Overspending driven by oversized single dose vials of cancer drugs
BMJ 2016; 352 doi: https://doi.org/10.1136/bmj.i788 (Published 01 March 2016) Cite this as: BMJ 2016;352:i788
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I do admire this provocative article that tackles a real and serious problem with simple possible solution. The waste of 3 Billion USD annually in the USA because of leftover cancer drugs shouldn’t continue any more. Making different sized vials of chemotherapy and biologics is not impossible. Otherwise different works and efforts to get better value cancer care would be contradictory to this non sense waste of cost. Bearing in mind that President Obama asked the congress for $1 billion in the 2017 budget for his to his proposal of cancer "moonshot,"
I would like that the authors and the readers view the web of the Win-Win scientific initiative http://www.icedoc.org/winwin.htm that aims at increasing affordability of better value cancer treatment in the world via exploring scientific approaches. All the stakeholders- particularly cancer patients and their families- could win. This also includes flourishing the business of pharmaceutical companies and Manufacturers of radiotherapy machines and medical systems, but, without incorrect ways that affect a country or individuals economies and that could put the whole system in question about sustainability of cancer care . You can browse the web http://www.icedoc.org/winwin.htm and download its documents. Also, view The proposal of “ The Fourth Way” http://www.icedoc.net/anticancer5.htm.
Science, realistic, smart and ethical approaches –by actions and not slogans- are the ways to increase affordability of better value cancer treatment in the real world.
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The article supposes that there is $282million waste on Avastin. My clinic wastes approximately $0. :) It's stable for 28 days under refrigeration. Many other single - & multi-dose vials have extended stability data available like this. If you really want savings, sponsor more extended stability studies and change ISMP and JCHAO policies to let us actually use that data.
Other respondents mentioned per-milligram billing... In the USA there are now J-codes for all multi-dose vials and some sinlge-dose vial products. You only bill & get paid for multiples of the Jcodes.
And no... Socialised medicine is not the answer. More regulations will only decrease development, and increase costs to Pharma, who will gladly pass those costs in to either consumers, or government, or both. Taxpayers always have to foot the bills of the government - would YOU appreciate paying $3000 for your cancer treatment, then have the government raise your taxes to also... pay for your cancer treatment. Not such a rosey deal.
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The increasing expenditure on cancer drugs is a significant concern to patients, health professionals, hospitals, health insurers and governments, thus making the article by Bach and colleagues particularly relevant.1 Expanding the range of vial sizes is one area where the pharmaceutical industry should be doing more to contain spending. Nearly 10 years ago, an Australian study evaluated the use of trastuzumab for metastatic breast in 1469 patients enrolled in a medicine access program over a 40 month period.2 As only 150 mg vials were available at that time, an estimated 24% of trastuzumab dispensed was discarded, at a cost of A$ 21.1 million.
While vial sharing is an obvious way of reducing wasting, this is not always feasible. Drugs prepared by individual hospital pharmacy departments may not have enough patients on the same medication at that specific time to do this. In Australia, many cancer centres outsource manufacturing of cancer drugs to accredited commercial suppliers, who, for drugs that are high usage items, will charge on a per milligram basis rather than per vial, thus enabling significant cost savings.
There are other strategies that could be utilized by the pharmaceutical industry to assist in the reduction of cancer drug expenditure.3 To ensure that patients receive the full prescribed dose of medication, pharmaceutical companies should guarantee that all vials contain some overage. Drugs such as azacitidine, bleomycin, bortezomib, cisplatin, dacarbazine and epirubicin have been implicated in not containing sufficient excess volume.3 Due to technical issues in the reconstitution process, it is often difficult to withdraw the entire contents from a vial, necessitating the use of another vial. Forcing manufacturers to provide a specific overage in vials, e.g. 5%, would solve this problem.
