Med Oncol (2015) 32:16 DOI 10.1007/s12032-014-0457-y
ORIGINAL PAPER
An Anticancer Drug Unit for the whole provincial oncologic network of Piacenza: improving safety and savings Patrizia Mordenti • Stefano Vecchia • Enrico Damonti • Alessandra Riva • Monica Muroni • Maria Rosa Cordani • Gabriele Cremona • Luigi Cavanna
Received: 11 December 2014 / Accepted: 15 December 2014 / Published online: 9 January 2015 Ó Springer Science+Business Media New York 2014
Abstract In recent years, the expenditure for cancer care is increased largely due to the increase in cancer prevalence, demographic changes and incorporation into clinical practice of new and expensive drugs. For these reasons, solutions to contain costs are necessaries. The drugs-related expenditure is proportionally higher in oncology than in other medical specialties and overcomes staffing costs for outpatient care. The introduction of additional measures to contain and reduce expenditures such as waste reduction and human resources optimization is highly desirable. On April 2013, we started a day-to-day monitoring of the consumption of drugs and developed an internal protocol for waste minimization, consisting of five measures. A
P. Mordenti (&) M. Muroni M. R. Cordani G. Cremona L. Cavanna Dipartimento Oncologia - Ematologia, Ospedale Guglielmo da Saliceto, Via Taverna 49, 29121 Piacenza, PC, Italy e-mail: [email protected]; [email protected] M. Muroni e-mail: [email protected] M. R. Cordani e-mail: [email protected] G. Cremona e-mail: [email protected] L. Cavanna e-mail: [email protected] S. Vecchia E. Damonti A. Riva Unita` Farmaci Antiblastici, Ospedale Guglielmo da Saliceto, Via Taverna 49, 29121 Piacenza, PC, Italy e-mail: [email protected] E. Damonti e-mail: [email protected] A. Riva e-mail: [email protected]
computerized research through Medline, Cancerlit and Embase was performed, applying the words drug waste, cost-containment, Anticancer Drug Unit and stability instructions. Articles and abstracts were also identified by back-referencing from other relevant papers. Selected for the present review were papers published in English without limit of year. The day-to-day monitoring of the consumption of drugs and the internal protocol for waste minimization were able to achieve a saving of €15,700 every month. The projection of an annual cost-saving result of €188.00 corresponds to a recovery of 4 % on the spending for oncologic drugs. Our data show that in a proper structure working according to the standards of quality, safety and sterility, preserving and reusing the drug waste within the limits imposed by the datasheets, it is possible to achieve a cost-containment policy and produce durable benefits. Keywords Drug waste Cost-containment Anticancer Drug Unit Stability instructions
Introduction In the last years, the expenditure for cancer care is increased largely due to the increase in cancer prevalence, demographic changes and incorporation into clinical practice of new and expensive drugs. For all these reasons, solutions to contain costs and improve the safety for patients are needed. Among possible solutions, the more desirables are measures to help oncologists in using cost-effectiveness information and discussion on drug costs with their patients [1]. The total attributable expenses for cancer care include direct costs such as the expenditure for drugs and indirect costs, mainly loss of productivity in individuals of working age [2].
123
16
Page 2 of 5
Although the expenditure for the prescribed drugs represents only a small percentage of health costs, the antineoplastic alone is a significant and growing part of this spending and are the leading source in hospital drug expenses [3]. The drugs-related expenditure is proportionally higher in oncology than in other medical specialties and overcomes staffing costs for outpatient care [4, 5]. The European countries have faced the problem in many different ways such as a direct price control by government (France, Greece and Spain), a risk sharing policy (Italy) or a value-based pricing scheme (Germany and UK) [6]. In this scenario, the introduction of additional measures to contain and reduce expenditures such as waste reduction and human resources optimization is highly desirable. The drug waste may be defined as the consequence of an inappropriate disposal of the ampoules, vials or syringes of drugs unused or partially used [7]. The inefficient use of the drugs and the waste production may lead to a distinct economic loss, though experiences are limited and most studies are dated and focused on other therapeutics areas [7–11]. In the year 2013, at the Oncology– Haematology Department of the Hospital of Piacenza (North Italy) was started about 1,200 new oncologic chemotherapies. The department allows oncologic treatments in four hospitals of the province of Piacenza and hosts a centralized unit for the preparation of anticancer drugs with a computerized system for the programming of chemotherapy (Log80). In this framework, a project of surveillance of both drug use and recovery of drug waste was designed and launched in April 2013. The main aims were to (1) monitor the global amount of chemotherapy waste during a period of 6 month, (2) estimate the resulting economic saving and the influence of each drug, (3) measure the cost-saving effect of some corrective measures, like a reasonable rounding of the drug dose, use of multi-dose vials and the reuse of the drug waste according to the stability imposed by the technical datasheet, (4) adopt a drug-day policy concentrating all the therapies with the same drug on a single day and (5) evaluate the safety profile for the patients.
