Norman Swan: Hello and welcome to the Health Report with me, Norman Swan.

Today, what's four times a quarter, 0.25, all you maths experts? One, you might
say. Well, it's actually two when it comes to reducing your risk of heart attack and
stroke. Well, it could be.

Also on the Health Report today, how to get better behaviour in diabetes control.
How it really matters who you are referred to when it comes to your chances of
surviving cancer. And shocking news about what's really in that fish oil capsule a
lot of you swallow every day.

A US study which, as you'll discover, replicates findings in New Zealand and

Australia, has found that it is far from what you think you are paying for. Preston
Mason is a pharmacologist (that's someone who studies the action of drugs) at
Brigham and Women's Hospital and Harvard Medical School in Boston.

Preston Mason: It's a huge industry. We went to the local stores and started
purchasing a number of very popular brands of these dietary supplements,
brought them back to the lab, opened up the capsules and began to examine
them for their content. And there were several interesting observations. One, the
omega-3 or the desired part of the fish oil supplement only represented in many
cases a third of the overall product, the other two-thirds being other fats,
including significant levels of saturated fat.

Norman Swan: Saturated fat? Where did that come from?

Preston Mason: That is just the way it comes from the source, and many of the
preparations, they do not remove these other fats, they just put it in as it's
harvested. The other problem which is as serious is that we found that the
omega-3 fatty acids themselves were generally oxidised…

Norman Swan: Meaning they had interacted with oxygen, like rust, like biological
rust.

Preston Mason: Absolutely, so they are no longer effective. So we actually

would test them. And because they were oxides they had no benefit, they were
not able to have some of the biological activity that we associate with these
important omega-3 fatty acids.
Norman Swan: So could this explain why when the Cochrane collaboration and
others bring all the trials together of fish oil, they are not finding a cardiovascular
effect, that in fact there is an effect from fish oil when it's not oxidised, but most
people are taking crap?

Preston Mason: Absolutely. Because of the quality issues we can't have any
confidence in any of these studies unless they have used a well-characterised or
well qualified product. But many of these trials don't involve such products.

Norman Swan: So how can a manufacturer avoid this oxidisation? It sounds as if

it's inevitable.

Preston Mason: In most cases, in order to produce a low-cost product, they do

not do any extraordinary efforts to isolate the unoxidised forms of the omega-3s.
The general production of omega-3 is a by-product in the formation of proteins
for poultry farmers.

Norman Swan: If we think this is an American problem, there has been a recent
study in our part of the world…

Preston Mason: Yes, so what got us interested is a large study done in New
Zealand, a group out of Auckland looked at 30 different products from both
Australia and New Zealand and found I believe over 80% had higher than
accepted levels of oxidation. They didn't look at some of these other parameters
we were looking at but they did see high levels of oxidation, and that has been
confirmed now in other labs in Canada, in other parts of North America.

Norman Swan: So what's the poor consumer to do?

Preston Mason: They have to be very careful. This is an industry that's not
carefully regulated, so it's consumer beware. It's not obvious or clear, at least in
our country because of a lack of oversight, we do not know exactly the levels and
the quality of the omega-3 fatty acids in fish oils.

Norman Swan: Preston Mason is at the Brigham and Women's Hospital in

Boston. As you heard, this all started a couple of years ago when a research
group at the Liggins Institute at the University of Auckland published an extensive
analysis of fish oil capsules. One of the authors was Professor David Cameron-
Smith who is on the line from New Zealand. Welcome to the Health Report,
David.

David Cameron-Smith: Good evening.

Norman Swan: David, so, broadly the same results?

David Cameron-Smith: Indeed that was exactly the case. We commenced our
research on the back of not demonstrating the effect that we thought we would
with fish oil. So we conducted a study to look at the ability of fish oil to mitigate
the risk of diabetes, particularly some of the oxidative effects or the inflammatory
effects of diabetes. To our surprise we kind of demonstrated two key events. One
was there was no mitigation of diabetes. And two, when we looked at some of
the inflammatory events that are associated with elevated blood glucose, we
tended to see a worsening of the effect. So that led us very naïvely to start the
process of trying to understand what was in the fish oil that we were giving our
participants in that clinical research.

