Bad Science

Another good measure is what happens when things go wrong. The British Medical Journal is probably the most important medical journal in the UK. It recently announced the three most popular papers from its archive for 2005, according to an audit that assessed their use by readers, the number of times they were referenced by other academic papers, and so on. Each of these papers had a criticism of either a drug, a drug company or a medical activity as its central theme.

We can go through them briefly, so you can see for yourself how relevant the biggest papers from the most important medical journal are to your needs. The top-scoring paper was a case-control study which showed that patients had a higher risk of heart attack if they were taking the drugs rofecoxib (Vioxx), diclofenac or ibuprofen. At number two was a large meta-analysis of drug company data, which showed no evidence that SSRI antidepressants increase the risk of suicide, but found weak evidence for an increased risk of deliberate self-harm. In third place was a systematic review which showed an association between suicide attempts and the use of SSRIs, and critically highlighted some of the inadequacies around the reporting of suicides in clinical trials.

This is critical self-appraisal, and it is very healthy, but you will notice something else: all of those studies revolve around situations where drug companies withheld or distorted evidence. How does this happen?

The pharmaceutical industry

The tricks of the trade which we’ll discuss in this chapter are probably more complicated than most of the other stuff in the book, because we will be making technical critiques of an industry’s professional literature. Drug companies thankfully don’t advertise direct to the public in the UK – in America you can find them advertising anxiety pills for your dog – so we are pulling apart the tricks they play on doctors, an audience which is in a slightly better position to call their bluff. This means that we’ll first have to explain some background about how a drug comes to market. This is stuff that you will be taught at school when I become president of the one world government.

Understanding this process is important for one very clear reason. It seems to me that a lot of the stranger ideas people have about medicine derive from an emotional struggle with the very notion of a pharmaceutical industry. Whatever our political leanings, everyone is basically a socialist when it comes to healthcare: we all feel nervous about profit taking any role in the caring professions, but that feeling has nowhere to go. Big pharma is evil: I would agree with that premise. But because people don’t understand exactly how big pharma is evil, their anger and indignation get diverted away from valid criticisms – its role in distorting data, for example, or withholding lifesaving AIDS drugs from the developing world – and channelled into infantile fantasies. ‘Big pharma is evil,’ goes the line of reasoning, ‘therefore homeopathy works and the MMR vaccine causes autism.’ This is probably not helpful.

In the UK, the pharmaceutical industry has become the third most profitable activity after finance and – a surprise if you live here – tourism. We spend ?7 billion a year on pharmaceutical drugs, and 80 per cent of that goes on patented drugs, medicines which were released in the last ten years. Globally, the industry is worth around ?150 billion.

People come in many flavours, but all corporations have a duty to maximise their profits, and this often sits uncomfortably with the notion of caring for people. An extreme example comes with AIDS: as I mentioned in passing, drug companies explain that they cannot give AIDS drugs off licence to developing-world countries, because they need the money from sales for research and development. And yet, of the biggest US companies’ $200 billion sales, they spend only 14 per cent on R&D, compared to 31 per cent on marketing and administration.

The companies also set their prices in ways you might judge to be exploitative. Once your drug comes out, you have around ten years ‘on patent’, as the only person who is allowed to make it. Loratadine, produced by Schering-Plough, is an effective antihistamine drug that does not cause the unpleasant antihistamine side-effect of drowsiness. It was a unique treatment for a while, and highly in demand. Before the patent ran out, the price of the drug was raised thirteen times in just five years, increasing by over 50 per cent. Some might regard this as profiteering.

But the pharmaceutical industry is also currently in trouble. The golden age of medicine has creaked to a halt, as we have said, and the number of new drugs, or ‘new molecular entities’, being registered has dwindled from fifty a year in the 1990s to about twenty now. At the same time, the number of ‘me-too’ drugs has risen, making up to half of all new drugs.

Me-too drugs are an inevitable function of the market: they are rough copies of drugs that already exist, made by another company, but are different enough for a manufacturer to be able to claim their own patent. They take huge effort to produce, and need to be tested (on human participants, with all the attendant risks) and trialled and refined and marketed just like a new drug. Sometimes they offer modest benefits (a more convenient dosing regime, for example), but for all the hard work they involve, they don’t generally represent a significant breakthrough in human health. They are merely a breakthrough in making money. Where do all these drugs come from?

The journey of a drug

First of all, you need an idea for a drug. This can come from any number of places: a molecule in a plant; a receptor in the body that you think you can build a molecule to interface with; an old drug that you’ve tinkered with; and so on. This part of the story is extremely interesting, and I recommend doing a degree in it. When you think you have a molecule that might be a runner, you test it in animals, to see if it works for whatever you think it should do (and to see if it kills them, of course).

Then you do Phase I, or ‘first in man’, studies on a small number of brave, healthy young men who need money, firstly to see if it kills them, and also to measure basic things like how fast the drug is excreted from the body (this is the phase that went horribly wrong in the TGN1412 tests in 2006, where several young men were seriously injured). If this works, you move to a Phase II trial, in a couple of hundred people with the relevant illness, as a ‘proof of concept’, to work out the dose, and to get an idea if it is effective or not. A lot of drugs fail at this point, which is a shame, since this is no GCSE science project: bringing a drug to market costs around $500 million in total.

Then you do a Phase III trial, in hundreds or thousands of patients, randomised, blinded, comparing your drug against placebo or a comparable treatment, and collect much more data on efficacy and safety. You might need to do a few of these, and then you can apply for a licence to sell your drug. After it goes to market, you should be doing more trials, and other people will probably do trials and other studies on your drug too; and hopefully everyone will keep their eyes open for any previously unnoticed side-effects, ideally reporting them using the Yellow Card system (patients can use this too; in fact, please do. It’s at http://yellowcard.mhra.gov.uk).

Doctors make their rational decision on whether they want to prescribe a drug based on how good it has been shown to be in trials, how bad the side-effects are, and sometimes cost. Ideally they will get their information on efficacy from studies published in peer-reviewed academic journals, or from other material like textbooks and review articles which are themselves based on primary research like trials. At worst, they will rely on the lies of drug reps and word of mouth.

But drug trials are expensive, so an astonishing 90 per cent of clinical drug trials, and 70 per cent of trials reported in major medical journals, are conducted or commissioned by the pharmaceutical industry. A key feature of science is that findings should be replicated, but if only one organisation is doing the funding, then this feature is lost.

It is tempting to blame the drug companies – although it seems to me that nations and civic organisations are equally at fault here for not coughing up – but wherever you draw your own moral line, the upshot is that drug companies have a huge influence over what gets researched, how it is researched, how the results are reported, how they are analysed, and how they are interpreted.

Sometimes whole areas can be orphaned because of a lack of money, and corporate interest. Homeopaths and vitamin pill quacks would tell you that their pills are good examples of this phenomenon. That is a moral affront to the better examples. There are conditions which affect a small number of people, like Creutzfeldt-Jakob disease and Wilson disease, but more chilling are the diseases which are neglected because they are only found in the developing world, like Chagas disease (which threatens a quarter of Latin America) and trypanosomiasis (300,000 cases a year, but in Africa). The Global Forum for Health Research estimates that only 10 per cent of the world’s health burden receives 90 per cent of total biomedical research funding.