Currently, many cancer drugs, once prepared for administration, have very short expiry dates due to a lack of reliable stability data. Approved product information contains minimal stability data. Reliable and useable data have to be obtained from published research or may only be available to commercial suppliers from studies conducted in-house. If medications with short expiries are pre-made or pre-purchased and patients are delayed or cancelled for any reason, products may be wasted. While every attempt is made to reuse these products prior to expiry, invariably expensive medications are discarded. Considering the millions of dollars that is invested in research and development by the pharmaceutical industry, surely a small percentage could be allocated towards conducting studies to extend drug stability?
The availability of a range of drug vial strengths and other strategies have the potential to save significant amounts of money. Government agencies, such as the US Food and Drug Administration and the Australian Therapeutic Goods Administration, should ensure that the pharmaceutical industry complies with these simple initiatives before granting drug approval.
1. Bach PB, Conti RM, Muller RJ, Schnorr GC, Saltz LB. Overspending driven by oversized single dose vials. BMJ 2016;352:i788. doi: 10.1136/bmj.i788
2. Pearson SA, Ringland CL, Ward RL. Trastuzumab and metastatic breast cancer: trastuzumab use in Australia – monitoring the effect of an expensive medicine access program. J Clin Oncol 2007;25:3688-93. Doi: 10.1200/JCO.2007.11.2516
3. Gilbar PJ. Should the pharmaceutical industry be doing more to reduce the cost of cancer drugs. J Pharm Pract Res 2011;41:4-5.
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I do not believe that anticancer drugs are priced on a mg basis and whatever the size of the vial the determinant of pricing (and expense) is the market size.
In fact, the overspending is driven by the overpricing of anticancer agents and the neanderthal dosing based on body size. To avoid costly leftover drug, anticancer agents should be developed in adult patients with a fixed dosing (unless it is proved that body size is a significant factor of clinical variability) and charged according to their true clinical value.
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It is unethical to deliberately produce wastage in order to maximise profit. Despite the problems highlighted by Bach et al; standardisation of vial size in specialised drugs itself is not an issue as it simplifies use whilst reducing manufacturing and shipping costs. The pertinent point is that pharmaceutical companies in the US have perverse economic incentives to increase waste.
Standardised single dose vial sizes help reduce manufacturing and shipping costs, costs that will otherwise be borne by patients. The small production runs of these drugs lead to high fixed costs and low marginal costs as the individual price of each additional unit manufactured is lower than the previous unit. The production of standardised vials rather than customised doses therefore helps reduce cost.
Specialist drugs have price inelasticity; demand does not vary based on their price. A patient either needs the drug or does not and in the US, for the vast majority of people their insurer will pay whatever the labelled cost, allowing pharmaceutical companies to charge extortionate prices. Notoriously, Martin Shkreli’s Turing Pharmaceuticals recently purchased the rights to and then increased the price of Daraprim, a treatment for toxoplasmosis by 5000%.1 One way to reduce the public opprobrium for price gouging is to increase the vial size. The marginal cost of additional dosage in the standardised vial size is low, but it brings down the apparent billed cost per mg. The price per mg is lower but the price per dose for the average person is higher. Perversely, this is the opposite of what happens in normal economic interactions where companies reduce the size of goods in order to keep the apparent price the same, witness the shrinking size of chocolate bars. The lack of alternatives means the drug has to be bought by patients, at the size and the price that the company is willing to sell.
The monopoly that the patent system confers on pharmaceutical companies and the price inelasticity of their product means that both vial size and price are almost irrelevant. Bach et al use the example of the cancer drug Bortezomib which is only available in 3.5mg vials, which at typical body weight leads to average wastage of around 30%. Wastage that is not necessary. Castro et al showed that even by producing standardised single vials of Bortezomib, but at a different dose of 3mg, the average wastage would decrease by 36.2%, without complicating the supply chain.2 This wastage could be reduced by 62.5% if taken further, and two varying vial sizes were produced although as discussed earlier this may increase unit costs.2
The US will continue to have these issues until it has a state run health system. Bach et al’s proposal of increased regulation would result in decreased waste but increased cost to pharmaceutical companies who would charge the same amount for a smaller dose. The way to counter monopoly providers is by having a monopsony buyer. A state run health system negotiates better prices on drugs, ensure caps on drug prices, and only pays for new pharmaceuticals that it deems clinically and cost-effective.3
1. Langreth R. Drugmaker Turing Suggests It Won’t Cut List Price of Daraprim - Bloomberg Business. Available at: http://www.bloomberg.com/news/articles/2015-11-24/drugmaker-turing-sugge.... Accessed March 2, 2016.
