Bad Science (16 page)

Anthony Brink

The document was described by the Rath Foundation as “entirely valid and long overdue.”

This story isn’t about Matthias Rath, or Anthony Brink, or Zackie Achmat, or even South Africa. It is about the culture of how ideas work, and how that can break down. Doctors criticize other doctors; academics criticize academics; politicians criticize politicians. That’s normal and healthy; it’s how ideas improve. Matthias Rath is an alternative therapist, made in Europe. He is every bit the same as some of the operators that we have seen in this book. He is from their world.

Despite the extremes of this case, not one single alternative therapist or nutritionist, anywhere in the world, has stood up to criticize any single aspect of the activities of Matthias Rath and his colleagues. In fact, far from it; he continues to be feted to this day. I have sat in true astonishment and watched leading figures of the U.K.’s alternative therapy movement applaud Matthias Rath at a public lecture (I have it on video, just in case there’s any doubt). Homeopaths’ mailouts continue to promote his work. Not one person will step forward and dissent.

The alternative therapy movement as a whole has demonstrated itself to be so dangerously, systemically incapable of critical self-appraisal that it cannot step up even in a case like that of Rath; in that count I include tens of thousands of practitioners, writers, administrators, and more. This is how ideas go badly wrong. In the conclusion to this book, written before I was able to include this chapter, I will argue that the biggest dangers posed by the material we have covered are cultural and intellectual.

I may be mistaken.

So that was the alternative therapy industry. Its practitioners’ claims are made directly to the public, so they have greater cultural currency, and while they use the same tricks of the trade as the pharmaceutical industry, as we have seen along the way, their strategies and errors are more transparent, so they make for a neat teaching tool. Now, once again, we should raise our game.

For this chapter you will also have to rise above your own narcissism. We will not be talking about the fact that your doctor is sometimes rushed or rude to you. We will not be talking about the fact that nobody could work out what was wrong with your knee, and we will not even be discussing the time that someone misdiagnosed your grandfather’s cancer, and he suffered unnecessarily for months before a painful, bloody, undeserved, and undignified death at the end of a productive and loving life.

Terrible things happen in medicine, when it goes right as well as when it goes wrong. Everybody agrees that we should work to minimize the errors, everybody agrees that doctors are sometimes terrible; if the subject fascinates you, then I encourage you to buy one of the libraries’ worth of books on clinical governance. Doctors can be awful, and mistakes can be murderous, but the philosophy driving evidence based medicine is not. How well does it work? One thing you could measure is how much medical practice is evidence based. This is not easy. From the state of current knowledge, around 13 percent of all
treatments
have good evidence, and a further 21 percent are likely to be beneficial. This sounds low, but it seems the more common treatments tend to have a better evidence base. Another way of measuring is to look at how much medical
activity
is evidence based, taking consecutive patients, in a hospital outpatients’ clinic, for example, looking at their diagnosis, what treatments they were given, and then looking at whether those treatment decisions were based on evidence. These real-world studies give a more meaningful figure: lots were done in the 1990s, and it turns out, depending on specialty, that between 50 and 80 percent of all medical activity is “evidence based.” It’s still not great, and if you have any ideas on how to improve that, do please write about it. Another good measure is what happens when things go wrong. The
British Medical Journal
, to take an example, is one of the biggest medical journals in the world. 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 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 that 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 that 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 those studies revolve around situations in which drug companies withheld or distorted evidence. How does this happen?

The Pharmaceutical Industry

The tricks of the trade that 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. There is also, of course, a whole separate book to be written about the marketing techniques. In the United States and New Zealand (but nowhere else in the developed world) drug companies are allowed to advertise their pills directly to the public, often with bizarre results, including my own personal favorite, “Clomicalm tablets are the only medication approved for the treatment of separation anxiety in dogs.” The U.S. pharmaceutical industry’s annual spend on promotion is more than three billion dollars, and it works, increasing prescriptions and doctor visits.

