Why I’m furious at PBAC

Cross-posted from Begin Rant

You may have seen or heard me in the news a little last week talking about Aimovig being withdrawn from the PBS. This sucks, but it’s not the only reason I’m furious at the Pharmaceutical Benefits Advisory Committee (PBAC).

Some of this stuff is complicated, so I’m going to step it out. Apologies to those who know what I’m talking about. And I’m really angry, so it’s going to be a long rant.

What is PBAC?
Firstly: let’s walk through the players. PBAC is an independent advisory committee that has the job of recommending that new drugs be put on the PBS or not. 

When a new drug is released, the Therapeutical Goods Authority (TGA) assesses it, determines that it’s safe, and ‘schedules’ it – says it can be used in Australia, by whom, for what, and how you get it. So for example, x drug can be used by patients over 18 who aren’t pregnant for pain relief, and you need a prescription to get it.

Once approved by the TGA, the drug is legal in Australia. But you need to pay full price for it, which is usually insanely expensive for new drugs (that aren’t generics of old drugs). So we have this system called the PBS – Pharmaceutical Benefits Scheme. Under this scheme, considered one of the best in the world, the Government buys the nation’s supply of the drug at a ‘special buy’ heavily discounted price. We pay a set rate at the pharmacy, part of which goes to the pharmacist, which is $6.50 if you’re on a concession or pension card, and up to $40.30 if you don’t have a concession card.

(That the PBS co-payment we pay – introduced at $2.50 in 1990 – has been growing faster than the spread of fake news on Facebook is a matter for another rant.)

In order to get a medicine on the PBS, the drug must first be approved by the TGA, then must get a ‘positive recommendation’ from this mysterious opaque PBAC process. Members of the public and organisations (such as Migraine Australia) can make submissions to support a drug company’s application to PBAC, but we are not allowed to see the application we are making a submission on… only the name of the drug.

This is an insanely slow and bureaucratic process with a language all of its own that puts an episode of Utopia to shame. To submit a major application (major applications are new drugs, minor application is usually a change to an existing listing), the drug company needs to notify intention to list 21 weeks prior to the meeting where the drug will actually be considered; the public summary document – essentially the minutes of the meeting that explains the decision – is not available until 18 weeks after the meeting. Because of this slow and bureaucratic process, if an application is rejected – like Aimovig’s was twice – you can’t have it considered again at the next meeting in 3 months, you have to wait 6 months. And throughout most of the period that an application is being considered by PBAC, a drug company cannot say anything public about it.

Following a positive recommendation by PBAC, there are still a number of steps to go through before a drug is successfully listed on the PBS. They have to negotiate the price, any restrictions, caps and risk-sharing agreements with a special unit in the Department of Health. If they manage to get that done, the Health Minister can sign off if the listing is under $20m; over $20m and it has to be approved by the full cabinet. This process takes a minimum 5 months; fail to reach a price agreement in six months and the application will be listed as inactive.

Got all that? Ok.

PBAC making budget decisions
A drug cannot be listed on the PBS without a positive recommendation from PBAC. This is specified in the authorising legislation that creates the body, the National Health Act 1953. This legislation defines the committee’s work:

shall give consideration to the effectiveness and cost of therapy involving the use of the drug, preparation or class, including by comparing the effectiveness and cost of that therapy with that of alternative therapies

Nowhere in the authorising legislation does it indicate, suggest or imply that a committee of mainly doctors should be even considering economic impact, let alone making budget decisions for the government. Yet this is what the PBAC have been doing. I asked Minister Hunt to explain this, and the departmental boffin who drafted up the ministerial response directed me to PBAC’s guidelines.

