Paul Cornes MD FRCR MRCP
Bristol Haematology & Oncology Centre, Bristol, UK
Email: [email protected]
With tighter cost constraints and more generic and biosimilar medicines available, including biosimilar monoclonal antibodies, hospital pharmacists will be increasingly called upon to make informed decisions on drug choices.
Cancer death rates are falling and there has been a strong association between novel drug introduction and increased cancer survival.(1,2) As the world’s population ages there will be more cancer to treat. The World Health Organization estimated that cancer became the world’s top killer in 2010. Estimates are that 15 million new cases and 10 million new deaths are expected in 2020 even if current rates remain unchanged.(3) New cancer cases will likely increase to 27 million annually by 2030, with deaths hitting 17 million.
Driven by the increased numbers of patients and the higher cost of drugs, the global spend on oncology drugs doubles every four years. Cancer drug costs rise five-times faster than other classes of medicine, making oncology the number one priority for introducing cost controls.(4) Economists worry that this will become unaffordable, even in the richest countries of the world. At current rates of increase, healthcare will be 25% of the US GDP by 2025.(5,6)
Cost control strategies
Central to the continuous improvement of cancer care across Europe is advancing the role of the hospital pharmacist in the treatment pathway.(7) In Europe, with universal government tax or insurance-based healthcare, thresholds for reimbursement are being developed to concentrate care to the most cost-effective treatments.(8)
Simply rationing care is only one solution. There are a number of ways that hospital pharmacists could contribute to cost-effective cancer programmes.
Biosimilar use offers great potential for significant savings. Biological therapies are a key driver of increased cancer costs. Because the use of these products is growing at twice the rate of prescription drugs health plans, employers and government insurers have concerns about their potential financial impact, while patients are concerned about continued access to potentially beneficial therapies.(9-11) As high cost, high volume drugs, even moderate reductions in costs will create significant cost benefits.
Therefore, budget impact/cost effectiveness considerations are of paramount importance in the assessment and recommendations of solutions for new therapies, of the sort provided by the National Institute for Health and Clinical Excellence in the UK.
One demonstration of the cost-effectiveness of biosimilars has concerned epoetin biosimilars in Germany, where a saving of €60 million was achieved in their first year on the market. Projected savings, through to 2020, are in the region of €8 billion.(12)
A second demonstration involved a cost-efficiency comparison of three granulocyte colony-stimulating factors filgrastim (Neupogen, Amgen), biosimilar Zarzio (Sandoz) and pegfilgrastim (Neulasta, Amgen) across the Europe G5 countries (Germany, France, Italy, Spain and the UK).(11)
In the EU, filgrastim was one of the first targets of biosimilar manufacturers; in the EU, there are three filgrastim biosimilars approved under seven brand names.
Their cost efficiency model looked at the direct costs a buyer or payer would incur when purchasing any of the three agents during one chemotherapy cycle. The focus was on the actual reimbursement cost, and therefore no indirect costs were taken into account.
There were a number of key assumptions in their modelling, of which two are as follows:
- Their first assumption was that there were no significant differences in efficiency or safety between the three products in the five countries included in the study. This was based on comparative non-inferiority trials of Neupogen and Neulasta, and the approval process for Zarzio, with Neupogen as its reference product.
- Their second assumption was that incidence was constant, any variability in incident and prevalent febrile neutropenia during any cycle of chemotherapy being a function of the relative size of the country’s population.
The results make a compelling argument for the cost effectiveness of biosimilars. For example, the cost of Neulasta remained fixed, the cumulative cost of treatment with Neupogen ranged from a €128.(16) (one day) unit dose cost to €1794.30 for a 14-day course. This compared with a range of €95.46 to €1336.46 for Zarzio. In other words, the cost savings associated with Zarzio (biosimilar) over Neupogen (reference product) evolved from €32.70 for a one-day regimen to €457.84 for a 14-day regimen.
