Up Close & Personal
The Great (or Agonising) New Zealand Herceptin Debate: 
Part 2
Words: Dr. Sue Walthert
Dear Readers,
I had my last Herceptin dose a few days ago, 51 weeks of treatment, costing $47,052.32 of our own money. Part of me never wants to hear the word Herceptin again. But, I promised to write to you and let you know how things were between Pharmac and myself following my very public disagreement over how they handle high cost, low-volume drugs like Herceptin and low cost, high volume drugs like indigestion favourite, Losec. So here I am, full of Herceptin aches, writing to tell you about one of the most intriguing experiences of my life.
The Great New Zealand Herceptin Debate or, TGNZHD for short, has kept the media busy for over three years reporting on a multitude of opinions from a multitude of players. The courageous group of patients known as the Herceptin Heroines took Pharmac to court and won a ruling in April this year, directing the powerful body to reconsider its 2007 decision to not fund 12 months of Herceptin treatment for early Her2+ breast cancer. Pharmac received over 300 submissions and in early August 2008 announced it would continue to fund nine weeks treatment, basing their decision on the small nine week Herceptin FinHer trial, a trial that they seem to have fallen deeply in love with.
My article published in this magazine’s April 2008 edition described my decision to take 12 months of Herceptin as well as taking issue with how Pharmac dealt with various drug groups, hinting that commercial factors influenced which drugs were funded to the disadvantage of high-cost drugs like Herceptin. I said New Zealand had no strategy to manage the increasing demand for expensive drugs and that it now seemed the ideal time to start developing one. Pharmac responded to my challenge by coming to my Dunedin home and having a chat over soup and rolls!
We discussed several issues; the Herceptin evidence, Pharmac’s patient information leaflets on Herceptin, and the issue of how high-cost drugs are handled. We agreed that New Zealand faces increasing demand for high-cost targeted drugs; currently we don’t know what the ideal length of Herceptin treatment is because of a lack of trials set up to directly test one length against the other. We agreed that low-cost, but commonly prescribed drugs like Losec were over prescribed in New Zealand and needed containing; a responsibility for patients, doctors and supply agents like Pharmac. Significantly, we agreed that the patient information leaflets written to help New Zealand women make informed decisions about their Herceptin treatment failed to inform about the difference between the evidence for the nine week and 12 month treatments. Pharmac agreed to amend this and sent me their first draft just a few days ago. We did not agree on what Pharmac should fund or that Herceptin had been unfairly handled.
Pharmac is not the enemy here, nor is drug company, Roche. The enemy is the huge cost of new targeted biological drugs like Herceptin. Money is always going to limit treatment, that is a fact of life. Investors in drug companies are always going to expect increasing profits and that is a problem this world needs to address, but I am not critical of the drug industries need for research and drug development money. Pharmac was formed in 1993, and according to Medical Director, Peter Moodie, initially held a belligerent, fortress-like mentality against the drug industry. They were set up to provide a commercial structure to negotiate the best deals on drugs for the good of us all. They are a Crown owned enterprise but tell us they are unable to be influenced by any government. They say they made their decision using a standard process that involved advice received by an independent cancer committee; CaTSOP; and therapeutics advisory board, PTAC; a cost effectiveness analysis and negotiations with drug companies for the best price. They then put the case through nine decision criteria before the Pharmac board made its decision.
Pharmac say their system is a world first and pride themselves on making the tough decisions, so that the DHB providing the actual treatments don’t have to. They give the example of British oncologists having to remove funding from other patients after being directed by the British version of Pharmac to provide 12 months of Herceptin but without being given the extra funds. Pharmac reminded me of the role of media influence on health policy formulation. By presenting real people in distress, news reports often invoke Jonsen's ‘rule of rescue’ - described as the ‘psychological imperative to rescue identifiable individuals facing avoidable death without giving too much thought to the opportunity cost of doing so’. Pharmac and I had been angry with the media incorrectly presenting an overhyped portrayal of Herceptin’s ability to influence Her2+ breast cancer and suggesting Her2+ breast cancer is unsurvivable without the drug. Pharmac has a tendency to swing the other way and that is also not helpful.
So let us look at where we now are with TGNZHD. It is as clear as a muddy puddle! We have Pharmac saying they have looked at every bit of evidence, published and not published, and have decided once again that having 12 months Herceptin gives no additional health benefits than nine weeks of treatment. They say that the benefit of Herceptin is small and may not last past a few years after treatment. Pharmac have also supplied several million dollars to fund a direct comparison trial of nine weeks versus 12 months, the SOLD trial. On the other side of the debate are most New Zealand oncologists and almost all overseas experts and drug commentators. Of note is the quiet voice of our own drug regulator, Medsafe, which has repeatedly refused Pharmac’s request to have their favourite baby, the nine week treatment, sanctioned. Medsafe say there is not enough evidence to support nine weeks so it remains an ‘off-license’ treatment in New Zealand (doctors are lawfully able to prescribe off-license drugs in New Zealand).
