Prime Minister Rt Hon Jacinda Ardern Deputy Prime Minister Hon Winston Peters Minister of Health Hon Dr David Clark Minister of Māori Development Hon Nanaia Mahuta Chair of the Health Select Committee Hon Louisa Wall Chair of the Māori Affairs Select Committee Hon Rino Tirikatene Director-General of Health Dr Ashley Bloomfield Deputy Director Māori Health MOH, Allison Thom Chairman of PHARMAC Hon Steve Maharey 16/10/2018 Re: URGENT INQUIRY INTO UNFUNDED MEDICINE IN NEW ZEALAND AND PHARMAC WITH A SEPARATE FOCUS ON MĀORI Tēnā koutou. EXECUTIVE SUMMARY 1. New Zealand cancer rates are 62% higher than the world average. 2. New Zealand cancer survival rates are lower than other comparable countries. 3. Māori constitute 27% of incidences of cancer and the total cancer mortality rate for Māori is 1.5 times higher for Māori than non- Māori. 4. New Zealand has consistently been ranked the last out of 20 OECD countries when it comes to funding of modern medicines; from 2011 to 2017 New Zealand funded the fewest modern medicines with other comparative countries. 5. For people with advanced breast cancer, the median survival rate is approximately half in comparison with comparable countries; the survival rates are widening in comparison with other countries; the median survival rate for Māori is worse than non- Māori, and the five-year survival rate is considerably worse. 1 6. PHARMAC receives much less than it did in 2007 (in real terms when taking into account inflation and population growth) and receives much less than other drug purchasing organisations in comparable countries. 7. PHARMAC have returned millions of dollars in recent years to Vote Health. 8. PHARMAC will not receive an increase in budget for new medicines until 2022. 9. There are 124 medicines recommended by PTAC that are awaiting a final PHARMAC funding decision. 10. The median waiting time for medicine to be funded by PHARMAC is 4 years. 11. PHARMAC has consistently demonstrated a pattern of poor behaviour regarding the funding of cancer medicines. 12. PHARMAC have never been externally reviewed or had a Government inquiry in their 25-year existence. RECOMMENDATIONS This letter recommends that the Health and Māori Affairs Select Committees conduct an urgent inquiry into unfunded treatments and PHARMAC with a separate focus on Māori. This follows a similar call by the New Zealand Māori Council for an urgent inquiry by the Māori Affairs Select Committee into the cost of medicines, the scheduling of medicines and their availability to Māori with specific reference to PHARMAC1. In particular, this letter recommends the that the Health and Māori Affairs Select Committees do the following: 1. Prioritise investigating and reporting on the 11 unfunded cancer medicines that are on the PHARMAC waiting list, consider urgently the applications for Ibrance and Kadcyla to be funded, and have the recommendations of the Health and Māori Affairs Select Committees urgently sent to the Minister of Health and PHARMAC; 2. Investigate why Māori have a lower survival rate in comparison with non-Māori in relation to cancer and why Māori have higher rates of avoidable cancer deaths in comparison with non-Māori; 3. Investigate long-standing systemic issues concerning PHARMAC including why the budget allocated for PHARMAC is lower than comparable countries such as Australia and the United Kingdom and is capped, why PHARMAC return millions of dollars to Vote Health, why PHARMAC are so slow in approving funding for new medicines, why PHARMAC consistently demonstrate a history of poor behaviour regarding the 2 funding of cancer medicines, and why such a long list of approved medicines for funding remain on the waiting list. MY WIFE WIKI On May 31st 2018 the world of our small whānau was devastated. My wife and the mother of our three children, Wiki, was diagnosed with ER+/HER2- de novo metastatic breast cancer that had spread to her bones. This type of cancer belongs to a wider cancer group known as advanced breast cancer (ABC), metastatic or stage four breast cancer. Sadly, we were informed by her oncologist that her condition is treatable but not curable. The first course of medicine prescribed to Wiki was Tamoxifen. After ten weeks of treatment, her cancer had progressed to her lungs and therefore the Tamoxifen was considered ineffectual. At this point her oncologist presented two options; either a low dose course of chemotherapy (known as ‘MMM’; mitomycin, methotrexate, mitoxantrone) or the unfunded drug Ibrance. We opted for the low dose course of chemotherapy in the hope that sometime in the near future PHARMAC will subsidise Ibrance. At this juncture we decided to ‘go public’ with Wiki’s plight in the hope of raising awareness for women, both Māori and non-Māori, who are facing a similar struggle and in the hope of raising some funds via a Givealittle Page to fund Ibrance for Wiki when the low dose chemotherapy is deemed ineffective2. Since that time Wiki has become something of a ‘focal point’ for women in a similar position and there have been numerous conversations had with a number of advocacy organisations including Breast Cancer Foundation NZ3, Sweet Louise4, the Breast Cancer Aotearoa Coalition5 and Metavivors6. Even more important are the number of women and whānau who have contacted Wiki, expressing their support to her for raising awareness of the need for new breast cancer medicine to be funded by PHARMAC. At times this has been difficult as we are told first-hand the financial hardship some whānau experience with questions such as “Do I live for another month or do I sell my family’s house?” not being uncommon. Wiki herself stated that “I don't want to leave my family in a terrible [financial] position, but all they want is me to be alive, so we are walking this tightrope all the time. Do you prepare to die or do you live? 7" There are women with breast cancer who are consigned to dying sooner because their whānau cannot even remotely contemplate raising enough for one month’s worth of Ibrance (the cost is $6800 per month). Their experiences 3 are not heard and they feel ‘unseen’, ‘forgotten’ and ‘isolated’ 8. To be frank, their stories are heart-breaking and very hard to hear9. CANCER IN NEW ZEALAND Each year, over 23,000 people in New Zealand will be diagnosed with cancer 10. Cancer is responsible for taking the most lives in New Zealand each year, claiming almost 10,000 lives or just under one third of all deaths11. The cancer survival rate is lower in New Zealand than Australia12. Of 18 cancers, 14 showed lower survival rates in New Zealand in comparison with Australia. The five-year survival rate is 4.2% lower in women and 3.8% lower in men. 3661 cancer deaths could have been avoided between 2006 and 2010 if New Zealand’s survival rates were as high as Australia 13. Recently Australian cancer researcher Professor John Zalcberg was interviewed on Radio New Zealand. He stated “The data pretty well confirms that New Zealanders have a worse outcome for the same cancers than they do in Australia. That is significant and it’s not just one or two or three, if you look at twenty odd different cancer types New Zealanders have a worse outcome14.” When questioned as to why that might be, Zalcberg cited the difference in the number of modern medicines that are funded between Australia and New Zealand. He stated that for both bowel and lung cancers, none of the modern drugs that are used worldwide to treat the diseases are used in New Zealand15. Furthermore, Zalcberg commented “There are things that are common [between New Zealand and Australia] but one of the things that is certainly different is that…there are a hundred drugs available in Australia that are not available in New Zealand.16” The following two tables illustrate the gulf between New Zealand and Australia when it comes to the access of cancer medicines and the breast cancer drugs that are available in Australia but not in New Zealand. TABLE ONE: NEW ZEALAND AND AUSTRALIA ACCESS TO CANCER MEDICINES17 