Evidence from Randomised Trials and Systematic Reviews (Pulse Article 2001)

This article is part of a series on Critical Reading.

The main threats to validity in non-randomised studies is related to BIAS due to differences in the populations of patients who do and do not receive the experimental treatment. Randomisation should overcome this problem because the random allocation of patients to the treatment or control groups should create an equal spread of known and unknown risk factors between the two groups. Whilst statistical techniques can be used to adjust for known confounding factors in non-randomised studies, by definition the unknown ones can only be overcome with randomisation.

Allocation concealment

Even in randomised controlled trials it is important to check that the allocation of patients to the active and comparison groups is well concealed. The quality of allocation concealment is routinely used by the Cochrane Collaboration in grading trials included in systematic reviews because empirical research has shown that studies which do not have well concealed allocation tend to show more inflated results than those that do. Why should this be? The problem is selection bias: if I was carrying out a randomised trial of my favourite wart paint it is important that I do not know which treatment the next patient will receive, otherwise I can influence the results by choosing the milder wart infections for treatment with the paint. This is quite easy in practice as I would only have to find an excuse to rule the next patient out of the trial if they were due to have the paint and had a horrendous crop of warts!

Similarly if I know the treatment used I may be more optimistic in deciding that a wart has completely gone if the patient had my special paint than if they did not. This is a form of detection bias. Secure double blinding (using an identical wart paint substitute prepared by an outside agency) will overcome both problems, and again has been shown to reduce the size of treatment effects compared with the results of unblinded (open) studies.

What about other trials?

Finally after checking all these quality measures for the paper do not forget that the study being reported is only one of a larger group of other studies that have been carried out on the same topic all over the world. It is for this reason that the Cochrane Collaboration has set out to collect together all the evidence from controlled clinical trials that has a bearing of questions related to clinical practice and published the results in the Cochrane Database. Systematic reviews of this kind are one way to combat the increasing volume of papers published each year, but I am often asked what exactly is a systematic review and how does it differ from a meta-analysis.

Narrative reviews

Traditionally reviews of interesting topics have been commissioned by journals that ask an expert in the area to give a viewpoint; the problem is that all experts have their favourite approach to a topic and will tend to be most familiar with those papers that support their own view. (How often do you keep a copy of something that you have read that you think is wrong?) This type of narrative review is therefore inherently likely to be biased.

It is helpful to think of a review as being a scientific investigation but of papers rather than patients. Would you trust a trial that reported the results of a new drug where only a few of those treated have their data for you to see and the choice of which ones in entirely up to the investigator. I certainly would not, and in the same way caution is needed when reading the results of narrative reviews.

Systematic Reviews

So what exactly is a Systematic Review? Mulrow has defined a Systematic review as “an efficient scientific technique to identify and summarise evidence on the effectiveness of interventions and to allow the generalisability and consistency of research findings to be assessed and data inconsistencies to be explored.” (1)

The difference is that the review sets out to find all the appropriate evidence on a topic, not just the bits that suit the writer. Ideally the review should start with a protocol that is decided in advance, and for Cochrane reviews these are also published on the Cochrane database. This helps to avoid data-dredging for results that happen to be show ‘statistical significance’. Post hoc analysis done after the data is collected is equivalent to firing an arrow into a large wooden wall and then drawing a target around the place the arrow lands – much easier that drawing the target first and then hitting the bulls-eye!

The methods section of the systematic review should make clear how the search for evidence was carried out, how the identified trials were selected for inclusion or exclusion from the review, and how the data from the trials was combined. The data pooling is termed Meta-analysis and is no more than using mathematical techniques to combine the results from two or more individual trials. A systematic review sometimes does not include Meta-analysis if the data is not suitable for pooling, and nor does a Meta-analysis mean that all the data has been systematically searched out.

In other articles I unpack some of the techniques used in Meta-analysis and explore the use of meta-analysis in systematic reviews.


1. Mulrow CD. Rationale for systematic reviews. BMJ 1994;309:597-9