This finding paints a clear picture of the biosimilar comparison studies to come, wherever more expensive next-generation monoclonal antibodies reach markets of already over-stretched healthcare expenditure.
Such examples of increased affordability of biosimilars over their reference products also allows for the treatment of more patients with the same resources.
With tighter and tighter cost constraints and more and more generic and biosimilar medicines available, including biosimilar monoclonal antibodies, hospital pharmacists will be increasingly called upon to make informed recommendations and decisions on drug choices in hospitals.
Pharmacists can contribute to writing evidence-based clinical care pathways or treatment guidelines and protocols. These create savings by standardising care, directing drug use to the most cost- effective versions in each class and reducing waste from inappropriate drug use.(13,14) In a landmark study, eight practices in the US Oncology network introduced a single guideline for non-small cell lung cancer treatment. Overall, outpatient costs were 35% lower for patients on clinical pathways, with an average 12-month cost of $18,042 for pathway versus $27,737 for individualised non-pathway treatment. Survival was unaltered by cost control.(15) Savings were realised from both reduced primary drug costs and also from a 23% reduction in the use of supportive care medicines by advocating less toxic regimens.
Savings and improved care have been shown following the introduction of evidence-based guidelines for managing a wide range of conditions, including arthritis, dysuria and heart failure.(16-18)
Better information technology
Better information technology (IT) is associated with better outcomes. Pharmacists can advocate for better access to health IT to access evidence-based medicine in a hospital. A study conducted in 2009 showed that each 10% increase in health IT to access evidence-based medicine in a hospital saved 15% fewer deaths and 16% fewer complications per admission and cuts costs.(19)
Poor compliance makes treatments less effective and can drive up overall costs. The example of endocrine therapy in women with breast cancer is striking. Non-compliance with adjuvant hormone therapy reduces survival by 9%. Fewer than half of breast cancer patients adhere to hormone therapy while only 72% took their medication more than 80% of the time.(20,21)
Dose banding offers a further chance to minimise drug waste, reduce pharmacist time and maximise cost avoidance. In a three-month study, one pharmacy department processed 126 prescriptions for biologic anticancer agents. Dose banding could reduce drug wastage for 42% of these orders. Potential cost savings from dose banding in one clinic was estimated at $24,434 for a 3-month interval evaluated.(22)
Expensive biologic medications may have significant reactions. After this, the unused infusion is discarded. These tend to occur most frequently on the earlier cycles of treatment. A study showed that by giving a test dose of rituximab before starting the infusion saved about $2000 per patient in costs.(23)
Generic substitution and formulary restriction can have significant impact. Each 1% increase in generic prescribing in the UK saves £155 million.(24) In the UK, the average cost of a generic is a quarter of the original brand (£3.83 and £20 respectively). Despite these massive savings to reinvest elsewhere in healthcare, the uptake of generics varies widely between countries in Europe.(25)
In 2006, the WHO encouraged pharmacists to focus their actions on patients rather than on medications.(26) There are already several areas where further advancing the role of the hospital pharmacist in the treatment pathway could promote more cost-effective care. Research, ideas and best practice need to be shared to have impact.
- Driven by the increased numbers of patients and the higher cost of drugs, the global spend on oncology drugs doubles every four years. Cancer drug costs rise five-times faster than other classes of medicine, making oncology the number one priority for introducing cost controls.
- Central to the continuous improvement of cancer care across Europe is advancing the role of the hospital pharmacist in the treatment pathway.
- Biosimilar use offers great potential for significant savings. Biological therapies are a key driver of increased cancer costs.
- With tighter cost constraints and more generic and biosimilar medicines available, including biosimilar monoclonal antibodies, hospital pharmacists will be increasingly called upon to make informed decisions on drug choices.
- Jemal A, Ward E, Thun M. Declining death rates reflect progress against cancer. PLoS ONE 2010;5(3):e9584.
