[11]). When cross-reactive immunity (i.e. vaccine-induced protection against some of the non-vaccine types) cannot be excluded on the basis of vaccine composition, the reference set should include only those non-vaccine types against which the vaccine has no antigenic

components. In head-to-head trials of two or more pneumococcal vaccines, all serotypes common to the vaccines being compared learn more should be excluded from the reference set (cf. Section 5 in [14]). Based on assigning each sample of colonisation into one of the reference or target states, the data in a vaccine study can be summarised in terms of total numbers of samples in the different states of colonisation. Table 2 provides an example on how to define target and reference sets, how the data are summarised and how to calculate Tenofovir nmr the vaccine efficacy. Although the object of estimation (estimand) has the form 1-RR, where RR is a ratio of acquisition rates or a ratio of risks of T, the estimate in a cross-sectional study is calculated in the form of 1-OR. The trial design is a prospective cohort and is valid irrespective of the vaccinated/control ratio. The method generalises the indirect cohort method [12] to a recurrent (transient) endpoint (colonisation),

introducing a natural interpretation of the estimated parameter as VET. Ideally, three underlying assumptions must be met when data from a cross-sectional study are used to estimate VET[11]. The first assumption is stationarity which means that the prevalence of carriage and the serotype distribution are at the steady-state, i.e. they do not essentially change with age in the study cohorts. Soon after birth, the processes of colonisation are clearly not in the steady-state, and soon after vaccination, the intervention will induce a transient disturbance on the turnover of different serotypes. However, after some time these changes are expected to disappear when averaged over the study subjects. The problem of how soon

after vaccination one can rely on the steady-state assumption being met is further investigated mafosfamide in [14]. The second assumption to be met in cross-sectional estimation is that vaccination does not slow clearance of VT pneumococci. If the assumption does not hold, the estimates will be too small compared to the true vaccine efficacy of VET. By contrast, if the vaccine accelerates clearance of the vaccine types, there is essentially no bias of the estimates relative to true vaccine efficacy, so that the estimation of VET is generally possible (see [11]). Thirdly, for the estimation of direct vaccine effects, the method relies on there being no indirect effects in the study population. Further research on the effect of indirect protection on estimation of direct vaccine efficacy is needed. Finally, if the assumption of no effect of vaccination on clearance of colonisation is made, estimates of VETare equivalent to those of VEacq, i.e.