Reading these confusing opinions reminds me of a quote by Evan Esar, who said “a statistician is a man who believes figures don’t lie, but admits that under further analysis some of them don’t stand up either”. Pharmac uses words very carefully and their argument comes undone by looking at these words. They say “Pharmac is not confident that there would be additional health gains from funding any 12 month treatment regime compared with the currently funded concurrent nine week treatment regime.” I would agree with them if the two sets of evidence are equally trustworthy. But they are not, and Pharmac was told this by their own cancer treatment sub-committee, CaTSOP. I quote from minutes of an October 2006 meeting, ‘It was considered that the data from the FinHer study (nine weeks) were valid and of good quality, though in a limited patient population (232 women). More scientific weight was attached to the data from the HERA study (12 month) and other US studies (12 month) given the larger number (>11,000) of patients involved in these studies’. Pharmac then says, “The only way to tell for sure whether the additional cost and risk of extending treatment duration is worth it is to conduct a head-to-head study.” Why do they need to put money towards this study if they are so convinced of the nine weeks efficacy?
Pharmac continue to say the decision is not because of the high cost of funding the 12 months, around $25 million for about 350 patients diagnosed each year with this more aggressive cancer. PTAC, the Pharmac Therapeutics Advsory Committee, tells us something different, when in November 2006 they said ‘In the absence of availability of funding for 12 months Herceptin treatment, nine weeks would be reasonable’. Why was 12 months Herceptin not available? Because Pharmac had decided in advance of CatSOP’s advice that 12 months would not be funded. Has Pharmac stopped listening to the advice of the cancer specialists they set up to advise them?
In reviewing the revised Pharmac patient information leaflet on Herceptin, it is clear that Pharmac are struggling to present complex statistical analysis to the public in easy to understand language, and I sympathise with them. They could just quote CaTSOP and PTAC’s sentences I used in the last paragraph. It is true that the results of even small trials like FinHer can be statistically significant and I agree with them when they say the trial was well done. It is just too small to raise confidence that the result has not been influenced by chance events. It needs to be repeated before it is reliable.
Pharmac are required by law to look at what funding 12 months would mean to their overall budget. They often say that Herceptin’s effects are small and my cynical mind wonders if they do this to minimise Herceptin’s place in the rich heritage of advances in breast cancer treatment. Before 1890 women were expected to die from breast cancer, the introduction of the radical mastectomy changed all that, giving women a 50:50 chance of surviving 20 years. Since then the 20 year survival rate has inched its way forwards. Survival rates are hard to pinpoint as new treatments keep being introduced all the time. Results can be given as relative, i.e. the reduction in risk of dying, or as absolute, the actual number of women surviving. They can describe women surviving overall or surviving disease free. Results can be given just a few years after treatment or at five year intervals up to 20 years. Herceptin research can only give us published results up to three years after treatment and giving absolute numbers will end up with the number looking small because most women survive the first few years. For example, 12 months Herceptin taken alongside chemotherapy allows seven women out of 100 to live. Pharmac telling you that this is small and that they don’t believe the effect will last naturally makes you think it’s too much money to spend on just seven women! In fact, I have to admit that before I was diagnosed with breast cancer, I felt like this too! When you read more about the ways treatment can impact on survival in breast cancer you learn that seven out of 100 is an amazing improvement and if this effect holds, or even increases, for the next five to 10 years (as all our other effective drug treatments for breast cancer have) the number of survivors starts to look more impressive because breast cancer kills most of us later on, not in the first few years!
Statisticians, clinicians and Pharmac’s health economists have trouble working their way through the muddy maze that is Herceptin research. How can an ordinary patient make an informed decision about their own treatment? If you are facing this fraught decision, find someone to support you, your GP, a friend, a breast cancer group advocate or ask to talk with someone who has also been in this same situation. I would like to think Pharmac’s leaflet will help you become a truly informed patient but I am concerned it will continue to be Herceptin according to Pharmac
I asked both major political parties about their policy for high-cost drugs. Labour said they had none and recognised this was an increasingly difficult issue and it needed attention. National said they would fund 12 months Herceptin, but have no actual policy. Both parties need to come up with a strategy fast. My suggestion is a tiny ACC like add-on to our tax to fund all high cost treatment.
I believe that 12 months Herceptin treatment is currently the most secure option for women with early Her2+ breast cancer. Time and further research will help clarify if the nine week treatment is equally as effective. My experience with Pharmac tells me they need to make house calls more often, chatting over dinner is much nicer than conversations through lawyers in the High Court!
Sue Waltherth is a mother of two 20-somethins, and lives with her Swiss husband on a small farmlet just a few minutes from the centre of Dunedin. She has been a doctor for 30 years, a GP for nearly 20 of those and now works as a teacher at the University of Otago Medical School. Sue was diagnosed with Her2+ breast cancer in April 2007 and has had surgery, chemotherapy and just finished 12 months of Herceptin. She is having a bilateral breast reconstruction in December 2008, and although apprehensive about the surgery is looking forward to new boobs for Christmas.
