Chambers, Carole R.

Gilbar, Peter J.

University of Queensland eSpace

Commentary
How can we ensure value for money from
expenditure on injectable cancer drugs?
Peter J Gilbar1,2 and Carole R Chambers3
Keywords
Cancer drugs, drug wastage, expenditure, stability, vial sizes
Date received: 27 March 2017; accepted: 29 March 2017
Global expenditure on cancer drugs is increasing at an
alarming rate and consequentially is of considerable
concern to consumers, health professionals and govern-
ments. Research progress has led to the continual intro-
duction of novel high cost medications for use in the
management of cancer, putting an enormous ﬁnancial
burden on society.1,2 The ability to ensure equitable
access to new innovative drugs and provide high-qual-
ity care to patients worldwide is virtually impossible in
the current economic climate. The market for antican-
cer drugs is worth billions of dollars in the USA, rank-
ing ﬁrst by therapeutic class in terms of global
spending.3 Achieving global prices for cancer drugs
that are equitable and consistent appears to be
unachievable. While some nations regulate prices and
reimbursement of high-cost cancer medications, this
does not occur in every country, including the USA.4
The pharmaceutical industry has been criticised for not
doing enough to contain rising drug prices.5,6
Strategies, involving minimal ﬁnancial outlay to imple-
ment, have been proposed to ensure consumers receive
better value for money spent on parenterally adminis-
tered cancer medications. 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 suit-
able form for administration.6–8
A study we recently published in the journal Future
Oncology identiﬁed numerous injectable cancer drugs
that are amenable to strategies for reducing expenditure
and avoiding drug wastage.8 Information was obtained
from 20 diverse countries on 45 drugs used in the treat-
ment of malignancy. Data were sourced from the
medication’s Product Information (PI), if marketed,
in each individual country. Pharmacists, the majority
of whom were ISOPP members, 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 avail-
ability of vial sizes between countries, with often only
single vial sizes supplied for numerous medications.
Information on overage was generally lacking.
Stability data were inconsistent and variable between
countries, with the majority of drugs only given a
24-h expiry.8 A series of recommendations were devel-
oped. These were designed to achieve considerable
monetary savings, not from a reduction in drug
prices, but rather by minimising wastage of both
drugs and time, 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.
Spending on cancer drugs, available in the USA as
single dose vials, was investigated by Bach et al.7 to
evaluate the extent of drug wastage. By examining the
1Cancer and Palliative Care Services, Toowoomba Hospital, Toowoomba,
Australia
2Rural Clinical School, Faculty of Medicine, The University of Queensland,
Toowoomba, Australia
3Department of Cancer Services Pharmacy, Alberta Health Services,
Alberta, Canada
Corresponding author:
Peter J Gilbar, Cancer and Palliative Care Services, Toowoomba Hospital,
PMB 2, Toowoomba, QLD 4350, Australia.
Email: peter.gilbar@health.qld.gov.au
J Oncol Pharm Practice
0(0) 1–4
! The Author(s) 2017
Reprints and permissions:
sagepub.co.uk/journalsPermissions.nav
DOI: 10.1177/1078155217706195
journals.sagepub.com/home/opp
top 20 cancer drugs dosed by body size and packaged
as single dose vials, they estimated the total amount of
drug left over in vials after preparation for administra-
tion 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.
A perfect example of wastage that can occur is pem-
brolizumab, which was available as a 50mg vial in 11
countries, in 2 countries as a 100mg vial and only in the
USA as both.8 Pembrolizumab is dosed at 2mg/kg;
therefore, a 70 kg patient would require a dose of 140
mg. Utilising 50mg vials (3) the unused portion
would be 10mg. With 100mg vials (2), 60mg would
be left over. With this drug likely to have multiple indi-
cations in more and more countries in the near future
and with treatment durations potentially lengthy, mas-
sive amounts of money can be involved. Despite being
aware of the problem with vial sizes, the pharmaceut-
ical industry has been slow to react. A 2007 Australian
study examining the use of trastuzumab, available only
as a 150mg vial, in a medicine access program for meta-
static breast cancer over a 40-month period, reported
that 24% of trastuzumab was discarded.9 Despite the
authors concluding that an extra vial size could signiﬁ-
cantly reduce waste, it took another six years to intro-
duce a 60mg vial. Five countries surveyed still only
have access to a 150mg vial.8
Many anticancer drugs, once reconstituted and pre-
pared for administration, are given very short expiry
dates due to a lack of reliable stability data.
Approved PI provides minimal extended stability data
and what is provided is variable between countries.8
Benziri et al.10 reported a lack of stability data provided
by manufacturers for compounded anticancer drugs.
Data that were provided was mostly incomplete and
diﬃcult to put into practice, particularly for older
drugs. Additional extrapolation and consensus on
interpretation is frequently required to address issues
not covered by data from manufacturers.11 Stability
studies performed by the pharmaceutical industry are
only designed to fulﬁl licencing requirements and there-
fore are commonly restricted to 24 h for bacteriological
reasons regardless of the true chemical stability, which