NEW ZEALAND Sample size (i.e. number of submissions for 4 15 AUSTRALIA Sample size (i.e. number of submissions for 24 cancer initial cancer drugs that went from initial PBAC registration to PHARMAC reimbursement consideration to PBS listing in the period in the period from 1 Jan 2010 to 31 Dec from 1 Jan 2010 to 31 Dec 2016) 2016) Time drugs from that went Medsafe from registration PHARMAC listing (in months) Time from first positive to 44.1 Time from TGA registration to PBS listing 18.6 PTAC 15.7 (in months) Time from PBAC recommendation to PBS 7.6 recommendation to PHARMAC listing (in listing (in months) months) TABLE TWO: BREAST CANCER DRUGS AVAILABLE IN AUSTRALIA BUT NOT IN NEW ZEALAND18 T-DM1 DRUG (Trastuzumab Emtansine or Kadcycla) EFFECTS For people with HER 2 Positive advanced Breast Cancer. The head of Genentech’s Global Product Development and its chief medical officer, Dr. Hal Barron says, “We are extremely pleased to announce that people treated with trastuzumab emtansine survived significantly longer than those who received a standard option for this aggressive advanced breast cancer.19” T-DM1 improves both progression-free survival and overall survival of women who have been previously treated with trastuzumab and a taxane for advanced HER2- Denosumab (Xgeva) positive breast cancer20. Prevents serious bone problems for patients with bone metastasis from solid tumours. 18% of patients are less likely to have serious bone problems with Xgeva compared with a funded treatment available in New Zealand, Zoledronic Eribulin (Halaven) Acid21. Improves overall survival rate in women with metastatic breast cancer whose disease has progressed despite multiple Fulvestrant (Faslodex) rounds of chemotherapy22. Used alone as the first treatment for postmenopausal women diagnosed with hormone-receptor-positive, HER2-negative, advanced-stage breast cancer that has not been treated with hormonal therapy and to treat postmenopausal women diagnosed with metastatic hormone-receptor-positive breast cancer that has stopped responding to other hormonal therapy medicines, such as Tamoxifen23. Taken in conjunction with Liposomal Doxorubicin (Caelyx, Myocet or Palbociclib. Doxorubicin is a type of chemotherapy drug called an Doxil) anthracycline. It works by blocking an enzyme called topo 5 isomerase 2 that cancer cells need in order to divide and grow24. This liposomal formulation has significantly reduced Everolimus (Afinitor) toxicity for patients than the currently funded formulation.25 Everolimus is an antineoplastic chemotherapy drug. Treatment (in combination with exemestane) of advanced breast cancer in postmenopausal women following failure of Nab-Paclitaxel (Abraxane) letrozole or anastrozole therapy26. Used as a treatment for breast cancer that has spread. It works by stopping cancer cells separating into two new cells, so it blocks the growth of the cancer 27. Nab-Paclitaxel has significantly fewer toxicities and longer time to next treatment (TTNT) than the currently funded paclitaxel.28 In 2016 PHARMAC released a self-commissioned report titled “Mind the Gap” 29. The document was written in response to reports that suggested access to fewer cancer medicines in New Zealand results in poorer health outcomes. The report claimed that of the 35 medicines not funded in New Zealand that are funded in Australia, only three provide meaningful benefit30. Dunedin medical oncologist and Medical Director of the Cancer Society NZ Dr Chris Jackson responded “… [Mind the Gap] was a deeply misleading, deeply flawed study which was rejected by every oncologist who I have spoken to. Several oncologists have written in international journals, criticising the methodology and the practise of that study. PHARMAC listed some drugs there that they said were no good, which they then went on to fund. One of them that they said was no good was Pemetrexed and only a few months after having published that study, they [PHARMAC] went ahead and funded it. Either they [PHARMAC] are funding drugs that are no good or their methodology was no good, one of the two.31” Some of the oncologists who wrote to oppose the findings of “Mind the Gap” included Drs. Laird Cameron, Richard Sullivan, Brendan Luey and Professor Ben Solomon who co-authored “Mind the Graph. Foregone Health Gains in Lung Cancer 32”, and Professor John Zalcberg and Michael Wonder who wrote “Mind the Gap Revisited”33. Cameron, Sullivan, Luey and Solomon stated “However, as clinicians treating lung cancer within these funding constraints we cannot let PHARMAC’s misrepresentation of the crizotinib data from PROFILE1007 [3] go uncontested. To conclude that crizotinib causes an “accelerated time…to death” compared to the available second-line treatment option [docetaxel] in New Zealand is simply incorrect. 34” Zalcberg and Wonder wrote “…a more 6 rigorous scientific approach is required to measure the impact of such rationing on the health and well-being of the population.35” CANCER IS ON THE RISE IN NEW ZEALAND: WHO REPORT The World Health Organisation’s International Agency for Research on Cancer recently released their Globacan 2018 Database and estimated that within New Zealand and Australia, one out of very two men and one out of every three women will develop cancer before the age of 7536. The risk of getting cancer in Australasia is the highest of all regions in the world. Breast cancer in New Zealand specifically is estimated to be the fourth highest killer of all cancers and take the lives of 632 people each year 37. WHO have calculated that New Zealand’s average cancer rates are over 62% higher than the world average and the Ministry of Health have calculated that the cost of treating cancer will rise over time38. ABC DRUGS IN NEW ZEALAND: A CRISIS Until very recently there existed no comprehensive report regarding people with ABC [Advanced Breast Cancer] in New Zealand. In September 2018 Breast Cancer Foundation New Zealand released their report “I’m Still Here” to “…address the severe deficit of information about advanced breast cancer incidence, treatment and survival in New Zealand, which is in marked contrast to the comprehensive data available for early breast cancer. 39” The report explains further “The Ministry of Health does not collect data about metastatic breast cancer, so the Breast Cancer Foundation National Register is the only repository of such data.40” The report suggests that there are approximately 700 to 1000 people with ABC in New Zealand, with between three and four hundred being diagnosed every year, and more than 600 people dying from ABC each year (aligning to the statistics stated by the Globacan 2018 Database)41. Some of the key findings of the report are as follows42: 1. Median survival after diagnosis of ABC in New Zealand is 16 months, considerably worse than overseas (it is estimated that people with ABC overseas live, on average, for two to three years43); 7 2. One and five-year survival rates are also worse in New Zealand than overseas, with the gap widening in recent years; 3. Median survival for Māori with ABC is worse than non-Māori, and the Māori fiveyear survival rate is considerably worse. Regarding new drugs to extend the lives of people with ABC, the report states “Our healthcare professionals feel keenly the lack of publicly funded access to the latest medicines.44” This is supported by Dr Chris Jackson who states “When it comes to cancer drugs the question is ‘Have we got access to world’s best medicines?’. The answer is no. ‘Are we keeping up with other countries?’ The answer is no. 45” ‘Priority 3’ within the “I’m Still Here” report recommended that what is required is “Faster access to new and “still waiting” drugs. New Zealand lags severely behind Australia and other comparable countries in access to new drugs like Kadcyla, palbociclib (Ibrance) and ribociclib. Other drugs on the “still-waiting” list with proven ability to delay breast cancer progression include Everolimus, Nab-Paclitaxel, Eribulin.46” As the following table highlights, as of June 2018 there were 11 cancer medicines on the waiting list to be publicly funded for the first time and 6 cancer medicines were on the waiting list for widened access for new indications 47. Of these drugs, 9 are used for metastatic breast cancer and 4 are used for breast cancer. TABLE THREE: CANCER DRUGS ON THE PHARMAC WAITING LIST AS OF 201848 NEW Fulvestrant WIDENED ACCESS Nab-paclitaxel Trastuzumab cutaneous) Bevacizumab (sub- INDICATION Breast cancer (advanced or TIME (YEARS) 11.67 metastatic) Breast cancer (advanced or 7.67 metastatic) Breast cancer 3.66 Colorectal (metastatic), Enzalutamide Atezolizumab Ibrutinib 7.92 essential thrombocythemia Mantle cell lymphoma (relapsed/refractory) 8 1.91 0.91 advance/metastatic NSCLC) Polycycthemia ruba vera and 8.41 and 2.92 Cervical cancer (metastatic) Prostate cancer (metastatic) Lung cancer (2nd or 3rd line for Pipobroman cancer 2.41 Pomalidomide Multiple Ruxolitnib Ibilibumab (relapsed/refractory) Leukaemia (myelofibrosis) Melanoma 1.66 2.41 Trastuzumab Emtansine (advanced/metastatic) Breast Cancer (2nd line for 0.66 metastatic) Lung 2.16 Nivolumab myeloma cancer 2.41 (advanced/metastatic Pembrolizumab NSCLC) Lung cancer 1.66 (advanced/metastatic Ruxolitnib Lenalidomide Trastuzmab NSCLC) Hairy cell Leukaemia Multiple Myeloma (not eligible cell for stem transplant) Gastric cancer (metastatic) 2.66 0.91 7.41 It is estimated that some 529 deaths to breast cancer in New Zealand from 2006 to 2010 could have been avoided in these same people lived in Australia 49. The evidence-based 12month ttrastuzumab (Herceptin) treatment for early breast cancer was funded in New Zealand (in November 2008), two years and 3 months after it was funded in Australia (August 2006). PHARMAC did not support this funding but it was introduced by the incoming Government. Herceptin applies to women with HER2 positive breast cancer with 600 being diagnosed each year50. Therefore, approximately 1350 women did not receive funded Herceptin within New Zealand over a 2.25-year period despite multiple trials demonstrating an increase in overall survival, progression free survival and disease-free survival, when taken in conjunction with chemotherapy51. One medical oncologist stated in the “I’m Still Here” report “I think the main issue affecting MBC [Metastatic Breast Cancer] patients is lack of access to state of the art drugs. We have fallen behind Australia in this regard. The problem is that these drugs are not funded and most patients cannot afford to access them in private. These drugs would need to be funded by PHARMAC.52” An ABC patient stated in the report “Treatment options are not always discussed, as the price tags that come with the drugs required are too high, so I think oncologists just talk about the current treatments, as it is likely stressful for them too, knowing there are drugs that can keep us alive, but without a lottery win these drugs are out of reach for most.53” 9 MĀORI AND ABC: A LOSING BATTLE Under Section 4 of New Zealand Public Health and Disability Act 2000, the legislation that governs PHARMAC, it states that the principles of the Treaty of Waitangi will be observed and that improving health outcomes for Maori is a focus 54. According to the PHARMAC website “The primary goal of Te Whaioranga [PHARMAC Māori Responsiveness Strategy] is to ensure that Māori have access to subsidised medicines and use these medicines appropriately and safely.55” Māori represent 11% of ABC diagnoses and their survival with the disease is far worse. As stated prior in the report “I’m Still Here”, while the median survival is worse for Māori than non-Māori (12.8 months compared to 16.5 months 56) Māori survival five-years after diagnosis is 5% compared with non-Māori which stands at 15%57. The report suggests that a reason for the lower survival rate “…may be related to treatment access issues. 58” Given the earlier rates of those living with ABC and those who are diagnosed every year, for Māori one could estimate that approximately there are one hundred living with ABC and an additional thirty to forty diagnosed every year. In terms of cancer overall, Māori constitute 27% of incidences of cancer and the total cancer mortality rate is 1.5 times higher for Māori than non-Māori 59. For Māori, the rate of avoidable cancer deaths (the number of excess deaths that would not have occurred if the five-year relative survival in New Zealand in each age-sex group for each cancer had been the equivalent to that in Australia between 2006-2010) is higher than that of non-Māori. The following table stresses the wide gap of avoidable cancer deaths between Māori and nonMāori with specific cancers. TABLE FOUR: AVOIDABLE CANCER DEATHS FOR MĀORI AND NON-MĀORI60 TYPE OF CANCER Bowel Breast Lung Non-Hodgkin Lymphoma Prostate Stomach Melanoma MĀORI 39.6% 49.8% 15.6% 44.7% 71.9% 17.2% 68.7% NON-MĀORI 11.9% 26.4% 8.9% 18.8% 31.8% 6.5% 20.1% Wider issues also need to be considered when addressing the inequality between Māori and non-Māori. For example, the Breast Cancer Aotearoa Coalition’s ‘Incoming Brief to the 10 Minister of Health’ commented that Māori women are less likely to be diagnosed through mammographic screening, receive chemotherapy, Herceptin or surgery61. One suggestion to address the imbalance is to introduce mammographic screening at the age of 40 in populations with a younger breast cancer profile, such as Pacific Island and Māori, to increase the likelihood of detecting cancer earlier62. IBRANCE: ‘A GAME CHANGER’ As previously stated, the drug that Wiki and other women with HER 2- requires is Ibrance. There are three drugs in the ‘ciclib’ range that can treat ABC. They are known as CDK 4/6 inhibitors: palbociclib63 (also known as ‘Ibrance’ and produced by Pfizer that was the first ciclib produced), ribociclib64 (also known as Kisqali and is produced by Novartis) and abemaciclib65 (also known as Verzenio and is produced by Lilly). Cyclin-dependent kinases (CDKs) have been identified as key regulators of cell growth and division. Clinical trial results of palbociclib from 2012 showed a statistically significant improvement in progression-free survival. A UCLA Department of Medicine study presented at the 2016 Annual Meeting of the American Society of Clinical Oncology found that the median progression-free survival rate was 24.8 months when Ibrance was used in conjunction with Femara (letrozole)66. When produced it was hailed as a ‘game changer’ and “…one of the most important advances in 20 years for treating breast cancer 67” for women with hormone receptor positive and HER 2- breast cancer. Dr Reuben Broom, an oncologist from Auckland, said “…the treatment represents a significant advance for more than 400 New Zealand women who are diagnosed with the common type of advanced breast cancer.68” This is the most common form of breast cancer in New Zealand. The current cost of Ibrance is $5800 per month. This does not include the fee of $1300 per month for it to be infused in a private clinic nor the additional $1000 for the drug Fulvestrant when required as a second-line treatment for ABC which is an additional $1000 per month. An application for Fulvestrant was originally made to PHARMAC in 2006 and BCAC lodged a further application for its funding in May 2018. In Australia, Ibrance was registered with the Therapeutics Goods Administration in May 2017.69 In April 2018 the Government Advisory Board was prepared to subsidise Ibrance and Kisqali from $5000 per month to $39.50 a month. 