Intended for healthcare professionals

Rapid response to:


NICE appraisals should be everybody's business

BMJ 2007; 334 doi: (Published 03 May 2007) Cite this as: BMJ 2007;334:936

Rapid Response:

Dealing with opportunity cost – a New Zealand perspective on trastuzumab funding

Jane Wells and Claire Cheong-Leen [1] tell a familiar story about funding of trastuzumab (Herceptin) in early breast cancer. We agree with their conclusion about the risk of making poor trade-offs if national policy decisions about treatment do not consider affordability in the context of all healthcare provision. New Zealand’s approach has differed to other countries, including funding nine weeks’ treatment.

In New Zealand, the Pharmaceutical Management Agency (PHARMAC) applies nine decision criteria when making pharmaceutical funding decisions (, has a fixed budget, and integrates clinical and economic assessment to help determine the next best use of this funding. This framework allows PHARMAC to explicitly understand the opportunity costs that would arise from national medicines funding decisions – that is, to prioritise in the context of other medicines or health services [2], as highlighted internationally with the opportunity costs of trastuzumab.[3, 4]

This framework has led PHARMAC to a different conclusion than other funding bodies on various occasions, including trastuzumab. Public funding for a 9-week course of trastuzumab for early breast cancer will be made available in New Zealand from 1 July 2007[5] – see

A major issue with trastuzumab has been the lack of comprehensive information to inform a funding decision. This is often the case for funding applications, where company-sponsored clinical trial data mainly aims to satisfy criteria for regulatory approval. However, to enable well-informed funding decisions, funders need data that inform judgements about the relative effectiveness of medicines, including optimal treatment regimens (dose/duration/combinations etc). Worldwide, the need to ensure companies face the right incentives for data provision is only becoming greater as more expensive medicines, with potentially small incremental clinical benefits, become available.

This lack of relevant information for funding decisions has been evident in the cost effectiveness analyses of trastuzumab in early breast cancer performed internationally [6, 7, 8, 9] and by PHARMAC [10] – see All were forced to give wide ranges of plausible outcomes, largely driven by uncertainty around the long-term durability of treatment benefit. In the New Zealand setting, none of the plausible outcomes gave sufficient confidence that 12 months of trastuzumab treatment would provide sufficient health gains to justify its high cost or opportunity cost.[*]

However, unlike NICE’s single technology appraisal process [1, 11], PHARMAC was able to consider additional information generated from the FinHer study, which examined a nine week course of trastuzumab given concurrently with taxane chemotherapy.[12] ( Even with conservative assumptions about the extent and duration of treatment benefit, PHARMAC’s revised analysis [10] indicated that the reduced costs associated with this regimen (considering the benefits available at that cost) ensured the regimen would be a good investment relative to other options [**]. From the data currently available, this nine week regimen appears to provide at least similar health benefit to the longer duration (12 month) schedules, but is a more practical regimen, with reduced impact on health budgets, hospital service delivery, and patients’ time (

The optimal sequence and duration of trastuzumab has yet to be identified. PHARMAC remains open to the possibility of funding longer regimens of trastuzumab, if data indicate such funding does not result in unacceptable opportunity costs.[*] To this end, PHARMAC has already committed funding for international efforts (the SOLD trial) to resolve the question of duration.[13]

Scott Metcalfe, Steffan Crausaz, Jackie Evans, Matthew Brougham

Email address for correspondence: scott.metcalfe{at}


* PHARMAC's original CUA estimate for the 12 month sequential regimen (base case NZ$75,000 per QALY [10]) might in fact have been optimistic, given now the apparent lack of significant benefit in the unpublished results from trial N9831 arm B comparing 12 months sequential therapy with usual care (n=1,964) [14, 15] and the reduced effect after 2 years median follow-up from HERA.[16, 17] ( PHARMAC waits with interest for further publications arising from these two studies.