And very broadly we had exactly the same results that Preston described. The
first thing was that we were shocked at the level of saturated fatty acids and
other things that are normally present in different forms of fatty foods within those
capsules. Two, we were unable to demonstrate that the capsules gave you the
doses of omega-3 fatty acids that we thought you would get. And then really to
our surprise we started to discover that there was very high rates of oxidation.

Norman Swan: Meaning that it had gone off, basically.

David Cameron-Smith: Yes, meaning that…so one of the important things to

remember is that long chain omega-3 fatty acids are one of the most unstable
compounds on earth. They are long, they are very complicated, and they are
very prone to oxidation. So they start to go rancid very quickly, just like leaving
fish on the bench, it starts to go rancid and taste awful very quickly.

Norman Swan: But David, this morning I get an email from a CSIRO researcher
saying they had published a similar study in November, sent me a copy of it,
saying they found exactly the opposite from you and from Preston Mason.
David Cameron-Smith: Indeed that was the data that they've presented just
prior to Christmas. But I'd like to draw you back to a number of anomalies with
that research. So we've recently published an open letter to the editor of that
journal where we've made two important points. The first important point is all of
the authors were involved in the Omega-3 Centre. So that's effectively a
mouthpiece or an organisation that is devoted to propagating the benefits of
omega-3, irrespective of where those omega-3s come from.

The second is the study was conducted by a commercial laboratory, and all the
analyses were performed using techniques that were commercially in confidence.
So despite our best efforts to understand what they did, how they did it, why they
chose those supplements, exactly what the methodologies were that
underpinned their results, all we've got back from the company so far is a lovely
letter stating that their methodologies are confidential and I would like to be able
to describe them but I cannot.

Norman Swan: So what's the poor consumer to do? Because you talk about this,
that really fish oil supplements are just a by-product of a huge industry for food
stock.

David Cameron-Smith: That's exactly right. At least 75% of the fish oil…and so
let's remember where most fish oil comes from. Most fish oil is farmed from
ocean fish off the coast of Peru and Chile. They are hauled out of the water in
very large trawling vessels. They are then processed onshore, so the conditions
from a ship to the shore, subsequently the processing, is all done under
conditions that I simply can't verify the quality of that.

Secondly, that fish oil is then transported right across the ocean, to places like
China where it engages in high throughput processing. And really it's designed to
achieve two things. One is, most of that fish oil goes back to feeding fish. Fish
meal is the single biggest product of those fisheries. The second, the smaller by-
product and be less valuable by-product is to turn it into fish oil.

Norman Swan: Are there any reliable products on the market, do we know?

David Cameron-Smith: My advice is to go back to the source, and the source

is…we have an abundant supply of fresh oily fish. It's unfortunate that our salmon
is increasingly farmed under conditions where there is less fish meal fed to those
salmon, so there is less omega-3s. And so I'd go to the reliable source. And the
other thing to remember is increasingly we are able to manufacture omega-3s
from algal sources, and that's an unoxidised source of omega-3.

Norman Swan: So if it says 'algal sources' on the bottle you might be in a bit
better shape.

David Cameron-Smith: Exactly.

Norman Swan: David Cameron-Smith, thanks for joining us on the Health

Report.

David Cameron-Smith: My pleasure.

Norman Swan: Professor David Cameron-Smith is a human nutritionist at the

Liggins Institute at the University of Auckland.

And you're listening to the Health Report here on RN, ABC News Radio and CBC
Radio across Canada. I'm Norman Swan.

High blood pressure, hypertension, along with smoking and cholesterol, is one of
the most potent risk factors for stroke and heart attacks. As covered by
the Health Report, when you do have hypertension and are at high total risk of
heart attack or stroke, the lower the blood pressure you aim for with treatment
the better. But in the real world, the level of blood pressure control is pathetic.
One problem is side-effects from higher medication doses, which is what an
Australia group of researchers have tried to solve, and they seem to have
achieved it by going small. Clara Chow is professor of medicine and director of
the cardiovascular division at the George Institute.

Clara Chow: If you look at all people that have got high blood pressure, in
Australia it would probably be about a third of them that might have control.

Norman Swan: So what was the hypothesis?

