NICE (the organisation that provides guidance to doctors in the UK) recently updated their recommendations regarding lower back pain. In the updated guidance, they say that exercise, in all its forms (for example, stretching, strengthening, aerobic or yoga), is the most important step in managing back pain. Previously, NICE also recommended acupuncture or massage, but this has now been altered. Massage can still be used alongside exercise, but the guidelines no longer recommend acupuncture, as "evidence shows it is not better than sham treatment".This is not entirely surprising as, despite widespread acceptance of acupuncture, the evidence that it works for any illness or disability is very scant (as I have described in a previous post). Most studies are poorly carried out, and many show no difference between it and sham acupuncture.Unfortunately, the authors of these studies often conclude that both acupuncture and sham acupuncture work, rather than the actual conclusion (that acupuncture doesn't work). If a medicine works no better than a sham medicine (a sugar pill for example), we cannot conclude that both the medicine and the sugar pill work.For those suffering from back pain, the new recommendations also encourages people to continue with normal activities as far as possible, and recommends that non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen or aspirin should be tried. Unfortunately, at present there is no evidence to back up other interventions.A recent study found that back pain caused more disability than any other condition, and is also responsible for 37% of all chronic pain in men and 44% in women. While it is understandable that people seek relief from their symptoms, it is obvious that the NHS can't fund a treatment that does not work.
The cost of a cancer breakthrough
A new combination of drugs marketed by Bristol-Meyer Squibb has been hailed as a breakthrough in cancer treatment. Almost every media outlet carried a story about the results of a trial that were announced at a conference in Chicago yesterday, with the usual hype. The results are quite remarkable. 58% of metastatic melanoma patients treated with this new drug combination saw their tumours shrink, with the tumours stable or shrinking for a median of 11.5 months. This is amazing when you consider that metastatic melanoma was thought to be largely incurable as recently as 5 years ago. The drugs are each a form of immunotherapy. This refers to a therapy that works by making the patient’s own immune system attack the tumour. In this case, the combination targets two separate mechanisms tumours use to avoid the immune system. Firstly, one drug (Ipilimumab) targets CTLA-4, which is made by the tumour to suppress the immune system. The second drug (nivolumab) targets a protein called PD-1, which prevents the immune system from killing the tumour cells, even if it does recognise them as bad.This is quite a significant breakthrough in the treatment of melanoma but it does come at a cost however. The treatment has significant side effects, with over 80% of patients experiencing these. Furthermore, 55% experienced severe side effects, and 36% of patients had to stop treatment as a result.There is also the issue of cost, a problem I have discussed in a previous blog. Ipilimumab has already been approved by NICE at a cost of at least £42,200 per QALY. Nivolumab hasn’t yet been appraised by NICE, so it’s cost per QALY isn’t available, but in the US it is slightly more expensive than Ipilmumab, costing roughly $150,000 dollars per patient per year. As a combination, it is estimated that it will cost patients in the US $295,000 per year. This may well prove a stumbling block for an already creaking NHS. However, as both Merck and Roche have their own versions of these drugs, the hope is that the competition will force the manufacturers to drop their prices. Whether they will or not remains to be seen.Unfortunately, this breakthrough isn’t the cure that some articles say it is. Between cost and side-effects, there will be problems prescribing it to many patients. It is a welcome advance however, and does herald the development of immunotherapy as another arm in our treatment of cancer.Edit (03/06/05): The $295,000 figure comes from adding the list price of the two drugs. Some outlets are reporting that a discount may be applied to that, making the drug considerably cheaper, potentially bringing it closer to $200,000 per patient per year. While this is a significant discount, $200,000 per patient per year is still a staggering cost. To put it in perspective, if every patient with late stage melanoma was given this drug, Bristol-Meyer Squibb would make over $2,000,000,000 per year from it. When you consider that this is from only the late stage patients, with only one type of cancer, you can see why some people have a problem with the pricing of this and other drugs.
Why are some drugs not provided on the NHS?