Materials and methods The use of a prescription software makes possible to record every single therapy prepared in the Anticancer Drug Unit (ADU) and thus analyse production data. The analysis took place from April to September 2013. We chose this period because the internal protocol for waste minimization and reuse has been extended to the whole department. The protocol consists of five major measures: 1)
A distribution of the chemotherapy during the week based on a per pathology and drug scheme, in order to reuse the leftovers in different patients on the same
123
Med Oncol (2015) 32:16
2)
3) 4)
5)
day or on the following day, while respecting the chemical and microbiological stability of the drug [12, 13]; The choice whenever possible, of multi-dose vials, able to maintain the microbiological stability for up to 24 h; A reasonable rounding of the drug dosage, within the 5 % of calculated dose [14]; The choice of the most convenient size of the drugs according to the daily consumption of each drug [15]; The evaluation of the possible reuse or discharge of the leftover in order to respect the chemical stability imposed by the technical datasheet.
Once collected the data, we proceeded to compare the cost of therapies prepared according to the protocol with the cost of therapies previously prepared by nurses according to the practice in place before the ADU, for a same subset of patients. The main difference between the two ways of work is linked to the fact that according to the technical datasheet, in the ADU the leftovers can be recovered under sterile conditions while respecting the chemical stability, whereas with the previous system at the end of every day, all the remains must be discharged. The cost has been calculated according to the current prices per milligram of drug used in the practice [16]; when the recovery of the remains was impossible the cost has been rounded to the expense of the whole vial. The analysis was focused on four ‘‘hot drugs’’, namely Cetuximab, Trastuzumab, Bortezomib and Azacitidine which impact for an 80 % on the saving generated by the reuse of the leftovers.
Results The activity of the ADU has been counted in about 1,400 bags of oncologic drugs for every month (Fig. 1). The creation of a work environment with controlled and validated aseptic conditions [17–19] has allowed a significant recovery of resources that has been estimated on €15,700 every month (Fig. 2). From April 2013 to April 2014, a total of 16,800 bags were prepared for 1,182 patients with a recovery of resources of €188,400, that is, just over the 4 % of the annual expenditure for injective anticancer drugs supported by our hospital. A detailed analysis reveals as the result is strongly influenced by the entity of the use of few high-cost molecules (Fig. 3). In particular, we assessed the recovery of Cetuximab, Trastuzumab, Bortezomib and Azacitidine showing that these four molecules alone have an estimated recovery of €150,000, corresponding to the 80 % of the total recovery (Fig. 4).