in many cases could be longer.12 A 2011 European con-
sensus conference identiﬁed a need to close the gap in
knowledge on drug stability for anticancer drugs
between the insuﬃcient data available in PI and what
was required in clinical practice.12 It was suggested that
drug development programs of the pharmaceutical
industry should generate enough stability data to
allow for a more ﬂexible clinical application and that
these data be made available to the pharmacy
community.
The ability to subcutaneously administer set dose
drugs, such as denosumab, rituximab and trastuzumab,
via a pre-ﬁlled syringe oﬀers a number of advantages.
Signiﬁcant time and resources are saved as manufactur-
ing is not required and administration is quicker, bene-
ﬁting pharmacy, nursing, and patients. These
formulations should have long-term stability and also
reduce the risk of occupational exposure to staﬀ hand-
ling 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 h. Safe handling require-
ments 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. Recent
reviews have concluded that safe handling data on
MABs is based on low levels of information due to a
lack of studies evaluating the risk of occupational
exposure with these agents.13–14 While uncertainties
remain, a precautionary approach is warranted with
consideration given to using interventions greater
than for non-hazardous medications.14
A number of strategies were suggested to aid in the
reduction of spending on cancer drugs.8 The objective
of these strategies is to achieve savings, not from redu-
cing drug acquisition prices, but rather from better uti-
lising current medications in order to achieve greater
value for money by minimising wastage in both drugs
and time, and improving occupational safety.
1. 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. If only one vial size is available, government
organisations should negotiate with industry to ensure
that this is rectiﬁed before drug approval is given.
2. Encourage the use of vial sharing options
Vial sharing is a proven cost-saving method15: 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 micro-
biological stability of anticancer drugs to facilitate vial
sharing and subsequent cost savings.16,17 In Australia,
compounding company charges for commonly used
2 Journal of Oncology Pharmacy Practice 0(0)
drugs are based on a per mg basis rather than on the
standard per vial cost basis. Paying for only the quan-
tity of drug that is actually used allows customers to
make signiﬁcant cost savings. Unfortunately, the prac-
tice of vial sharing is discouraged in a number of coun-
tries, including Japan and the USA. In the USA, both
the Centers for Disease Control and Prevention and the
US Pharmacopeial Convention call for single dose vials
to be used only once.18 Government organisations
should review current legislation to permit vial sharing
in manufacturing facilities with appropriate
accreditation.
3. Explore the use of dose rounding and dose
banding options
Dose rounding is the practice of rounding the pre-
scribed 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.19–21 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.7 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%.22,23 This enables a
range of pre-ﬁlled syringes or infusions to be manufac-
tured or purchased which can then be used to admin-
ister 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 all
Hospital Trusts.24
4. 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 insuﬃ-
cient volume that can commonly arise during the recon-
stitution and manipulation of vials.6
5. 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 sta-
bility studies to enable extended expiries for all pre-
pared injectable drugs.6 Study results should be
published and made available for use by compounding
companies and accredited manufacturing pharmacies.
6. Ensure that the most appropriate presentation
forms are provided for all anticancer drugs
Drugs prescribed as set doses and fulﬁlling require-
ments of stability, storage, dosing volume and method
of administration, should be provided as pre-ﬁlled syr-
inges or pens.
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.25 Once a new
drug is marketed, companies have a limited time to
recoup outlay and maximise proﬁts before patents
expire and competing generic options become available.
There is no motivation for them to introduce strategies
to reduce drug wastage as this would result in less mer-
chandise sold and a subsequent reduction in proﬁts.
The 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.
The ability to streamline their formulation presenta-
tions on an international basis may be an incentive for
the pharmaceutical industry. From our study, it
appears that multiple presentations of the same product
occur internationally, but with diﬀerent vial sizes avail-
able 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 motivation
for industry to improve their current products by intro-
ducing better formulations and providing new stability
information.
How can we, as oncology pharmacy practitioners,
drive the implementation of these strategies on a
global basis? If these strategies are to be successful it
will require a drastic change in approach from many
countries, probable changes in legislation, and the
cooperation of the pharmaceutical industry, govern-
ment organisations and healthcare professionals.
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,
do not have the statutory authority to dictate a certain
vial size or delivery system. Unless legislative changes