70 In July 2018 Pharmaceutical Benefits 11 Scheme (PBS) subsidised Kisqali for under $500 per month 71. Under the ‘Ibrance Access Scheme’ offered by Pfizer in Australia since March 2018, women are offered the drug for a one-off cost of $50 and it is then free of charge72. My understanding is that to date, PBS has not reached an agreement with Pfizer on price for Ibrance. The cost of Ibrance and Kisqali is free in the United Kingdom under the National Health Service (NHS)73. In November 2016 it was approved for use by the European Union74 and my understanding is that Ibrance became available under the NHS scheme in July, 2017. TABLE FIVE: MEDSAFE/PHARMAC POTENTIAL TIMELINE FOR A DECISION ON FUNDING OR NOT OF PALBOCICLIB DATE September 2017 February 2018 21st September 2018 PROCESS Approved for use by Medsafe Filed by Pfizer with PHARMAC Cancer Treatment Sub-Committee (CATSoP) will meet and discuss 1st and 2nd of November Palbociclib Pharmacology and Therapeutic Advisory Committee Meeting (PTAC). PHARMAC has stated that it is unlikely that the minutes from the meeting of st 21 and 22 nd of February September 21st will be available by the time of the November meeting. PTAC Meeting. The minutes of CATSoP will need to be filed by November 19th. Given the average timeframe it takes for the minutes of CATSoP to be 2019 filed with PTAC (3-4 months) many advocates are pessimistic that the rd th 23 and 24 of May 2019 CATSoP minutes will not be submitted by November 19th. PTAC Meeting. The minutes of the CATSoP meeting on the 21 st of September 2018 will need to be submitted by February 25 th 2019 for them to be considered by PTAC. This is more in keeping with the timeframe of 3-4 months for the minutes of the CATSoP meeting to be filed with PTAC. The above timeframe does not allow for the time required for the Board of PHARMAC to approve or decline the recommendations from PTAC, the time taken to rank the application against that of others, the public consultation process, the time taken to negotiate between PHARMAC and Pfizer for Ibrance, or the time taken for patients to receive the drug. When asked why the delay regarding the minutes of CATSoP being tabled with PTAC take historically three to four months, Pharmac responded “We appreciate that it can take time for the subcommittee minutes to be reviewed and presented at quarterly Pharmacology and Therapeutics Advisory Committee (PTAC) meetings. If the timing between a subcommittee meeting and a PTAC meeting are too close, this may result in presenting subcommittee 12 minutes at the next available meeting. We also need to ensure that there is a robust process in taking and reviewing minutes, so that information is captured correctly. Given the subject matter and members of the committee who review these, it can take time. 75” For patients with ABC the delays in producing minutes and sending medicines for consideration by CaTSoP or PTAC cause considerable stress as funding delays can be life-shortening. PHARMAC was asked why they take such a lengthy process to approve Ibrance given that eighty-seven countries have approved the drug for ‘market entry’ as of August, 2018 76 and why, if so many other countries have approved the drug because the efficacy of it has clearly been demonstrated, PHARMAC still undertakes a slow process in comparison with international standards (noting that any concerns regarding Māori and Pacific Island populations that might be deemed unique to New Zealand have already been addressed by PBS in Australia; as of the 2016 Australian Census over 200,000 people claimed Pacific ancestry77 and there are over 140,000 Māori living in Australia 78). PHARMAC responded “Because of the relative priority of funding one medicine compared with other medicines can change over time, we are unable to provide a definitive timeframe for if, or when, a positive funding decision would be made for palbociclib. Details like the relative health benefits, the amount of funding available, the success of negotiations with the suppliers and/or new clinical data, and the mix of other funding applications being considered at any one time, are all examples of factors that might change the relative funding priorities of funding choices.79” At the time palbociclib was approved for use by Medsafe in September 2017, the Breast Cancer Aotearoa Coalition called for the ‘immediate funding’ of the drug by PHARMAC and stated that ‘hundreds of women’ would benefit from the drug 80. ‘Provisional Consent’ allows accelerated access to medicines which are still undergoing clinical assessment but has not been applied in this instance for the funding of Ibrance. Under ‘Provisional Consent’, the medicines lack clinical data for full consent but show early promising results and are seen as clinically beneficial so patients have early access. Provisional consent can be granted for up to two years and can be renewed for an additional two years until the medicine can be converted to full consent once there is sufficient data to meet the requirements. In response to why ‘Provisional Consent’ has not be instigated with regard to Ibrance, PHARMAC stated “…while we recognise the challenges faced by patients and their whanau, and their understandable desire to try new treatments, our job is to look at all the evidence and make a decision that is in the interests of all New Zealanders. 13 Ideally, funding applications should be supported by long-term data that establish the long-term benefit of a treatment. The flipside is considering the benefits of funding a treatment with high uncertainty about its results, with the reality that it would take funding away from more proven treatments.81” The response provided by PHARMAC contradicts the purpose of ‘Provisional Consent’ that, as stated prior ‘allows for medicines which are still undergoing clinical assessment’, despite the highly dubious claim that Ibrance is ‘still undergoing clinical assessment’. MODERN MEDICINES: NEW ZEALAND IS BEHIND THE REST OF THE WORLD When comparing the funding of modern medicines that have been registered and publicly funded, again New Zealand is behind other countries and only register and funds 22% of modern medicines; Australia sits at 45% and the United Kingdom stands at 86% 82. From 2011 to 2017 New Zealand funded the fewest modern medicines and innovative biologics (12) in comparison with other comparative countries 83; Australia funded 66, the United Kingdom 105, and Portugal 4384. Between 2009 and 2017, New Zealand was ranked last out of 20 OECD countries for access to new medicines85. Medicines New Zealand argue that modern medicines have contributed to a decline in cancer mortality rates since 1991. For example, in Australia, cancer mortality rates have decreased by 26%; in Canada by 21%86. Medicines Australia have highlighted the slowness of the PHARMAC process in the time taken to fund a modern medicine with New Zealand taking, on average, 517 days; in comparison Australia take 370 days and the United Kingdom take 134 days 87. Over 80 medicines have priority to be funded and sit on the New Zealand medicines waiting list and Medicine New Zealand argue that patients can wait for up to 10.75 years (although Fulvestrant has been on the waiting list for 12 years now); for medicines given high priority recommendations by PTAC, funding can be delayed up to 6.75 years 88. Medicines particular to cancer that are on the PHARMAC waiting list number 13 89. These medicines are available to over 45 countries including Cyprus, Estonia and Moldova90. WIDER ISSUES REGARDING PHARMAC 14 Section 47 of the New Zealand Public Health and Disability Act 2000 provides for the objectives of PHARMAC. Section 47 (a) and (b) reads 91: (a) to secure for eligible people in need of pharmaceuticals, the best health outcomes that are reasonably achievable from pharmaceutical treatment and from within the amount of funding provided; and (b) any other objectives it is given by or under any enactment, or authorised to perform by the Minister by written notice to the board of PHARMAC after consultation with it. The ‘PHARMAC Incoming Briefing to the Minister of Health’ recognised that one of its main aims is to ‘eliminate inequalities in access to medicines’92. NZIER state that the budget for PHARMAC is considerably less when compared to 2007 when PHARMAC received 6.2% of the overall Vote Health budget. A decade later, PHARMAC received only 3.6% of the Vote Health budget. To return PHARMAC to 2007 funding levels and allowing for inflation and population growth, some $682 million is required as of 201793. For the 2018-2019 financial year, and despite an increase of funding, only 5.4% of Vote Health is allocated to medicines 94. Even then New Zealand lags far behind the rest of the world as countries such as Australia spend 10% of their Vote Health on publicly funded medicines or the United Kingdom that spends 11% of their Vote Health 95. 