Introduction

work in the pharmaceutical industry. Sort of. Actually, I'm an academic researcher who works for a nonprofit research institute that wants to be a pharmaceutical company. So my soul is not owned, technically (yet) by Big Pharma. But I am sympathetic to it, and I have always been curious about why so many people hate them with such intensity. Are these people just left-wing Luddites, or are they ignorant anti-capitalists, so common these days, who think that making a profit is evil? Or am I really a minion of Satan?

To find out, I bought a copy of Bad Pharma, the latest in a long series of pharma-bashing books. In this book, a guy named Ben Goldacre makes the typical accusations that we've all seen: the industry is “greedy” because they don't give their products away at cost. They bias their research to push dangerous drugs onto the marketplace, knowing they are unsafe, but they don't care because they're corrupt and only interested in making money. Regulators are too lenient because they're all in bed with industry. Goldacre calls it “a murderous disaster.” The goal of this book, according to the author, is to make you angry. It worked for me. But maybe not in the way the author intended.

My conclusion after reading his book is that this author doesn't understand the pharmaceutical industry. This book is a masterpiece of manufactured outrage. There are many problems in industry these days, and that goes for pharma as well. But falsifying the results of their clinical trials, even if it sometimes happens (and I'm still not convinced) isn't one of them. Maybe this guy means well, and maybe he even thinks he's doing a public service. But what he says about big pharma, based on my personal experience with them, is inaccurate, dangerous, and destructive.

What really happens in a pharmaceutical company?

“The bar is very low,” says Goldacre, when it comes to getting a drug on the market. That's what we minions of Satan call spit-take material. I'm not going to bother to go through every misleading statement in this book. Here's just one example, from page xiv:

“...drugs must only prove they are better than nothing, even when there are highly effective treatments on the market already. This means that real patients are given dummy placebo pills for no good reason, but also that drugs appear on the market which are worse than the treatments we already have.”

Every sentence in that paragraph, which is typical, is either misleading or false. Goldacre goes on for 369 pages like this. Almost everything the industry does is “concerning,” “worrying,” “horrifying,” or “appalling.” More government agencies and more regulations are needed. More and bigger drug trials should be mandated. To make his case, Goldacre relies on his audience not understanding why the drug companies and regulators do what they do, how science and statistics work, or how clinical trials are designed.

Here is what really happens in a pharmaceutical company. There are variations, of course, but in general, these days a new drug often starts out, not in the big pharma R&D labs, but in a small company. Somebody has an idea about how to cure a disease. So they start a small company to develop this idea into a drug. Along the way, they discover, if they didn't know beforehand, that it is insanely expensive.

To take one small aspect of it, consider the act of packaging a drug into vials. In the case of a sterile injectable, that's something a lab technician could do in a few hours, at a cost of a few bucks. But we weren't allowed to do it that way. Government regulations inflated our cost to between $150,000 and $200,000—just to put a few milliliters of liquid in a few thousand vials. Government regulations make it not two or three times as expensive, but a thousand times. The amount of drudgery and work that's required to work out each detail of this process, to do it in the way the government wants, and document it to the FDA's satisfaction, is mind-boggling. And everything in pharma is like this. A New Drug Application, or NDA, which is a form required by the government for all new drugs, covers all these steps, as well as every other detail of the clinical trials. If it were printed out, a typical NDA would be a stack of paper 33 feet high.

Clinical testing—again, done to almost absurd lengths, with huge populations of patients, because the government is almost completely risk-averse—is astronomically expensive. So drug companies have to screen hundreds of drugs, throwing over 99% of them away, just to get one that meets the government's criteria of safety, so they don't have to risk spending tons of money on a drug that has some unknown hazard for some small part of the population.

You might think that this means only the best drugs get through the process. Wrong. The most potent drugs almost always have some low level of toxicity. But by the government's logic, it's better to have ten people die of the disease than to cure nine of them and have one die from the drug. If that happens, the news media play it up to support their anti-business bias, and whip up people into hatred of the company even more, maybe driving it out of business. So most of the time only the harmless drugs that don't do much, either good or bad, make it through.

Most of the problems in pharma today are caused by these huge costs, and by the need to make the huge amounts of money needed to pay for them and stay afloat while doing it. In the last 15 years, these pressures have drastically changed how they discover new drugs. Although some drug discovery is still done internally in the big companies, more and more often they're created by small biotechs through in-licensing. In these small labs, just as in industry, researchers don't have tenure. Unlike in academia, the scientists don't have the freedom to pursue ideas that might lead to a cure. So finding a cure isn't even on the table for them. Regardless of their original goals, eventually they end up spending all their time chasing the money they need to survive.

