By Peter Gilbar for oncologynews.com.au
The Problem
Spending on cancer drugs is increasing at a frightening rate and affects every country. This should be of considerable concern to consumers, health professionals, health insurers, hospitals and, particularly, governments.
Successful research initiatives have led to the development of numerous innovative, but more and more costly, medications for use in the management of cancer, putting an enormous financial burden on society. The ability to ensure equitable worldwide access to these drugs and consistent affordable prices is virtually impossible in the current economic climate.
The market for cancer drugs is economically immense, ranking first within pharmaceuticals in terms of global spending. While nations, such as Australia, have regulated pricing and reimbursement of high-cost cancer medications, this does not occur in every country, including the biggest market, the USA. With hundreds of cancer drugs currently in various phases of pre-approval testing, there is the obvious ability for the pharmaceutical industry to generate immense financial returns. Not only are new drugs being developed, but new indications are being identified for current drugs, further increasing earning potential. For example, drugs approved in metastatic disease are under investigation in combination protocols, adjuvant and neo-adjuvant settings, other malignancies and non-cancer indications. This increases the number of patients eligible for treatment and length of time they are treated for.
Spending on cancer drugs, available in the USA as single dose vials, has been investigated to evaluate the extent of drug wastage. By examining the top 20 cancer drugs dosed by body size and packaged as single dose vials, researchers estimated that the total amount of drug left over in vials after preparation for administration and calculated the resulting revenue received by drug companies for the unused and wasted drug. Discarded drug costs were judged to be in the billions. Despite being aware of the problem with vial sizes, the pharmaceutical industry has been slow to react. A 2007 Australian study examined the use of trastuzumab, available only as a 150 mg vial, in a medicine access program for metastatic breast cancer over a 40 month period and reported that 24% of trastuzumab was discarded. Despite the authors concluding that an extra vial size could significantly reduce waste, it took another 6 years to introduce a 60 mg vial.
Research should include stability studies to enable extended expiries for all prepared injectable drugs.
Many anticancer drugs, once reconstituted and prepared for administration, are given very short expiry dates due to a lack of reliable stability data. Approved Product Information (PI) for injectable drugs provides minimal extended stability data and what is provided is variable between countries.
Stability studies performed by the pharmaceutical industry are only designed to fulfil licensing requirements and therefore are commonly restricted to 24 hours for bacteriological reasons, regardless of the true chemical stability of the drug, which in many cases is much longer. It has been suggested that drug development programs of the pharmaceutical industry should generate enough stability data to allow for a more flexible clinical application and that this data be made available to the pharmacy community.
The ability to subcutaneously administer set dose drugs, such as some monoclonal antibodies (MABs), via a pre-filled syringe offers a number of advantages. Significant time and resources are saved as manufacturing is not required and administration is quicker, benefiting pharmacy, nursing, and patients. These formulations should have long term stability and also reduce the risk of occupational exposure to staff handling them. Currently these drugs are prepared for administration in a syringe from the vial using a range of methods from nursing staff on the bench to pharmacy staff in cytotoxic safety cabinets or isolators. These products do not contain preservatives so stability once drawn into a syringe is 24 hours. Safe handling requirements during the preparation of MABs are still open to conjecture. While these agents do not pose the same occupational exposure risks as cytotoxic anticancer medications, there is still a need for safe handling guidelines to protect healthcare personnel.
What can be done?
The pharmaceutical industry has received criticism for not doing enough to contain rising drug prices. Strategies, involving minimal financial outlay to implement, have been proposed to help contain expenditure on parenteral cancer drugs. These include increasing the range of drug vial sizes available, ensuring vials contain some excess or overage, providing extended stability data, and ensuring drugs are supplied in the most suitable form for administration. To further elucidate this problem we conducted an international collaborative study to identify drugs that may be amenable to these strategies.
Our study
This study, “Opportunities to significantly reduce expenditure associated with cancer drugs”, recently published in the journal Future Oncology, identified numerous injectable cancer drugs that are amenable to strategies for reducing expenditure and avoiding drug wastage. Information was obtained from 20 diverse countries to provide a global perspective, with Europe (6), Asia (6), North (2) and South America (2), Africa (2) and Australasia (2) represented. Forty-five drugs, cytotoxic agents (29) and MABs (16), used in the treatment of malignancy were investigated.
Data was sourced from the medication’s PI, if marketed, in each individual country and obtained on the range of vial sizes available, overage provided in vials, stability data on final products prepared for administration to the patient and product availability in a prefilled, ready to use syringe. Specialist oncology pharmacists provided data through a survey format.
Drug availability was lowest in Kenya (37.8%) and highest in Australia and Germany (97.8%). Significant variations occurred in the availability and range of vial sizes between countries, with often only single vial sizes supplied for numerous medications. Information on overage was generally lacking. Stability data was inconsistent and variable between countries, with the majority of drugs only given a 24 hour expiry.
A series of recommendations were developed which were designed to achieve considerable monetary savings, not from a reduction in drug prices, but rather by minimising wastage of both drugs and time spent on preparation, and improving occupational safety. Determination of the amount of money that could be saved was beyond the scope of the study as the acquisition cost of cancer medications varies widely, both between countries and within countries.
