By Ruth Whittington (

Part 2 – How do observational studies and randomised controlled trials differ?

Last month, I described observational studies and where they fit into the hierarchy of evidence. Randomised controlled trials (RCTs) provide some of the fundamental answers to important questions about a drug’s efficacy and safety, and so are considered top of the hierarchy of medical evidence.

It is easy to be persuaded into thinking (as some of our customers and colleagues do) that RCTs are the be-all and end-all of the evidence needed for a drug. However, looking at one treatment in isolation will not reflect the likely situation in real life clinical practice.

The first major difference between observational studies and RCTs is in how patients are enrolled. For an observational study the question of whether the patient is suitable for enrolment occurs after treatment has been decided, whereas for an RCT it occurs before treatment has been assigned.

Steps in patient recruitment

Randomised controlled trials Observational studies
Step 1: Patient visits doctor Step 1: Patient visits doctor
Step 2: Suitable for trial? Step 2: Doctor assigns treatment
Step 3: Doctor enrols patient in trial Step 3: Suitable for study?
Step 4: Treatment assigned randomly Step 4: Patient enrolled

Once patients have been enrolled in the study, there are a number of ways to differentiate between randomised controlled trials and prospective observational studies. Compare and contrast these in the following table:

Differences between the conduction of a randomised controlled trial and the observational study:

Randomised controlled trials Observational studies
Control groups may include patients on placebo. All study patients are given the treatment that is thought best for them.
The trial design seeks to eliminate bias by keeping the physician and patient out of the treatment
selection process.
The physician selects the treatment physician with the patient’s knowledge and any bias in treatment assignment may be of interest in itself.
Patients who stop taking the treatment are removed from the trial. Patients who stop taking the treatment are asked why and offered alternatives.
Strict criteria applied for recruiting patients, such as age, gender, pre-existing conditions, medical history, etc. The only criteria are that the patient meets the disease definition and receives one of the treatments of interest at the outset of the study.
The population is intentionally homogenous in order to maximise the chance of detecting a possible effect of treatment. The population is more likely to be representative of patients receiving treatment in ordinary clinical practice.
Care protocol may be strict and other drug use is usually limited, to reduce confounding factors and possible drug interactions. Only normal levels of testing and limited interventions are allowed, so cost and resource use will reflect normal practice.
Care is usually provided by specialist clinics and may involve frequent physician visits, resulting in the highest standards of care; extensive patient testing and interventions may be involved. Care is provided by those physicians who would normally treat the patients, resulting in typical standards of care.
Objective clinical end points are measured Outcomes of most relevance to patients and those treating or caring for them are measured.
The trial can demonstrate treatment efficacy. The study can demonstrate overall effectiveness.