Cancer: the problem.

I read an interesting blog recently entitled “The War on Cancer” (http://sten.astronomycafe.net/the-war-on-cancer/). Apparently, in the US a little under 600,000 people die of it each year. The author, Dr Sten Odenwald, then set out to illustrate that funding for cancer research is far too low. I think it was President Nixon who coined the phrase, “war on cancer”, and set it as an objective, in the same way Kennedy had set the Moon landing as an objective, but this was doomed to fail, at least in the spectacular way. The reason is the nature of cancer, which, as an aside, is not one disease. We have been trying to cure this for a very long time, but with mixed results. Gaius Plinius Secundus recommended a poultice of broccoli for breast cancer, and asserted it works. There are indeed agents in broccoli that will deal with some breast cancers, but by no means all, and even then, the cancer would need to be near the surface. There are at least twenty different types of breast cancer. Drugs like tamoxifen stop the growth of at least one type, monoclonal antibodies help in some others. So we have made some progress, but there are still severe problems, especially if the tumour metastasizes (dislodges cells to other parts of the body).

It is the nature of cancer that is the problem. Cells grow around nucleic acid, and nucleic acids reproduce by base pairing, then splitting, each strand now being the frame for the production of more nucleic acid. Thus after splitting, when a new double helix is finished being assembled, the amount of nucleic acid has doubled, so a new pair of cells is possible, the old cell having been destroyed. So what can go wrong? You will usually read that copying is not correct, or something is added to the double helix, but I don’t believe that. It is the peculiar nature of the hydrogen bonding that either the correct nucleic acid goes onto the growing strand or nothing does. That is why reproduction is so accurate. In the double helix, the reactive sites are protected, as they are in the interior of the helix, and the outside is the phosphate. A further substitution on the phosphate to make a tri-ester would be a nuisance, but it would not be very stable, and it would repair itself. Further, it would require a highly reactive reagent to do this, as it is exceedingly difficult to make phosphate esters in cold water other than through enzymatic catalysis. No, I think the problem probably arises during the splitting stage when the reactive sites become exposed. If something happens to the nitrogen functions, then that will block the formation of the next double helix at that point.

At that stage, the body will attack the nucleic acid at that point, and the next usual outcome will be that the various parts of the strand will be degraded, and the bits reused or excreted. But if the problem occurred in certain places, it may be that what is left can start reproducing. If that happens you have something growing that has no function for you, BUT it looks like it is part of your body, because up to a point it is. The growth just keeps growing, and reproducing itself. The reason there are so many different cancers is there are so many places where a nucleic acid could go wrong, and each different place that can reproduce will lead to a growth that is slightly different from any others. Because it looks like part of your body, your natural defences ignore it.

So far, we have largely relied on surgery, radiation or drugs. So, how is progress? In some cases, such as leukemia, progress is good, and it is often curable. In other cases, life can be extended, but according to Wikipedia, since Nixon declared war on cancer, the US alone has spent $200 billion on research. Between 1950 and 2005, the death rate, adjusted for population size and age has declined by five per cent. On the other hand, while in remission many patients have had life extended.

However, we should ask, are we doing anything wrong? I think we are, and one problem relates to intellectual property rights. Here is an example of what I mean. In the 1980s I was involved in a project to extract an active material from a marine sponge. My company developed some scale-up technology and made a few grams of this material, which, from reports I received, if the odd microgram was introduced to a solid tumour, the tumour blistered and died, leaving a well-repaired skin outside wherever the organ was. This property was limited to studies on rats, probably with external carcinoma. Anyway, the company that hired us ran into difficulty with its source of funds and went bankrupt, however, somehow ownership of the intellectual property lived on. At the time, there was no known technique of introducing a material as reactive as this to internal tumours, nor did we know whether that would even be beneficial. Essentially, the project was in an early stage, and maybe the material would not be beneficial. Who knows? The problem is, now we don’t know and nobody is likely to work further because the patents have expired. Any company working on that will have all the expense, and then somebody else can come in and take the benefits. In my opinion, this is not a desirable outcome. We should not have a situation where promising knowledge simply gets lost because of formal procedure.

