What’s happening in PHARMAC—where do all the
submissions go? On the trail of gemcitabine
The process and progress of submissions to PHARMAC for
funding of new treatments is unclear. There appears to be a lack of
communication or transparency regarding funding applications, decisions, or
expected timelines to reach an endpoint. It is difficult to have confidence in a
process that lacks such definition. A recent clinician submission for funding of
an oncology treatment (gemcitabine) for bladder cancer highlights these
Locally advanced or metastatic transitional cell carcinoma
(TCC) of the urothelium.
dose and duration
Gemcitabine 1000mg/m2 IV day 1, 8, and 15, with cisplatin 70
mg/m2 day 2, each 28 days, receiving a maximum of 6 cycles.1
Without chemotherapy, the prognosis for patients with
locally advanced or metastatic TCC of the bladder is limited with a median
survival of 4–6 months.2 With chemotherapy, survival and quality of life
can be increased. MVAC chemotherapy (methotrexate, vinblastine, doxorubicin
[adriamycin], and cisplatin) was defined as the standard of care for the
treatment of TCC during the 1980s and 1990s, with reported median survival of
over 12 months.3
However this drug regimen is associated with significant
toxicity—including severe mucositis, neutropenic sepsis, and
treatment-related deaths in up to 4% of patients in early reports.1,3 Research
continues to define new treatment regimens that provide greater benefit with
increased effectiveness (or similar benefit) with lesser toxicity than those
funded at present.
Gemcitabine in combination with cisplatin has been shown in
a pivotal phase III study to be equally effective as MVAC in this tumour type
but associated with significantly less toxicity.
The median survival of the patients with locally advanced or
metastatic TCC of the bladder treated with gemcitabine and cisplatin was
equivalent to that of MVAC at 14 months, and 13% of those treated on study were
still alive at 5 years.1
The ‘cancer drug basket’ (Part V of Schedule H)
was established in October 2001 as a result of a ministerial directive.
‘High cost’ cancer drugs within the basket are funded only for
specific indications. Extension of funded treatment indications or addition of a
new agent to the basket is considered upon application to PHARMAC.
Pharmaceutical companies submit the majority of applications
to PHARMAC, although this facility is also available to individual clinicians.
The request for a funded extension to the treatment indications for gemcitabine
to include locally advanced or metastatic TCC of the bladder was the first
clinician-sponsored application to PHARMAC for funding of an oncology drug, and
as such has been watched with interest by the oncology community. This
submission was forwarded to PHARMAC January 2004. CaTSOP (Cancer Treatments
Sub-committee of PTAC) considered the submission in March 2004.
The committee considered that gemcitabine with a platinum
analogue had equal effectiveness with current therapy (MVAC) but with markedly
reduced adverse effects. It was noted that number of patients currently treated
is low, but that more patients would be suitable for gemcitabine therapy due to
the decreased toxicity of treatment. The committee estimated that approximately
70–90 patients would receive treatment per annum.
A preliminary pharmacoeconomic
analysis has been performed4 but to date a final decision from PHARMAC is not
Gemcitabine was initially licensed in December 1998 by
MedSafe for use alone or in combination with cisplatin for the first-line
treatment of patients with locally advanced or metastatic non-small cell lung
cancer. In June 1999, gemcitabine was also licensed for treatment of patients
with locally advanced or metastatic adenocarcinoma of the pancreas. This was
followed in May 2000 with licensing of gemcitabine for the treatment of patients
with advanced bladder cancer (TCC).
Although licensed for use in TCC from May 2000, gemcitabine
is currently not funded for this indication. Currently gemcitabine is listed in
Part V of Section H (July 2005) of the Pharmaceutical Schedule5 for the
restricted indications of:
lung cancer (non-small cell lung cancer and mesothelioma);
fallopian tube or primary peritoneal cancer—post taxane therapy; and
fallopian tube, or primary peritoneal cancer—initial therapy when taxane
By comparison, gemcitabine has been funded for TCC in
Australia since August 2001,6 and is used for this indication within the NHS in
the United Kingdom.
Gemcitabine for use in TCC can be obtained through
prescription at a cost of $1983 per cycle (3 doses calculated at average body
surface area of 1.8m2), but is not able to be administered in the public health
sector for this indication, although it is commonly used in public hospital
oncology units for the above funded indications.
PHARMAC’s cost-utility analysis4 based on the data
from the pivotal study calculates a cost of $817,808 per QALY (Quality Adjusted
Life Year) gained when using gemcitabine and cisplatin for advanced bladder
cancer compared to the historical regimen of MVAC. This figure was generated
from an incremental treatment cost calculated for cisplatin and gemcitabine over
that of MVAC of $4276.60, and an estimated incremental benefit of 0.00523 QALYs
The calculated incremental cost of treatment is similar to
those calculated in other countries of GBP £2976(7) and AUD $5035
(communication Eli Lilly8), however the incremental utility gained was 25 times
greater in the UK study at 0.13 QALYs than that proffered by PHARMAC. If the UK
utility is used for PHARMAC’s calculations, the cost decreases by the same
magnitude to $32,900 per QALY.