Med Oncol (2015) 32:16
Page 3 of 5 16
Fig. 1 Activity of the Anticancer Drug Unit (from April 2013 to September 2013)
Fig. 4 Recovery for high-cost drugs with and without Anticancer Drug Unit
Discussion
Fig. 2 Recovery of resources for month (from April 2013 to September 2013)
The strategies proposed to contain health costs are medium to long-term solutions whose impact on high and rising costs is hardly predictable and expected to be appreciable in the future. In this perspective, a simple policy of control and reuse of the drug waste may significantly decrease the impact on the pharmaceutical expenditure and allow a cost saving in the short time. The recovery of the resources depends on several factors: 1)
2)
3) 4) Fig. 3 Recovery for all drugs (high-cost and other)
Controlled aseptic environment in which to set up the therapies respecting the highest standards for quality and safety [20]; in fact, without a sterile work place, the microbiological stability of the remains is less than 24 h; Stability assessment of the different drugs by the pharmacist. In this perspective, it is reasonable to use multi-dose vials that retain much longer microbiological and chemical stability. Similarly, if the available sizes of the vials are few, it makes sense to round up the dose to the closest size of the vial; this rounding is acceptable within a 5 % of the calculated dose since that based on clinical issues this dose adjustment is not expected to have a significant effect on the activity or toxicity; Management of the reuse of the process residues; Qualitative/quantitative evaluation of the consumption of high-cost drugs. The recovery policy would not apply to drugs showing a minor fluctuation in the
123
16
5)
Page 4 of 5
monthly wastage rates, so there is a physiologic loss. Furthermore, a centre using low rate of high-cost drugs will have less saving; Centralized preparation in ADU of Piacenza for the whole provincial oncologic network.
In Piacenza, there are four hospitals in which are admitted onco-haematologic patients, namely Piacenza, Bobbio, Castel San Giovanni and Fiorenzuola. The centralization of all the dilutions in the ADU of Piacenza with the resulting saving was possible thanks to the close collaboration between the oncologists and pharmacists. This collaboration has led to the definition of a shared protocol of chemotherapy which in addition to ensuring the quality of care for the patients, allowed us to have uniformity in the prescription, use the drugs in a more homogeneous manner (type of drug and trademark) and consequently having a better management of the warehouse and remnants of processing. The limitations of our study include that it is a monocentric experience and that we did not consider the impact of oral drugs. In fact, in a near future, it is possible that the use of intravenous drugs decrease being partially replaced with oral formulations; moreover, the availability of biosimilars even in oncology will help in reducing the costs. Finally, the saving after the first year tends to reach a plateau because of the ability of the system to reach a steady state after 1 year of optimization [21]. Possible future researches include the evaluation of a rounding dose other than the 5 %, since recent studies suggest that a rounding up to the 10 % can be applied without detrimental effect on efficacy [14, 18]. The drug–target interactions, neutralizing-antibody formation and the biologic characteristics of the disease impact on the activity of the drug more than does the drug usage itself. Thus, the administered dose should be adequate to yield systemic concentrations able to saturate or modulate the target optimally. The application of these observations to our protocol might increase the drug waste saving from intravenous drugs and could be applied to the oral formulations to save remnants, also reducing the healthcare costs. The application of the protocol was possible thanks to the centralization of all the dilutions in only one ADU, accomplished through the construction of a suitable environment to work in sterile conditions so allowing a significant recovery of resources. In conclusion, the centralization allows to merge similar therapies of different patients optimizing the use of the drugs and consents to recover the remains of production that would otherwise be disposed of. This recovery when monetized represents a considerable amount of resources. Further analysis have also shown how this volume consists largely of a few molecules for high-cost, so having major saving when using more therapies containing these molecules. The ability to recover and therefore to allocate those resources differently is an example of clinical
123
Med Oncol (2015) 32:16
governance in which the figures involved in the construction and implementation of an ADU (oncologists, pharmacists and nurses) participated in an improvement in performance in terms of quality and safety for the citizens. Conflict of interest The authors have no conflicts of interest to declare; this study did not require funding for its completion.