The decision not to provide a drug on the NHS can have a devastating impact on patients and their families, and often causes a negative public reaction. However, therapies are getting increasingly expensive (particularly cancer therapies) and NHS has a very limited budget. As a result, in spite of the impact on patients and public opinion, 36% of cancer drugs evaluated since the start of 2014 (see pie chart) have been rejected, usually on the basis of cost.Whether a drug is made available or not on the NHS is decided by the National Institute for Health and Care Excellence (NICE). This is an independent body that looks at the efficacy and cost-effectiveness of any new therapies, and makes recommendations based on their findings. In Scotland, there is a separate organisation (the Scottish Medicines Consortium) that makes the decision.The main metric that NICE uses to make these decisions is the Quality Adjusted Life Year (QALY). This takes into account the quantity AND quality of extra life given to the patient by a particular chemotherapy. So if a drug gives a patient an extra year of perfect health, it is given a QALY of 1.0. If the extra year is not in full health, it is given a value below 1 to account for this. For example, if a new treatment allows a patient to live for 2 additional years compared to the old treatment, but only with a quality of life weight of 0.6 (perhaps the patient is in severe pain as a result), then the treatment gives 2 * 0.6 = 1.2 QALYs to the patient.NICE has set guidelines on how much it can pay per QALY gained. That price is around £30,000, but can rise to £50,000 in some rare circumstances. Now compare that figure with the table below showing NICE recommendations on cancer drugs since the start of last year, and you can begin to see why it has had problems with some cancer therapies, with many drugs estimated to cost over the £30,000 threshold.
| Drug | Recommendation | Cost per QALY* | |
| Pixantrone | Optimised¶ | £22,000 | Link |
| Aflibercept1 | Not Recommended | £44,000 | Link |
| Pemetrexed | Not Recommended | £74,500 | Link |
| Afatinib | Recommended | £11,000 | Link |
| Bortezomib2 | Recommended | £17,800 – £39,600 | Link |
| Enzalutamide | Recommended | £22,600 | Link |
| Ipilimumab | Recommended | £28,600 | Link |
| Dabrafenib | Recommended | £11,000 | Link |
| Imatinib | Recommended | £16,700 - £30,000 | Link |
| Sipuleucel-T | Not Recommended | £48,700 - £512,000 | Link |
| Axitinib | Recommended | £33,500 | Link |
| Pomalidomide3 | Not Recommended | £50,000 - £70,000 | Link |
*depending on treatment ¶Recommended for a smaller group than applied for 1Aflibercept in combination with irinotecan and fluorouracil-based therapy 2Bortezomib in combination with dexamethasone, or with dexamethasone and thalidomide 3Pomalidomide in combination with dexamethasoneThis problem has been partially addressed by the creation in 2010 of the Cancer Drugs Fund, which provides funding for treatments that NICE haven’t judged on yet, or has deemed too expensive. This fund is due to finish in March 2016, but for the time being it provides an additional £340 million per year to pay for cancer drugs. The UK government have yet to comment on the long-term prospects of this fund.It must also be pointed out that this is not a problem with cancer drugs specifically. Many other diseases are facing the same problems. The cystic fibrosis drug Ivacaftor, for example, has had the same issues after it was priced as one of the world’s most expensive medicines (between £335,000 and £1,274,000 per QALY). Despite the cost, this drug is being used for a small number of patients in the UK. There was an extremely good article about the ethical concerns the over pricing of this drug in the British Medical Journal last year that I would encourage everyone to read it (available here for those with access, and by e-mailing us via the contact page on this site for those without).This all brings up another issue: are pharmaceutical companies over-charging for their treatments? According to a 2014 report, the cost of developing a new drug is now $2.6 billion (£1.7 billion), and takes over 10 years. The pharmaceutical companies argue that they have to make their drugs expensive in order to recoup their costs, and this is a valid point. This statement is slightly dented however, by the fact that the industry spends more on marketing than on research, a point well made by John Oliver in his show Last Week Tonight (below). Add to this the fact that the pharmaceutical industry makes a higher profit margin than any other industry, and the pricing of these drugs begins to look unreasonable. This issue is beyond the scope of this blog but you can find more information in this excellent BBC article.It is said that we are beginning the era of “personalised medicine”. Each person will receive a specific treatment for their cancer depending on the genetics of their disease. While this will mean more effective treatment of the disease, it also means that fewer patients will be getting any one drug. Cancer drugs will be used on smaller and smaller subgroups of people, which is likely to increase their price, as the cost of drug development is unlikely to drop. This raises difficult questions for an already struggling NHS. In a time of increasing drug prices and increasing cancer incidence, the challenge of funding these therapies will be a pressing issue for years to come.
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