124 positive recommendations made by PTAC are still awaiting a final PHARMAC funding decision on inclusion in the Pharmaceutical Schedule as of 30 th of June 201896. The mean waiting time for all medicines of this list stands at just under 4 years97. NZIER in ‘Insights & Analysis: PHARMAC Economic Analysis and “Savings” Claims’ noted98: 1. PHARMAC’s process is one of the slowest in the OECD with nearly a year longer than the OECD average from registration to reimbursement; 2. PHARMAC is particularly slow to act on PTAC’s recommendations to fund new medicines with an average time from recommendation to reimbursement of 2.8 years – some medicines wait up to 5 years or longer; 3. PHARMAC’s constrained budget presents an inability to set a cost-effectiveness threshold for funding results in the cost-effectiveness of newly funded medicines varying wildly from year to year; 4. From 2010 to 2015, New Zealand ranked lowest in the OECD for the proportion of new medicines that are subsidised – 12%, compared with 48% for Australia, and 58% on average across the OECD. 15 When PHARMAC was questioned regarding the lack of overall transparency of the processes they employ, they responded “You may be interested to know that we consulted with people around New Zealand in May and June 2018 about the way that we engage with New Zealanders. Some feedback we received echoed your comments regarding increased transparency of our processes. Right now, we are reviewing and summarising all of the feedback. We’ll be sharing this, and what improvements we will make as a result, later in the year.99” Professor Zalcberg provided some useful insights when asked about what is required to change the focus and modus operandi of PHARMAC. He commented “The thing that is required first, and it has only happened in Australia recently, is saying that as a Government that represents the community, in a democratic system, the Government needs to say that our first responsibility is to look after the sick… There has to be a culture change within the agencies [that fund drugs on behalf of the Government] … There are people dying. Do we want to wait until they die? I don’t think we should. 100” Dr Chris Jackson comments further regarding issues with PHARMAC. He states “Are there possible improvements to the PHARMAC model that could achieve better outcomes? I think the answer is yes. Currently it takes PHARMAC three years to review a new oncology drug application. Why does it take that long? In the UK they have published timeframes for: we are going to review a drug on this date, we are going to have a consultation process, we are going to have feedback, and they make a decision by a set date. There are no timelines in New Zealand. PHARMAC say we review the evidence but they have got no goalposts which say if you reach a certain cost effectiveness threshold, then you will get funded. In the UK the goalposts are clear. In Canada, the goalposts are clear. Here [New Zealand] the goalposts move. There are objective evidence scales like the European Medical Oncology Magnitude Benefit Scale that you can use to put a ruler over the strength of evidence to look at it and they [PHARMAC] are not using those sorts of objective measures.101” There have never been any statutory inquiries, reviews or investigations since the existence of PHARMAC in 1993102. 16 PHARMAC’S PATTERN OF BEHAVIOUR: THE STRUGGLE OF PATIENTS TO HAVE CANCER DRUGS HERCEPTIN, KEYTRUDA AND PERJETA FUNDED PHARMAC has a history of conflict when the public request cancer medicines to be funded. Herceptin (trastuzumab, for early breast cancer) and Keytruda (pembrolizumab, for melanoma) were both funded only after a public outcry. The resultant acrimony is still reflected in PHARMAC’s continued reference to the high costs of these medicines 103, despite there being costlier medicines funded for conditions such as hepatitis and auto-immune disorders104. Herceptin The Herceptin case demonstrates the lengths that New Zealanders had to go to in order to obtain an effective new breast cancer medicine. In 2005, unprecedented positive results from international clinical trials with Herceptin were published 105 and applications were filed with Medsafe and PHARMAC for its registration and funding in New Zealand. In March 2006 Medsafe registered Herceptin as safe and efficacious106. In June 2006 an 18,000-signature petition for public funding of the drug was presented to Parliament and submissions were made to the Health Select Committee107. In July 2006, PHARMAC published an opinion that Herceptin was very expensive and that they predicted its effects would not last 108. In August 2006 Australia funded the proven 12-month course of Herceptin for women109. In New Zealand breast cancer patient groups put their case to the media and PHARMAC responded with their own media campaign, claiming there was not enough evidence and blaming the pharmaceutical company for making Herceptin too expensive110. In January 2007 strong evidence from the HERA clinical trial showed that Herceptin significantly improved overall survival111, but PHARMAC continued to dispute this. In May 2007, PHARMAC agreed to fund an unproven reduced regime of 9-weeks of Herceptin 112. Medsafe declined to change the data sheet for Herceptin to cover this regime, citing “insufficient data of a regulatory quality and quantity to justify a change in the existing indication”113. PHARMAC also set aside $3.2 million over ten years to help fund the SOLD clinical trial aimed at demonstrating that the 9-week regime was non-inferior to the 12-month standard114. In December 2017 the final results of this trial were presented at the San Antonio Breast Cancer Symposium, with the lead researcher stating that “Noninferiority of the 9-week treatment could not be demonstrated for Disease Free Survival. 12 months remains the standard of care.115” Results showed that women who received only 9 weeks of treatment 17 were 39% more likely to have their cancer return116. PHARMAC responded to this with their own contradictory and misleading announcement that “This study confirms the results of earlier smaller trials which suggested that the effectiveness of a shorter course might be similar, but with reduced side effects, costs, and inconvenience for patients.117” Between 2007 and 2008, eight women who were paying for their own Herceptin took PHARMAC to court in a judicial review of their decision not to fund 12 months of Herceptin. In 2009 the Judge did not overturn the decision but ordered PHARMAC to consult and reconsider118. Patient groups then raised the issue throughout 2008 with politicians and the National Party made funding 12 months Herceptin an election promise119. Subsequently National won the election and Herceptin was funded within 30 days. The Prime Minister offered PHARMAC the funding to cover the cost of Herceptin but they refused and a separate Ministry of Health fund had to be established 120. In 2010 PHARMAC finally approved funding121. This year researchers at University of Waikato published data from New Zealand’s extensive Breast Cancer Registers showing that women with HER2 positive breast cancer treated with Herceptin are 42% more likely to be alive after five years, but that Māori and Pasifika women are less likely to receive this treatment122. Keytruda In 2016, Melanoma cancer patient Leisa Renwick took a petition that was signed by over 11,000 people to Parliament asking that the drug Keytruda (pembrolizumab) be funded 123. As a Radio New Zealand report states “PHARMAC says it's effective in one third of patients and that two thirds do not benefit, but this is disputed by cancer specialists who say Keytruda causes major shrinkage of tumours in one third of patients, but a further third also get some shrinkage of their tumours.124” The response from Keytruda manufacturers, Merck, Sharp and Dohme, accused PHARMAC of under-playing the drug’s effectiveness125. Following a PHARMAC decision not to fund Keytruda, Dr Chris Jackson in the capacity of Medical Director of the Cancer Society of New Zealand stated that everyone familiar with the drug agreed it is effective, safe and it is affordable. He noted that the results of trials were compelling enough for it to be funded in the UK, Canada, Australia and many other countries and that New Zealand has one of the highest rates of melanoma in the world yet we had no effective therapy for advanced melanoma126. 