Life's a trial

When I'm doing research roundups, I quite often talk about clinical trials being "Phase 2" or "Phase 3". But what do these terms mean? The development of a new drug or other intervention is a long-term process. commonly taking 12 or more years before being available to patients. The regulatory process adds another hefty chunk of time.What's happening for it all to take so long?

Research begins in the laboratory, where potential treatments are tested on animals: for instance, there is a strain of mice which have a condition very like MS. Testing drugs on them gives a reasonable idea of whether they're likely to help people with MS. Around 1000 potential drugs are tested for each one that makes it to clinical trials.

The use of animals in drug trials is a whole other question, one I might discuss in a future blog post. If the drug is helpful for the animals (and how that's worked out is again a subject for a future blog post), the researchers will look for more funding to test it out on people, in clinical trials. The clinical trial process has four phases.

Phase 0 Very low doses of the drug are given to 10-15 people to see whether the drug does what was expected in humans. Tests are carried out to check what the drug does to the body, and what the body does to the drug.

Phase I The drug is tested on usually 20-100 healthy volunteers, to check that it is safe. These volunteers are normally paid, as they won't get any health benefit from participating, and are taking the risk of being given an untested drug. Some of you may remember news coverage of a Phase 1 trial in 2006 where 6 healthy volunteers became violently ill after taking a new drug.

Phase II Designed to assess how well the drug works, and what is the best dosage. Between 100 and 300 volunteer patients take either the drug or something else - the existing treatment if there is one, or a placebo.

Phase III The drug is tested on a large number of patients over a number of sites. This phase aims to be the definitive assessment of how effective the drug is, compared with any current treatments. Sometimes a manufacturer wants to prove that their drug works for other patients or other conditions than those originally established. In that case the Phase 2 or 3 trial would be the first stage.

Phase IV This is the period of surveillance once the drug is on the market. Safety continues to be checked, and technical support is available.

Clinical trials can take a long time to run. It can be difficult to recruit the number of people needed, particularly in Phase III. For many long-term conditions, it can take several months to see any effect from the drug. I recently participated in a Phase II trial for a full year.

Most Phase III trials (and some Phase II) are randomised, double-blind and controlled.

• Randomised means that participants are randomly assigned to the treatment or placebo groups
• Double-blind means that neither the participant nor the researchers know whether they're receiving the treatment or the placebo. It's important that the researchers don't know, as they might subconsciously behave differently to people in the two groups.
• Controlled means that one group receives a placebo (or the existing treatment, if there is one).This means that the effect of the new drug can be isolated. Is it better than the existing treatment? If so, how much better?
• Some trials are designed to cross-over, This means that halfway through the trial period, the participants swap over to receiving the other treatment. Those who were gettng the active drug will change onto the placebo, and vice versa.

After the trial process, the manufacturer will apply for the drug to be licensed, which has to be done separately in different parts of the globe.Here in the UK, once it's been licensed, the action then moves to an agency called NICE, who decide whether the NHS should fund treatments.

Their decisions are based on cost-effectiveness, potentially leading to some controversial outcomes. Recently they've refused funding to the new MS drug Gilenya, and there have been several decisions where funding has been refused for expensive cancer drugs which were likely to give only a few more months of life.

In some cases, local Primary Care Trusts still have to agree to fund the treatment. There have been problems recently with Sativex, which is licensed for use in MS spasticity if other treatments don't help. Many PCTs are refusing to fund it. The MS Society is campaigning on this: if you have funding for Sativex refused, they provide advice on what steps to take.

You're most likely to find out about trials through your consultant. If you'd be interested in participating in a research project (without commiting yourself to anything!) let them know.

It can't be denied that there are some risks involved, as there are with any treatment. But I found trial participation interesting, and if the drug concerned goes on to be approved I'll feel quite proud: I was part of that!