Is it worth becoming a human guinea pig? The risks and rewards of clinical trials

It’s estimated that millions of people worldwide take part in clinical trials, but when things go wrong in medical research there can be tragic consequences. Annabelle Quinceinvestigates the ethical dilemmas of testing drugs on humans.

In January, a clinical trial in France went badly wrong. One young man died and several others suffered brain damage. The drug for treating mood disorders such as anxiety was being tested by a Portuguese pharmaceutical company, and the accident happened during phase one—that is, the first time it had been tested on humans.

As investigations into the incident continue in France and Portugal, questions are being raised about how it could have happened at all, and whether there are adequate procedures in place to protect people involved in clinical trials.

Alex O’Meara, a type I diabetic who has himself been involved in a clinical trial, says observers should remember that clinical trials are big business.

‘The way it happens these days is a clinical research organisation, which is a private company, will test a drug after a pharmaceutical company or a manufacturing company has an idea for something that they want to develop and sell,’ says O’Meara, the author of Chasing Medical Miracles: The Promise and Perils of Clinical Trials.

‘It rarely starts with a creative or substantially altruistic idea in mind … The typical model is a corporate-run idea, much in the same way that most of the hamburgers we eat today are corporately made and not the idea of someone who is a gourmet chef.’

O’Meara estimates that around 20 million people in the United States take part in clinical trials each year, as well as 50 million or so worldwide—a $24 to $30 billion a year industry.

‘It’s massive, and it has grown up very quietly because, again, nobody really notices,’ he says.

‘Drugs come out, they don’t know where they come from, they’re happy they are there, and they just exist. But everything has to be tested, sometimes repeatedly, in multiple and very far-flung studies.’

While most of the major drug companies are based in America and Europe, clinical trials are conducted across the globe. They are increasingly run by specialised companies called contract research organisations (CROs). It is these organisations that are responsible for maintaining protocols around informed consent. Many are based in the developing world.

Laura Stark, a professor at the Centre for Medicine, Health and Society at Vanderbilt University and the author of Behind Closed Doors: IRBs and the Making of Ethical Research, explains that many clinical trials are conducted in a language different to that used in the country where the drug is manufactured. The layers of interpretation around this, she says, can lead to variability.

‘One thing also to bear in mind is that it’s just a highly privatised system,’ she says. ‘So both drug manufacturers, the ones doing the drug development, and also the research organisations with whom the companies contract, have incentives other than simply the production of scientific knowledge.

‘They have a lot of moving parts to keep in mind, not only regulation but their own bottom line.’

Out of the lab and into the human guinea pigs

Bruce Neal, senior director at the George Institute for Global Health and professor of medicine at the University of Sydney, says the process for getting a new drug to market starts with someone identifying a signal that a chemical might be of benefit for a particular health problem.

‘This is all chemistry, tubes, petri dishes: that sort of laboratory-based research. Many of the things that get looked at there will get dropped pretty quickly and it’s just a small proportion of them that will then progress through,’ he says.

‘The next substantive phase of research would be animal research, where you would actually start to test these agents in small animals and then potentially in some larger animals to get a better indication of what benefits they are likely to cause, as well as what adverse effects there are likely to be.

‘Once you reach a certain point in your research, you obviously have to start testing it in humans.’

He says the first round of human testing—what would be called a phase one clinical trial—is done in very controlled conditions, with small numbers of people, typically healthy young men, in western countries. Researchers usually don’t use women because new drugs may affect their fertility.

‘The idea is to give the drug and then track in incredible detail what happens to it when you put it into the body,’ he says.

‘You’re not really looking, at this point, for the potential benefit of it for the condition, but you are looking to understand how does the kidney manage it, when it goes in what does it gets turned into, does it get broken down by the liver, and you obviously get potentially a little bit of an idea then about potential safety and efficacy.’

You might wonder how they get healthy young men to consent to be human guinea pigs. Roberto Abadie, the author of The Professional Guinea Pig: Big Pharma and the Risky World of Human Subjects, says it’s as simple as offering money.

Clinical trials can be particularly attractive to homeless people, people with addiction problems, the recently unemployed and people who run into discrimination in the job market—black youths and Latinos, for example.

‘Some people went once and never showed back again, because it is painful and it’s risky; some people with more options had better things to do,’ he says.

‘For some it became their strategy or main way of getting an income, so they kept going back and back and back: people who are unemployed, unemployable, people who actually came out of prison.

‘The companies recruit at the gates of the prisons in the US, they are waiting for them outside. They cannot get them when they are inside, of course, but they are waiting for them.’

Professional volunteers and the question of informed consent

In the United States, volunteers are meant to wait 30 days in between trials, but there is no centralised registry, so there’s no way of policing that. Abadie says some people will do eight to 12 clinical trials in a year, making $20,000 or more.

He says these ‘professional volunteers’ often do have a sense of the risks they might be taking. ‘They have a sense, for example, that some drugs are bad for them, psychiatric drugs, psychotropics, cancer drugs, HIV drugs, which they feel are very toxic, are not good for them,’ he says.

‘But the problem is that even when they have a sense that some drugs are not good for them … those are the highest paying drugs. They pay more than $5,000 to participate in a clinical trial, and they do that because they know people don’t want to do it.’

According to Laura Stark, one of the key ethical questions relating to clinical trials, especially at the phase one stage, is whether the volunteer has given his informed consent, or even what true, informed consent could possibly look like.

‘It really speaks to issues of structural inequalities, disparities in socio-economic circumstances,’ she says. ‘That is something that is beyond consent. It’s something that is a broader but equally as important political issue to address and acknowledge in the clinical trials system.’

If and when a drug passes phase one trials, it then has several more phases to go through before it gets onto the market. The volunteers used in phase two and phase three trials are typically people who have the medical condition the new drug is trying to help. Often they are not in it for the money, but are rather looking for a cure.

Taking risks and hoping for rewards

The clinical trial that Alex O’Meara was involved in took islet cells—which produce insulin in the human pancreas—from cadavers and transplanted them into his liver.

‘What I realised was if you have a condition—I have type I diabetes—you are skewed in being very agreeable to all kinds of things to do to yourself, with the possibility of curing type I diabetes,’ he says.

‘I also realised that people, when I told them I was in a clinical trial, thought I was getting something wholesale and not retail, like somehow I had an in and I was going to try this cool new thing. Well, it’s not a cool new thing. It might kill me. The immunosuppression I took increases my chance of getting cancer in my life by 900 per cent.’

O’Meara says the experience taught him there is a lot of desperation in clinical trials.

‘So many people go through this. This is not a unique circumstance by any means; it’s getting more frequent in people’s lives,’ he says.

‘You are sitting there going, “Is it going to work?” [The results are] miraculous things, debilitating things, very dramatic. But I came eventually to … describe clinical trials as being like the extreme sports of medicine.’

Despite his criticism of the corporate nature of medical research, O’Meara says he doesn’t regret participating.

‘My own clinical trial did not end up successfully for me. The cells died, I was no longer cured,’ he says.

‘Am I regretful that I did it, even with that in mind? No, absolutely not. Because it was the first time since having type I diabetes since the age of 11 that I could actually go on the offence, that I could take some steps toward maybe affecting my own condition and my own life with this condition in my own way, and that’s a great feeling.’