There is no accessible site on PHARMAC’s webpage that
provides up-to-date information on drug submissions made.9 Recent accessing of
the site reported applications that had been made up until July 2005, but does
not include the submission for gemcitabine. This site also only lists the drug
and the applicant, but not the treatment indication for which the submission has
There are several issues that are highlighted from this
first clinician-sponsored application for an oncology drug to be funded.
The first is the time to receive a decision from the
process. The application was submitted early 2004, and reviewed by CaTSOP within
a few months. Since that time there has been no formal decision notified, and it
is unclear where the application is in the PHARMAC process. It is now over 18
months since the submission was made. During this process, gemcitabine is not
available for use in advanced TCC bladder, at least not within the public
This lack of transparency of the process regarding
submissions has also been true of subsequent clinician applications. It is also
unclear from PHARMAC’s own website which submissions have been made or are
being currently considered. The cited PHARMAC report in this commentary was made
available under the Official Information Act and the fate of the gemcitabine
application is unknown at present (9 months after the PHARMAC report).
PHARMAC’s pharmacoeconomic analysis is admittedly a
preliminary analysis, however these analyses are instrumental in decisions
regarding funding of new treatments. It is of concern that there is such a large
discrepancy in the utility calculated by PHARMAC and that reported in a
peer-reviewed journal, especially as the magnitude of the difference leads to a
cost per QALY of $817,808 rather than $32,900.
Decisions to fund or not fund treatments need to be based on
robust analysis. Large discrepancies between reports raise the question of the
accuracy of the assumptions and calculations made. To gain confidence in the
process used there needs to be complete transparency such that the assumptions
made are seen to be evidence based, inaccuracies can be challenged, and the
resulting calculations or decisions are robust and able to withstand
At a time when there are new treatments becoming available
internationally and an increasing public awareness of new therapies and
treatment indications, the funding of drugs within the public health system
needs to be considered in a timely and evidence-based manner. Transparency is
paramount if there is to be confidence in this process for all concerned.
interest: Andrew Simpson has no conflict of interest to declare.
Andrew Simpson, Honorary
Secretary for the New Zealand Clinical Oncology Group and Consultant Medical
Oncologist, Wellington Blood & Cancer Centre, Wellington Hospital,
Andrew Simpson, Wellington Blood & Cancer Centre, Wellington Hospital,
Riddiford St, Wellington South. Fax (04) 385 5984; email: firstname.lastname@example.org
der Masse H, Hansen SW, Roberts JT, et al. Gemcitabine and cisplatin versus
methotrexate, vinblastine, doxorubicin, and cisplatin in advanced or metastatic
bladder cancer: results of a large randomised, multinational, multicenter, phase
III study. J Clin Oncol. 2000;17:3068–77.
J, de Wit R, Albiol S, et al. New drugs and new approaches in metastatic bladder
cancer. Critical Reviews in Oncology/Hematology. 2003;47:195–206.
PJ, Einhorn LH, Elson PJ, et al. A randomised comparison of cisplatin alone or
in combination with Methotrexate, vinblastine, and doxorubicin in patients with
metastatic urothelial carcinoma: a cooperative group study. J Clin Oncol.
access to gemcitabine in the Pharmaceutical Schedule for patients with advanced
bladder cancer. PHARMAC Draft Technology assessment Report No. 66, January 2005.
Released under the Official Information Act.
New Zealand Pharmaceutical Schedule: Schedule H for Hospital Pharmaceuticals,
effective 1 July 2005. Wellington: PHARMAC; 2005. Available online. URL: http://www.pharmac.govt.nz/pdf/SectionH.pdf
Accessed November 2005.
Government, Department of Health and Ageing. Schedule of Pharmaceutical Benefits
for Approved Pharmacists and Medical Practitioners. Canberra: Australian
Government; 2005. Available online. URL: http://www1.health.gov.au/pbs/
Accessed November 2005.
P, von der Masse H, Bhalla S, et al. Cost-utility analysis of the GC versus MVAC
regimens for the treatment of locally advanced or metastatic bladder cancer.
Expert Rev Pharmacoeconomics Outcomes Res. 2004;4:27–39.
Lilly and Company (NZ) Limited. PO Box 109197, Newmarket, Auckland. URL: http://www.lilly.co.nz/
Applications received for new investments since 1 July 2002. Wellington:
PHARMAC; 2005. Available online. URL: http://www.pharmac.govt.nz/pdf/230905.pdf
Accessed November 2005.