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Therapeutic decision-making in oncology

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The treatment of cancer is a multidisciplinary team process, and includes the expertise of the oncology pharmacist, which can contribute to decisions regarding the best strategies for patient treatment in many ways

Sophie Perrin
Pharm D
Department of Pharmacy
University Teaching Hospital
Besançon
France

Virginie Nerich
Pharm D, Ph D

Samuel Limat
Pharm D, Ph D
Department of Pharmacy
University Teaching Hospital
Besançon
France

INSERM U645 EA-2284 IFR-133
Besançon
France

Cancer is now considered a chronic disease. Cancer treatment has been evolving and developing constantly in recent years. The availability of many new anticancer agents has significantly redefined the therapeutic approaches for many different cancers. With the emergence of targeted therapies and the development of pharmacogenomics, biologic parameters are major criteria in the decision-making process. Modern protocols and the availability of oral anticancer agents make ambulatory treatment a possibility for many patients. For these reasons, defining and applying the best strategy for each patient is a complex and major challenge.[1]
In this setting, the decision-making process has to be adapted to new parameters and constraints and the role of the oncology pharmacist should be reviewed. Considering the complexity of appropriate use of drugs in cancer, the position of oncology pharmacists in decision making should be complementary and useful to the medical staff. Pharmacists’ expertise can be developed in many directions that will optimise the benefit–risk ratio such as: organisation of therapeutic processes; involving cancer care networks; choice of treatment based on evidence-based medicine; evaluation of daily practices; and promotion of cost-effective practices.[2]

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Organisation of the therapeutic process
The cancer care networks have a significant impact on medical practice.[3] Oncology pharmacists are invited to coordinate the standardisation and develop protocols for treatment schedules. In the Franche-Comté area (1.2 million inhabitants), anticancer drug prescriptions are fully computerised, from the medical office to the clinical pharmacy unit. A multicentric software tool, which includes a specific thesaurus with a list of validated protocols for each tumour, is used by all oncology-authorised centres. The thesaurus resulted from a regional consensus meeting that included input from oncology pharmacists. For example, our pharmaceutical team is mandated by the regional oncology network to coordinate the regional guidelines committee, as well as to evaluate the conformity of daily practice according to a number of guidelines. This standardisation of practice allows evaluation, analysis and diffusion of regional and national data.
The regional organisation of cancerology through networks is a major objective of French Public Health, and is supported by the National Cancer Institute. The equity of access to the best treatment for each patient is a major challenge in this context.

Prevention of medication errors
The complexity of anticancer treatment can potentially increase medication and prescription errors. Prescription of anticancer drugs should be carried out through computerised physician order entry (CPOE) systems. Organising and securing the CPOE are priorities in healthcare institutions. Computerised prescribing of anticancer drugs improves the quality of physician order entry, and limits the risk of prescribing medication errors.[4] However, errors do occur, and the residual risk of error should be evaluated in each institution. In a recent prospective study, including 14,854 medical orders, the incidence of medication errors with a CPOE system was 1.5%. In 63% of cases, medication errors could lead to potential clinical impact.[5] If computerised medication order prevents medication errors, a clinical pharmacy validation of the prescription is clearly required. 
The risk of medication errors has to be assessed in each institution, even if optimal conditions of prescription and preparation have been established. Furthermore, a daily clinical pharmacy practice remains mandatory to prevent medication errors. With regards to pharmacokinetic characteristics of many anticancer drugs, non-cancer-specific therapies should be checked for each patient to guarantee efficacy and safety of treatment.
The combination of hospital treatment and home treatment can induce new types of medication error.[6,7] The risk of non-adherence to oral drugs in ambulatory care is evident.[8] Medication reconciliation and/or therapeutic education programmes are able to enhance safety and quality of life of cancer patients.[9,10] It is unquestionable that a better cooperation between ambulatory and hospital pharmacists is mandatory for cancer patients.