And indeed, the fifth version of the PBAC guidelines released in 2016 does put considerably greater emphasis on the economics – even says that’s what the changes were in the intro. But the economic assessment guidelines – section 3 – do not actually stray outside of the authorising legislation to include fiscal impact. Here’s the key components of the economic evaluation as listed in the guidelines:

It is in the assessment of how the medicine will be used that this fiscal impact element has snuck in, and PBAC is exceeding its mandate – section 4 of the guidelines. If it was just identifying the impact, that would be fine, but the guidelines extend to ‘justify’ and ‘minimise’… which would be PBAC doing the Government’s dirty work for them.

It is this part of the guidelines, 4, and the drug use subcommittee (DUSC) of PBAC, that are responsible for all the heartache we are having with the new migraine drugs. The medications *are* groundbreaking and amazing, and they *are* cost-effective on a per-patient basis and get the tick from the economics subcommittee… but are very likely to be used outside the far too restrictive conditions proposed, and there’s too many migraine patients, so –  in the case of Aimovig – application rejected twice; in the case of Emgality – recommended at no net cost to the government because you’ll need to share the existing cap with Botox. I’ll come back to this.

Is this how we get this list of drugs recommended but not on the PBS?
Yes. This is what’s happening:

1. PBAC is recommending drugs be added to the PBS at no net cost, or some other unworkable condition. But they made a positive recommendation, so they look like good guys.
2. The drug is permanently stalled ‘in negotiation’ with the Department of Health. Drug company eventually gives up. Drug company looks like the bad guys for pulling out or failing to agree to with the Department to give their product away for free or near enough to it.
3. The Government didn’t ‘not’ list the drug on the PBS, so they can still claim to be good guys.

This is how the Government (and Labor did it too) can promise to list every recommended drug, without fear of ever having to actually do so.

This is what Chris Bowen has been banging on about, but he’s banging at the wrong end (in my view, or he may be privy to information I’m not, or perhaps he’s just trying to score cheap points) – Hunt isn’t the bad guy, it’s PBAC. PBAC is a law unto itself, unable to be lobbied, influenced or directed (individual members can be fired by the Minister, but that’s it). The reason it exists like that, and you must have a PBAC recommendation to list a drug on the PBS, is so that big pharma (or average citizen) can’t lobby for their drugs with politicians or anyone else susceptible to public pressure. That also means that PBAC can be the biggest bully in the yard, and do such completely unacceptable things as deny breakthrough treatment for years, or bully the companies into pulling out of the PBS system.

Sue Dunleavy recently did an exclusive piece in the News Limited papers listing a number of the drugs caught in the no-drug land between PBAC recommendation and PBS Listing. So I went for a read through their Public Summary Documents… and in far too many of them I saw a very familiar format. Does the drug work? Yep. Is it better than current drugs on side effects? Yep. Is it cost effective? Yep.

Then we hit the bit where it talks about drug utilisation and fiscal impact, and it all goes pear shaped. The hand wringing over more people than estimated using it, that people outside the restrictions may use it, “estimated financial implications were highly uncertain”… Ugh.

If it is DUSC’s job to be the fiscal worry warts, and again, I don’t think that is anchored in the authorising legislation as something PBAC should be doing at all, then it should be PBAC’s job to take it into consideration but balance it against the need in clinical care. Instead they seem to be dealing with the DUSC reports by imposing unworkable and unreasonable restrictions and caps.

Ok, what else is PBAC doing dodgy?
There are also very clear indications of bias in PBAC decisions. To put it bluntly: cancer drugs get the money, a few concessions for old people, the odd bit for diseases that pull on the heartstrings and maybe little kids, everyone else good luck. The fast-tracked applications are almost exclusively cancer drugs, and, in the last round, the PBAC suggested($) to the Health Minister that new mechanisms are developed to encourage greater uptake of new cancer meds.

A condition like migraine that is most keenly felt by working-age women? Forget it.

I want to be clear here that I’m not implying intentional wrongdoing or that they are aware of said bias. All organisations have a natural bias. It’s how you manage it that matters, and I haven’t been able to find any process or indication that PBAC does have a check on its own internal bias.