References 1. Berry SR, Bell CM, Ubel PA, Evans WK, Nadler E, Strevel EL, et al. Continental Divide? The attitudes of US and Canadian oncologists on the costs, cost-effectiveness, and health policies associated with new cancer drugs. J Clin Oncol. 2010;28:4149–53. 2. Khayat D. Innovative cancer therapies: putting costs into context. Cancer. 2012;118:2367–71. 3. Hoffman JM, Shah ND, Vermeulen LC, Doloresco F, Martin PK, Blake S, et al. Projecting future drug expenditure–2009. Am J Health Syst Pharm. 2009;166:237–57. 4. Bach PB. Costs of cancer care: a view from the centers for medicare and medical services. J Clin Oncol. 2007;25:187–90. 5. Fasola G, Aprile G, Aita M. A model to estimate human resource needs for the treatment of outpatients with cancer. J Oncol Pract. 2012;8:13–7. 6. Cheema PK, Gavura S, Migus M, Godman L, Yeung L, Trudeau ME. International variability in the reimbursement of cancer drugs by publically funded drug programs. Curr Oncol. 2012;19: e165–76. 7. Nava-Ocampo AA, Alarco´n-Almanza JM, Moyao-Garcı´a D, Ramı´rez-Mora JC, Salmero´n J. Undocumented drug utilization and drug waste increase costs of pediatric anesthesia care. Fundam Clin Pharmacol. 2004;18:107–12. 8. Diehl LD, Goo ED, Sumiye L, Ferrell R. Reducing waste of intravenous solutions. Am J Hosp Pharm. 1992;49:106–8. 9. Favier M, Fliche E, Bressolle F. Economic benefit of a centralized reconstitution unit of cytotoxic drugs in isolator. J Oncol Pharm Pract. 1996;2:182–5. 10. Gillerman RG, Browning RA. Drug use inefficiency: a hidden source of wasted health care dollars. Anesth Analg. 2000;91:921–4. 11. Chaudhary K, Garg R, Bhalotra AR, Anand R, Girdhar K. Anesthetic drug wastage in the operation room: a cause concern. J Anesthesiol Clin Pharmacol. 2012;28:56–61. 12. AAVV, Gruppo di Lavoro in Oncologia SIFO Lombardia. Compendio farmacologico e tecnico-farmaceutico alle linee guida SIFO in Oncologia. Schede monografiche di tecnica farmaceutica. Il pensiero Scientifico Editore; 2013. p.173–257. 13. Trissel LA. Handbook on injectable drugs. American Society of Health-System Pharmacists, Inc., 15th ed. 2009. 14. Field K, Zelenko A, Kosmider S, Court K, Ng LL, Hibbert M, et al. Dose rounding of chemotherapy in colorectal cancer: an analysis of clinician attitudes and the potential impact on treatment costs. Asia Pac J Clin Oncol. 2010;6:203–9. 15. Dooley MJ, Singh S, Michael M. Implications of dose rounding of chemotherapy to the nearest vial size. Support Care Cancer. 2004;12:653–6. 16. Italian Medicine Agency (AIFA) Official Hospital drug prices. http://www.agenziafarmaco.it/wscs_render_attachment_by_id/111. 84470.1172743348645ce4c.pdf?id=111.81951.1172658490314 17. EU GMP guide annexes. Supplementary requirements: Annex 1 Manufacture of sterile medicinal products. 2010. http://ec.europa. eu/health/files/eudralex/vol-4/2008_11_25_gmp-an1_en.pdf 18. European Standards EN 12469. Biotechnology—performance criteria for microbiological safety cabinets. European Committee
Med Oncol (2015) 32:16 for Standardization. 2000. https://www.google.it/url?sa=t&rct=j& q=&esrc=s&frm=1&source=web&cd=3&ved=0CEIQFjAC&url= https%3A%2F%2Filnas.services-publics.lu%2Fecnor%2Fdown loadPreview.action%3FdocumentReference%3D26816&ei=j690 U52LoaTG0QwallCgCg&usg=AFQjCNFsfUWvEOtc37hBKeNN Tj1lYjTxJA 19. Ministero del Lavoro della Salute e delle Politiche Sociali, Istituto Superiore Sanita`. Norme di buona preparazione dei medicinali in farmacia. Aspetti microbiologici dei preparati. In: Farmacopea Ufficiale della repubblica Italiana, 12th edn. Libreria dello Stato; 2008. p. 1423–25.
Page 5 of 5 16 20. Dipartimento della programmazione e dell’ordinamento del Servizio Sanitario Nazionale, direzione generale della programmazione sanitaria, ufficio III ex DGPROGS. Raccomandazione per la prevenzione degli errori in terapia con farmaci antineoplastici, Raccomandazione n° 14. 2012. http://www.salute.gov.it/ imgs/C_17_pubblicazioni_1861_allegato.pdf 21. Fasola G, Aprile G, Marini L, Follador A, Mansutti M, Miscoria M. Drug waste minimization as an effective strategy of costcontainment in oncology. BMC Health Serv Res. 2014;14:57.
