1) You lump together unlicensed and unproven drugs, but there is an important distinction to be made. The primary consideration with any new drug must always be one of safety rather than efficacy. If evidence of safety (to the extent that this can be ever considered proof) cannot be provided through a phase 1 trial, then the NHS MIGHT be considered justified in not offering treatment related to drug related toxicity – although I cannot imagine many doctors turning away a critically ill patient regardless of the cause.

Unproven drugs (and by that I mean those which NICE has not approved for NHS use) is an entirely different matter. To see why, consider the constant state of flux of cancer research; New drugs and novel targets are being discovered at an impressive rate (for an example, read some of the papers and poster presentations at the recent annual meeting of the American Society of Clinical Oncology). In order to authorise NHS usage of a particular drug, NICE must run some fairly abstruse econometric models, which are predicated on a number of assumptions (which clearly can alter the outcome). The implications of this are twofold. Firstly, it will take time for most drugs to be sanctioned irrespective of the efficacy data, and this is a commodity many patients do not have. Secondly, whilst it is correct that we defer to expertise to make the objective judgements which help decide which drugs are available for free provision for all, this should not preclude individual patients from picking up the tab for that drug if they so desire to do that with their money. There is a vital distinction (made by mens sans) between cost-effectiveness and effectiveness. The failure of NICE to recommend a new treatment, does not rule out the possibility that it could help a particular patient (For example, consider the use of Aricept for mild Alzheimers disease). It might, it might not – but where is the harm in letting them try if they pick up the cost?

Indeed, as you rightly conclude, many of the cancer drugs remain at the trial stage for clinical effectiveness for treatment of a specific cancer. They are are therefore, by their very nature, “unproven” in the sense of statistically significant results in a large sample. Nevertheless, a patient might wish to try a drug off-trial, if it has shown promising results in smaller samples. Once again, if they are willing to pay the cost of the drug, why not?

You might argue that the patient does not pay for any complications related to new drug use if we were to allow for co-payment of this sort, but the NHS covers the side-effects of more pernicious lifestyle choices such as smoking, drinking and illegal drug-use.

2)I am inclined to agree that if standard chemotherapy is required alongside the new drug in order to make it effective, then the patient should pay for their entire drug combination (IF they would not be having one without the other). My real concern is that everything will be withdrawn from the patient (correct me if I am wrong here). As far as I understand it, Cancer patients who try new drugs will have to pay for all their treatment thenceforth including doctor consultations, nurse care, blood tests, scans etc and for Cancer patients this is a considerable amount of care and by extension would not be cheap. For this to be the only factor which precludes an individual from trying to extend their life, and for it to be an active policy of the NHS seems cruel and inhumane.

A well drafted bill in parliament could put in place the necessary safeguards to stop the ‘creep’ of privatisation into the NHS, which so many of this issue’s opponents fear. If the bill stated unambiguously that patients can pay for a treatment regime (including associated chemo) if and only if their disease is refractory to all available NHS treatment modalities, then this would strictly rule out any shrinkage of the NHS for ailments which can be cured or effectively managed and treated. Indeed, if managed correctly it could serve as an opportunity to restate the importance of the NHS for the general population as a whole, but provide new treatment opportunities for patients with recalcitrant disease.

If these safeguards can be put in place, then such a move may provide hope for patients who have none. That is surely reason enough.

“…..only Jane should, in my view, get the full NHS care package, with the chemotherapy, free of charge while the others should pay for the chemo but not the ancillary care component because it would be unethical for the NHS to provide the chemotherapy element as this would amount to aiding and abetting patients in their efforts to obtain unlicensed, unproven treatments”.

Thanks for clearing up the confusion by explaining your position fully. From your statement quoted, we now agree that patients paying for additional treatment should not be forced to pay for (standard) NHS treatment. Funny there was that confusion, as that was exactly my point. I must have not have made myself clear enough!

1. The Press often do not tell the whole story – especially human interest stories.
2. Cetuximab and Bevacizumab limited effectiveness in a small (as yet poorly characterised) group of people.
3. Despite this there are patients who are willing to clutch at straws (and doctors who will encourage them).
4. NICE has reasonably decided that the economic cost of subsidising these treatments is not justified.
5. Hospitals / the NHS are not willing to subsidise (even in part) the cost of these treatments, and as a disincentive is not willing to provide any subsidised services for patients who pay privately for these treatments.
6. The reason for this disincentive is the policy that NHS health care is free, and that a most excellent series of committees have decided what is statistically best for all patients and is implementing this without exception. If you or your doctor disagree then you must go fully private.
7. Doctors for reform thinks that point number 6 is Bunkum (they might be right, they might be wrong).
8. Doctors for Reform and its steering committee members have not fully disclosed their political or non-clinical interests in this issue
9. Doctors for Reform members have deliberately used DfR to push for a change in the principles of the NHS which is commercially advantageous to them, without full disclosure.
5. You disagree with DfR’s position on co-payments, and the concept of a safety net with a larger private insurance system, as well as their lack of disclosure.