Clara Chow: So the hypothesis was that a single dose of a usual drug…usually
you start on one drug, then you see your blood pressure in six or eight weeks,
then you start on another drug. The majority of people require at least two drugs
to lower their blood pressure, if not more. But people are having side-effects with
regular therapy. It has been around in the literature that maybe if we combine
lower doses of blood pressure lowering medications, we might be able to achieve
that effect with lower side-effects. So we took it to an extreme, if I take a quarter
dose of a blood pressure lowering medication, it doesn't give quarter of the blood
pressure lowering effect, it actually gives 60% of the blood pressure lowering
effect. So if I take four quarters, I have a much better blood pressure lowering
effect, theoretically, than one whole.

Norman Swan: Just before you go on, that seems counterintuitive that a quarter
of a dose doesn't give you quarter of an effect. Why is that?

Clara Chow: Well, as dose increases, the relationship is what we call not linear,
it actually starts falling off. So each doubling of does actually doesn't give
doubling effect. So that's thinking of it the other way.

Norman Swan: So if you imagine a steep line that then evens off, the steep line
is at the lower dose end of it, and once you get to higher doses, the benefit is
relatively less because that's where the curve evens off.

Clara Chow: Exactly. So a quarter dose, you are already getting effect and it
happens to be at about 60%.

Norman Swan: Is it 60% of the side-effects, or is it a quarter of the side-effects?

Clara Chow: Yes, so that's what's interesting, side-effects are linear for the
majority of blood pressure lowering effect. So if you run down dose, at a quarter
dose the majority of quarter doses actually have 0% side-effects. So we
confirmed that in our systematic review, we looked at a whole lot of studies.
Actually we identified over 40 that had information on a quarter dose of lots of
different types of blood pressure drugs to confirm that a quarter dose had about
60% of the blood pressure affect, and a quarter dose has 0% side-effects.

Norman Swan: So it seems too good to be true.

Clara Chow: We are pretty excited, yes.

Norman Swan: What did you do in the study?

Clara Chow: Part of it was that systematic review, but then it had to be a proof of
concept, can we actually do this in practice, because this is based on bringing
together a number of pieces of information now. So in this study we made a four-
quarters (or quad-pill we called it) tablet. And how we did that is using the
process called encapsulation. Then we randomised, a randomised crossover
trial. All patients would either start on the drug or on placebo, and then they
would crossover. What that means is that every single patient in the study at
some stage was actually receiving active treatment. And that means that when
we compare when you are on quad-pill with when you are on placebo, you can
get quite an accurate estimate of the differences in blood pressure between the
two.

The other piece of the puzzle is are four quarters additive in terms of their blood
pressure lowering effect, and that's what we weren't sure about. That's what we
thought. If each quarter gave five millimetres, additive would be 20. And that's
excitingly what we found, that four fives, we got about 20 millimetres of blood
pressure difference.

Norman Swan: That's huge.

Clara Chow: It is huge.

Norman Swan: Did you have them falling down and fainting?

Clara Chow: No, we didn't. We had no side-effects. I mean, it was a tiny trial.
Definitely we need a larger trial. So actually in about a week's time, NHMRC has
supported the Quartet Trial, which is comparing the quad-pill to a single dose of
irbesartan. So the patients won't know that they will either receive the quad-pill or
the other single agent, and then if they need to, they can add another agent.

Norman Swan: So is it four times the price, quarter of the price? What's the story
in terms of cost for something like this, and can you get the manufacturers to
agree to have their competitors' drugs in one pill?

Clara Chow: You're jumping a few steps ahead…

Norman Swan: Because you've kind of got to get to that stage.

Clara Chow: Absolutely, and these are all generic medications that have been
on the market for many, many years. They are all off patent. The medications
can be combined, though there has to be a company that will take to it. We have
combined it using a process called encapsulation, the capsule approach, but
probably we would want it all properly combined. So we haven't got a company
yet.

Norman Swan: And what are the four drugs?

Clara Chow: The four drugs are: a beta-blocker, we've chosen Bisoprolol; a
diuretic, we've chosen indapamide; an angiotensin-receptor blocker, we've
chosen irbesartan; and a calcium antagonist, and we've chosen amlodipine. I
mean, there are many different options that could have potentially be used but
we used common drugs that are all once a day, because we wanted it to be a
once-a-day medicine.

