Therapeutic Drug Monitoring in an era of cost-containment and outcomes-oriented strategies
Over the past 25-30 years the clinical use of TDM has expanded tremendously. Since the emergence of the discipline in the early sixties TDM has gone through several major stages of development. In those early years primary focus was on the measurement itself, and evaluation of appropriate indications was performed against the background of an increasing awareness of concentration-response relationships of drugs such as phenytoin and phenobarbital. Prior evaluation of the effects of these forms of early TDM service on patient outcome were not part of the development process and therefore not readily available.
The transitional stage that followed, with a broad spectrum of clinical diagnostic kits available focused primarily on establishment of routine TDM services. The context was control of unpredictable serum concentrations, but the TDM engine was mostly toxicity driven.
In the 1990's when entering a more patient-oriented rather than drug (assay)-oriented stage, the important maxim for many laboratory professionals has become 'to treat the patient and not the level'. This approach also encompasses more outcomes-oriented strategies.
Outcome analysis of clinical laboratory tests offered in a TDM service, is a relatively new activity for most laboratory scientists. Outcomes studies are performed to demonstrate the impact of laboratory assays on overall patient health, the cost of patient care and other factors such as patient satisfaction with the service. The laboratory professionals have the opportunity and responsibility to demonstrate clear links between the results generated by the laboratory and the specific impact of that service on patient care. To accomplish a full economic evaluation, both the costs (inputs) and consequences (outcomes) of the competing alternatives must be examined. In our field a cost-effectiveness analysis (CEA) is a well suited method to study benefits from TDM programs on patient outcome. In CEA, the net healthcare costs of the program or treatment are expressed in monetary terms and become the cost proportion of the cost-effectiveness ratio. Net health-care costs are comprised of the cost of the program or treatment itself, plus the costs of treating side effects, plus the health-care costs incurred during additional hospital stay, less the resources saved if an illness is better cured or prevented. The effectiveness portion of the ratio is expressed in terms of non-monetary units that measure the desired objective. Commonly used measures are lives saved, years of lives saved, quality of life, cases successfully treated or diagnosed. The cost-effectiveness ratio is then: dollars per life saved, dollars per year of life saved, dollars per patient discharged alive, or dollars per case treated or diagnosed.
In recent years many studies have addressed the impact of different types of TDM services provided. The vast majority of these articles evaluate the effect of TDM primarily by using surrogate end-points such as: more patients with levels in the desired target range, reduced numbers of inappropriately drawn and/or non-interpretable levels, decreased (concomitant) drug dosages with associated lower hospital costs. Relatively few studies have actually evaluated the impact of TDM on patient outcomes in a thorough pharmacoeconomic fashion by measuring direct outcome parameters such as decreased mortality, decreased morbidity, decreased treatment length, decreased length of hospital stay and decreased number of adverse events from drug therapy. Since this type of outcomes study remains a cornerstone in the evaluation of the usefulness and added value of TDM services, continuing research in this field should be encouraged. Therefore, during the IATDM-CT Annual Meeting during the 5th International TDM-CT congress held in Vancouver, Canada, November 10-14, 1998 a committee on the impact of TDM on pharmacoeconomics was installed. On Friday November 14th the committee's first meeting was scheduled. And although advertised during the congress only a few members were able to attend the actual business meeting. It is this committee's goal to provide encouragement and guidelines for further prospective research in the field of pharmacoeconomics and TDM. To date, most studies have focused on 'traditional' drugs for which immunoassays are available: aminoglycosides, vancomycin, digoxin, theophyllin and anticonvulsant. In the committee's 'view it would be a challenge to expand outcomes analysis to newer areas where it is anticipated that TDM will contribute even more e.g. in the area of tricyclic antidepressants monitoring (with geno4phenotyping), oncology, AIDS and immunosuppression.
The committee would like to use this IATDMCT newsletter to recruit further members who have an active interest in this field and who wish to serve on the committee. Please contact:
Prof. dr. A.A. Vinks,
Chairman, Research Professor of Pediatrics, Pharmacology Research Center & Clinical Trials Office, Children's Hospital Medical Center 3333 Burnet Avenue Cincinnati, Ohio 45229-3039; email: sander.vinks@chmcc.org
Present members of the committee:
J.S. Bertino, Cooperstown NY, USA, C.J. Destache, Omaha Nebraska USA, C Neef, Enschede Netherlands, DJ Touw, Amsterdam Netherlands, L. Binder, Gottingen Germany