Is that a fair summary of what you are trying to say?

wrt your other comments.

Cetuximab is an antibody to the EGF receptor. This receptor is “overexpressed” in a high proportion of colorectal cancer cases. The drug is licensed for use “in colorectal cancers expressing the EGFR” ie in whom it can be detected by testing their tumours. The drug works-no question. Although as stated above for avastin, only in a small minority of cases. HOWEVER, research has shown that the expression of the receptor is not necessary for the drug to be effective. In fact I think this says more about the diagnostic test than the drug. If I haven’t bored you sufficiently then I could tell you that there is a test for a protein called KRAS which if abnormal does predict non-response (but not response) to cetuximab. This fact supports the biological hypothesis for the mode of action of cetuximab through inhibiting the EGF pathway as KRAS is “downstream” of the EGFR

NICE does not dispute the effectiveness, only the cost-effectiveness. Cetuximab when combined with chemotherapy is approximately twice as effective as when used alone.

Avastin in breast cancer (and indeed all drugs in breast cancer) is another issue entirely. It is to my mind definitely the case that drugs for breast cancer are fast tracked for approval, and are often approved with limited evidence for efficacy. This is partly because J Hoffmann LaRoche is a very effective marketing and lobbying company, but also because of the power of the breast cancer lobby. No health secretary likes to be attacked by hordes of pink-ribbon wearing articulate middle class women (cf Mrs Hewitt and Herceptin).

Thus far The Times has highlight four specific cases in the course of its campaign.

Two of them, Collette Mills and Debbie Hirst wanted Avastin as a treatment for secondary cancer following breast cancer and at the time they wanted this Avastin was not licensed for that purpose either here or in the US.

It has since been licensed for that purpose in the US (April 2008) but only on appeal after it was initial turned down by the FDA’s panel on a 5-4 vote against and only because the lack of solid evidence for its clinical effectiveness in this context was pretty much disregarded.

The other two case, Jack Hose and Linda O’Boyle wanted cetuximab to treat colorectal cancer. Cetuximab is licensed for that purpose but, as yet, there is no sound clinical effectiveness data and its been found that the pre-treatment test that is used to identify suitable candidates is unreliably because the drug doesn’t function as expected.

The ONLY specific case where a patient is considering treatment for one of these drugs (Avastin) for a condition for which it is both licensed and has sufficient clinical effectiveness data to allow for properly informed to choice to made is that of Jane, which Mens Sana raised in comments.

Now in order to avail yourself of this treatment you need a care package that comes in what is effectively three parts.

There is the ancillary care which includes assessments, nursing care and palliative care. It’s not at all clear from anything in the press whether this is part of what the NHS is withdrawing if people go private but if it is then they shouldn’t be doing it in my view.

There is, of course, the Avastin or cetuximab, which the NHS doesn’t provide because its not cost-effective and because, depending on type of cancer were dealing with the drugs may still be at the trial stage for clinical effectiveness.

And then there’s the course of chemotherapy that needs to be administered along with the Avastin/cetuximab in order to get the full benefit of the drug.

Now that is the component that the NHS is, in my view, quite justified in withdrawing from patients if they wish to use unlicensed and/or unproven treatments, which is the case for Mills, Hirst, Hose and O’Boyle but not the case for ‘Jane’.

So even if the system did allow for co-payments, only Jane should, in my view, get the full NHS care package, with the chemotherapy, free of charge while the others should pay for the chemo but not the ancillary care component because it would be unethical for the NHS to provide the chemotherapy element as this would amount to aiding and abetting patients in their efforts to obtain unlicensed, unproven treatments.

Money is not the issue here, for me, behaving ethically and taking reasonable measures at least try to protect vulnerable individuals from exploitation is.

Does that sort out the confusion?

“Not to mention that giving patients the information necessary to make an informed choice is not an option but a matter of professional ethics.”

Yes. Agreed…..And? What does that have to do with forcing a patient to pay for all of their treatment if they to pay for something extra? I do not understand how a matter of professional ethics adds up to forcing a patient to pay for all of their NHS treatment if they want to pay extra for additional treatment.

“What it has to do with the NHS withdrawing certain treatments is that it would be unethical for the NHS to act in a manner which facilitated access to an unlicensed and/or unproven treatment using taxpayers money.”

Who was taking about using taxpayers money? Look through the previous comments. No-one is talking about trying to get the NHS to pay for dubious, unlicensed or ineffective treatment. It is about withdrawing NHS treatment because someone what to pay for an additional treatment using THEIR OWN MONEY.