123
ORIGINAL PAPER
An Anticancer Drug Unit for the whole provincial oncologic network of Piacenza: improving safety and savings Patrizia Mordenti • Stefano Vecchia • Enrico Damonti • Alessandra Riva • Monica Muroni • Maria Rosa Cordani • Gabriele Cremona • Luigi Cavanna
Received: 11 December 2014 / Accepted: 15 December 2014 / Published online: 9 January 2015 Ó Springer Science+Business Media New York 2014
Abstract In recent years, the expenditure for cancer care is increased largely due to the increase in cancer prevalence, demographic changes and incorporation into clinical practice of new and expensive drugs. For these reasons, solutions to contain costs are necessaries. The drugs-related expenditure is proportionally higher in oncology than in other medical specialties and overcomes staffing costs for outpatient care. The introduction of additional measures to contain and reduce expenditures such as waste reduction and human resources optimization is highly desirable. On April 2013, we started a day-to-day monitoring of the consumption of drugs and developed an internal protocol for waste minimization, consisting of five measures. A
P. Mordenti (&) M. Muroni M. R. Cordani G. Cremona L. Cavanna Dipartimento Oncologia - Ematologia, Ospedale Guglielmo da Saliceto, Via Taverna 49, 29121 Piacenza, PC, Italy e-mail: [email protected]; [email protected] M. Muroni e-mail: [email protected] M. R. Cordani e-mail: [email protected] G. Cremona e-mail: [email protected] L. Cavanna e-mail: [email protected] S. Vecchia E. Damonti A. Riva Unita` Farmaci Antiblastici, Ospedale Guglielmo da Saliceto, Via Taverna 49, 29121 Piacenza, PC, Italy e-mail: [email protected] E. Damonti e-mail: [email protected] A. Riva e-mail: [email protected]
computerized research through Medline, Cancerlit and Embase was performed, applying the words drug waste, cost-containment, Anticancer Drug Unit and stability instructions. Articles and abstracts were also identified by back-referencing from other relevant papers. Selected for the present review were papers published in English without limit of year. The day-to-day monitoring of the consumption of drugs and the internal protocol for waste minimization were able to achieve a saving of €15,700 every month. The projection of an annual cost-saving result of €188.00 corresponds to a recovery of 4 % on the spending for oncologic drugs. Our data show that in a proper structure working according to the standards of quality, safety and sterility, preserving and reusing the drug waste within the limits imposed by the datasheets, it is possible to achieve a cost-containment policy and produce durable benefits. Keywords Drug waste Cost-containment Anticancer Drug Unit Stability instructions
Introduction In the last years, the expenditure for cancer care is increased largely due to the increase in cancer prevalence, demographic changes and incorporation into clinical practice of new and expensive drugs. For all these reasons, solutions to contain costs and improve the safety for patients are needed. Among possible solutions, the more desirables are measures to help oncologists in using cost-effectiveness information and discussion on drug costs with their patients [1]. The total attributable expenses for cancer care include direct costs such as the expenditure for drugs and indirect costs, mainly loss of productivity in individuals of working age [2].
123
16
Page 2 of 5
Although the expenditure for the prescribed drugs represents only a small percentage of health costs, the antineoplastic alone is a significant and growing part of this spending and are the leading source in hospital drug expenses [3]. The drugs-related expenditure is proportionally higher in oncology than in other medical specialties and overcomes staffing costs for outpatient care [4, 5]. The European countries have faced the problem in many different ways such as a direct price control by government (France, Greece and Spain), a risk sharing policy (Italy) or a value-based pricing scheme (Germany and UK) [6]. In this scenario, the introduction of additional measures to contain and reduce expenditures such as waste reduction and human resources optimization is highly desirable. The drug waste may be defined as the consequence of an inappropriate disposal of the ampoules, vials or syringes of drugs unused or partially used [7]. The inefficient use of the drugs and the waste production may lead to a distinct economic loss, though experiences are limited and most studies are dated and focused on other therapeutics areas [7–11]. In the year 2013, at the Oncology– Haematology Department of the Hospital of Piacenza (North Italy) was started about 1,200 new oncologic chemotherapies. The department allows oncologic treatments in four hospitals of the province of Piacenza and hosts a centralized unit for the preparation of anticancer drugs with a computerized system for the programming of chemotherapy (Log80). In this framework, a project of surveillance of both drug use and recovery of drug waste was designed and launched in April 2013. The main aims were to (1) monitor the global amount of chemotherapy waste during a period of 6 month, (2) estimate the resulting economic saving and the influence of each drug, (3) measure the cost-saving effect of some corrective measures, like a reasonable rounding of the drug dose, use of multi-dose vials and the reuse of the drug waste according to the stability imposed by the technical datasheet, (4) adopt a drug-day policy concentrating all the therapies with the same drug on a single day and (5) evaluate the safety profile for the patients.
