Selection of Registry Cases
All cases from the EBMT and Dutch registries
who met the eligibility criteria as described above
were included. However, only a subset of transplantations
facilitated by the NMDP in the United States
was included, based on the availability of high-resolution
HLA typing and informed consent. Between
1990 and 1999, the NMDP performed retrospective
high-resolution typing for 4156 of 7594 transplantations.
This subset had to have available donor and
recipient pretransplantation samples for retrospective
typing and is representative of all transplantations
facilitated by the NMDP. The NMDP retrospectively
obtained consent for study participation from surviving
patients or parents/legal guardians for transplantations
that it facilitated in the United States during
the study period; the NMDP Institutional Review
Board waived consent for patients who died before
soliciting consent.
To address bias introduced by the inclusion of
only a proportion of surviving patients (those consenting)
but all deceased patients, a sample of deceased
patients was selected using a weighted randomized
scheme that adjusts for overrepresentation of deceased
patients in the consented cohort. This weighted randomized
scheme was developed based on all survivors
in the NMDP database. A logistic regression model
was fit to identify the factors that predicted whether a
patient had consented or not consented to use of data
collected by the NMDP. This analysis found that the
following factors were associated with the likelihood
of a patient consenting: age at transplantation, disease
type, race, sex, cytomegalovirus serologic status, and
country of transplantation (United States vs non–
United States). Using estimated consenting probabilities
from this model based on the characteristics of
dead patients, the biased coin method of randomization
was performed to determine which of the dead
patients likely would have consented to participate had
they been alive. Thus this procedure includes the
preconsented dead patients at the same probability as
surviving patients who consented to participate. Approximately
13% of the surviving patients failed to
consent, and 12% of the dead patients were deleted by
the weighted randomized method. The above-described
methods were tested several times, and on
every occasion the proportion of deleted dead patients
was similar.