Norman Swan: Would the same be true of statins to lower cholesterol?

Clara Chow: Interesting. I mean, I suppose there is not four equally good agents
that could lower cholesterol. I suppose each of these agents are targeting slightly
different mechanisms to lower blood pressure, but we don't yet have I suppose
that many different types that are effective in cholesterol lowering. Theoretically
maybe it's possible. And certainly at the moment you've got statin-ezetimibe type
combinations. But at the moment I don't think there are four that are equally able.

Norman Swan: Clara Chow is professor of medicine and director of the

cardiovascular division of the George Institute in Sydney.

According to a visiting expert at the Victorian Comprehensive Cancer Centre in

Swinburne University last week, there is no cause for complacency in the
standards of care that people with cancer receive. There are big gaps in quality
and it affects survival rates. Professor Fred Ashbury is in the school of public
health at the University of Toronto. Welcome to the Health Report.

Fred Ashbury: Thank you, my pleasure to be here.

Norman Swan: We should just get your credentials I suppose to start with
because you were visiting Australia last week and giving a talk on quality of care
and cancer. What are your credentials to talk about this?

Fred Ashbury: So I am a PhD in behavioural sciences, I've been working in

oncology since the early '90s, I was a young scientist at the National Cancer
Institute of Canada, and subsequently working with hundreds of practices across
North America in particular and looking at harmonising cancer care delivery
based on evidence.

Norman Swan: The evidence of variation in cancer care, as presented by you, is

extraordinary; 35% of treatment plans deviate from the evidence-based
guidelines, 45% of patients don't adhere to prescribed medications, which is…the
evidence is right there, that at least 50% (if not more) of that problem is the
clinician. And around 10% of cancers are misdiagnosed. This makes you a bit
wobbly in terms of your confidence of cancer care.

Fred Ashbury: It does, and especially for patients, and I think there are often
some good reasons for the unevenness in care delivery such as individualising
care to a patient's needs. For instance, you may not offer certain treatments if the
patient is unwell, and so you'll offer a treatment plan that might deviate from
normal practice in response to that patient's personal condition. So there are
some good explanations for it.

In other cases it's not understanding the evidence or applying the evidence
differently based on falling back to normal practice behaviours rather than
embracing new evidence and applying it, lack of tools in practice or reports on
practice so that people can't make the right decisions at the right moment in time
in the absence of those tools.

And I think it's as well that we lack tools to know, especially with oral therapies
where patients will take them at home, our ability to ensure that they understand
what they should be taking, when they should be taking it, what problems they
may have, how to report those problems. And what people do often when they
are at home, at least these are patient reports that we've received, if they are
having bad experiences with it they often don't take the drugs if they think that
the problem is as a result of taking them. And there's a bit of fear to go back to
the doctors and say 'I'm not adhering to the plan that you've offered me'.

Norman Swan: Are these statistics valid for Australia too, do you think?

Fred Ashbury: I wouldn't say that because these are based on studies that have
been done in North America, but I have talked with a number of Australian
colleagues over two decades that would say to me that they know that a
standard is not in place at all centres for all treatments, and that they recognise
that there are opportunities to improve. And that's why you have some of your
national agencies and state agencies identifying performance criteria for quality
and examining or measuring that against practice so that they can help and
improve the quality of care delivery there.

Norman Swan: What evidence is there that it's having an effect on, say, cancer
survival, including quality of survival?

Fred Ashbury: Quality of survival as well, you're right. I mean, people have great
concerns about symptoms and side effects of their treatments, perhaps
sometimes more than the cancer itself…

Norman Swan: And you've shown huge variation in that, that doctors are much
more likely to treat nausea than they are fatigue, although fatigue, to be fair, is
much harder to treat.

Fred Ashbury: Yes, they have a tendency to go after the more physical
symptoms than the psychosocial symptoms as well. So these are problems,
however, that need to be addressed thoroughly, otherwise we see that patients
don't participate in the care that we intend for them to have.

Norman Swan: And my question about survival and the effect of these statistics
on survival?