Materials and methods The use of a prescription software makes possible to record every single therapy prepared in the Anticancer Drug Unit (ADU) and thus analyse production data. The analysis took place from April to September 2013. We chose this period because the internal protocol for waste minimization and reuse has been extended to the whole department. The protocol consists of five major measures: 1)
A distribution of the chemotherapy during the week based on a per pathology and drug scheme, in order to reuse the leftovers in different patients on the same
123
Med Oncol (2015) 32:16
2)
3) 4)
5)
day or on the following day, while respecting the chemical and microbiological stability of the drug [12, 13]; The choice whenever possible, of multi-dose vials, able to maintain the microbiological stability for up to 24 h; A reasonable rounding of the drug dosage, within the 5 % of calculated dose [14]; The choice of the most convenient size of the drugs according to the daily consumption of each drug [15]; The evaluation of the possible reuse or discharge of the leftover in order to respect the chemical stability imposed by the technical datasheet.
Once collected the data, we proceeded to compare the cost of therapies prepared according to the protocol with the cost of therapies previously prepared by nurses according to the practice in place before the ADU, for a same subset of patients. The main difference between the two ways of work is linked to the fact that according to the technical datasheet, in the ADU the leftovers can be recovered under sterile conditions while respecting the chemical stability, whereas with the previous system at the end of every day, all the remains must be discharged. The cost has been calculated according to the current prices per milligram of drug used in the practice [16]; when the recovery of the remains was impossible the cost has been rounded to the expense of the whole vial. The analysis was focused on four ‘‘hot drugs’’, namely Cetuximab, Trastuzumab, Bortezomib and Azacitidine which impact for an 80 % on the saving generated by the reuse of the leftovers.
Results The activity of the ADU has been counted in about 1,400 bags of oncologic drugs for every month (Fig. 1). The creation of a work environment with controlled and validated aseptic conditions [17–19] has allowed a significant recovery of resources that has been estimated on €15,700 every month (Fig. 2). From April 2013 to April 2014, a total of 16,800 bags were prepared for 1,182 patients with a recovery of resources of €188,400, that is, just over the 4 % of the annual expenditure for injective anticancer drugs supported by our hospital. A detailed analysis reveals as the result is strongly influenced by the entity of the use of few high-cost molecules (Fig. 3). In particular, we assessed the recovery of Cetuximab, Trastuzumab, Bortezomib and Azacitidine showing that these four molecules alone have an estimated recovery of €150,000, corresponding to the 80 % of the total recovery (Fig. 4).
Med Oncol (2015) 32:16
Page 3 of 5 16
Fig. 1 Activity of the Anticancer Drug Unit (from April 2013 to September 2013)
Fig. 4 Recovery for high-cost drugs with and without Anticancer Drug Unit
Discussion
Fig. 2 Recovery of resources for month (from April 2013 to September 2013)
The strategies proposed to contain health costs are medium to long-term solutions whose impact on high and rising costs is hardly predictable and expected to be appreciable in the future. In this perspective, a simple policy of control and reuse of the drug waste may significantly decrease the impact on the pharmaceutical expenditure and allow a cost saving in the short time. The recovery of the resources depends on several factors: 1)
2)
3) 4) Fig. 3 Recovery for all drugs (high-cost and other)
Controlled aseptic environment in which to set up the therapies respecting the highest standards for quality and safety [20]; in fact, without a sterile work place, the microbiological stability of the remains is less than 24 h; Stability assessment of the different drugs by the pharmacist. In this perspective, it is reasonable to use multi-dose vials that retain much longer microbiological and chemical stability. Similarly, if the available sizes of the vials are few, it makes sense to round up the dose to the closest size of the vial; this rounding is acceptable within a 5 % of the calculated dose since that based on clinical issues this dose adjustment is not expected to have a significant effect on the activity or toxicity; Management of the reuse of the process residues; Qualitative/quantitative evaluation of the consumption of high-cost drugs. The recovery policy would not apply to drugs showing a minor fluctuation in the
123
16
5)
Page 4 of 5
monthly wastage rates, so there is a physiologic loss. Furthermore, a centre using low rate of high-cost drugs will have less saving; Centralized preparation in ADU of Piacenza for the whole provincial oncologic network.