occur in all countries, collaboration becomes the most
eﬃcient option to eﬀect change.
Gilbar and Chambers 3
Oncology pharmacy is well represented by a number
of professional organisations or societies at both
an international, continental and national level.
These include the International Society of Oncology
Practitioners (ISOPP), European Society of Oncology
Pharmacists, Hematology/Oncology Pharmacy
Association, Canadian Association of Pharmacy in
Oncology and British Oncology Pharmacy
Association. As an organisation, ISOPP is in the pro-
cess of forming alliances with a number of these groups
with the aim of achieving common goals. The Global
Oncology Pharmacy Summit, held prior to the ISOPP
XVI in Budapest, can facilitate this process as a theme
of the meeting is ‘‘to mobilise the oncology pharmacy
community around collaborative advocacy issues.’’ We
hope that these groups can assist in the promotion and
dissemination of the results and recommendations of
this research to governments at state, province and
national levels.
Declaration of conflicting interests
The author(s) declared no potential conﬂicts of interest with
respect to the research, authorship, and/or publication of this
article.
Funding
The author(s) received no ﬁnancial support for the research,
authorship, and/or publication of this article.
References
1. Shih YT, Ganz PA, Aberle D, et al. Delivering high-qual-
ity and affordable care throughout the cancer care con-
tinuum. J Clin Oncol 2013; 31: 4151–4157.
2. Meropol NJ and Schulman KA. Cost of cancer care: issues
and implications. J Clin Oncol 2007; 25: 180–186.
3. Howard DH, Bach PB, Berndt ER, et al. Pricing in the
market for anticancer drugs. J Econ Perspect 2015; 29:
139–162.
4. Siddiqui M and Rajkumar SV. The high cost of cancer
drugs and what we can do about it. Mayo Clin Proc
2012; 87: 935–943.
5. Angell M. Excess in the pharmaceutical industry. CMAJ
2004; 171: 1451–1453.
6. Gilbar PJ. Should the pharmaceutical industry be doing
more to reduce the cost of cancer drugs? J Pharm Prac Res
2011; 41: 4–5.
7. Bach PB, Conti RM, Muller RJ, et al. Overspending
driven by oversized single dose vials of cancer drugs.
BMJ 2016; 352: i788.
8. Gilbar PJ, Chambers CR and Gilbar EC. Opportunities to
significantly reduce expenditure associated with cancer
drugs. Future Oncol. [in press] 2017.
9. Pearson SA, Ringland CL and 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: 3688–3693.
10. Benziri F, Bonan B, Ferrio AL, et al. Stability of anti-
neoplastic agents in use for home-based intravenous
chemotherapy. Pharm World Sci 2009; 31: 1–13.
11. De Lemos ML and Hamata L. Stability issues of paren-
teral chemotherapy drugs. J Oncol Pharm Pract 2007; 13:
27–31.
12. Bardin C, Astier A, Vulto A, et al. Guidelines for the
practical stability studies of anticancer drugs: a
European consensus conference. Ann Pharm Fr 2011;
69: 221–231.
13. Alexander M, King J, Bajel A, et al. Australian consensus
guidelines for the safe handling of monoclonal antibodies
for cancer treatment by healthcare personnel. Intern Med
J 2014; 44: 1018–1026.
14. King J, Alexander M, Byrne J, et al. A review for the
evidence for occupational exposure risks to novel antic-
ancer agents – a focus on monoclonal antibodies. J Oncol
Pharm Pract 2016; 22: 121–134.
15. Smith RSV. A 2-year retrospective review of vial sharing
options for the compounding of cytotoxics. Eur J Hosp
Pharm 2015; 22: 161–164.
16. Edwards MS, Solimando DA Jr, Grollman FR, et al.
Cost savings realized by use of the PhaSeal closed-
system transfer device for preparation of antineoplastic
agents. J Oncol Pharm Pract 2013; 19: 338–347.
17. Juhasz A, Batka G and Szucs A. Responding to drug
shortages and rising costs: IV chemotherapy drug use
optimization achieved by closed safety devices in hospital
pharmacies. Drugs Ther Perspect 2016; 32: 170–176.
18. Lien K, Cheung MC and Chan KKW. Adjusting for drug
wastage in economic valuations of new therapies for
hematologic malignancies: a systematic review. J Oncol
Pract 2016; 12: e369–379.
19. Dooley MJ, Singh S and Michael M. Implications of dose
rounding of chemotherapy to the nearest vial size.
Support Care Cancer 2004; 12: 653–656.
20. Field K, Zelenko A, Kosmider S, et al. Dose rounding of
chemotherapy in colorectal cancer: an analysis of clin-
ician attitudes and the potential impact on treatment
costs. Asia-Pac J Clin Oncol 2010; 6: 203–209.
21. Francis SM, Heyliger A, Miyares MA, et al. Potential
cost savings associated with dose rounding antineoplastic
agents. J Oncol Pharm Pract 2015; 21: 280–284.
22. Plumridge RJ and Sewell GJ. Dose-banding of cytotoxic
drugs: a new concept in cancer chemotherapy. Am J
Health-Syst Pharm 2001; 58: 1760–1764.
23. Chatelut E, White-Konig ML, Mathijssen RHJ, et al.
Dose banding as an alternative to body surface area-
based dosing of chemotherapeutic agents. Br J Cancer
2012; 107: 1100–1106.
24. NHS England. How to use the NHS England dose band-
ing tables, www.england.nhs.uk/commisioning/wp-con-
tent/uploads/sites/12/2013/05/dose-banding-tables-how-
to.pdf (accessed 18 December 2016).
25. Kanttarjian HM, Fojo T, Mathisen M, et al. Cancer
drugs in the United States: Justum Pretium – the just
price. J Clin Oncol 2013; 31: 3600–3604.
4 Journal of Oncology Pharmacy Practice 0(0)


How can we ensure value for money from expenditure on injectable cancer drugs

http://espace.library.uq.edu.au/view/UQ:724016/UQ724016_OA.pdf

How can we ensure value for money from expenditure on injectable cancer drugs

Abstract

Similar works

Full text

Available Versions

University of Queensland eSpace