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Estimation of dynamic treatment strategies for maintenance therapy of children with acute lymphoblastic leukaemia: an application of history‐adjusted marginal structural models
Author(s) -
Rosthøj S.,
Keiding N.,
Schmiegelow K.
Publication year - 2011
Publication title -
statistics in medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.996
H-Index - 183
eISSN - 1097-0258
pISSN - 0277-6715
DOI - 10.1002/sim.4393
Subject(s) - dosing , medicine , maintenance therapy , guideline , intensive care medicine , pediatrics , chemotherapy , pathology
Childhood acute lymphoblastic leukaemia is treated with long‐term intensive chemotherapy. During the latter part of the treatment, the maintenance therapy, the patients receive oral doses of two cytostatics. The doses are tailored to blood counts measured on a weekly basis, and the treatment is therefore highly dynamic. In 1992–1996, the Nordic Society of Paediatric Haematology and Oncology (NOPHO) conducted a randomised study (NOPHO‐ALL‐92) to investigate the effect of a new and more sophisticated dynamic treatment strategy. Unexpectedly, the new strategy worsened the outcome for the girls, whereas there were no treatment differences for the boys. There are as yet no general guidelines for optimising the treatment. On basis of the data from this study, our goal is to formulate an alternative dosing strategy. We use recently developed methods proposed by van der Laan et al. [1] to obtain statistical models that may be used in the guidance of how the physicians should assign the doses to the patients to obtain the target of the treatment. We present a possible strategy and discuss the reliability of this strategy. The implementation is complicated, and we touch upon the limitations of the methods in relation to the formulation of alternative dosing strategies for the maintenance therapy. Copyright © 2011 John Wiley & Sons, Ltd.