I can only repeat it again to make it crystal clear. The discussion is not about funding dubious, unlicensed or ineffective treatment through the NHS or forcing Doctors to go against their professional ethics. It is about forcing a patient to pay for their NHS treatment if they want to pay extra for additional treatment with THEIR OWN MONEY. I really do not understand why there is confusion on this point.

Not to mention that giving patients the information necessary to make an informed choice is not an option but a matter of professional ethics.

What it has to do with the NHS withdrawing certain treatments is that it would be unethical for the NHS to act in a manner which facilitated access to an unlicensed and/or unproven treatment using taxpayers money.

Why? What does that have to do with the NHS withdrawing treatment. An imformed choice is obviously a good thing, and the more informed the better (how could it be otherwise?), but, again, what does that have to do with the patients choice. If a patient chooses to try to cure their condition by buying a treatment using light crystals infused with moonbeams harminised with the lifegiving energy from nature, that is their choice. Just because informed, expert (or even sane) opinion is that a particular treatment does not work, why is that a logical argument for making the patient pay for all of their treatment

Very few bloggers would the time to provide the context of a quote: thanks again.

Provide, of course, that they’re in a position to make an informed choice, which is not the case when it comes to the use of Avastin for breast cancer or with cetuximab due to the problems that have emerged over testing for EGFR.

‘It might not be effective’. So what – its not your money. If someone want to spend their last £10,000 on the hope that it will lengthen their lives by 4 months, it is their choice, not yours.

‘It might lengthen the patients life and cost the NHS more’. Well – Duh. Isn’t lengthening the patients life the point?
‘It might not be effective’. So what – its not your money. If someone want to spend their last £10,000 to lengthen their lives by 4 months, it is their choice, not yours.
‘If they can afford additional treatment, they can afford standard treatment’. A good argument for the NHS not treating anyone with any savings (including you!).
‘It will create a two tier NHS’. Yes those who have worked and saved enough to afford additional treatment, and those who havn’t. Why should the first be disadvantaged because of the second?

In summary, nothing in any of the patient examples, the drug’s effectivness, or the background to some medical group spells out a reasoned argument as to why a patient should not be allowed to pay for additional treatment. 0/10 for answering the exam question.

If ever a comment deserved a response then your does…

As I’ve already noted I think you patient’s situation is qualitatively different from those that The Times has been featuring. Avastin is licensed for use as a treatment for colorectal cancer and as I’m assuming here that their test results show them to have a form of cancer that would respond to the treatment and that you’ve given them the full rundown in terms of costs, possible benefits and chances of success/failure then your patient is in a position to make an informed decision about whether or not to take the option.

In that situation, were I her doctor, I would be going in to bat for her and doing everything I can to help her gain access to the treatment if that is genuine what she wishes.

So far as priorities go, survival is number one, so she should take what the NHS has to offer regardless of whether she intends to push the issue on Avastin. If I’m reading the guidance correctly then, in clinical terms, accepting the NHS package at this stage does not rule out having another go with Avastin a bit further down the line although, depending on how her condition progresses, delaying the Avastin treatment might have some effect on her quality of life.

The number two priority would be to get her into a cancer support group and make damn sure that no matter what else happens she has a chance to make the most of the time she has left.

After that’s sorted, then it time to look at what might be done to challenge the co-payments issue and or bring the cost of treatment down to a more affordable level, which means a two-pronged attack.

One strand would be to get on to the relevant NHS trust and appeal the policy on grounds of exceptional circumstances. All trusts will have noted the adverse publicity these issues generate and yours may not be for the fight and minded to exercise a bit of discretion on the budgets provided its all done quietly and without getting the press involved.

I would also follow what some doctors have done in the US and make a bit a noise about the cost of this treatment and pose a question or two about whether it can be justified. In my experience, there’s as much of a good story in a tale of Big Pharma screwing the little guy as there is the government doing the same thing and they can be just as sensitive about the effect of bad press on their share price as politicos can be about the effect they might get at the ballot box.

I’d also suggest that she cast around for a lawyer who might take on her case on a pro bono basis but I would not advise her to join in any litigation taken forward by Doctors for Reform if that is going to be based on cases in which the drug that being sought isn’t yet fully licensed or evaluated. She has a better case for Avastin being licensed and evaluated for her condition than any of the others that The Times have raised and, I think, quite a strong argument as the courts generally do not like arbitrary decisions.

That said, anyone who thinks that a judicial review will actually force the NHS to accept co-payments doesn’t understand how judicial reviews work as the most anyone will get is a ruling that sets aside the use of a blanket policy in favour of requiring NHS trusts to consider co-payments on a case-by-case basis, in which case the trust is still in a position to consider each case on its merits and then turn it down anyway.

