ESSAY

ESSAY

Randomised controlled trials

Essay 1

Randomised controlled trials are the most rigorous way of determining whether a cause-effect relation exists between treatment and outcome and for assessing the cost effectiveness of a treatment. They have several important features:

Random allocation to intervention groups

Patients and trialists should remain unaware of which treatment was given until the study is completed—although such double blind studies are not always feasible or appropriate

All intervention groups are treated identically except for the experimental treatment

Patients are normally analysed within the group to which they were allocated, irrespective of whether they experienced the intended intervention (intention to treat analysis)

The analysis is focused on estimating the size of the difference in predefined outcomes between intervention groups.

A clinical trial is defined as a prospective scientific experiment that involves human subjects in whom treatment is initiated for the evaluation of a therapeutic intervention. In a randomized controlled clinical trial, each patient is assigned to receive a specific treatment intervention by a chance mechanism. The theory behind these trials is that the value of a treatment will be shown in an objective way, and, though usually unstated, there is an assumption that the results of the trial will be applicable to the care of patients who have the condition that was treated (Altman 2006).

Trials of potential treatments, for ethical reasons, tend to involve multiple stages, starting with small safety tests of the drug or other therapy. Once there is evidence of safety, and preliminary clinical trials, the effort moves to a larger scale: large multicentre clinical trials that are randomised, controlled, and double-blind using a control group of patients (i.e., "arm" of the trial) and an experimental arm.

Trials should be large, so that serious adverse events might be detected even when they occur rarely. Multi-centre trials minimise problems that can arise when a single geographical locus has a population that is not fully representative of the global population, and they can minimise the effect of geographical variations in environment and health care delivery. Randomisation (if the study population is large enough) should mean that the study groups are unbiased. A double-blind trial is one in which neither the patient nor the deliverer of the treatment is aware of the nature of the treatment offered to any particular individual, and this avoids bias caused by the expectations of either the doctor or the patient.

Other study designs, including non-randomised controlled trials, can detect associations between an intervention and an outcome. But they cannot rule out the possibility that the association was caused by a third factor linked to both intervention and outcome. Random allocation ensures no systematic differences between intervention groups in factors, known and unknown, that may affect outcome. Double blinding ensures that the preconceived views of subjects and clinicians cannot systematically bias the assessment of outcomes. Intention to treat analysis maintains the advantages of random allocation, which may be lost if subjects are excluded from analysis through, for example, withdrawal or failure to ...