Mind the gap - an analysis of cancer medicines in New Zealand and Australia
When it comes to making a difference in people’s lives, it’s not about how many medicines you have, but having the ones that work.
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This has been backed up by a study published in the Seminars in Oncology journal. The study, Mind the gap: An analysis of foregone health gains from unfunded cancer medicines in New Zealand, comparing cancer medicines access in New Zealand and Australia – shows that more medicines don't automatically mean better health outcomes.
The animation below simply explains the results of the study, and why the results are important for all New Zealanders to consider.
Objective of the research
The Mind the Gap research, was commissioned by PHARMAC in response to reports that suggested access to fewer cancer medicines in New Zealand results in poorer health outcomes. It looked at the health benefits of cancer medicines funded in Australia compared to those funded in New Zealand, to see if there were any clinically meaningful benefits that New Zealanders were missing out on.
Dr Matthew Strother: So fundamentally the objective of the cancer gap study was looking at those medications that have been funded in Australia vs New Zealand, and determining if the drugs funded had good relationship to actual clinical benefit.
Dr George Laking: It’s something pretty well described in the literature. You can do research and you can measure a difference in the effect between two treatments and that can be a statistically significant measurement so you can be confident that you’ve picked up a signal. However, the actual size of the difference in effect can be quite small in clinical terms and that’s where we start thinking about clinical significance.
For example, in our work we’d really like to see treatments that can increase life expectancy by some years. We might do some research and we might find out that the treatment offers on average an increase in life expectancy by one month, so obviously one month would be of less clinical significance than if we found something that could increase life expectancy by some years.
Dr Matthew Strother: Fundamentally that ties in well with the general concept of value for the medicine and that’s a growing interest across a variety of countries of looking not just at if something statistically beneficial but if its clinically beneficial. Because if it is purely statistically beneficial but you’re adding very marginal gains in anything meaningful such as survival or how the patient feels, it becomes a questions about if its worth paying that amount of money for no gain in terms of how the patient feels or how long they’re living.
Dr George Laking: Especially when the sums of money involved are extremely large for an average increase, that in clinical terms is still pretty small, it has to be said.
The findings of the study showed:
There are 89 cancer medicines that are funded in both New Zealand and Australia.
There are 13 cancer medicines that New Zealanders have access to, that Australians don’t.
There are 35 cancer medicines that Australia has funded, that we don’t.
Out of the 35 not funded in New Zealand, only three provide real, meaningful benefit. PHARMAC has already funded one of these, pertuzumab for breast cancer, and is considering funding applications for the two others.
A further 17 medicines provide only moderate or poor benefits, and five potentially caused harm or worse health outcomes compared to currently funded treatments in New Zealand.
Dr George Laking: The idea of harm in terms of our research is more on average. So for a person who starts out on one of these drugs, what the research can tell us is, is it more likely that their life will be extended, for example, as a consequence of taking that drug.
Very interestingly we found that four of the medicines in the relevant research, where on average actually people’s lives were shorter who used that drug compared to what is available in New Zealand.
It’s very true isn’t it because hat harm has very specific meaning in this research. I think whenever one uses the word harm, one really has to think about the values that go alongside that. So we’ve taken a very specific notion of progression free survival or overall survival and these have got quite specific definitions in the oncology literature.
So as an example I’ve referred to four medicines where on average people lived less long, actually to be honest a short amount of time less long in the research, so probably not clinically significant but still statistically significant. And so you might say what would be the value in a medicine where people don’t expect that they’ll live as long, on average. In a strange way such a medicine still could a value, if it was able to improve their quality of life by a large amount. But that is not a dimension that the American Society for Clinical Oncology methodology goes into at this time and it’s not a dimension that we go in to.
Dr George Laking: Setting aside the interest the we have, and the statistical methods used to evaluate medicines, there are a large number of things that are paid for in Australia but not in New Zealand that don’t make a great deal of difference in how the illness turns out for people, yet frequently have a very high price tag attached to them.
Should New Zealand fund the same cancer medicines as Australia?
New Zealand spends $130m annually (gross cost) on its cancer medicines. Careful selection of these medicines has enabled us to avoid additional costs of at least another $130 million each and every year, much of which would not help people with cancer any more than at present. The research shows that, with only three exceptions, those unfunded cancer medicines offer little, or relatively low, clinically meaningful health gain.
What is a clinically meaningful health gain?
The study looked carefully at how much benefit there would be for patients taking the medicines available in Australia, but not in New Zealand.
To compare the relative benefits of medicines, the study used internationally recognised measures: progression-free survival (PFS) and median overall survival (OS). Benchmarks, independently set by the American Society of Clinical Oncology (ASCO), were also used.
The difference in these measures are important: the time you enjoy better health before the disease returns (PFS) might be superior, but you may die even earlier from the disease once it returns (OS). So it is important to understand both. There is an increasing trend in cancer research for studies to be stopped once PFS gains are shown; before the OS is known.
Overall survival vs progression free survival and surrogate endpoints
Included in the Mind the Gap study, is a graph (figure seven) that shows the changes in progression free survival and then incremental changes in overall survival, and whether progression free survival is a good predictor of long term benefit. Dr Matthew Strother explains why this is important:
Narrator: So there were quite a few tables in the paper and one of the ones that is really interesting is figure seven. Can you talk to us about what that particular table is trying to demonstrate and the difference between overall survival and progression free survival gain.
Dr Matthew Strother: So figure seven can be potentially confusing and it is worth highlighting what it is exactly trying to show. It’s trying to show how accurate the surrogate endpoint of progression free survival is in relation to overall survival.
The reason that we use progression free survival and the reason we accept it is that we accept it as a surrogate endpoint for regulatory purposes because it is a shorter term therefore less expensive end point in the context of a clinical trial.
What figure seven nicely highlights is that it questions the potential value of that surrogate end point. And that’s been a fairly intense debate in the literature as a whole.
Effectively what it’s doing is its taking a difference between the progression free survival and the eventually reported overall survival. And it highlights that in studies where approvals occur at an early endpoint, when all you have is progression free survival data, there may be changes in how you interpret that data with the eventual overall survival data gets put out.
What do others say?
The Editor-in-Chief of the Seminars in Oncology journal, Tito Fojo, MD, PhD, wrote about the study in his editorial "The high cost of ignorance in oncology".
Dr Fojo noted:
“.. thought-provoking contribution from PHARMAC in New Zealand. At a time when discussions about drug costs leads to agreement that “this trajectory is not sustainable” but provide no clear solutions, PHARMAC shows us what a society must do to deal with this problem. Benchmarking outcomes to the American Society of Clinical Oncology Cancer Research Committee (ASCO-CRC) recommended targets for clinically meaningful health gains has allowed PHARMAC to achieve “good value for money” and deliver the best health outcomes for all New Zealanders.
“This is a commendable, courageous endeavour that many can learn from and emulate – and if widely adopted could incentivize drug development to achieve truly meaningful outcomes”.