Estimation of optimal dynamic anticoagulation regimes from observational data: a regret-based approach.

A complication of long-term anticoagulation is that the optimal dose level varies not only between patients but over time within patients, in response to short-term changes in lifestyle. Consequently, doseage needs to be adaptive but there are as yet no accepted decision rules. Since anticoagulant use is increasing worldwide there is a need for more objective and routine procedures. In this paper, we describe an analysis of observational longitudinal anticoagulant data, aimed at determining an optimal reactive dose-changing strategy. We use the regret parameterization approach advocated by Murphy (J. R. Stat. Soc. Ser. B 2003; 65:331-366). Practical problems encountered in the implementation of the approach are discussed and illustrated.

[1]  Monitoring the effectiveness of anticoagulation control. , 2005, International journal of health care quality assurance incorporating Leadership in health services.

[2]  L B Sheiner,et al.  Computer-aided long-term anticoagulation therapy. , 1969, Computers and biomedical research, an international journal.

[3]  Patrice Degoulet,et al.  An overview of the effect of computer-assisted management of anticoagulant therapy on the quality of anticoagulation , 1998, Int. J. Medical Informatics.

[4]  L Aarons,et al.  Software for Population Pharmacokinetics and Pharmacodynamics , 1999, Clinical pharmacokinetics.

[5]  R. Beyth,et al.  Anticoagulant-related bleeding: clinical epidemiology, prediction, and prevention. , 1993, The American journal of medicine.

[6]  James M. Robins,et al.  Optimal Structural Nested Models for Optimal Sequential Decisions , 2004 .

[7]  H. Billett,et al.  Impact of Adherence, Knowledge, and Quality of Life on Anticoagulation Control , 2005, The Annals of pharmacotherapy.

[8]  Kenneth Levenberg A METHOD FOR THE SOLUTION OF CERTAIN NON – LINEAR PROBLEMS IN LEAST SQUARES , 1944 .

[9]  F R Rosendaal,et al.  A Method to Determine the Optimal Intensity of Oral Anticoagulant Therapy , 1993, Thrombosis and Haemostasis.

[10]  M G Amato,et al.  Comparison of an anticoagulation clinic with usual medical care: anticoagulation control, patient outcomes, and health care costs. , 1998, Archives of internal medicine.

[11]  P. M. Aggeler,et al.  Determinants of the response to oral anticoagulant drugs in man. , 1970, Pharmacological reviews.

[12]  S. Tandy,et al.  Warfarin for non-rheumatic atrial fibrillation: five year experience in a district general hospital , 2004, Heart.

[13]  S. Murphy,et al.  Optimal dynamic treatment regimes , 2003 .

[14]  M. Moia,et al.  Effect of computer-aided management on the quality of treatment in anticoagulated patients: a prospective, randomized, multicenter trial of APROAT (Automated PRogram for Oral Anticoagulant Treatment). , 2001, Haematologica.

[15]  J. Hirsh,et al.  Oral anticoagulants: mechanism of action, clinical effectiveness, and optimal therapeutic range. , 2001, Chest.

[16]  D. Mungall,et al.  Outpatient management of warfarin therapy: comparison of computer-predicted dosage adjustment to skilled professional care. , 1991, Therapeutic drug monitoring.

[17]  J. Hirsh,et al.  Interactions of Warfarin with Drugs and Food , 1994, Annals of Internal Medicine.

[18]  J. Jespersen,et al.  Multicentre randomised study of computerised anticoagulant dosage , 1998, The Lancet.

[19]  J Wakefield,et al.  An application of Bayesian population pharmacokinetic/pharmacodynamic models to dose recommendation. , 1995, Statistics in medicine.