In Piacenza, there are four hospitals in which are admitted onco-haematologic patients, namely Piacenza, Bobbio, Castel San Giovanni and Fiorenzuola. The centralization of all the dilutions in the ADU of Piacenza with the resulting saving was possible thanks to the close collaboration between the oncologists and pharmacists. This collaboration has led to the definition of a shared protocol of chemotherapy which in addition to ensuring the quality of care for the patients, allowed us to have uniformity in the prescription, use the drugs in a more homogeneous manner (type of drug and trademark) and consequently having a better management of the warehouse and remnants of processing. The limitations of our study include that it is a monocentric experience and that we did not consider the impact of oral drugs. In fact, in a near future, it is possible that the use of intravenous drugs decrease being partially replaced with oral formulations; moreover, the availability of biosimilars even in oncology will help in reducing the costs. Finally, the saving after the first year tends to reach a plateau because of the ability of the system to reach a steady state after 1 year of optimization [21]. Possible future researches include the evaluation of a rounding dose other than the 5 %, since recent studies suggest that a rounding up to the 10 % can be applied without detrimental effect on efficacy [14, 18]. The drug–target interactions, neutralizing-antibody formation and the biologic characteristics of the disease impact on the activity of the drug more than does the drug usage itself. Thus, the administered dose should be adequate to yield systemic concentrations able to saturate or modulate the target optimally. The application of these observations to our protocol might increase the drug waste saving from intravenous drugs and could be applied to the oral formulations to save remnants, also reducing the healthcare costs. The application of the protocol was possible thanks to the centralization of all the dilutions in only one ADU, accomplished through the construction of a suitable environment to work in sterile conditions so allowing a significant recovery of resources. In conclusion, the centralization allows to merge similar therapies of different patients optimizing the use of the drugs and consents to recover the remains of production that would otherwise be disposed of. This recovery when monetized represents a considerable amount of resources. Further analysis have also shown how this volume consists largely of a few molecules for high-cost, so having major saving when using more therapies containing these molecules. The ability to recover and therefore to allocate those resources differently is an example of clinical
123
Med Oncol (2015) 32:16
governance in which the figures involved in the construction and implementation of an ADU (oncologists, pharmacists and nurses) participated in an improvement in performance in terms of quality and safety for the citizens. Conflict of interest The authors have no conflicts of interest to declare; this study did not require funding for its completion.
