Any research study that looks at treatment for patients is called a clinical trial. Trials usually look for benefits and side effects of new drugs, or new ways of using old drugs, like changing their dose or frequency. But trials can also test new measures to prevent or diagnose illness, like using MRI scans to diagnose MS, or new methods of patient care, like physiotherapy for tremor, or even new ways of providing patient information. Trials are the only accurate and reliable way of showing whether a new intervention is safe, effective or better than one that’s already available.

Step by step – a phased approach

A new drug is tested on people only if extensive laboratory work and animal studies show promising results. If a treatment does go on to trial stage, the trials themselves have to progress through a set sequence of ‘phases’ – one to four – to ensure that the information obtained is reliable and everyone taking part is protected. Phase one must be completed successfully, before moving to phase two and so on for the remaining phases. Trials stop if there is any cause for concern.

Phase I trials are small, with between ten and 50 people – and everybody gets the new treatment. Phase I studies reveal how best to give a drug and how much can be given safely. Side effects are unpredictable so people are watched very closely. If the risks are high, for example, a treatment might only be offered to people who can’t be helped any other
way.

Phase II trials find out whether a new treatment is of real benefit to people. They set the optimum dose and continue to monitor side effects. Usually 100 to 300 people are recruited for a relatively short time, around
six months to two years.

Phase III trials are huge studies with anything up to 1,000 to 3,000 participants, often from many different countries. They look at the benefits and side effects of a new drug in the long term – over two to four years –
and nowadays often assess people’s perceptions of their ‘quality of life’ on a new treatment.

Phase III trials need to be large to make sure they can detect small differences between treatments. In the case of a treatment for relapsing remitting MS, for example, even larger numbers may be required to distinguish real effects of the drug from spontaneous recovery.

Recruiting such large numbers of people can take years. As a result, it can be five to ten years before a trial reaches its conclusion. Because each person has to be followed for the same amount of time (two to four years), the last people to be recruited may only be just starting their treatment when the first people are finishing.

Phase IV: Success in phases I to III usually means that the drug will be given a European license, which 3 gives the manufacturers permission to market the drug. Once it is marketed, if it’s then prescribed, monitoring continues for any new side effects that might emerge.

 

Removing the bias

Clinical trials have to be designed to remove any bias or influence from researchers or participants.

In randomised, controlled trials, people are put into two separate groups. The allocation is random, so there is an even mix of people across the two. One group gets the treatment that’s being tested (whether that’s a new drug or a form of physiotherapy), the other group gets an alternative, or ‘control’ treatment.

Sometimes the control group is given whatever is the best alternative to the treatment on trial: it would be unethical to deny people treatment that works. This is also important to show whether the new treatment is any better than what’s already available. In 50% of cases, it’s not.

Sometimes, the control group receives a sugar-pill or placebo. This tests for the placebo effect. This is a ‘psychological’ effect, where people begin to feel better even though the ‘pill’ they’re taking is not active. In a trial, if the results with the drug are the same as the placebo, you can conclude that the drug isn’t having any significant impact.

During many trials no one knows which treatment people are getting. This is known as a double-blind trial and is important to ensure that neither the researchers’ nor the participants’ expectations influence the outcome.

Such strict conditions ensure that clinical trials give reliable information about the effects of treatment. But it also means that if you choose to participate, you’ll only have a one in two or three chance of receiving a new treatment and you’re unlikely to know which you’ve received until the end. 

Taking part

The researchers running a trial produce a protocol. The protocol explains why the research is being done, how it will be carried out and how the results will be collected and analysed.

The protocol is independently assessed to ensure that it meets the necessary standards. Increasingly, participants and their carers are being involved in this review. A research ethics committee (REC) also checks the protocol to make sure that the research respects the dignity, rights, safety and well being of participants.

One of the most important functions of the REC is to check that the information about a trial clearly explains the risks and benefits to those involved. Your agreement to participate in a trial, based on a full understanding of what’s involved, is known as ‘informed consent’.

It’s important to remember that during a trial:

• If it’s a phase III trial, there’s no guarantee that you will receive a new drug – you’re just as likely to be given a placebo or an existing treatment


• The new drug may not be effective for you – it may turn out to be worse than the alternative
  
• There may be side effects


• Extra tests and monitoring mean more trips to the hospital


• It’s important to discuss and clarify what happens at the end of a trial before agreeing to take part

However, many people do agree to accept these risks because of the potential to help others. People also remark that taking part is a way of becoming better informed about their MS, too.

People must meet the inclusion criteria for a trial before they can join. For example, there may be an age requirement or a requirement for a particular type of MS. Participants may need to demonstrate a certain appearance of lesions in MRI scans, or points on a scale of disability. So far, there have been many more large-scale clinical trials for treatments of relapsing remitting MS than the other disease types. 

What’s going on?

For most people with MS, the gateway to taking part in a trial is to be invited by the neurologist at the clinic where they receive treatment. But this is rather a hit and miss affair. Not all clinics have the facilities to take part in trials. Not all neurologists are aware of research outside their area of expertise and not all people are eligible for the particular trials in their vicinity. We desperately need a more systematic way of matching willing participants to on-going trials. The internet now offers an exciting opportunity for such a transformation.

Through several websites, you can now get ‘access to all the information that previously only doctors could get’. Not only do these sites provide useful background material, but they are also beginning to provide lists of all the clinical trials currently recruiting participants all over the world (see www.controlled-trials.com ). Iain Chalmers, Director of the UK Cochrane Centre, has said, ‘What people need is reliable information about what trials are going on, explaining clearly to them what a trial is about and whether they are eligible to take part. But people also need to see the results of the trials – the good and the bad. Only then can they get a balanced picture of what new treatments can realistically achieve.’  

Directing future research

There is a new move to involve people in the design, running and interpretation of the results of clinical trials. In a recent survey of 48 trials where participants had been actively involved, researchers commented that the participants’ input had helped to develop better research questions, improve the quality of information provided to people and made the trial more relevant to people’s needs. 

Useful websites

www.controlled-trials.com

www.clinicaltrials.gov

www.nelh.nhs.uk/clinicaltrials

 

Last Updated

Reviewed December 2004 by the MS Society Research Team.