Can you trust what you read? Why we need Randomised Trials (Pulse Article 1999)

How can you tell if a paper is reliable? This was the question that many of the registrars wanted to have answered at a recent half-day release session on critical reading.

The Challenge of Archie Cochrane

Before he died Archie Cochrane expressed his sadness that no-one had gathered together the most reliable data available so that it could be used a basis for practice and research in Health Care. In response to this challenge the Cochrane Collaboration has emerged as a group of dedicated individual doctors and health care professionals who have set out to collect together data from controlled clinical trials, and summarise what they have found in the form of systematic reviews. The Collaboration is an international organisation and is structured by health problem areas to avoid duplication of effort. Many Journals have been hand-searched to identify controlled trials, and the reviews are structured so as to reduce bias at each stage of the process (which includes a ban on drug companies sponsoring individual reviews). In the UK many of the editorial bases are funded through the NHS Research and Development Programme.

The output of the Collaboration which includes a database of over 250,000 controlled trials identified and over 600 systematic reviews, is published in electronic form in the Cochrane Library, and a future article in this series will give an example of how it can be used.

The place of RCTs

There is considerable misunderstanding at this point about the place of Randomised Controlled Trials (RCTs). It would be unfair to say that you should not bother to read anything that is not an RCT, but it is also true to say that the most reliable way to study causation is with a systematic review of randomised controlled trials.

The way I like to look at the issue of randomisation is as follows; ask yourself the question “Could this trial have been randomised?” If you decide that it could have been randomised but it was not, then a large question mark should be placed over conclusions about whether the paper can reliably answer any questions related to the intervention causing good or bad outcomes.

Evidence for HRT

Hormone Replacement therapy is a good current example of this. Most of the current evidence relating to the purported benefits of HRT comes from non-randomised studies, and the results are therefore likely to be biased by differences between the type of women who opt for HRT and those who do not. An excellent editorial in the British Journal of General Practice in 1998 presents the current state of play in this area is recommended reading. Randomised Controlled Trials are currently under way to assess the effects of using HRT, but these will not report findings for a few years yet.

Sometimes you cannot randomise

There are of course some areas in which Randomisation is either impossible or unethical; you could not carry out a trial in which patients were randomised into cigarette-smoking or not! The very strong evidence on the dangers of smoking comes from large well conducted cohort studies, which are quite enough to leave little doubt about the size of the dangers involved.

Does it matter how you do it?

Whilst on the subject of Randomisation, how it is done matters too. The technical term to describe the actual randomisation is “allocation concealment” and if you read reports of older trials this often used to be done by using the patient’s hospital number to decide which treatment type they should receive or even alternate between treatments. It has been shown that trials with inadequate allocation concealment of this sort tend to show larger benefits of the intervention under study and it is not too difficult to imagine why.

Magic cure for warts?

Imagine you have developed a new treatment for removing warts and you arrange a trial to test it against one of the current methods. A patient walks into your surgery with a whole mass of horrible looking large warts, which you think that no treatment on earth will remove, and you can tell from the unconcealed alternated or random allocation that they would be in turn to receive your new technique. What will you do? Human nature is such that you will find some reason that this person will not quite fit into the trial and you will move on to another patient who has a nice small wart to treat next time. Obviously in this instance the advantage of randomisation in removing bias in the allocation process has been lost.

A better way to do it

When assessing the allocation concealment in Randomised trials I would look for at least opaque sealed envelopes which contain a random sequence of numbers to determine the next patient’s treatment. Even better would be a separate centre (such as the hospital pharmacy) to randomly allocate the treatment to the patient after the decision has been made to include the patient in the trial.

Try it yourself

So next time you are reading a paper, after you have asked yourself what is the question the paper was trying to answer, just pause to consider whether the trial could have been randomised. If it was randomised how easy would it have been to tell which treatment the next patient was getting? If you are satisfied on both of these fronts then read on, and if not perhaps move on to another paper.


1) Schulz KF, Chalmers I, Hayes RJ, Altman DJ. Empirical evidence of bias: dimensions of methodological quality associated with estimates of treatment effects in controlled trials. JAMA 119;273:408-12

2) Hannaford PC. Is there sufficient evidence for us to encourage the widespread use of hormone replacement therapy to prevent disease? BJGP 48;427:951-2

Further Reading

So what’s so special about randomisation? Kleijnen J, Gotzsche P, Kunz RA, Oxman AD, Chalmers I. Chapter 5 in Non-random reflections on Health Services Research (Eds Maynard A and Chalmers I) BMJ Publishing Group 1997, pp93-106.