Are we falling behind Australia in terms of access to new cancer drugs? Our reply to PHARMAC's report

PHARMAC report on funding of cancer medicines in Australia and NZ

Breast Cancer Foundation NZ objects strongly to the misleading nature of the report released this month by PHARMAC, pertaining to a study your organisation commissioned into the funding of cancer medicines in Australia and New Zealand.

Our objection is on four grounds:

• A misleading overemphasis on late diagnosis downplays the role of medicines and shifts the blame for poor survival to patients, the primary care sector and screening programme
• Inaccuracies in the number of drugs presented and misrepresentation of the extent of funding
• Inadequate basis for determination of benefit / value of medicine
• Failure to obtain peer review

I have provided further detail on each of these points below, along with recommendations for next steps that PHARMAC could take in order to improve the accuracy of information presented to the public and media and to provide a more realistic comparison.

1. A misleading overemphasis on late diagnosis downplays the role of medicines and shifts the blame

- The context given at the start of the PHARMAC report is overly general, since diagnosis, treatment and survival vary widely by cancer type. However, even the general claims in the report are overstated.

- PHARMAC’s report claims that the public’s concern about unfunded medicines is “despite other research clearly showing that a key driver of the difference in life expectancy is that New Zealanders do not have their cancer diagnosed as early as Australians”, citing as its source a study by Phyu et al. [1]The cited study does not “clearly show” this; rather, it suggests there is an implication that diagnosis and treatment differences both play a part: “…the lower survival in NZ found in the current study, supported by the differences in cancer mortality, implies that NZ is lagging behind in diagnosis and treatment.” It is a distortion to suggest that the report is conclusive in this matter, or that late diagnosis is a “key driver”, or that it might shoulder an equal or greater share of blame than lags in treatment.

- With regard to breast cancer, NZ has a screening rate of 70% of the eligible population, against Australia’s 55%, so there is no reason to suggest that diagnoses lag behind. Indeed the Phyu study says, “For breast cancer,…survival difference increased with time…. This suggests that early diagnosis, including successful mammographic screening, may be comparable in the two countries but there may be differences in further treatment. Reductions in breast cancer mortality in Australia have been shown to be linked with the increased use of adjuvant hormonal and chemo-therapy” (my emphasis). Therefore, insofar as the Phyu study reaches any conclusion about the difference in mortality in breast cancer, that difference is attributed to a lag in treatment in NZ.

- Some relevant statistics here include the fact that 55.4% of the breast cancers diagnosed in the Auckland regions from 2000-2012 were Stage 1[1]. In New South Wales, just under 50% of breast cancers diagnosed 2006-2010 were classified as “early” – most likely encompassing Stages 1 and 2[2]. This suggests a much greater number of early diagnoses in NZ, yet we have a higher mortality. (Note: neither NZ nor Australia collect national data about the stage at which breast cancer is diagnosed, and since in NZ the staging data available for breast cancer is far in excess of that available in other cancers (thanks to the Breast Cancer Patient Registers funded by the NZBCF), I have to assume the same applies to other tumour streams.)

- The PHARMAC report does not present any evidence that Australia has faster treatment times than NZ, so the reference to the MoH’s Faster Cancer Treatments initiative cannot be linked to future improvements in survival in the context of comparison with Australia.

- Attributing poor survival to late diagnosis, while refusing to simultaneously acknowledge that lack of new medicines is a significant contributing factor in at least some tumour streams, distances PHARMAC and NZ’s medicines budget from disease outcomes and implies failure on the part of patients, primary care physicians or screening programmes.

2. Inaccuracies in numbers and drugs compared

- The report omits to cover medicines that are funded for more indications in Australia than in NZ. For example, in Australia, lapatinib is funded for metastatic breast cancer patients who have progressed on trastuzumab, but in NZ, in the metastatic setting, it’s only funded for patients who have not had trustuzumab. Similarly, everolimus is not included in the PHARMAC comparison. While everolimus is PHARMAC-funded for renal cell and SEGA cancers, it is not funded for breast cancer in NZ, while it is in Australia. The failure to include extended indications for drugs like lapatinib and everolimus in the PHARMAC report disguises and understates the gap between the two countries.