** PHARMAC estimated the revised CUA for a nine-week concurrent regimen, under fairly conservative assumptions with respect to the extent and duration of benefit, to be NZ$14,500 -NZ$16,500 per QALY.[10] Trastuzumab in this setting would therefore be as, or more, cost-effective than many other medicines PHARMAC has funded. The nine-week concurrent regimen is likely to be at least four times more cost-effective than the 12 month sequential regimen (50 QALYs per million dollars spent for nine-weeks trastuzumab, 12.5 QALYs per million spent for 12 months trastuzumab).


[1] Wells J, Cheong-Leen C. NICE appraisals should be everyone’s business. BMJ 2007; 334:936-938

[2] Brougham M, Metcalfe S, McNee W. Our Advice? Get a budget! HealthCare Papers 2002;3:83-6.

[3] Herceptin and early breast cancer: a moment for caution. Lancet. 2005 Nov 12;366(9498):1673.

[4] Barrett A, Roques T, Small M, Smith RD. How much will Herceptin really cost? BMJ. 2006 Nov 25;333(7578):1118-20.

[5] PHARMAC media release 3 May 2007. 350 women each year to benefit from Herceptin funding decision.

[6] Ward S, Pilgrim H, Hind D. Trastuzumab for the Treatment of Primary Breast Cancer in HER2 Positive Women: A Single Technology Appraisal. University of Sheffield School of Health and Related Research (ScHARR), May 2006.

[7] Belgian Health Care Knowledge Centre (KCE). Trastuzumab in early stage breast cancer. KCE reports vol. 34C, 2006.

[8] Liberato NL, Marchetti M, Barosi G. Cost effectiveness of adjuvant trastuzumab in human epidermal growth factor receptor 2-positive breast cancer. J Clin Oncol. 2007 Feb 20;25(6):625-33.

[9] Kurian AW, Thompson RN, Gaw AF, Arai S, Ortiz R, Garber AM. A cost-effectiveness analysis of adjuvant trastuzumab regimens in early HER2/neu-positive breast cancer. J Clin Oncol. 2007 Feb 20;25(6):634-41

[10] PHARMAC TAR 75 Trastuzumab (Herceptin) in HER-2 positive early breast cancer with 9 week regimen CUA. Released May 2007.

[11] Hind D, Pilgrim H, Ward S. Questions about adjuvant trastuzumab still remain. Lancet 2007; 369:3-5.

[12] Joensuu H, Kellokumpu-Lehtinen PL, Bono P, Alanko T, Kataja V, et al; FinHer Study Investigators. Adjuvant docetaxel or vinorelbine with or without trastuzumab for breast cancer. N Engl J Med. 2006;354(8):809-20.

[13] PHARMAC media release 16 February 2007. PHARMAC supporting international trial and continuing assessment of funding options.

[14] Perez EA. Further Analysis of NCCTG-N9831. Slide presentation ASCO annual meeting 2005, available online at,1003,_12-002511-00_18-0034-00_19-005815-00_21-001,00.asp

[15] Romond, EH, Perez EA, Bryant J, et al. Trastuzumab plus Adjuvant Chemotherapy for Operable HER-2 positive breast cancer. N Engl J Med 2005;353(16):1659-1672.

[16] Piccart-Gebhart M.J. Procter M, Leyland-Jones B, et al. Trastuzumab after Adjuvant Chemotherapy in HER2-Positive Breast Cancer. N Engl J Med 2005;353(16):1659-1672.

[17] Smith I, Procter M, Gelber RD, Guillaume S, Feyereislova A, et al. 2 year follow up of trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer: a randomised controlled trial. Lancet 2007;369:29-36.

Competing interests:
None declared

Competing interests: No competing interests

11 May 2007
R Scott Metcalfe
Chief Advisor Population Medicine, public health physician
Steffan Crausaz, Jackie Evans, and Matthew Brougham
PHARMAC, Level 14 Cigna House, 40 Mercer St, PO Box 10 254, Wellington 6143, NEW ZEALAND