2. Clark L, Castro AP, Fortes AF, et al. Ideal vial size for bortezomib: real-world data on waste and cost reduction in treatment of multiple myeloma in Brazil. Value Health. 14(5 Suppl 1):S82–4. doi:10.1016/j.jval.2011.05.013.
3. NICE technology appraisal guidance | NICE guidance | Our programmes | What we do | About | NICE. Available at: https://www.nice.org.uk/about/what-we-do/our-programmes/nice-guidance/ni.... Accessed March 2, 2016.
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An informative article highlighting an issue that has been already been addressed in the UK. The UK solution to this problem is vial sharing where a number of patients doses are made a same time and vials shared, so that the amount of waste is minimised and money saved. The UK has a different payer /provider system. The payer for cancer medicines is NHS England a single national commissioner, who has provided an incentive to encourage provider Trusts who make and administer chemotherapy to adopt vial sharing. This saves public money and contributes to reduction in spend on Cancer Medicines. Vial sharing is undertaken by Trust pharmacy departments and indeed has been championed by the British Oncology Pharmacy Association with examples of vial sharing research presented at its annual conference. Billing does become more complex but there are solutions. The other way of reducing waste is to use ready made doses prepared in commercial units, which are priced on a per mg basis.
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I suspect the cost savings proposed here are grossly overstated due to the simple fact that the cost to manufacture the drugs is essentially unrelated to the cost of the drug. The drug companies are selling their intellectual property and pricing the drugs to provide a certain number of treatments based on what the market will bear. This is a cute paper, but the prices for the treatments would simply rise in the years it would take to establish systems to reduce waste. Waste should be reduced when possible but this article is hyperbole.
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Re: Overspending driven by oversized single dose vials of cancer drugs
A very intriguing article which highlights a growing issue with regards to high cost newer drugs in oncology and in other disease areas, where patient specific doses are assembled. Vial size for high cost oncology medicines have always been an issue. In the UK vial sharing is accepted practice as advised by the MHRA - despite the fact that there is nothing within the product license for any of these drugs to support this. What is also not studied is the actual level of vial sharing activity.
If there were smaller vial sizes then there would certainly be less wastage in respect of the compounding of these drugs prior to administration. If vial sharing is not adopted practice then inevitably this would create waste based on the current vial sizes if the SPC was followed specifically for the dosing or if hospitals are unable to vial share due to scheduling and patient cohorting
We have taken a multi-disciplinary approach to this working with a team of people looking at the issue from another perspective. We have been using pharmacokinetic simulation to look at these drugs and observe the theoretical effect to guide dosing by smallest available vial size. The work is a modified version of dose banding which traditionally has been applied to low cost, high usage products which are batch produced. By looking at the simulation results for a number of drugs it is clear that dosing based on body size parameters such as mg/kg or BSA is often not optimal for every individual, especially those with extreme body sizes. This has led us to look deeper in to the problem and revise whether there is a more optimal way of dosing these drugs than advised by the product licence in a way that is most cost effective. What we have found is that with some of the monoclonal antibody agents is that small changes of ±10% to the calculated dose are very unlikely to affect the outcome to the patient. The traditional dose escalation MTD design of the trials carried out to determine the doses could be considered as not the most appropriate trial design for these agents. In addition a number of the trial protocols used to license these drugs have flexibility in the dosing to only change the dose if the patient's weight changed by more than 10% from baseline.
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