Fred Ashbury: Yes, we are seeing improvements now where you have quality
standards in place where you are measuring things like process in terms of who
is doing what and when they are supposed to do it and making changes in those
so it's more efficient and effective.
Norman Swan: So when you see places that are doing that, do they get better
survival than places that don't?

Fred Ashbury: Certainly.

Norman Swan: By what sort of percentage?

Fred Ashbury: Well, it's hard to quantify some of it but we are seeing some
experiences in shift in as much as 5% to 15% range, depending on the cancer.
So it can be quite significant, the difference.

Norman Swan: Particularly if it's a cancer with very high mortality rates, if you
get 5% or 10%, that's huge.

Fred Ashbury: Yes, it's huge. And now with the complexity introduced by
genomic science, it can be challenging for doctors to keep pace with the volume
of information that is coming in.

Norman Swan: Coming back to the causes of this, in Australia you have more
and more people being treated in the private sector. In Canada you don't really
have that issue because it's mostly public. But the argument is that the private
sector in Australia is pretty much opaque, apart from some notable exceptions, to
quality of care, the individual oncologists can just get on with whatever he or she
wants to do, whereas the public system tends to be a bit more quality controlled,
and there are financial incentives to perhaps do the extra round of chemo in the
private sector. So what role does incentives play here, or does it happen
wherever you look?

Fred Ashbury: I think it does happen wherever you live. The US of course has
been wrestling with this for some time. The costs of cancer care have gone up…

Norman Swan: But my question was really about incentives and perverse
incentives. In a system such as the Australian private system where the incentive
is to do more because you get paid more, do you see lower quality of care and
lower adherence to evidence-based guidelines? 'We'll just give you another
round of chemo.' So if you compare the Canadian system to the American
system, which is more fee-for-service, do you get a variation?
Fred Ashbury: Yes, we absolutely do. We've seen this in comparison studies,
that there are tendencies to offer more chemo to patients in United States for
instance, and in fact we have a metric now in Canada and the US about the
delivery of chemotherapy in the last two weeks of life where it is considered
inappropriate to do but nevertheless there have been studies that have shown
that a percentage of patients do receive chemotherapy in the last two weeks.

Norman Swan: So what are the answers here?

Fred Ashbury: Well, certainly measuring what's taking place is important and
this has been a big change. In the absence of data and reports on performance,
people tend to do what they normally do. I think we also need to provide
educational interventions on what's appropriate when we see challenges in
performance. So remediation, if you will, of the actions that are taking place. I
think we have to have better tools in place for people to manage. There are
instances where people are still doing a lot of pen and paper work or they are
using electronic medical record systems inappropriately, and so that's not
necessarily helpful to them and helpful to us to be able to measure. And I think
we have to align incentives (to your earlier questions) better to the right
performance that we expect, rather…

Norman Swan: But what's the poor patient to do or the general practitioner? So
you go to see your GP, the GP says, 'It looks like bad news, I'm going to have to
refer you to a surgeon or an oncologist here,' mostly a surgeon in the first
instance when you've got cancer…I mean, how are you supposed to know who
to get referred to who is adhering most closely to evidence-based guidelines and
diagnosing accurately?

Fred Ashbury: Yes, I think there are a couple of things that can happen, and
one that I would like to see more of is public accountability of the reporting, so
having performance measures in a system. For instance, the province of Ontario
has performance measures, 30 or 40 published on a website on various
elements of cancer care delivery, and those performance reports are broken
down by location or cancer program that's providing that care. So it gives people
the opportunity to actually view what's happening in those centres and make
decisions that are right for them. Patients talk with other patients of course, they
ask questions about the doctors that they've visited, and when they are in clinic
or in waiting areas they…

Norman Swan: Yeah, but those conversations are really, you know, 'I went to
see my urologist and he must be the best because it cost me $10,000 out of
pocket and what you pay for is what you get,' which is completely…any doctor
will tell you that's complete rubbish.

Fred Ashbury: Of course, yes, of course…

Norman Swan: So patients talking to each other doesn't necessarily give you
quality.

Fred Ashbury: It doesn't necessarily give you quality but it's impressive
increasingly how that communication is getting out into the public about bad
performers. I mean, you certainly see a lot more social media around people that
patients don't like, or disguise the kind of care perhaps that they've received in
the context of, well, it cost more money therefore it must be better.

