The preparation for a trial

The detailed plan for a trial is called a protocol. It lays down procedures for how the treatment will be given, who is eligible to take part, the timetable for tests and visits for participants, the length of the study, how the results will be assessed and so on.

The protocol is written by a group of doctors or other researchers or by a pharmaceutical company. First, the trial planners will examine previous research on a particular experimental treatment. They then work out the remaining unanswered questions, and design a new trial to try to find out the answers.

Before a study can begin, an ethics committee responsible for each clinic that wants to run the trial must approve the protocol. The members of the ethics committee may vary, but usually include doctors, nurses, at least one lay person and often a lawyer or chaplain. They are responsible for protecting the rights and interests of the people in the trial, and work independently of those running or financing the trial.

It is very important that any clinical trial should be run with the approval of an ethics committee. Such an approval is a good indication that a trial is ethically sound, even though the committee does not monitor the day-to-day running of the trial.

Recruiting participants

The next step is to recruit participants and start the trial. The more quickly participants are recruited to the trial, the sooner it can be completed and the treatment's benefits and risks can be assessed. The difference between the effect of a new drug and another treatment could be small. The drug may have to be tested in a large number of people to get a clear picture of whether it is better, as good as or worse than other treatments that are currently available.

So, a clinical trial may be seen as a partnership between researchers and people with HIV. Researchers need people to join their trials so that they can improve medical knowledge about HIV infection. People with HIV may want to help this research, but will also want to make sure that their individual interests are being looked after in the trial.

Researchers want people to join their trials because they share the researchers' uncertainties about which of the options being tested in the trial is the best. This is known as the 'uncertainty principle'.

Who can join a trial?

Each clinical trial has its own rules about who can and who cannot take part. These are known as inclusion and exclusion criteria, or eligibility criteria.

The inclusion criteria spell out the characteristics that will allow a person into the study. This is to make sure that the people in the trial are similar enough so that it will be clear which groups of people might benefit most from the new treatment. Trials of new treatments are usually run in several different groups of people at once in order to build up a bigger picture of the way drugs should be used best.

For example, a particular trial might aim to test the effect of a drug for people who are at a particular stage of HIV disease. So a typical inclusion criterion might state that participants in a trial have to have a CD4 (T-cell) count between, say, 200 and 350, or a viral load above 10,000.

The exclusion criteria are intended to protect the trial participants. For example, you may be excluded from a trial if there is a risk of a dangerous interaction between the trial drug and other treatments that you use. A common exclusion criterion forbids trial participants from taking other drugs at the same time which are similar to the one being studied. For example, people in a trial of an anti-fungal drug will not be allowed to take other anti-fungal drugs while they are on the trial.

Trials sometimes exclude whole groups of people. Most trials exclude pregnant women, because of a fear that the treatment might harm the unborn baby. They also exclude women who are breastfeeding because the drug might be passed onto the child through breast milk. Most trials insist that women are using contraception.

These attitudes are starting to change as doctors realise that everyone should be given the opportunity to take part in trials. It is important to know whether drugs are also safe and effective for women and drug users, as well as everyone else. This need has to be balanced against the researchers' legal and ethical obligation to ensure that the fetus is safe.

The right time to join a trial

There is no right or wrong time to join a trial. People join trials at different times and for different reasons. Some people are not able to join trials because of particular inclusion and exclusion criteria. Some people choose never to join a trial, and there is nothing wrong with saying no. It is something that is best decided in close consultation with your doctor or nurse.

If you are ill and a doctor recommends an experimental drug as the best chance of treatment or offers a new drug as part of a comparative trial, you may have to decide whether or not to take part in the trial at quite short notice. But otherwise, it is worth taking plenty of time to think carefully about your treatment options before deciding whether joining a trial is the best option for you.