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A similar set of numbers may be A similar set of numbers may be

generated by a computer that is
programmed to do so or by most
scientific calculators. The procedures
and rules that the investigators must
follow are identical to those described
for the random number tables.
generated by a computer that is
programmed to do so or by most
scientific calculators. The procedures
and rules that the investigators must
follow are identical to those described
for the random number tables.

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sequences will group C. Equally, if 2 corresponds to each of the blocks. In to each of the blocks.
blocks: ABC, ACB, BAC, BCA, CAB, CBA. If they use a die to generate the sequences, then they can decide how each
of the six numbers of the die will correspond to each of the blocks. In this case, however, each of the sequences will
determine the allocation of three participants at the same time, not only one at a time. For instance, if it is decided that 1
corresponds to the sequence ABC, then the three participants that enter the study after a die has shown 1 will be allocated
in that order: the first participant to group A, the second to group B, and the third to group C. Equally, if 2 corresponds to
ACB, then the first participant to be included in the study after the die shows 2 will be allocated to group A, the second to
group C, and the third to group B. The blocks can be of any size, but ideally the size should correspond to a multiple of
the number of groups in the study (that is, six blocks for a study with two or three groups). 3

Stratified randomisation is used to keep the characteristics of the participants (that is, age, weight, or functional status) as
similar as possible across the study groups. To achieve this, investigators must first identify factors (or strata) that are
known to be related to the outcome of the study. Once these factors are identified, the next step is to produce a separate
block randomisation scheme for each factor to ensure that the groups are balanced within each strata.

On occasion, investigators may not desire the same number of participants in each of the study groups and can decide to
allocate unequal numbers to each group, while preserving the homogeneity of the distribution of the characteristics of the
participants across the study groups. This is called weighted or unequal randomisation. This type of randomisation tends
to be used by investigators who wish to expose fewer participants to the experimental group because of concerns about
unexpected adverse events. In the example of ibuprofen versus perfectafen, the investigators may decide to allocate one
patient to perfectafen for each four patients who receive ibuprofen.

Unfortunately, the methods of allocation in studies described as ‘randomised’ are poorly and infrequently reported, even
when such studies are published in prominent journals.5,6 As a result of these poor descriptions, it is not possible to
determine, on most occasions, whether the investigators used a proper method to generate random sequences of
allocation.

On the other hand, when the reports of studies described as randomised provide details of the methods of allocation, it
has been shown that 5-10% do not use methods that generate random sequences.7,8

The reporting of randomisation and other aspects of RCTs will be discussed in detail in Chapter 5.

What can be randomised in RCTs?

The most frequent unit of allocation in RCTs is individual people, either patients (the most common) or caregivers (that is,
treating physicians or nurses).

Sometimes, however, it is more appropriate to randomise groups of people rather than individuals. This is known as cluster
randomisation. Examples of these groups or clusters are hospitals, families, and geographical areas. Investigators
frequently use this approach when the RCTs are designed to evaluate interventions that may affect more than one
individual within a particular group (that is, an RCT evaluating the effect of a videotape on smoking cessation on prison
inmates or the effects on parents following early discharge from hospital after childbirth). It is also used when the way in
which the participants in one study group are treated or assessed is likely to modify the treatment or assessment of
participants in other groups. This phenomenon is known as contamination. For example, contamination is present in an
RCT comparing a booklet with strategies to increase patient participation in treatment decisions versus conventional
practice, if clinicians who have given the booklet to a group of participants start using the strategies described in the
booklet during the treatment of participants who do not receive the booklet.
In other cases, investigators may decide to randomise not only individuals or groups of individuals, but also the order in
which the measurements are obtained from each participant. For instance, in an RCT evaluating the effects of morphine
on cancer pain, the investigators could randomise the

The corollary is that, before you start reading an RCT, or even searching for one, you should take into account that there
are other study designs that may be more appropriate than an RCT to answer your particular questions (a brief description
of studies other than RCTs is provided in Chapter 7). Even if an RCT is available, you must be aware that one RCT in
isolation, even when it is appropriate and perfectly designed, is unlikely to provide all the answers that you need. You
should consider the information provided by a single RCT as an important piece in a puzzle with many empty spaces.
This information will have to be assessed and used in conjunction with other types of information (for example, data from
other RCTs or from other study designs, and your own clinical experience), and the values and preferences of the people
involved in the decisions, depending on the circumstances in which the decisions are being made.