Randomised control trials

Reviewed and revised 26 August 2015

OVERVIEW

The Randomised Controlled Trial (RCT) is the ‘gold standard’ in evidence-based medicine, representing the highest levels of evidence

• level I and II evidence
• allocates volunteers or subjects to one of two groups (ie. control & treatment group)
• the technique of allocating subjects in clinical trials, thus overcoming bias when samples are compared, ensures descriptive characteristics are randomly distributed amongst groups and that any difference is due to chance alone

TYPES OF RANDOMISATION

(1) simple – no restriction on allocation (groups may be unequally sized)
(2) block – allocation is performed in blocks, so that groups are equally sized within each block.
(3) stratified – factors such as age, sex… are randomised separately, so that they are equally distributed amongst the groups.

Computer-generated random numbers are usually used to generate the group that a patient goes into.

STRENGTHS AND WEAKNESSES OF RCTs

Strengths

• only type of study able to establish causation
• ability to assign and administer treatment or intervention in a precise, controlled way.
• decreases selection bias and minimises confounding due to unequal distribution in a chosen population
• measurements can be chosen precisely making it easier to make observations consistently (especially parametric data)
• blinding is easier improving credibility
• decreasing patient or observer bias
• controlling of group allocations enhances similarity of baseline features so it is easier to form basis for statistical hypothesis
• can make trial large -> may detect clinically relevant conclusions
• can have subgroup analysis enhancing usefulness for clinical practice
• a successful RCT with conclusive or inconclusive results is eminently publishable.

Weaknesses

• high cost
• increased time (clinical practice may move on while the study is being performed)
• logistically challenging (e.g. difficulty organising/supervising multiple sites & locations)
• results may not always mimic real life treatment situation (e.g. inclusion / exclusion criteria; highly controlled setting)
• risk of choosing treatments or subjects whose consent is not valid or unethical treatment is involved
• is a small trial has very stringent parameters -> type II errors decreased at the expense of applicability for a chosen population
• practice misalignment can occur
• knowledge translation into clinical practice does not always occur

HOW TO CONDUCT A CLINICAL TRIAL

• See How to conduct a clinical trial

HOW TO ANALYSE A CLINICAL TRIAL

• See How to analyse a clinical trial

WHEN AN RCT SHOULD NOT BE PERFORMED

Reasons

When unnecessary

• If the effect of an intervention is dramatic and unequivocal (e.g. insulin for type I diabetes, parachutes for jumping out of planes)

When inappropriate

• If measuring infrequent adverse outcomes
• If evaluating interventions designed to prevent rare events
• If the outcomes of interest are far in the future
• If random allocation may reduce the effectiveness of the intervention

When impossible

• If there is reluctance or refusal of clinicians and other key people to participate If there are ethical objections
• If there are political obstacles
• If there are legal obstacles
• If there are interventions that cannot be allocated on a random basis
• If there is potential contamination
• If the scale of the task is too great

When inadequate because their external validity, or “generalizability,” is too low because

• Health care professionals who participate may be unrepresentative
• Patients who participate may be atypical
• Treatment may be atypical

References and Links

LITFL

• CCC — How to conduct a clinical trial
• CCC — Early stopping of trials

Journal articles

• Ospina-Tascón GA, Büchele GL, Vincent JL. Multicenter, randomized, controlled trials evaluating mortality in intensive care: doomed to fail? Crit Care Med. 2008 Apr;36(4):1311-22. doi: 10.1097/CCM.0b013e318168ea3e. Review. PubMed PMID: 18379260.
• Smith GC, Pell JP. Parachute use to prevent death and major trauma related to gravitational challenge: systematic review of randomised controlled trials. BMJ (Clinical research ed.). 327(7429):1459-61. 2003. [pubmed]
• Vincent JL. We should abandon randomized controlled trials in the intensive care unit. Crit Care Med. 2010 Oct;38(10 Suppl):S534-8. doi: 10.1097/CCM.0b013e3181f208ac. PubMed PMID: 21164394

FOAM and web resources

• CONSORT Statement Website