What about his claim that drugs only have to prove they're better than no treatment? Tell that to Merck, which dropped its anti-cholesterol pill Tredaptive after tests showed it was no more effective than statins. If a drug doesn't work better than an existing drug, it's almost always dropped.

Pharmacology vs. discovery research

Pharmacology research is distinguished from discovery research, which is the only research that leads to a cure. Only a few big companies can afford to do discovery research. Academic labs do some, but they have almost no chance of being able to afford the costs of developing their discoveries into a drug without an industry sponsor.

In his book, Goldacre complains about companies testing drugs in China and India. Guess what: that is where these companies' headquarters are likely to be in ten years. They know they're not wanted here, and they're testing their drugs in what they expect to be their own back yard. There is a widespread feeling that there is less government oppression and more freedom for companies to grow in a Communist dictatorship than there is in the United States of America.

As a result, it's only a matter of time before the pharmaceutical industry is either completely based in China, or gone altogether. Once it's gone, you can kiss any new drugs goodbye. You can also kiss your grandmother or your spouse or your child goodbye, because if they're unfortunate enough to get sick, there won't be anyone around to translate a discovery into a treatment, no matter what the academic labs discover.

So what about the claim that they lie to the FDA and EMA about their research results? That's the impression you'd probably get if you only read their press releases. Those press releases have to be glowingly positive, because investors will dump a company's stock at the slightest whiff of negativity. A company might say, for instance, that even though their drug bombed out in Phase 3 testing, it showed positive results in some small segment of the patient population. In male smokers who were Eskimos between the ages of 34 and 34½ who had two or more scars on their left cheek, there was an almost-significant trend toward improvement, if you turn the graph counterclockwise by 45 degrees and squint. These statements are for the investors and stockholders. Nobody in the industry, or at the FDA, is fooled by them.

Goldacre also makes a big deal about researchers not publishing negative results. When they don't publish, Goldacre accuses drug companies of hiding data. When they do, he calls it a marketing ploy. I'm all in favor of publishing negative results myself, but the benefits would be minimal. Most of the time, when researchers (or drug companies) get all negative results, it's because they started with a really stupid idea. That's why negative results are so hard to get published. Who wants to read about the discovery that some chemical already known to be innocuous didn't do anything? (“We put 6.0 milligrams of compound A into a test tube. Nothing happened!”) Publishing that would just be a waste of ink. If you publish a negative result without realizing your experiment was stupid (and there are lots of papers where people have done this), you just make yourself look incompetent.

Or the researchers may have realized they screwed up the experimental design or made a technical mistake, like accidentally giving the rats Campbell's Homestyle™ Chicken Noodle Soup instead of the drug. I admire the courage of the researchers who admit doing something dumb, but I doubt it will advance science much. In clinical trials, when the main result is a big “adverse event,” that's not a negative result at all, just an unfortunate one, and of course it should be published. But it's a competitive business. Companies will always resist giving information to the competition. Knowing which of a company's products didn't work gives you a tremendous advantage.

It's also expensive. It can take months to write a paper. Companies don't want to tie up their expensive research staff to document something that didn't work out. When you see a clinical trial left unfinished, it's safe to assume it was dropped because it failed.

We can talk about companies having an agenda, but pharma-bashers, too, have an agenda: most of them want government to get bigger. So they focus on things that can be solved by giving more taxpayer money to the FDA. That's the wrong solution to the wrong problem. It will reduce risk-taking even more. Instead of solving the problem, it will make it worse.

Most pharma-bashers have an agenda, too: they mistrust corporations. They want more regulations, they want government health care, and they want government generally to get bigger and have more control. That would only make things worse. The real problem is not that the companies lie, but that they don't take enough risks. Risk aversion stifles the drug discovery process and kills innovative research. Risk aversion comes from government regulators, whose jobs depend on inventing new rules and enforcing old ones.

The sad truth is that money, not curing diseases, is what keeps a company going. Patients are keenly interested in finding cures. So are scientists. But the hard truth is that, despite its assertions to the contrary, our society is not. Society doesn't reward it. Society punishes it by inflating the cost, blaming big pharma, and demonizing the scientists and doctors who work for the pharmaceutical industry.

But it's fair to ask: does Goldacre seriously believe that doctors can't evaluate the scientific literature, and that they get all their information about drugs from the manufacturer? Does he really think pharma execs are so stupid they would knowingly risk their company's future by spending millions to put a useless or harmful drug on the market? Or is he just cashing in? I don't know. But when the industry eventually dies, and people start dying from diseases that could have been cured, but weren't, some of the blame will fall on the authors of pharma-bashing books like this one.