But here we are pulling apart not the marketing but the distortions in the science, and the tricks they play on doctors, who are harder to bluff, as an audience. 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, 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 gets diverted away from valid criticisms—its role in distorting data, for example, or withholding lifesaving AIDS drugs from the developing world—and channeled 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 United States, the pharmaceutical industry has been one of the most profitable industries over the last twenty-five years. It only lost its first-place standing in 2003, and is currently in third place after Internet and communications companies. The country spent $227.5 billion a year on pharmaceutical drugs in 2009, and much of that goes on patented drugs, medicines that were released in the last ten years. Globally, the industry is worth more than $800 billion.

People come in many flavors, but all corporations have a duty to maximize 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 license to developing world countries, because they need the money from sales for research and development. And yet, of the biggest U.S. companies’ $200 billion sales, only 14 percent is spent on R & D, compared with 31 percent 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 percent. 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 its own patent. They take huge effort to produce and need to be tested (on human participants, with all the attendant risks) and trialed 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, first 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, when 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; bringing a drug to market costs around five hundred million dollars in total.

Then you do a Phase III trial, in hundreds or thousands of patients, randomized, 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 license 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 we hope everyone will keep their eyes open for any previously unnoticed side effects, ideally reporting them to their country’s drug regulator (anyone can report an adverse event to the FDA’s MedWatch system online).

Doctors make their rational decision on whether they want to prescribe a drug on the basis of 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 percent of clinical drug trials, and 70 percent 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 organization 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 organizations 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 analyzed, 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 that affect a small number of people, like Creutzfeldt-Jakob disease and Wilson’s disease, but more chilling are the diseases that are neglected because they are found only in the developing world, like Chagas’ disease (which threatens a quarter of Latin America) and trypanosomiasis (three hundred thousand cases a year, but in Africa). The Global Forum for Health Research estimates that only 10 percent of the world’s health burden receives 90 percent of total biomedical research funding.

Often it is simply information that is missing, rather than some amazing new molecule. Eclampsia, say, is estimated to cause fifty thousand deaths in pregnancy around the world each year, and the best treatment, by a huge margin, is cheap, unpatented magnesium sulfate (high doses intravenously, that is, not some alternative medicine supplement, but also not the expensive anticonvulsants that were used for many decades). Although magnesium had been used to treat eclampsia since 1906, its position as the best treatment was only established a century later in 2002, with the help of the World Health Organization, because there was no commercial interest in the research question; nobody has a patent on magnesium, and the majority of deaths from eclampsia are in the developing world. Millions of women have died of the condition since 1906, and many of those deaths were avoidable.

To an extent these are political and development issues, which we should leave for another day, and I have a promise to pay out on: you want to be able to take the skills you’ve learned about levels of evidence and distortions of research and understand how the pharmaceutical industry distorts data and pulls the wool over our eyes. How would we go about proving this? Overall, it’s true, drug company trials are much more likely to produce a positive outcome for their own drugs. But to leave it there would be weak-minded.

What I’m about to tell you is what I teach medical students and doctors—here and there—in a lecture I rather childishly call drug company bullshit. It is in turn what I was taught at medical school,
¹²
and I think the easiest way to understand the issue is to put yourself in the shoes of a big pharma researcher.

You have a pill. It’s OK, maybe not that brilliant, but a lot of money is riding on it. You need a positive result, but your audience aren’t homeopaths, journalists, or the public; they are doctors and academics, who have been trained in spotting the obvious tricks, like “no blinding,” or “inadequate randomization.” Your sleights of hand will have to be much more elegant, much more subtle, but every bit as powerful.

What can you do?

Well, first, you could study it in winners. Different people respond differently to drugs: old people on lots of medications are often no-hopers, whereas younger people with just one problem are more likely to show an improvement. So study your drug only in the latter group. This will make your research much less applicable to the actual people that doctors are prescribing for, but you hope won’t notice. This is so commonplace it is hardly worth giving an example.