Would the composition of PBAC have anything to do with what appears to be favouring of cancer drugs? Two oncologists and two haematologists on the main committee which gives cancer 4 seats out of 20. There’s also:

• 2 GPs,
• 2 epidemiologists (academic doctors who study patterns of disease),
• 1 cardiologist, read: old people
• 1 nephrologist (kidneys), read: old people
• 1 geriatric medicine (old people), read: and cancer
• 1 endocrinologist (Diabetes), read: kids and old people
• 1 rheumatologist (arthritis), read: old people
• 1 psychologist,
• 1 infectious diseases;

and a health economist (plus a subcommittee full of them), an industry nominee from Medicines Australia, a pharmacist, and two patient advocates (from AIDS and kids/chronic illness backgrounds respectfully).

So I’m gonna go ahead and say yeah, the composition of the committee may be part of the problem. A lot of the 15 doctors are academics or in labs rather than dealing with patients too, which doesn’t help matters, as they tend to be out of touch with the murkiness and grey required in clinical practice. PBAC is more black-letter than the High Court and less willing to admit their mistakes than Peter Dutton.

I have asked Greg Hunt, in writing, to put a clinical neurologist on PBAC. One of the epidemiologists has ‘cognitive neurologist‘ as part of his description, but I am told this is very different from a clinical neurologist, and miles away from a headache specialist (the way it was explained to me is it would be like someone who works for Google coding search algorithms trying to fix the computer in your car). As a side note and just to demonstrate this isn’t all just a migraine whinge, how they get away with not having a gynaecologist on the committee in this day and age is pretty interesting… obviously they thought that achieving gender parity thanks to the non-doctors was enough.

Does it really matter who is on the committee?
Yes. Despite repeated assurances that they have access to whatever experts they need, the extent to which they do not understand migraine is as plain as day. Here’s a few red flags from the public summary documents of the unlikely to succeed recommendation for Emgality; the first and second rejections of Aimovig; and the refusal to lift the cap for Botox for migraine.

• All of the PSDs use out of date language, talking about ‘migraines’ rather than migraine disease or migraine attacks, refer to ‘headache’ excessively, do not use ‘most bothersome symptom’ as the measurement point, and generally use a range of terminology rejected by the community. And yes, PBAC, the Department and the Minister have all been sent a copy of the CHAMP language guide and asked to use it.
• The definition of chronic migraine they are using is inconsistent across the various PSDs, but none of them use the current ICHD-3 definition (nor acknowledge that the language is problematic as all migraine is chronic, but that’s advanced level understanding of the community).
• A common restriction criterion is “Patient must have experienced an inadequate response, intolerance or a contraindication to at least three prophylactic migraine medications prior to commencement of treatment” and then they go on to list what those medications are – with different lists for each. There are no prophylactic migraine medications other than the CGRPS – and if we are being generous Sandomigran, which has so many side effects it’s never really preferred therapy and isn’t approved by the FDA. There are drugs for other things that are used in a weak attempt at migraine prophylaxis. Botox and the CGRPS are not in the list of ‘fail-first’ medications; candesartan, verapamil, nortriptyline, and sodium valproate are all off-label for migraine and should not be on the list. Migraine Australia opposes all ‘fail first’ restrictions as both bad for health outcomes and fundamentally unethical – we don’t require someone with a heart condition to take an anti-depressant before they can access a heart medication, and it shouldn’t be demanded of migraine patients.
• They require that patients a) have 15 headache days per month, at least 8 of which are migraine days, for a period of 6 months prior to commencing treatment; and that they decrease migraine days by 50% to continue the treatment.
  • This would require patients to keep migraine diaries forever, which is incredibly bad for mental health and not at all recommended.
  • In the second Aimovig rejection they descend into a farcical discussion about whether GPs will be able to determine what is a migraine day – but patients make that determination, not doctors.
  • Patients complete migraine diaries as a self-assessment tool and to help identify triggers. If they know that the required benchmark is 15 days, and a 50% reduction, then they will fill in the diaries to meet that criteria. This has been clearly communicated to PBAC – and is beautifully illustrated in the Stark 2017 review of Botox use, which found that a stunning three-quarters of patients had achieved more than a 50% reduction in headache days!  News for you Starkie, no, that’s just what they had to say to keep getting Botox. The real rate is closer to the third (or less) found in clinical testing.