18 However, by July the same year, PHARMAC had decided to fund the drug with the Director of Operations for PHARMAC, Sarah Fitt, stating "Since we first received the funding application for pembrolizumab, new information has emerged that has given PHARMAC the confidence we needed to progress the funding decision. 127". Sadly, the decision came too late for many New Zealanders, including young architecture student and melanoma patient Jeff Paterson who had campaigned strongly to have the drug funded but who died while waiting for a positive decision by PHARMAC128. Following the death of Paterson, Dr Jackson stated that there needs to be a system where we can have temporary access to drugs whilst PHARMAC go through their processes129. Perjeta Perjeta (pertuzumab, for women with HER2-positive metastatic breast cancer) is another example of a cancer medicine for which New Zealanders have had to wait for funded access and even then, some have been left out entirely. Women who were receiving Herceptin for their advanced breast cancer at the time of PHARMAC’s decision to fund Perjeta are still not eligible for funded access. This decision has resulted in 160 women who could benefit from this medicine, having to fundraise and pay for their treatment themselves130 . In 2015 Perjeta was funded for women with advanced HER2 positive breast cancer in Australia131. Women who were already being treated with Herceptin for their advanced breast cancer at the time of this decision were covered, as well as all new cases. In New Zealand, the manufacturer of this drug, Roche, applied to PHARMAC in November 2013 but approval was not granted until December 2016 and funding not until January 2017132 with the proviso that women already diagnosed with advanced HER2-positive breast cancer and receiving Herceptin would not receive funded Perjeta. Despite repeated pleas to PHARMAC from the Breast Cancer Foundation NZ and the Breast Cancer Aotearoa Coalition133, PHARMAC has continued to deny this group of women access to this medicine. Given that these women have incurable cancer, Roche estimates that 32 will now have died134. PHARMAC: SAVING MONEY OVER LIVES? Under the PHARMAC Savings Proposal, it is envisaged that savings costed at $188.7 million over four years will be returned to Vote Health from a lower Combined Pharmaceutical 19 Budget (CPB) spend than the current combined funding trajectory for the CPB and DHB hospital medicines135. In order for this to be achieved, the proposal recommended that PHARMAC would add the remainder of DHB medicines (expenditure of approximately $130 million per year) to its CPB and return savings to Vote Health so that it can be reprioritised in other areas136. Since the bid was submitted, PHARMAC have indicated that a further $22 million from the CPB in 2017/18 will be provided in additional savings by commencing the proposal two months earlier than intended. Treasury supported the proposal “…as it allows reallocation to highest value interventions.137” Treasury however were concerned with the “perception” of reduced DHB funding for medicines. In terms of funding for new medicines, there is no planned increase in the budget from 2019 to 2022138. According to PHARMAC, it can fund its available pipeline of good value for money new medicines while returning savings and considered that the funding identified for reprioritisation is best returned to Vote Health “…as more cost-effective options to utilise the funds may be available elsewhere in the sector.139” The savings are predicated on savings in medicine and other product prices. “If they do not occur to the level expected, it may not be able to fund high value new medicines or may exceed the CPB. However, from a budget risk assessment, PHARMAC has a strong record of managing within the CPB and has never exceeded agreed levels since it was formed in 1993.140” Further advice was sought from Treasury after “…the likelihood of public concerns around a perceived reduction in Government medicine funding and how it may affect access to new products.141” With regard ‘Options for using the $22 million PHARMAC savings in 2017/2018’, Treasury’s recommended option was to have Ministers ask DHB’s to use the savings to reduce deficits and meet other expected cost measures. When discussing the pros and cons of the preferred option from Treasury, it stated “While this option does not return savings to the centre [PHARMAC], it increases the likelihood that the savings strengthen DHB’s balance sheets, reducing funding requests for deficit support. It also helps DHB’s to manage higher than expected cost measures which might otherwise result in other funding requests. Unlike the deficit support option above, there is a much closer alignment between the per DHB PHARMAC savings and reducing the risk of concerns being raised by DHB’s around uneven treatment.142” 20 In 2015/2016 PHARMAC savings totalled $9.8 million and was returned to the Ministry of Health to manage cost pressures 143. This has been ongoing, thus for 2016/2017, 2017/2018, and for the coming 2018/2019, $9.8 million dollars has been returned each financial year to the Ministry of Health (totalling $39.2 million dollars144). CONCLUSION I would like to thank you all for reading and considering this letter that asks for the Health and Māori Affairs Select Committees to hold an urgent inquiry into unfunded medicine in New Zealand and PHARMAC with a separate focus on Māori. I leave you with the words of the late Tamara Malone who provided inspiration for the title of the report commissioned by Breast Cancer Foundation New Zealand on advanced breast cancer. The mother of five in her late thirties stated “I’m still here” and spoke her own experience of how vastly different her experience as an ABC patient was from her first diagnosis of breast cancer and how she felt the health system had given up on her. Sadly, Tamara is not “still here” and died in January this year, aged only 41145. I hope her words echo in your thoughts as you consider whether or not to hold this urgent inquiry. Ngā mihi mahana Malcolm Mulholland 14 Ward Street Palmerston North 76mulholland@gmail.com 022 097 5899 21 1 http://www.scoop.co.nz/stories/PO1809/S00125/call-for-inquiry-as-breast-cancer-ratesincrease.htm 2 For example, please see: https://www.stuff.co.nz/national/health/106696126/expensivelifeprolonging-drug-not-an-option-for-many-women ; https://www.newshub.co.nz/home/newzealand/2018/08/woman-s-desperate-plea-to-PHARMAC-to-fund-6000-month-cancer-drug.html ; https://www.Māoritelevision.com/news/regional/cancer-sufferer-uses-daffodil-day-raise-awareness Wiki’s Givealittle Page can be found at: https://givealittle.co.nz/cause/wikis-treatment-for-stagefour-breast-cancer 3 https://www.breastcancerfoundation.org.nz/ 4 Sweet Louise is an organisation that offers support for incurable breast cancer. Please see: https://sweetlouise.co.nz/ 5 https://www.breastcancer.org.nz/ 6 Metavivors is a closed Facebook group for people with ABC. The page has approximately 240 members and the membership is limited to people with ABC. 7 https://www.stuff.co.nz/national/health/106696126/expensive-lifeprolonging-drug-not-an-optionfor-many-women 