References 1. Berry SR, Bell CM, Ubel PA, Evans WK, Nadler E, Strevel EL, et al. Continental Divide? The attitudes of US and Canadian oncologists on the costs, cost-effectiveness, and health policies associated with new cancer drugs. J Clin Oncol. 2010;28:4149–53. 2. Khayat D. Innovative cancer therapies: putting costs into context. Cancer. 2012;118:2367–71. 3. Hoffman JM, Shah ND, Vermeulen LC, Doloresco F, Martin PK, Blake S, et al. Projecting future drug expenditure–2009. Am J Health Syst Pharm. 2009;166:237–57. 4. Bach PB. Costs of cancer care: a view from the centers for medicare and medical services. J Clin Oncol. 2007;25:187–90. 5. Fasola G, Aprile G, Aita M. A model to estimate human resource needs for the treatment of outpatients with cancer. J Oncol Pract. 2012;8:13–7. 6. Cheema PK, Gavura S, Migus M, Godman L, Yeung L, Trudeau ME. International variability in the reimbursement of cancer drugs by publically funded drug programs. Curr Oncol. 2012;19: e165–76. 7. Nava-Ocampo AA, Alarco´n-Almanza JM, Moyao-Garcı´a D, Ramı´rez-Mora JC, Salmero´n J. Undocumented drug utilization and drug waste increase costs of pediatric anesthesia care. Fundam Clin Pharmacol. 2004;18:107–12. 8. Diehl LD, Goo ED, Sumiye L, Ferrell R. Reducing waste of intravenous solutions. Am J Hosp Pharm. 1992;49:106–8. 9. Favier M, Fliche E, Bressolle F. Economic benefit of a centralized reconstitution unit of cytotoxic drugs in isolator. J Oncol Pharm Pract. 1996;2:182–5. 10. Gillerman RG, Browning RA. Drug use inefficiency: a hidden source of wasted health care dollars. Anesth Analg. 2000;91:921–4. 11. Chaudhary K, Garg R, Bhalotra AR, Anand R, Girdhar K. Anesthetic drug wastage in the operation room: a cause concern. J Anesthesiol Clin Pharmacol. 2012;28:56–61. 12. AAVV, Gruppo di Lavoro in Oncologia SIFO Lombardia. Compendio farmacologico e tecnico-farmaceutico alle linee guida SIFO in Oncologia. Schede monografiche di tecnica farmaceutica. Il pensiero Scientifico Editore; 2013. p.173–257. 13. Trissel LA. Handbook on injectable drugs. American Society of Health-System Pharmacists, Inc., 15th ed. 2009. 14. Field K, Zelenko A, Kosmider S, Court K, Ng LL, Hibbert M, et al. Dose rounding of chemotherapy in colorectal cancer: an analysis of clinician attitudes and the potential impact on treatment costs. Asia Pac J Clin Oncol. 2010;6:203–9. 15. Dooley MJ, Singh S, Michael M. Implications of dose rounding of chemotherapy to the nearest vial size. Support Care Cancer. 2004;12:653–6. 16. Italian Medicine Agency (AIFA) Official Hospital drug prices. http://www.agenziafarmaco.it/wscs_render_attachment_by_id/111. 84470.1172743348645ce4c.pdf?id=111.81951.1172658490314 17. EU GMP guide annexes. Supplementary requirements: Annex 1 Manufacture of sterile medicinal products. 2010. http://ec.europa. eu/health/files/eudralex/vol-4/2008_11_25_gmp-an1_en.pdf 18. European Standards EN 12469. Biotechnology—performance criteria for microbiological safety cabinets. European Committee
Med Oncol (2015) 32:16 for Standardization. 2000. https://www.google.it/url?sa=t&rct=j& q=&esrc=s&frm=1&source=web&cd=3&ved=0CEIQFjAC&url= https%3A%2F%2Filnas.services-publics.lu%2Fecnor%2Fdown loadPreview.action%3FdocumentReference%3D26816&ei=j690 U52LoaTG0QwallCgCg&usg=AFQjCNFsfUWvEOtc37hBKeNN Tj1lYjTxJA 19. Ministero del Lavoro della Salute e delle Politiche Sociali, Istituto Superiore Sanita`. Norme di buona preparazione dei medicinali in farmacia. Aspetti microbiologici dei preparati. In: Farmacopea Ufficiale della repubblica Italiana, 12th edn. Libreria dello Stato; 2008. p. 1423–25.
Page 5 of 5 16 20. Dipartimento della programmazione e dell’ordinamento del Servizio Sanitario Nazionale, direzione generale della programmazione sanitaria, ufficio III ex DGPROGS. Raccomandazione per la prevenzione degli errori in terapia con farmaci antineoplastici, Raccomandazione n° 14. 2012. http://www.salute.gov.it/ imgs/C_17_pubblicazioni_1861_allegato.pdf 21. Fasola G, Aprile G, Marini L, Follador A, Mansutti M, Miscoria M. Drug waste minimization as an effective strategy of costcontainment in oncology. BMC Health Serv Res. 2014;14:57.
123