This last bit is important. The Stark 2017 paper is referenced heavily in the rejection of an increased Botox cap, and the numbers from the paper are referenced in the PSDs for the CGRPs.  It is because of that false flag of the success of Botox, created by these utterly silly exclusion criteria that are both meaningless and easily evaded, that is causing PBAC to repeatedly assert that Botox is just as good as Aimovig and Emgality.

The very suggestion of this is laughable.

Botox has a list of side effects literally a page long, is expensive (as it has to be administered by a specially trained neuro), painful and inconvenient. And, the *best* you can hope for is a 50% reduction in frequency, some reduction in severity. For Botox, that’s a really good result. A more typical response is a reduction in severity and no real change in frequency.

For the CGRP meds, the *average* response is a 50% reduction in frequency, significant reduction in severity. The *best* you can hope for is complete remission or close to it. And they all literally have one tiny paragraph about side effects, most of which is an allergic response to the drug or pain at the injection site (and the wonderful constipation of Aimovig).

PBAC says these are just as good as each other. Repeatedly. Seriously. No, I’m not kidding.

Even the US insurance world who gave us the evil that is fail first admit the CGRPs are significantly better than Botox.

If Botox was just as good as CGRP therapies, then Allergan (maker of Botox) wouldn’t be rushing to market with two of its own CGRP medications.

There’s a reason the migraine world didn’t get very excited about Botox, but is doing absolute backflips about the CGRPs. Botox was just another bandaid, CGRP, for many people, gives them their lives back – a real chance to manage our condition for the very first time.

Just astonishing.

Ok, so they mucked up the details, but do they respect migraine as a serious thing?
No. Hell no. 6 months at chronic before eligible. Take a year worth of these other preventers we know don’t work but we don’t care. No clarity about whether GPs will be able to prescribe ongoing treatment or not. Excessive delay in access. Clear indications that despite being bombarded with submissions, they didn’t change anything about the way they thought about the drugs or disease at all.

Let’s get back to this bit about no net cost. That’s literally what the rejection of increasing the Botox cap says, point 7.12: “If any changes in the structure of the RSA were to be implemented, the PBAC advised that these should have no net financial consequence for the PBS.” And in the Emgality recommendation this clanger in 6.52 “The PBAC considered that a combined galcanezumab and Botox RSA would be appropriate in order to manage the risks identified by the ESC, and that the RSA should be based on the current Botox RSA…”

Let me translate: you remember the botox cap we refused to increase a year ago? Halve it, because any of these new migraine drugs are going to have to come out of the same pot of money… and yes we know that the existing cap is stunningly insufficient, don’t care, migraine isn’t important enough, there will be no new government money spent on your silly headaches. 

I’m not getting into the huge economic gain that would inevitably result from these medications (I’ve done that before) but suffice to say that PBAC is fundamentally not equipped to know whether the government wants to spend the money or not, what the fiscal impact will be, and has no business making such conditions.

Bullies. Said it.
When I said that the PBAC is bullying the drug companies this is what I was talking about. Your drugs aren’t better. You don’t deserve taxpayers money. Give your (utterly amazing, Time Magazine invention of the year) drugs away for free.

I am livid.

The PBAC’s role is to limit the medications available on the PBS to only those that are equivalent to or better than other drugs, and which are cost-effective. And it’s not new, it was established in 1953 – having doctors decide which drugs are listed has pretty much always been part of the PBS model. I don’t have a problem with that. But PBAC making budget decisions, rejecting drugs on the basis of fiscal impact, or imposing prohibitive caps, particularly on the basis of *absolute lies* about the benefit of the drugs, cannot be allowed to continue.

End rant.