8 These are commonly used words to describe how women with ABC feel. See: https://breastcancerfoundation.org.nz/Images/Assets/21327/1/BCFNZ-ABC-Report-2018-v2.pdf? _ga=2.136785332.506817362.1537134913-e098e922-4f13-4534-9c2a-5bf374e50ea0 p.9 9 Other recent media stories include the following: https://www.stuff.co.nz/national/107557733/devestating-diganosis-two-years-too-late-for-cancersupport-advocate ; https://www.nzherald.co.nz/hawkes-bay-today/news/article.cfm? c_id=1503462&objectid=12136178 ; https://www.nzherald.co.nz/northernadvocate/news/article.cfm?c_id=1503450&objectid=12137578 ; https://www.stuff.co.nz/auckland/107629337/Auckland-cancer-patient-Lynne-Hanson-faces-sellinghome-to-fund-treatment ; https://i.stuff.co.nz/national/health/107588622/dont-write-us-offadvanced-breast-cancer-patients-lobby-for-access-to-drugs ; https://i.stuff.co.nz/national/health/107675308/breast-cancer-mums-terrible-dilemma--morememories-or-more-money-for-her-children ; https://www.nzherald.co.nz/nz-herald-localfocus/news/article.cfm?c_id=1504150&objectid=12136280 10 Ministry of Health. (2016) New cancer registrations. Retrieved from http://www.health.govt.nz/publication/new-cancer-registrations-2016/ Ministry of Health. (2015) Mortality 2014 data tables. Retrieved from: https://www.health.govt.nz/publication/mortalityhistorical-summary-1948-2015 11 Ibid. 12 Phyu, S., et al, (2014) Comparison of cancer survival in New Zealand and Australia 2006 – 2010. New Zealand Medical Journal Vol. 127, No. 1407; ISN 1175-8716 13 Ibid. 14 Radio NZ Interview with Professor John Zalcberg and Richard Vines, 16 September 2018. 15 Ibid. 16 Ibid. 17 Medicines New Zealand in ‘New Zealand and its Battle with Cancer’ from PHARMAC and Medsafe New Zealand data. 18 Sandiford et al. (2015) How Many Cancer Deaths Could New Zealand Avoid If Five Year Relative Survival Ratios Were The Same as Australia? Australia New Zealand Journal of Public Health. 2015; 39: 157-161. 19 https://www.breastcancer.org.nz/news/research-news/T-DM1 20 Malcolm, there are two references to insert here: Verma, S. et al. 2012. Trastuzumab emtansine for HER2 –positive advanced breast cancer. N Engl J Med. 2012 Nov 8: 367(19):1783-91. Doi: 10.1056/NEJMoa1209124. ; Dieras et al. 2017. Trastuzumab emtansine versus capecitabine plus lapatinin in patients with previously treated HER2-positive advanced breast cancer (EMILIA): A descriptive analysis of final overall survival results from a randomised, open-label, phase III trial. Lancet Oncol. 2017, June: 18 (6), 732-742. Doi:10.1016/S1470-2045(17)30312-1. 21 https://www.xgeva.com/breast-cancer/ 22 https://www.cancer.gov/types/breast/research/eribulin-improves-survival 23 https://www.breastcancer.org/treatment/hormonal/erds/faslodex 24 https://www.cancerresearchuk.org/about-cancer/cancer-in-general/treatment/cancerdrugs/drugs/liposomal-doxorubicin 25 Ngan, Y and Gupta, M, “A comparison between liposomal and nonliposomal formulations of doxorubicin in the treatment of cancer: An updated review”, Archives of Pharmacy Practice 7:1:113 (2016) 26 http://chemocare.com/chemotherapy/drug-info/everolimus.aspx 27 https://www.cancerresearchuk.org/about-cancer/cancer-in-general/treatment/cancerdrugs/drugs/nab-paclitaxel 28 R Mahtani et al. “Comparative effectiveness of early-line nab-paclitaxel vs. paclitaxel in patients with metastatic breast cancer: a US community-based real-world analysis” Cancer Management and Research 2018:10 249–256 29 https://www.pharmac.govt.nz/assets/mind-the-gap-an-analysis-of-foregone-health-gains-fromunfunded-cancer-medicines-in-new-zealand.pdf 30 Interview with Dr Chris Jackson, oncologist and Medical Director of the Cancer Society, with John Campbell on Checkpoint, 30/08/2018. 31 Ibid. 32 Mind the Graph. Foregone Health Gains in Lung Cancer. December 2017, Seminars in Oncology. 33 “Mind the Gap Revisited”. October 2017, Seminars in Oncology. 34 Op.Cit. 35 Op.Cit. 36 https://www.stuff.co.nz/national/health/107108812/oneintwo-nz-australian-men-at-risk-ofcancer--highest-rate-in-world 37 Ibid. 38 Ministry of Health. (2014) www.health.govt.nz/publication/new-cancer-registrations-2014/ Ministry of Health. (2014). www.health.govt.nz/publication/mortality-2014-data-tables/ Blakely, T. et al. (2015). Med Care. 53:302-309. WHO International Agency for Cancer. (2012). Estimated cancer incidence, mortality and prevalence worldwide in 2012. 39 https://breastcancerfoundation.org.nz/Images/Assets/21327/1/BCFNZ-ABC-Report-2018-v2.pdf? _ga=2.136785332.506817362.1537134913-e098e922-4f13-4534-9c2a-5bf374e50ea0 p.10 40 Ibid, p.56. 41 Ibid, p.85. Also see: https://www.newshub.co.nz/home/new-zealand/2018/09/breast-cancersufferers-dying-twice-as-fast-in-nz.html 42 Ibid, p.12. 43 https://www.newshub.co.nz/home/new-zealand/2018/09/breast-cancer-sufferers-dying-twice-asfast-in-nz.html 44 Understanding the needs of healthcare professionals to optimise advanced breast cancer care, Ipsos, in Ibid, p.14 45 Interview with Dr Chris Jackson, Oncologist and Medical Director of the Cancer Society, with John Campbell on Checkpoint, 30/08/2018. 46 Op.Cit., p.17. 47 Della Barca, C. (2018) Funding Medicines in New Zealand: Revision of the Medicines Waiting List. Auckland: New Zealand. 48 Ibid. 49 Ibid. 50 Breast Cancer Foundation 2018 Collateral/Pharmaceutical Benefits Scheme Australia/PHARMAC Application Tracker. 51 https:///www.ncbi.nlm.nih.gov/pubmed/11248153/ https://www.nejm.org/doi/10.1056/NEJM200103153441101?url_ver=Z39.882003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dwww.ncbi.nlm.nih.gov/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3268553/ ; https://www.thelancet.com/action/showPdf?pii=S0140-6736%2816%2932616-2 These are the final results of the HERA trial, unequivocally showing the long-term benefits of 12 months of Herceptin treatment on early breast cancer. 52 Ibid, p.75. 53 Ibid. 54 http://www.legislation.govt.nz/act/public/2000/0091/latest/DLM80058.html 55 https://www.pharmac.govt.nz/maori/te-whaioranga-maori-responsiveness-strategy/ 56 Ibid, p.25. 57 Ibid, p.24. 58 Ibid. 59 Rameka, R. (2006). He Arakanihi ki te Oranga. Wellington, New Zealand/Ministry of Health (2015) National Cancer Programme: Work Plan 2013/14. Wellington, New Zealand/ Ministry of Health (2015) Māori Health Unequal Impact II. Wellington, New Zealand, in Ibid. 60 Sandiford et al, (2015) How Many Cancer Deaths Could New Zealand Avoid If Five-Year Relative Survival Ratios Were the Same as in Australia? Australia New Zealand Journal of Public Health. 2015; 39: 157-161. 61 BCAC ‘Incoming Brief to the Minister of Health’ 2017. 62 https://www.waikato.ac.nz/news-opinion/media/2018/countrys-most-comprehensive-study-ofbreast-cancer-highlights-inequities 63 https://www.ibrance.com/ 64 https://www.us.kisqali.com/metastatic-breast-cancer/ 65 https://www.verzenio.com/ 66 https://www.curetoday.com/articles/ibrance-showed-impressive-progressionfree-survivalbenefit-in-breast-cancer 67 https://www.independent.ie/irish-news/health/80k-drug-for-advanced-breast-cancer-may-befunded-by-hse-35885875.html 68 https://www.nzherald.co.nz/nz/news/article.cfm?c_id=1&objectid=11916431 69 http://www.pbs.gov.au/industry/listing/elements/pbac-meetings/psd/2017-11/files/palbociclibpsd-november-2017.pdf 70 https://www.sbs.com.au/news/subsidy-boost-for-breast-cancer-patients https://www.smh.com.au/politics/federal/government-set-to-subsidise-two-5000-per-month-breastcancer-drugs-20180420-p4zaur.html 71 https://www.news.com.au/national/south-australia/price-of-breast-cancer-drug-ribociclib-cutafter-being-placed-on-PHARMACeutical-benefits-scheme/newsstory/92615781c7e86439c3f96dc55a075ec2 72 https://www.bcna.org.au/news/2018/03/cdk-inhibitor-update/ 73 https://www.independent.co.uk/life-style/health-and-families/health-news/breast-cancer-drugsnhs-nice-approval-palbociclib-ribociclib-healthcare-a8057816.html https://www.telegraph.co.uk/science/2017/05/04/breast-cancer-patients-offered-wonder-drug-freenhs-makes-mind/ 74 https://www.pfizer.com/news/press-release/press-releasedetail/ibrance_palbociclib_receives_approval_in_european_union_for_the_treatment_of_women_wit h_hr_her2_metastatic_breast_cancer 75 Katie Sherriff, Communications Advisor, PHARMAC to Malcolm Mulholland, 26/09/2018. 