each year. The number of person-months at risk obtained from the DSS was included as an offset, and a gamma-distributed random effect was used to allow for correlation within clusters. Covariates included in the model were age group, calendar year, and indicator variables for the effect of SMC in children (under five years in 2008 and under ten years in 2009 and 2010) and for the indirect effect of SMC in older age groups. Interaction terms were included to compare effects in the two age groups, and combined effects were estimated where there was no evidence of interaction. The indicator variable representing SMC direct effects was set to 1 if that age group received SMC in that cluster in that year and set to 0 otherwise. The indicator variable for indirect effects was set to 1 for all non-SMC age groups if SMC was implemented in children in that cluster and set to zero otherwise. Thus the direct effect that was estimated represents the sum of direct and indirect effects, and the indirect effect estimated represents the indirect effect only.
- Briefly, this was a mixed methods model that modeled incidences of all-cause mortality and incidence of malaria, using a random effect at the cluster (health post) level to account for correlation between clusters. Model was adjusted for age group, calendar year, and dummy variables were included for SMC under 5 in 2009 and SMC for children 10 and under in 2009 and 2010.
- I don’t believe that a GEE model (population averaged model) would have been appropriate in this analysis as one of the drawbacks of GEE is that they suffer from inflated type 1 error when there are too few clusters and though this stepped wedge trial had 54 clusters, there were 3 different interventions which would have reduced the number of clusters per arm.