Equally, we should not have the situation where drugs become ridiculously expensive. Why should the unfortunates who get a rather rare cancer have to pay the huge prices of drug companies? I am not saying drug companies should not get a fair return, but I think society should pay for this. Think of it as compulsory insurance. The alternative is a family might have to decide whether to bankrupt themselves, kill the grandchildren’s education prospects to buy a year or so for grandmother, or whether to just let her die. What sort of society is it that allows this?

Cancer is one of those diseases that everybody comes into contact with one way or another. In my case, my father died of pancreatic cancer, and I am a widower because of cancer. Yes, these things happen, but isn’t it in everybody’s interest to try and do what we can to at least minimize the harsh effects?

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Are drug prices fair?

Recently in the Huffington Post, Allen Frances wrote a blog asking, “Why are most cancer drugs so expensive and so ineffective?” The link is below for those interested.
(http://www.huffingtonpost.com/allen-frances/why-are-most-cancer-drugs_b_8294392.html?utm_hp_ref=science&ir=Science )
That is most certainly a good question. A summary of his points includes that the pharmaceutical industry is essentially a monopoly, in that only one company will make any given patented product. In the US, it exerts far too much political pressure, and as an example, he claimed Congress denied the Medicare program the right to negotiate drug prices. He claims there is a price monopoly, for even when generic drugs can be made, the pharmaceutical companies buy up the companies. He claims patent lives are extended with phoney variations. But in my mind, even worse, drug companies test their own products, but do not have to release the data for analysis by neutral observers. The companies hype the benefits and minimize disclosure of any risks.

He then cites some data from a Dr Prasad. Some of his findings include, the price of Gleevac rose from $30,000 in 2001 to $70,000 today, despite the fact the cost to make it is $200 (for a year’s course). However, at least Gleevac actually works. According to Dr Prasad, the median improvement in survival for 71 drugs for solid tumours produced in the last decade is 2.1 months. That may well be an overestimate because only 36% of those over 65 yrs old were in the trial, but that age group represents 60% of the patients in the wider community. Another interesting question is, given that many of these drugs have very severe consequences to the patient, is that 2.1 months worth it?

So, how do the companies do? Seemingly, remarkably well, with returns of between 10 – 42%. I saw a recent article that stated one product that had been sold for $20 per prescription had it raised to $1,000. When asked why, a spokesman said they wanted to make more money. Well, yes, I suppose they do. Don’t we all? The products are grossly overpriced, and only too often it appears they don’t really work all that well. There is the argument that research costs a lot. Yes, it does, but despite this, these companies are hugely profitable. In my view, this is simply price gouging, and it shows the ugly side of capitalism. A further interesting question would be, how much tax do they pay on these profits? Given that some large companies pay very little, one suspects the answer is, not much.

Usually, economic theory works on the basis that if there is a bad product, people will not buy it. However, with cancer drugs, that theory goes out the window. The average person has no hope whatsoever of deciding whether the product is any good, and you find out it is not when you die, or come close to it. Earlier this year, my wife died of cancer, so I know the pressure on the relations. Who can tell someone dying that product B is a waste of money, and it will bring penury to the remaining family members? And no, this situation did not arise for me. Claire was diagnosed in November, some simple treatment was provided as a holding measure while various things were done, and proper treatment was to start after Christmas. As it happened, her funeral was on the day scheduled for the start of treatment. Nevertheless, when someone you love is dying, you cannot really think rationally. There is a temptation to grasp at straws, but think what the grasping is like if you hear promising things from the drug companies? The very least we could ask for is a fair and open discussion of the prospects, and the basis for saying that. And we should expect that where there is little to substantiate the claims, at the very least the straw to be grasped should involve only reasonable expenses. Price gouging for performance is, in my view, not justifiable, but price gouging for what may be little better than snake oil is in my view criminal.