76 https://markets.businessinsider.com/news/stocks/pfizer-s-breakthrough-innovative-drugibrance-r-palbociclib-receives-approval-in-china-1027437101 77 http://bellschool.anu.edu.au/sites/default/files/publications/attachments/201709/ib_2017_23_batley_revised_final.pdf 78 http://quickstats.censusdata.abs.gov.au/census_services/getproduct/census/2016/quickstat/SSC31 791 79 Ibid. 80 http://www.voxy.co.nz/health/5/292265 81 Katie Sherriff, Communications Advisor, PHARMAC to Malcolm Mulholland, 26/09/2018. 82 Ibid. 83 PHARMAC Incoming Briefing to the Minister of Health, 2017. 84 Milson, B., Theile, S., Zhang, Y., Dobson-Belaire, W., Skinner, B. (2016) Access to new medicine in public drug plans; Canada and comparable countries. Ontario, Canada: Innovative Medicines Canada. 85 https://medicinesaustralia.com.au/wp-content/uploads/sites/52/2015/03/20150331-pubCompare_Edition1_March2015-FINAL.pdf ; https://medicinesaustralia.com.au/wpcontent/uploads/sites/52/2015/03/MA-Compare-Edition-3-October-2017.pdf p.3. 86 American Cancer Society Statistics Centre (2016) in Ibid. 87 Comparison of access and reimbursement environments (COMPARE) 3rd edition. Canberra, Australia, in Ibid. 88 Ibid, p.3. 89 Ibid, p.4. 90 PTAC Minutes (2004-2018) and MNZ member survey responses (2018). Wellington, New Zealand, in Ibid. 91 http://www.legislation.govt.nz/act/public/2000/0091/latest/DLM80051.html 92 PHARMAC Incoming Briefing to the Minister of Health, 2017. 93 Siddarth, P. & Hogan, S. (September 2017). Community Pharmaceuticals Expenditure Trends NZIER Report to Medicines New Zealand, Wellington, p.i. 94 Vote Health: The Estimates of Appropriations 2018/19. (2018) Wellington, New Zealand: Treasury. 95 Ibid. 96 Della Barca, C. (2018) Funding Medicines in New Zealand: Revision of the Medicines Waiting List to 30 June 2018, Subscripts Limited, p.5. 97 Ibid. p.14. 98 Hogan, S. & Scott, C. (June 2018) Insights and Analysis: PHARMAC Economic Analysis and “Savings” Claims. 99 Katie Sherriff, Communications Advisor, PHARMAC to Malcolm Mulholland, 26/09/2018. 100 Radio NZ Interview with Professor John Zalcberg and Richard Vines, 16 September 2018. 101 Interview with Dr Chris Jackson, oncologist and Medical Director of the Cancer Society, with John Campbell on Checkpoint, 30/08/2018. 102 According to Parliamentary Library research, 103 See https://www.pharmac.govt.nz/assets/briefing-to-incoming-minister-2017-11.pdf; and PHARMAC Year in Review 2017: https://www.pharmac.govt.nz/assets/2017-Year-in-Review.pdf 104 PHARMAC Year in Review 2017: https://www.pharmac.govt.nz/assets/2017-Year-in-Review.pdf 105 Rabiya S. Tuma, Trastuzumab Trials Steal Show at ASCO Meeting, JNCI: Journal of the National Cancer Institute, Volume 97, Issue 12, 15 June 2005, Pages 870–871; Piccart-Gebhart M et al.2005. https://www.nejm.org/doi/full/10.1056/nejmoa052306 106 For a timeline of the PHARMAC process regarding the funding of Herceptin from 2005 to 2008 see: http://i.stuff.co.nz/national/herceptin-debate/445436/Herceptin-The-timeline ; http://www.scoop.co.nz/stories/BU0603/S00377/herceptin-approved-for-early-breast-cancer-innz.htm ; https://pharmac.govt.nz/2006/03/23/230506.pdf 107 https://www.nzherald.co.nz/nz/news/article.cfm?c_id=1&objectid=10373051 and ) http://www.scoop.co.nz/stories/GE0603/S00044/herceptin-petition-to-parliament-this-thursday.htm 108 Rosevear M. PHARMAC and Herceptin for early-stage breast cancer in New Zealand: Herceptin or deception? The New Zealand Medical Journal [02 Jun 2006, 119(1235):U2014]; Petersen S. Roche responds to the 'Herceptin or deception' article. The New Zealand Medical Journal [07 Jul 2006, 119(1237):U2069; author reply U2069]; Breast Cancer Advocacy Coalition, Burgess EP. Breast Cancer Advocacy Coalition responds to the 'Herceptin or deception' article. The New Zealand Medical Journal [07 Jul 2006, 119(1237):U2065; author reply U2065] 109 http://www.pbs.gov.au/info/news/2006/10/listing-of-herceptin 110 https://www.stuff.co.nz/national/herceptin-debate?rm=m ; https://www.pressreader.com/newzealand/the-southland-times/20070413/281689725368191 ; http://www.scoop.co.nz/stories/PA0705/S00084.htm 111 Smith I et al. 2-year follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer: a randomised controlled trial. Lancet 2007 Jan 6;369(9555):29-36. https://www.ncbi.nlm.nih.gov/pubmed/17208639 112 https://www.pharmac.govt.nz/assets/nzmj-2007-06-15-pharmac-funding-of-9-week-concurrenttrastuzumab.pdf 113 Letter from Medicines Assessment Advisory Committee to Dr Peter Moodie, 25 September 2007, obtained under OIA. 114 https://www.ncbi.nlm.nih.gov/pubmed/17589560 115 https://jamanetwork.com/journals/jamaoncology/fullarticle/2682589 116 Ibid. 117 https://www.radionz.co.nz/news/national/345704/medical-trial-reveals-herceptin-survival-rate https://www.pharmac.govt.nz/news/media-2017-12-08-sold-trial/ 118 https://www.newshub.co.nz/nznews/herceptin-heroines-devastated-as-further-fundingrejected-2008080717 119 https://www.nzherald.co.nz/nz/news/article.cfm?c_id=1&objectid=10539093 120 https://www.nzherald.co.nz/nz/news/article.cfm?c_id=1&objectid=10547373 ; http://www.stuff.co.nz/national/health/755654/Govt-goes-ahead-with-Herceptin-promise 121 https://www.pharmac.govt.nz/2010/06/04/2010-06-04%20Notification_%20approval%20of %20proposal%20to%20list%2012%20months%20trastuzumab.pdf 122 https://www.waikato.ac.nz/news-opinion/media/2018/countrys-most-comprehensive-study-ofbreast-cancer-highlights-inequities ; Lawrenson, R., et al., The use of trastuzumab in New Zealand women with breast cancer. Asia-Pacific Journal of Clinical Oncology, 2017. Lawrenson, R., et al., Treatment and survival disparities by ethnicity in New Zealand women with stage I–III breast cancer tumour subtypes. Cancer Causes & Control, 2017. 28(12): p. 1417-1427. 123 https://www.radionz.co.nz/news/national/297814/what%27s-keytruda-and-why-won%27tpharmac-fund-it and https://www.nzherald.co.nz/nz/news/article.cfm?c_id=1&objectid=11773509 124 Ibid. 125 https://www.radionz.co.nz/news/political/302860/pharmac-accused-of-downplaying-keytruda 126 https://www.nzherald.co.nz/medicine/news/article.cfm?c_id=255&objectid=11570587 127 https://www.nzherald.co.nz/nz/news/article.cfm?c_id=1&objectid=11685918 128 https://www.nzherald.co.nz/nz/news/article.cfm?c_id=1&objectid=11701179 ; https://www.stuff.co.nz/national/health/82952285/keytruda-too-late-for-jeff-paterson?rm=m 129 https://www.newshub.co.nz/home/health/2016/08/jeff-patersons-death-highlights-need-fortemporary-drug-access.html 130 https://www.nzherald.co.nz/nz/news/article.cfm?c_id=1&objectid=12065437 131 https://www.bcna.org.au/news/2015/07/new-drugs-on-pbs-from-today/ 132 https://www.pharmac.govt.nz/wwwtrs/ApplicationTracker.php?ProposalId=1173 ; https://www.pharmac.govt.nz/news/notification-2016-12-05-multi-product-proposal/ 133 https://www.nzherald.co.nz/nz/news/article.cfm?c_id=1&objectid=11760962 ; https://www.breastcancer.org.nz/content/bcac-and-nzbcf-plead-change-heart-perjeta-funding ; https://www.breastcancer.org.nz/content/submission-pharmac-requesting-funding-perjeta-all-whoneed-it ; https://www.nzdoctor.co.nz/article/undoctored/heres-evidence-time-play-fair-pharmac 134 Pers. Comms. Libby Burgess and Sarah Cato from Roche’s oncology experts. 135 Treasury Report: Further Advice on the DHB Funding Signal and the PHARMAC Savings Proposal, 28/02/2018. 136 Ibid. 137 Ibid. 138 Ibid. 139 Ibid. 140 Ibid. 141 Treasury Report: Further Advice on the PHARMAC Reprioritisation Bid. 142 Ibid. 143 Treasury Report: District Health Boards: Additional Funding, 22/04/2015, Report No: T2015/827, File Number: SH-1-6-9 144 https://treasury.govt.nz/sites/default/files/2018-04/est15-v6-health.pdf p.9. 145 https://breastcancerfoundation.org.nz/Images/Assets/21894/1/BCFNZ-ABC-Report-2018Executive-Summary.pdf p.5