A randomized controlled trial (RCT) is a form of clinical trial, or
scientific procedure used in the testing of the efficacy of medicines or medical
procedures. It is widely considered the most reliable form of scientific
evidence because it is the best known design for eliminating the variety of
biases that regularly compromise the validity of medical research.
Sellers of medicines throughout the ages have had to convince their patients
that the medicine works. As science has progressed, public expectations have
risen, and government health budgets have become ever tighter, pressure has
grown for a reliable system to do this. Moreover, the public's concern for the
dangers of medical interventions has spurred both legislators and administrators
to provide an evidential basis for licensing or paying for new procedures and
medications. In most modern health-care systems all new medicines and surgical
procedures therefore have to undergo trials before being approved.
Trials are used to establish average efficacy of a treatment as well as learn
about its most frequently occurring side-effects. This is meant to address the
following concerns. First, effects of a treatment may be small and therefore
undetectable except when studied systematically on a large population. Second,
biological organisms (including humans) are complex, and do not react to the
same stimulus in the same way, which makes inference from single clinical
reports very unreliable and generally unacceptable as scientific evidence.
Third, some conditions will spontaneously go into remission, with many extant
reports of miraculous cures for no discernible reason. Finally, it is well-known
and has been proven that the simple process of administering the treatment may
have direct psychological effects on the patient, sometimes very powerful, what
is known as the placebo effect.
Types of trials
Randomized trials are employed to test efficacy while avoiding these factors.
Trials may be open, blind or double-blind.
In an open trial, the researcher knows the full details of the treatment, and so
does the patient. These trials are open to challenge for bias, and they do
nothing to reduce the placebo effect. However, sometimes they are unavoidable,
particularly in relation to surgical techniques, where it may not be possible or
ethical to hide from the patient which treatment he or she received.
In a single-blind trial, the researcher knows the details of the treatment but
the patient does not. Because the patient does not know which treatment is being
administered (the new treatment or another treatment) there should be no placebo
effect. In practice, since the researcher knows, it is possible for them to
treat the patient differently or to subconsciously hint to the patient important
treatment-related details, thus influencing the outcome of the study.
In a double-blind trial, one researcher allocates a series of numbers to 'new
treatment' or 'old treatment'. The second researcher is told the numbers, but
not what they have been allocated to. Since the second researcher does not know,
they cannot possibly tell the patient, directly or otherwise, and cannot give in
to patient pressure to give them the new treatment. In this system, there is
also often a more realistic distribution of sexes and ages of patients.
Therefore double-blind (or randomized) trials are preferred, as they tend to
give the most accurate results.
Some randomized controlled trials are considered triple-blinded, although the
meaning of this may vary according to the exact study design. The most common
meaning is that the subject, researcher and person administering the treatment
(often a pharmacist) are blinded to what is being given. Alternately, it may
mean that the patient, researcher and statistician are blinded. These additional
precautions are often in place with the more commonly accepted term "double
blind trials", and thus the term "triple-blinded" is infrequently used. However,
it connotes an additional layer of security to prevent undue influence of study
results by anyone directly involved with the study.
The 'controlled' aspect comes from three main sources. The first is another
member of the research team, who will typically review the test to try to remove
any factors which might skew the results. For example, it is important to have a
test group which is reasonably balanced for ages and sexes of the subjects
(unless this is a treatment which will never be used on a particular sex or age
group). The second source of control is inherent in having a 'control' group,
that is, a group which is undergoing the same routine (seeing a doctor, taking
pills at the same time, etc.) but is not receiving the same treatment. This
control group will be receiving either no treatment (e.g., sugar pills) or will
be receiving the current standard treatment (if, for example, it would be
unethical not to treat their ailment at all). The third source of control is via
peer review and/or review by government regulators, who will examine the trial
when it is presented for publication or when the drug manufacturer applies for a
licence for the drug.
The importance of having a control group cannot be overstated. Merely being told
that one is receiving a miraculous cure can be enough to cure a patienteven if
the pill contains nothing more than sugar. Additionally, the procedure itself
can produce ill effects. For example, in one study on rabbits where these
subjects were receiving daily injections of a drug, it was found that they were
developing cancer. If this was a result of the treatment, it would obviously be
unsuitable for testing in humans. Because this result was reflected equally
between the control and test groups, the source of the problem was investigated
and it was shown in this case that the administration of daily injections was
the cancer risknot the drug itself.
The analysis of the trial results is a great skill in itself, and pharmaceutical
firms employ groups of statisticians to try to make sense of the data. Likewise,
regulators pay keen attention to the statistics, which can be used to hide
serious deficiencies in the effectiveness of a treatment.
A major difficulty in dealing with trial results comes from commercial,
political and/or academic pressure. Most trials are expensive to run, and will
be the result of significant previous research, which is itself not cheap. There
may be a political issue at stake (compare MMR vaccine) or vested interests
(compare homeopathy). In such cases there is great pressure to interpret results
in a way which suits the viewer, and great care must be taken by researchers to
maintain emphasis on clinical facts.
Most studies start with a 'null hypothesis' which is being tested (usually along
the lines of 'Our new treatment x cures as many patients as existing treatment
y') and an alternative hypothesis ('x cures more patients than y'). The analysis
at the end will give a statistical likelihood, based on the facts, of whether
the null hypothesis can be safely rejected (saying that the new treatment does,
in fact, result in more cures). Nevertheless this is only a statistical
likelihood, so false negatives and false positives are possible. These are
generally set an acceptable level (e.g., 1% chance that it was a false result).
However, this risk is cumulative, so if 200 trials are done (often the case for
contentious matters) about 2 will show contrary results. There is a tendency for
these two to be seized on by those who need that proof for their point of view.
Note: This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Randomized controlled trial".