Suggested Strategies for Implementation
A number of strategies were suggested to aid in the reduction of spending on cancer drugs. The objective of these strategies is to achieve savings, not from reducing drug acquisition prices, but rather from better utilising current medications in order to achieve greater value for money by minimising wastage in both drugs and time, and improving occupational safety. These approaches are also applicable to other parenteral medications, including antibiotics, and are an important tool in these times of increasing drug shortages.
Guarantee the availability of a reasonable range of vial sizes in all countries in which drugs are marketed.
If a range of drug vial sizes are already available in one country, it would seem reasonable that all countries, in which the drug is approved, have access to the same range.
Encourage the use of vial sharing options.
Vial sharing is a proven cost saving method. By making batches of doses of the same drug, quantities left in a vial, that would normally be discarded, can be used in the manufacture of the next product. Closed-system transfer devices can be used to extend the microbiological stability of anticancer drugs to facilitate vial sharing and subsequent cost savings. In Australia, compounding company charges for commonly used drugs are calculated on a per mg basis rather than on the standard per vial cost basis. Paying for only the quantity of drug that is actually used allows customers to make significant cost savings. Unfortunately the practice of vial sharing is discouraged in a number of countries, including Japan and the USA.
Explore the use of dose rounding and dose banding options.
Dose rounding is the practice of rounding the prescribed dose of drug, either up or down, to that of the nearest whole vial strength available. This has been proposed to be successful when multiple vial sizes are available and rounding gives a difference of not greater than +5% for cytotoxic agents and +10% for MABs. This approach has been criticised as it can lead to patients getting a too high or too low a dose, but also that it does not actually reduce spending on leftover drug.
Dose banding is a system where doses that fall within defined ranges or bands are rounded up or down to predetermined standard doses with the maximum variation set at 5%. This enables a range of pre-filled syringes or infusions to be manufactured or purchased which can then be used to administer the standard dose. NHS England is implementing a national system of dose banding and has introduced National Dose Banding Tables to ensure a standard approach of dose banding of chemotherapy across the country.
Guarantee that sufficient overage is available in vials for all parenteral drugs.
A specific excess amount of drug, say 5%, should be provided in all vials to overcome problems of insufficient volume that can commonly arise during the reconstitution and manipulation of vials.
Guarantee the availability of usable stability data on all manufactured products.
The pharmaceutical industry invests billions of dollars in research and development in getting new anticancer drugs to the market place. Research should include stability studies to enable extended expiries for all prepared injectable drugs. Study results should be published and made available for use by compounding companies and accredited manufacturing pharmacies. If patients are then delayed or cancelled for any reason, drugs could be used at a later date for the same patient or another patient on the same dose.
Ensure that the most appropriate presentation forms are provided for all anticancer drugs.
Drugs prescribed as set doses and fulfilling requirements of stability, storage, dosing volume and method of administration, should be provided as pre-filled syringes or pens.
Is Change Likely to Happen?
Is there an incentive for the pharmaceutical industry to support the introduction of these recommended changes? The high price of drugs has been justified by pharmaceutical companies as necessary to support their investment in research and development. Once a new drug is marketed companies have a limited time to recoup outlay and maximise profits before patents expire and competing generic options or biosimilars become available.
There is no motivation for them to introduce strategies to reduce drug wastage as this would result in less merchandise sold and a subsequent reduction in profits. Pharmaceutical companies are answerable to their shareholders and therefore not likely change their current approach to drug marketing without being forced to do so by the introduction of legislative changes. However, the ability to streamline their formulation presentations on an international basis may provide an enticement for the pharmaceutical industry.
From our study it appears that multiple presentations of the same product occur internationally, but with different vial sizes available in different countries. This was an interesting observation as one would have anticipated that global pharmaceutical companies would have introduced a “lean” approach to drug production. By standardising a suitable range of vials sizes that can be marketed in all countries, substantial cost savings can potentially be made. If the ability to gain market access for novel agents is impacted or competition arises within the same therapeutic space, this may provide incentive for industry to improve their current products by introducing better formulations and providing new stability information.
Despite the obvious huge financial savings to be made, are governments likely to be brave enough to introduce the necessary legislation?
Is there an incentive for governments to act on these suggestions? If these strategies are to be successful it will require a drastic global change in approach, definite changes in legislation, and the cooperation of the pharmaceutical industry, ruling and opposition political parties, government organisations and healthcare professionals. The pharmaceutical industry has the ability to influence government decisions through political donations and effective lobbying, particularly in their biggest market, the USA. Currently, in most countries it is presumed that the pharmaceutical manufacturer determines which vials sizes and product presentations that they want to market. Government organisations, such as the FDA or TGA, do not have the statutory authority to dictate a certain vial size or delivery system.
Despite the obvious huge financial savings to be made, are governments likely to be brave enough to introduce the necessary legislation? Unless legislative changes occur in all countries, collaboration becomes the most efficient option to effect change and is that likely to occur without significant public pressure being brought to bear?
Papers:
Peter J Gilbar, Carole R Chambers, Erin C Gilbar. Opportunities to significantly reduce expenditure associated with cancer drugs. Future Oncology. 2017; DOI: 10.2217/fon-2017-0033
Peter J Gilbar, Carole R Chambers. How can we ensure value for money from expenditure on injectable cancer drugs? Journal of Oncology Pharmacy Practice. 2017; DOI: 10.1177/1078155217706195
