Clinical Trials

Feelings about being in a placebo-controlled trial

In some trials (especially Phase 1 and Phase 2 trials) everyone taking part will get the treatment. (See ‘Different types of trial’ and ‘Non-randomised trial designs’). However, many trials compare a new treatment with the standard or usual treatment by setting up two groups of people. One group, the experimental group, is given the new treatment. The other group, the control group, is given the standard treatment. (See ‘Feelings about being allocated (randomised) to a treatment group’). If no standard treatment is available, the control group may not be given any specific treatment or may be given a placebo.
 
A placebo is a treatment with no active ingredient which is designed to appear very like the treatment being tested. By comparing people’s responses to the placebo and to the treatment being tested, researchers can tell whether the treatment is having any real benefit, rather than patients simply feeling better because ‘something is being done’. (See more below about the placebo effect).
 
The idea of being given a placebo was easy for some people to accept. Comments included, “You’ve got to satisfy the authorities that the drug is capable of doing what it says”, “It was all part of the experiment”, and “That’s how you’ve got to test it”.
As Tony explains, he was happy to take part, even though he guessed he was on the placebo. In his case he was offered the active drug at the end of the trial once it had been shown to work. This was also offered to Kate’s husband at the end of a placebo-controlled trial of immunotherapy (grass pollen injections) to reduce hay fever symptoms. Like Tony, he guessed he was in the placebo group, but carried on with the trial, even though it was quite a burden. (See also ‘Thinking about withdrawing from a trial’).
Kate suggested it might have been better to say at the start of the study that the active treatment – if it was found to work - would be offered to anyone who had had the placebo, as a way of keeping them motivated. This should be stated in the information given to people before they consent to take part, but Kate felt it had not been made clear in their case.
 
Several people assumed that if they had no change in symptoms they must be taking a placebo. However, this is not necessarily so, as not all drugs work on all patients in the same way.
Equally, people who are taking a placebo may sometimes experience improvements in their health. This is known as the placebo effect or placebo response. We still do not understand exactly why it happens, but it seems that believing a treatment will help can result in real physical changes. This is why new drugs are often compared against a placebo – if the patients on the drug do significantly better than those taking the placebo, it suggests the new drug really has an effect. If people were only given the new drug, we could not be sure if improvements were simply due to a placebo effect.
However, some people we talked to were unhappy with the idea of a placebo-controlled trial, usually because they were concerned that they would be denying themselves the possibility of a treatment which might work for them. (Of course, they might also be avoiding the side effects of a treatment which might not work for them).
In a well-designed trial, a treatment should only be compared against a placebo if no-one is being denied a standard treatment known to be helpful. Polly was not opposed to the principle of placebo-controlled trials, but she decided not to take part in one herself because she thought it did not meet this requirement, and was therefore unethical.
As Polly pointed out, you may still feel uneasy wondering if you were “missing out on something” and this may be harder to live with if you have a life-threatening illness. She commented elsewhere in her interview: “I think I would always have felt uneasy, say [the cancer] had recurred, and I’d never known whether I’d just been taking a sugar pill or whether I’d taken something that might have given me that 30 per cent extra chance.”
 
The idea of possible regrets and always wondering ‘what if?’ was a common worry about placebo-controlled trials in serious illness. Several people who had willingly volunteered for other types of trial felt differently about placebo-controlled trials.
However, several people pointed out that we do not know what side effects there might be from taking an active drug. Joanna wondered if most people understood that taking a new treatment might be quite risky, so getting the placebo could be better. There were several mentions of the Phase 1 trial at a commercial research unit based at Northwick Park Hospital in 2006 when 6 healthy volunteers became extremely ill. A copy of the Inquiry Report of this incident can be downloaded from the Department of Health website.
 
This had affected people’s views about the balance of risk, although it is important to note that ‘First-time-in-humans’ studies are done precisely because we need to find out about possible risks and side effects before using the treatment more widely. Most of the people we talked to took part in trials of treatments which had already been tested in humans.
Julian was in a Phase 1 trial, so he was especially conscious of the balance of risks and benefits. However, from his personal experience of seeing how the drug has worked for him, he would find it hard to see how it could ever be compared to a placebo in future.
This raises difficult questions about the level of evidence needed before a drug can be said to work. Julian’s personal experience had convinced him the drug was effective in his case. However, although his clinical team felt the drug was promising they also felt there was not yet enough evidence, so they needed to test the drug further in a Phase 2 trial. Sometimes, even when Phase 1 and 2 trials suggest a new drug is promising, when it is compared in Phase 3 trials with the standard treatment in a much wider group of people the results do not show it makes a significant difference. (See ‘Non-randomised trial designs and other research’ and ‘What are clinical trials and why do we need them?’)
 

Last reviewed July 2015
Last updated July 2011

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