Background. This paper is concerned with overcoming problems caused by
measurement error in multi-centre studies of diet and disease. Measur
ement error causes differential bias, so the information on the diet-d
isease relationship from different cohorts is not directly comparable.
Hence this information needs to be calibrated before the data are com
bined in an eventual meta-analysis. We consider the design of calibrat
ion substudies. We distinguish two forms of information from a multi-c
entre cohort study. The first is subject-level information, which come
s from the variation of disease rate within cohorts. The second is coh
ort-level information, which comes from the variation of disease rate
between cohorts. The requirements of the calibration study are differe
nt for these two forms of information. Methods. Calibration is carried
out by remeasuring diet in a subsample of each cohort using a standar
dized reference method. This reference measurement should yield unbias
ed estimates of habitual intake. Results. Using a criterion of efficie
ncy, relative to a perfectly calibrated study, we show that the sample
size should be a multiple of the expected number of cases in each coh
ort. To control for confounding, each cohort should be stratified and
the ratio of sample size to number of cases should be constant within
strata. Conclusions. Since the required sample size is related not to
the size of the cohort, but to the eventual number of cases of disease
, calibration samples need not be prohibitively large. They should, ho
wever, be concentrated on those parts of the cohort, such as older age
groups, which will yield most cases.