- The PHARMAC report misleads the public about the medicines available in New Zealand with this statement: “NZ funded 13 medicines that weren’t funded in Australia.” This may be accurate, but it is disingenuous – the presentation given to the NZ Society of Oncologists made it clear that the 13 NZ-only drugs are older drugs that have been superseded in countries like Australia by newer, better medicines.

- You acknowledge in the text of your report that Australia has approved an additional six medications since March, while PHARMAC has approved one more. However, these numbers are not reflected in your eye-catching graphic, which it seems should look like this:

3. Inadequate basis for determination of benefit / value of medicines

- The key metric used in PHARMAC’s report, derived from, "Lee M. Ellis et al (2014) “American Society of Clinical Oncology Perspective: Raising the Bar for Clinical Trials by Defining Clinically Meaningful Outcomes” Journal of Clinical Oncology April 20, 2014 vol. 32 no. 12 1277-1280" is not adequately described in the report, making it difficult to gauge the appropriateness of this measure.

- Many clinical trials produce significant differences in results across different patient subgroups, with some patients benefiting to an extent that isn’t revealed by reviewing the trial data as a whole. There is no indication that such subgroups have been considered in PHARMAC’s evaluation of clinical trial data.

- We would argue that the recognition afforded by regulatory agencies overseas should carry some weight with PHARMAC. The FDA’s Accelerated Approval recognises “allowed drugs for serious conditions that fill an unmet medical need”. Can PHARMAC say that those needs that older drugs cannot meet elsewhere in the world are somehow able met in New Zealand without the addition of new drugs?

- The medicines in your report that were accorded Accelerated Approval include everolimus, which you failed to list but which is funded in Australia for breast cancer, was granted Accelerated Approval. Many of the new drugs since approved by Australia (perjeta, T-DM1, pembrolizumab) also went down an accelerated pathway which suggests they are both effective to a clinically meaningful extent and needed.

- Quality of life is not included as a factor for consideration. The reduction of suffering, the medical costs of toxicity, and the ability of cancer patients to continue working and looking after their families should be taken into account when considering which medicines to fund. For example, the lower toxicity of IV-delivered nab-paclitaxel offered in Australia (cf. the infused paclitaxel funded by PHARMAC) makes a significant difference to patient quality of life and reduces hospitalisations. We would like to see quality of life factors considered and presented in reports like this.

- The report contains unsubstantiated statements such as, "Some of the medicines offer poorer health outcomes than the established NZ funded standard of care." Can you share the data to support this conclusion?

4. Failure to obtain peer review

- The PHARMAC report has not, to my knowledge, undergone any professional or peer review, nor been accepted or endorsed by any professional society. In particular, PHARMAC’s basis for selection of clinical trials to be included in (and those to be excluded from) its analysis should be the subject of independent peer review, as should the criteria set for meaningful gains.

In conclusion, the NZ Breast Cancer Foundation would like to acknowledge the difficulties facing PHARMAC in the application of funds to new medicines. We also acknowledge the need for the pharmaceutical sector to price its products more attainably and responsibly.

However, it is distressing for patients, clinicians, charities like the NZBCF and the well public to see New Zealand lagging behind comparable countries in the provision of medicines. It is distressing when we hear from pharmaceutical companies that they consider a submission to PHARMAC for funding of a new medicine to be a waste of effort and resources, due to the low likelihood of success.

The debate on new medicines needs to be transparent, honest and accountable. In our view the recent PHARMAC report does not reflect those qualities.

The NZ Breast Cancer Foundation therefore urges PHARMAC:

• To update its graphic representation of NZ and Australian drug funding to include new drugs funded since March 2015, and to be open with the public about the obsolete status of the 13 NZ-only drugs
• To include in its comparisons drugs that are funded for more indications in Australia than they are in NZ
• To more specifically compare drug availability and outcomes with Australia by tumour stream
• To include in its comparisons the wider value of new medicines, including improvements to quality of life, potential to fill a gap in existing treatment of difficult diseases, the wider cost to patients, families and the hospital system of toxicity, and the performance of medicines within subgroups
• To solicit independent review of the data and the resulting report comparing medicine availability in NZ and Australia.