- Uyl-de Groot CA et al. The economics of improved cancer survival rates: Better outcomes, higher costs. Expert Rev Pharmacoeconomics Outcomes Res 2010;10(3):283–92.
- World Health Organization. Cancer to be world’s top killer by 2010. USA Today 9/12/2008. www.usatoday.com/news/health/2008-12-09-cancer_N.htm.
- Bach P. Limits on Medicare’s ability to control rising spending on cancer drugs. N Engl J Med 2009;360:626-33.
- Brawley OW. The American Cancer Society and the American healthcare system. Oncologist 2011;16(7):920–5.
- Sullivan R et al. Delivering affordable cancer care in high-income countries. Lancet Oncol 2011;12(10):933-80.
- European Association of Hospital Pharmacists. World Cancer Day Press Briefing. www.eahp.eu/press-room/world-cancer-day-2012-eahp-and-esop-issue-joint-call-pharmacist-development-advance.
- Wagstaff A. Health rationing in Europe: can cancer get a fair hearing? Cancer World 2009 May/June:24-31.
- Grabowski H. The market for follow-on biologics: How will it evolve? Health Affairs;25(5):1291
- Cornes P. The economic pressures for biosimilar drug use in cancer medicine. Targeted Oncol 2012;7(suppl 1):57–67.
- Aapro M, Cornes P, Abraham I. Comparative cost-efficiency across the European G5 countries of various regimens of filgrastim, biosimilar filgrastim, and pegfilgrastim to reduce the incidence of chemotherapy-induced febrile neutropenia. J Oncol Pharm Pract 2012;18(2):171–9.
- Biosimilar monoclonal antibodies: the next frontier. An EGA symposium. 17th Congress of the European Association of Hospital Pharmacists; 21-23 March 2012. www.farmaactueel.nl/webcasts/extern/EAHP2012/InleidingEGA.htm.
- Arie S. Most OECD countries could save money by improving clinical guidelines and negotiating better drug prices. BMJ 2010;341:c5552.
- Kosimbei G, Hanson K, English M. Do clinical guidelines reduce clinician dependent costs? Health Res Policy Syst 2011;9:24.
- Neubauer MA, Hoverman JR, Kolodziej M, et al: Cost effectiveness of evidence-based treatment guidelines for the treatment of non–small-cell lung cancer in the community setting. J Oncol Pract 2010;6:12-18.
- Andrews G et al. Evidence-based medicine is affordable: the cost-effectiveness of current compared with optimal treatment in rheumatoid and osteoarthritis. J Rheumatol 2006;33(4):671-80.
- Stuart ME et al. Acute dysuria in adult women. HMO Practice 1997;11(4):150-7.
- Didomenico RJ et al. Impact of treatment guidelines on clinical and economic outcomes of acute decompensated heart failure. Ann Pharmacother 2008;42:327-33.
- Amarasingham R et al. Clinical information technologies and inpatient outcomes: a multiple hospital study. Arch Intern Med 2009;169(2):108–14.
- Printz C. Fewer than half of breast cancer patients adhere to hormone therapy. Cancer 2010;116(23):5342–3.
- Hershman DL et al. Early discontinuation and nonadherence to adjuvant hormonal therapy in a cohort of 8,769 early-stage breast cancer patients. J Clin Oncol 2010;28(27):4120–8.
- Winger BJ et al. Cost savings from dose rounding of biologic anticancer agents in adults. Oncol Pharm Pract 2011;17(3):246–51.
- Melton C. Cost-containment strategies. The Oncology Pharmacist. www.theoncologypharmacist.com/article/cost-containment-strategies
- BGMA. Briefing paper 2010. www.britishgenerics.co.uk/admin/files//1341332257_BGMAbriefing-030712.pdf.
- EGMA. Generic market shares in Europe. www.egagenerics.com/doc/fac-GxMktEur_2006.pdf.
- Wiedenmayer KSR et al. Developing pharmacy practice: a focus on patient care. World Health Organization and International Pharmaceutical Federation;2006.