Excessive pharmaceutical costs.

A recent item in a local newspaper on the price of pharmaceuticals caught my attention. The question is, are the drug companies price gouging? Thus in the 1960s, Thalidomide was sold as an “over the counter” drug as a sedative, and to help with morning sickness, so that was relatively cheap. It got into trouble, however, because there were birth deformities associated with its use. Notwithstanding that, it has had a resurgence and is of value for certain form of blood cancer, and prolongs life by a few months to a year. In New Zealand, however, and using $NZ, in 2002, a month’s course cost $360 (or so the news item quoted). Now we expect a higher price when a drug has only a specialist use, and there has to be allowance for inflation, but this seems grossly excessive.

However, there is worse. Lenalidomide is a very similar drug (for those with any chemical knowledge the phthalic anhydride part that is converted to a substituted imide is replaced by phthalide, with the equivalent substitution, except the substitution is to the amide rather than the imide). Now phthalic anhydride is extremely cheap, phthalide not seriously more expensive, and the more difficult part, the substitution, is the same. Lenalidomide apparently costs $8350 per month, while Wikipedia quotes it as $US163,000 per annum per patient. What justifies this price? More to the point, what justifies and annual difference of over $US 80,000 between two countries? Now, all prices here are list prices, and apparently negotiation can often lower this, but the point remains. Further, studies have shown no significant benefit in survival rates between these two. There is another drug that does the same job: bortezomib, which costs a little under $10,000 per month, and while its starting materials are arguably a little more expensive, they are not that much more.

According to the World Health Organization, over half the expenditure on health is on medicines. Here is another example. There is a drug called Sovaldi, which treats Hepatitis C with about a 90% success rate. Note that patients can survive with the disease for decades, but eventually they have a high probability of liver failure of one sort or another. The prices for a twelve-week course are of interest. In New Zealand, the cost was quoted in this article as $NZ 239,000 (~ $US 180,000). According to Wikipedia, the cost in the US is $84,000, in the UK about 2/3 of that, in Germany, about $US 46,000, and in India, $US 300. Now, these are listed prices, there are probably discounts around, but persuade me this is not price gouging. The company is getting what it thinks it can get from each country. One can argue for charity for India, but the other countries have prices depending on who knows what, other than greed?

The issue for me is the effect of this corporate greed on families of those affected. Thus if we look at this Solvadi, in New Zealand it would cost 1 billion dollars more than the total annual health spending to treat all those with the virus. It is simply not practical to send that sort of money on one subset of patients, yet by not treating them, do they die of liver cancer at some later date? In fairness, there are alternative treatments, and I have no idea what the real situation is. However, I understand the problems. My wife recently died of metastatic cancer, and as it happened, she died before the oncologists could sort out what, if anything, to do. But what would I have felt had I been left with an option that would require all my money to buy a few months more life for my wife? That is a terrible situation for both to be in. The patient will probably not want to beggar the survivors, while the spouse does not want to not take every chance for more life for the patient.

You will hear various justifications for such expense, such as the need to develop new drugs. This is true, up to a point, but if the drug companies can just charge what they like later, there is not much incentive to be efficient, is there? There is also the issue of the cost of getting approvals. Yes, this is expensive, but persuade me it is not in the interests of the drug companies to make this as expensive as possible. The point is, they can price what they like, and the higher the costs, the easier it is to keep upstart competition at bay.

The issue for me is simple. The provision of best medicine is a public good. There is an element of pure luck whether someone suffers cancer, and whether it is aggressive or not. Certainly you can help yourself by not smoking, and by taking care in the sun, but there is no guarantee, and the same goes for many other diseases. So the question then is, should your future, if you are unlucky, depend on the loading of your wallet? Would it not be better for the state to at least keep some check on the approvals process, and remove waste? What do you think?