Drug waste minimisation and cost-containment in Medical Oncology: Two-year results of a feasibility study

The past ten years have seen a significant and progressive cost rising in Medical Oncology [1], largely due to the increase in cancer prevalence and the incorporation into clinical practice of novel, highly expensive drugs [2]. Indeed, the formidable bounce of recent scientific progress has led to the development, approval and licensing of novel, both cytotoxic and biological agents; these drugs have shown efficacy in clinical trials, provide further hope to cancer patients but are among the costliest in medical care [1].

The cost of one cycle of chemotherapy may range from 2,500 $ for docetaxel 75 mg/m2 to 4,000 $ for pemetrexed 500 mg/m2, both delivered every three weeks [3]. As for biological agents, one month of treatment costs from 2,300 $ for erlotinib to more than 4,000 $ for both trastumuzab and bevacizumab [1, 4]. Even more expensive is cetuximab, that sells for 8,700 $ monthly [1].

Ims Health, provider of consulting services for pharmaceutical and healthcare industries, anticipates that by 2008 antineoplastic drugs will become the top therapeutic area and their market will total over 40 billions USD, an almost 50% increase as compared with 2004 [5].

Thus, the "oncologic time bomb" predicted in 1999 by an American Cancer Society task force has exploded [2] and the question of how patients and society will afford dramatically rising drug payments remains partly unanswered.

Several strategies have been suggested to this end: from the promotion of an evidence-based medicine to the adoption of validated endpoints both in clinical studies and in the process of drug approval [6]; from the search of relevant biomarkers for a better identification of responsive patients [7] to a proper allocation of health systems resources toward the fields of disease prevention and early detection [8]. Overall, it seems that comprehensive actions resulting from a thoughtful debate among the oncological community, the government, pharmaceutical industries and health insurers are needed to secure the financial future of health systems. Nonetheless, the formulation of satellite measures, short-run but also zero-cost may be highly desirable in such a scenario.

Drug waste may be defined as the consequence of an inappropriate disposal of unused or partially used ampoules, vials, or syringes of drugs [9]. It has been previously demonstrated that inefficiency of drug use and waste production may lead to a distinct economic loss, though experiences are limited and most studies are dated or focus on other therapeutic areas [9‐12]. Decreasing waste is an attractive cost-cutting strategy since it neither limits specific drug use nor affects quality of care.

Our Department of Medical Oncology is a research-oriented academic unit, admitting about two thousands new patients every year. Facilities include an eighteen-bed day-hospital service and a fourteen-bed ward. The Clinic hosts a centralised unit for drug preparation and is equipped with a homegrown computerised physician order entry (CPOE) system; these features offer a unique opportunity for a sound management of drug preparation, prescription and administration.

In this framework, a project of drug use surveillance and waste reduction was designed and launched at the end of 2004. The project aimed at:

Here we report on first two-year results.

In days when mankind's knowledge of cancer is greater than ever before [14] and the number and cost of new anticancer drugs are rising to unexpected heights, overcoming the disproportion between health needs and available resources represents a moral as well as an economic challenge [15].

Unfortunately, most of the strategies that have been proposed to escape the need for health care rationing [16] represent medium-long term solutions, whose impact on high and rising costs is expected to be appreciable in a hardly predictable future. Prompter suggestions are probably needed to control the problem in a short term-oriented manner.

In this perspective, our experience shows how a relatively simple policy of drug waste reduction may significantly decrease their cost impact on the overall pharmaceutical expenditure and allow a substantial cost-saving.

In 2005 a net loss of 180,000 €, corresponding to 6.4 per cent of the Department's annual expenditures (i.e. 2,800,000 €), could be attributed to futile drug leftovers. Waste cost of six high-priced and/or widely used drugs, i.e. cetuximab, docetaxel, gemcitabine, oxaliplatin, pemetrexed and trastuzumab, accounted for three-quarters of this loss and to 4.8 per cent of the Department's annual drug expenditures. A strict monitoring of drug use endorsed to acknowledge: first, that recovery policies would probably not apply to drugs showing minor fluctuations in monthly wastage rates, since low variability implied the existence of a somehow physiologic, thus unrecoverable, loss; second, that main reasons for drug waste were essentially the limited extent of CT medication shelf-life and the narrow availability of a range of vial sizes flexibly matching with possible drug dosages. Adopted corrective measures were the logical consequence of these findings: if drug instability is a basis for drug waste, it is reasonable to use, whenever possible, multi-dose vials, that retain a much longer microbial and chemical stability; and to operate a per pathology/per drug distribution system of chemotherapy sessions over the week, in order to allow the re-use of leftovers in other patients, while respecting drug stability. In the same way, if market available vial sizes are relatively few, it makes sense to round down the drug dose to the closest accessible vial size. Notably, dose-rounding has been considered acceptable to within 5% of calculated dose, since on the basis of pharmacokinetic and clinical issues this dose adjustment is not expected to have any significant effect on either response or toxicity [13, 17‐19].

In our work we show how the application of straightforward measures allowed to abate the waste amount of the most expensive antineoplastic drugs, its cost and its proportion of total drug expenditure. In particular, a direct comparison of 2005 figures with 2006 reveals how the overall waste amount for the six "hot" dugs dropped of 66%, its cost decreased of 45% (from 133,292 € to 73,975 €, using an average price per milligram) and its fraction of pharmaceutical global expenditure diminished from 4.8 to 2.2%.

Further expenditure cuts may hopefully emerge from other equally feasible solutions. The establishment of an ad hoc policy for recovering unused, unexpired oral antineoplastic drugs (including biological agents) would allow a considerable medication return and money-saving. A concrete cooperation with manufacturing companies should be solicited focusing on ways to improve and validate the stability of drugs, particularly those items that need to be used within hours, and on the production of more suitable final dosage forms (for example, the decrease in pemetrexed wastage rate was less important than for the other hot drugs, since the possibility of drug recovery suffered from the limits imposed by commercially available vial sizes).

Our study has some limitations. First, it was conducted at a single centre and its generalisability to settings of different size and with a potentially different mix of diagnoses and disease severity needs to be confirmed.

Second, the rigorous planning of chemotherapy sessions across the week – which plays a key role in waste containment – requires a strictly organised structure and such a policy may be difficult to pursue, especially in the absence of a clinical information system. The increase in cetuximab wastage rate during the second semester of 2006, which was probably due to a demanding 24-hour concentration of chemotherapy sessions for colorectal cancer patients, is an example of such a hindrance. At present, we are working toward the validation and inward testing of drug microbial stability, with the aim of easing the planning and escaping from the needs of a too rigid system.

Finally, it has been previously estimated that potential savings from the reduction of inefficiencies fall short of administration's cost containment [20]; thus, our strategy may best function as an interim measure, in hold of more comprehensive, long-term plans to achieve sustainable outcomes.

Our study demonstrates that in Medical Oncology drug waste reduction is feasible and economically convenient. The existence of a centralised unit for drug manufacturing, providing a continuous surveillance on drug prescription and utilisation, a meticulous planning of daily workload, granted by CPOE, and an actively shared information and feedback among staff members are key elements to successfully pursue the proposed strategies.

The concept of "sustainability" should not allude only to the mandate of reducing health care expenditure. A sustainable oncology is economically affordable; at the same time it provides to all the community an equal right to proper levels of physical and mental well-being and aims to ceaseless progress and innovation. In this sense, the identification of easily applicable solutions, that allow to control rising costs while maintaining or improving the quality of patient care, remains challenging but highly attractive.