Norman Swan: So sunlight is the answer.

Fred Ashbury: Yes.

Norman Swan: Fred, thank you very much for joining us on the Health Report.

Fred Ashbury: Well, certainly my pleasure, thank you for inviting me, and best
wishes.

Norman Swan: Professor Fred Ashbury is in the school of public health at the
University of Toronto.

Diabetes is a huge problem in Australia; 280 people diagnosed every day,

500,000 people who don't even know they've got it. And with poor diabetes
control risking people's hearts, brains, eyes and kidneys and feet, there is an
annual cost of about $14.6 billion a year, according to Diabetes Australia. So a
national strategy to deal with diabetes seems like a good idea, except that three
of the people who helped write advice to the government on a national strategy
for diabetes have written a letter to the Medical Journal of Australia essentially
saying that they are worried that the government hasn't listened to them very
well. The co-chair of this advisory group was Professor Paul Zimmet of the Baker
IDI Heart and Diabetes Institute and he's also professor of diabetes at Monash
University, and he's in our Melbourne studio. Welcome Paul.

Paul Zimmet: Thank you Norman.

Norman Swan: So what's the problem that the strategy is trying to solve, very
briefly?

Paul Zimmet: Well, the strategy…we were asked to advise the minister on a
strategy, and a specialist group of diabetes experts was set up. Widespread
community consultation throughout Australia and to interested groups, and we
presented a report or our advice to the minister in the middle of 2015. That
advice was handed on then to the department, and that's where some of the
problems start because some very key recommendations, and that was one of
the points made in the letter to the MJA that stimulated our letter, was that the
implementation was very unclear.

Norman Swan: So we still haven't got an implementation plan for the diabetes
strategy, is that right?

Paul Zimmet: No, so the government has set up an implementation working

group, constituted of state health representatives, but with only one diabetes
expert, and I think that is of some concern in the sense that given that the
recommendations of the expert group were diluted, what will now happen, and
whether we are just going to get another diabetes strategy, as several previous
ones in Australia, where there is very limited action and just the same…

Norman Swan: So what's missing from your recommendations and what the
governments have put through to this committee?

Paul Zimmet: Well, it's probably just worth pointing to two areas. The first goal of
the strategy was the prevention of type II diabetes, and I do have to admit that
the government has, outside the strategy, recently provided significant funding in
the area of type I diabetes. But in terms of prevention of type II diabetes, the
strategy is quite unclear. We recommended that there should be a national
strategy so that isolated states aren't just doing something different. And indeed
the issue also was how do you evaluate that strategy? So a major
recommendation was that every five years there should be a health study in
Australia which includes a diabetes component so we can actually monitor the
impact of the strategy, if we are going to get one.

Norman Swan: And you recommended going back to pregnancy and looking at
pregnancy and that's where you start, the process of prevention.

Paul Zimmet: Yes, look, everyone knows now that you should lose weight or
exercise if you are an adult at high risk of diabetes. But many of the new cases of
diabetes appear to be the result now of unhealthy pregnancies, and one of our
key recommendations which was almost wiped, except for the Indigenous
community, I have to say, is that a healthy pregnancy makes it much likely that a
baby in utero will actually develop diabetes, obesity, heart disease, and indeed
behavioural issues in adult life.

Norman Swan: Isn't that a bit late to be complaining, given that they are
probably about to release the implementation strategy, even though it's two years
later?

Paul Zimmet: Well, you're absolutely right. The issue came up about nine
months ago actually where it did get media attention in the daily papers. And I
must say I was told off by one of the senior advisers to the then Minister Ley, that
we were breaking a pact, so to speak, because we had helped with the strategy.
And I have been advised that one should stay in the tent and not criticise, but I'm
not the only person. We've been approached by many organisations now, and a
number of the people in the advisory group are very concerned that
recommendations based on contemporary issues are being judged by people
who don't have the qualifications necessarily to judge what's best for the strategy
to reduce not only diabetes in the community but the terrible complications that
you mentioned right at the beginning.

Norman Swan: Paul Zimmet, who is professor of diabetes at Monash University,

and he's also at the Baker IDI Heart and Diabetes Institute.

I'm Norman Swan, you've been listening to the Health Report, do join me next
week.