Evidence-based medicine
Defining the appropriate drug to use is a major challenge in cancer. The limitations of official approval of drugs are well documented.[11] A medical and pharmaceutical committee has been established by the French National Cancer Institute. Its objective is to define guidelines for the appropriate use of drugs, including off-label situations, supported by a sufficient level of evidence. Thus, evaluation of daily practices contributes to the optimisation of the decision-making process. Our team conducted a retrospective study of 1,211 patients with solid tumours in two oncology centres in our area.[12] Daily practices were compared to last published national guidelines. Although off-label prescription occurred in 286 cases (18.3%), 23.9% of the observed treatments were supported by results of phase II, and 73.8% by phase III, randomised trials. These results are in accordance with others studies conducted by pharmaceutical teams.[11] For example; off label use represent 6.7 to 33.2% of anticancer drug prescription.
In these studies, the majority of the deviations from guidelines were observed in the treatment of late stages of metastatic disease. The question of the best time to stop specific anticancer treatments is a topic of debate, but remains unanswered in daily practice. The pharmaceutical expertise of the oncology pharmacist in medicoeconomic considerations can contribute to multidisciplinary decision making. 

Pharmacoeconomics
Having several therapeutic options improves the prognosis for any disease but the costs associated with treatment can be enhanced dramatically.[13] For example, costs for anticancer drugs increased from €474 million to €975 million between 2004 and 2008 in French public hospitals (French National Cancer Institute report).[18] To help control healthcare spending, economic benefit/cost studies are necessary to determine the allocation of health resources. Economic evaluation data should be integrated into the decision-making process. Even though research in the field of oncology is expanding, few studies deal with pharmacoeconomics. A literature review published in 2008 shows the lack of true economic evaluation in the field of oncology.[14] Of a total of 1,589 references published on Medline between 1990 and 2006 and retrieved using specific search terms related to oncology and economics, only 8% of the articles were published in medical economic journal. Additionally, results of these studies often fail to represent daily practice. The oncology pharmacist has to develop more pragmatic economic studies that can compare different drugs, therapeutic strategies, or even administration schedules.[15–17] The addition of economic parameters in academic research programmes is a major challenge to promote pharmacoeconomics in oncology.

Conclusions
Treating the cancer patient is an increasingly complicated process, which needs to take into account both medical and economic considerations. The oncology pharmacist can play a significant role in cooperation with medical team, from drawing up guidelines to evaluating daily practice. The reconciliation between hospital and ambulatory care appears to be a priority.

References
1. Trédaniel J et al. Crit Rev Oncol Hematol 2005;54:165–70.
2. Liekweg A et al. Support Care Cancer 2004;12:73–9.
3. Ray-Coquard I et al. Bull Cancer 2006;93(2):13–20.
4. Bates DW. BMJ 2000;320(7237):788–91.
5.Nerich V et al. Int J Med Informatics, in press (validated and corrected proofs, 30/08/2010).
6. Walsh KE et al. J Clin Oncol 2009;27(6):891–6.
7. Weingart SN et al. Cancer 2010;116(10):2455–64.
8. Darkow T et al. Pharmacoeconomics 2007;25(6):481–96.
9. Weingart SN et al. Jt Comm J Qual Patient Saf 2007;33(12):750–7.
10. Perol D et al. Bull Cancer 2007;94(3):267–74.
11. Levêque D. Lancet Oncol 2008;9:1102–7.
12. Grangeasse L et al. Bull Cancer 2006;93(10):1–8.
13. Meropol NJ et al. J Clin Oncol 2009;27(23):3868–74.
14. Nerich V et al. J Pharm Clin 2008;27(2):108–12.
15. Limat S et al. Pharmacoeconomics 2004;22(10):633–41.
16. Fagnoni P et al. Pharmacoeconomics 2009;27(1):55–68.
17. Limat S et al. Eur J Health Econ 2006;7:107–13.
18. www.e-cancer.fr






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