Best case scenario for most people would, I suspect, be a ruling that the NHS cannot withdraw or ask for payment for ancillary/palliative care but whether a court would rule it must provide the chemotherapy that runs in conjunction with Avastin is another matter entirely and one I couldn’t call at this time.

What the developers believe[d] is that cetuximab works by binding to the extracellular domain of cells which express EGFR (epidermal growth factor receptor).

Now my ‘thing’ is neurobiology and not immunology, so while I can follow some of this I may be a little shaky on the fine detail, but as far as I can make out EGFR is a biochemical receptor that cells produce naturally anyway, but in cancer cells the production mechanism goes into overdrive and produces it in excessive quantities. This causes the body to produce antibodies in response to the oversupply of EGFR.

As such the test regime is analogous to that used in, say, testing for HIV, where you cannot test directly for the presence of the virus, because its too small to find, so what you test for is the presence of antibodies that the body generate to try to counter the virus, test being large enough to spot.

The test is not for EGFR itself but for the level of naturally produced EGFR antibodies, from which it can be determined as to whether or not the cancer that patient had is of a type suitable for treatment using cetuximab. If levels of EGFR antibodies are abnormally high then you have a winner and can move on to the next stage and start the treatment.

This is all well and good if the drug works exactly as expected, but what NICE appear to be indicating is that it doesn’t and that what it interacts with is not the EGFR receptors that the developer expected but some other relevant biochemical receptor. This doesn’t necessarily mean the drug is useless but it does mean that testing for EGFR antibodies ceases to be reliable means of identifying whether the drug is likely to prove to be effective for a particular individual.

The drafting of the committee may seem opaque but, to be honest, I suspect that that’s much more a function of the complexity of immunology than any fault on the part of the committee.

It may not quite fit in with your notion of what constitutes the clinical hierarchy of complexity, but compared to the immune system the biochemistry of the brain is relatively straightforward.

My point on the antibody / antigen (target) confusion, and it may be a pedantic on, was that it destroys a lot of confidence in the author: ..”the antibody identified via EGFR testing is different to the one tageted by cetuximab.” makes very little sense given that cetuximab is the antibody (cetuxim(onoclonal)a(nti)b(ody) and EGFR is the target (antigen) to which the antibody binds thereby (in theory…) having its effect. The drafting in the committee quote is quite opaque but that is my interpretation of what they have written. If that’s the case, I am not sure how much faith I have in their assertions in the rather more complex area of assessing the efficacy of a therapy, lack of or otherwise.

You are spot on regarding the co-payment issue: I am slightly bewildered that this is the case and, if it is, I would like to understand why it is the case.

My reading of what NICE has to say on cetuximab is that its been found that the drug doesn’t work in quite the manner that its developers predicted – its doing something but not in quite the manner that the company behind it thought it would.

The upshot is, as I read it, that while this doesn’t appear adversely alter the data on the performance of the drug when it works, what it does do is render the test, which the company thought would help identify whether a particular patient is likely to benefit from the drug, largely useless.

The co-payment issue is one I’ve picked up on in a follow-up post but the short version of my position is that I would have no problem with allowing co-payments on a case by case basis for drugs that are licensed for the purpose for which the individual patient is seeking them and where there is sufficient evidence from clinical effectiveness trials to give the patient an honest appraisal of what they might be able to expect in return for their money.

What I would not support is co-payments made in such a way as to facilitate access to unlicensed and/unproven treatments where there is insufficient evidence on clinical effectiveness to permit a patient to make an informed choice, which seems to be the case in all the cases highlighted by The Times but not the case in the example that Mens Sana cites a couple of comments back.

“…an apparently new phenomenon…”

- You (and, more worryingly, the NICE committee) appear to have confused antibody (the drug) with antigen (the target ie EGF) throughout. Please correct me if I am mistaken.
- You article concentrates more on QALYs, where the principles are of logic and effectiveness of therapies and have been debated to death, than on the issues around co-payment, an apparently phenomenon which I struggle to comprehend.

I think I can speak for most visitors to this blog when I say that it is one of the most useful sites you are ever likely to come across, regardless of whether you happen to agree with the final political conclusion the author reaches. (I’m with Tom & co on this one, and no, I don’t always agree with the author; he’s far too statist for my tastes.)

However, if you actually want to know what is going on, what stories mean and how much weight to attach to them, you can either spend weeks doing research and analysis – not forgetting a good academic substrate of statistics and formal subjects such as law and computing – or you can check in here and find it is done for free and translated in to English, no subscription necessary.

If you don’t know a bargain when you see one, you are the loser.