By Ruth Whittington ([email protected])

This is the first in a series of four articles about observational studies. It’s our impression that observational studies (also known as “naturalistic studies”) are becoming more and more important to healthcare authorities, and it behoves us all to understand more about the uses and abuses of this type of research.

So we have created this series to 1) describe what they are, 2) show how they differ from randomised controlled trials in the way data are collected, 3) have a brief look at how they should be conducted, and 4) describe how to interpret the results.

“Science is built up of facts, as a house is built of stones; but an accumulation of facts
is no more science than a heap of stones is a house.”
Henri Poincare (mathematician, 1854–1912) Science and Hypothesis, 1905

Part 1 – What are observational studies?

While randomised, controlled clinical trials (RCTs) are the cornerstone of the drug development process, they cannot replicate actual clinical practices. Observational studies help close the evidence gap by providing insights into real life situations, and thus aid our understanding of how both patients and their clinicians manage healthcare problems.

Observational studies are characterised by the lack of intervention when treatment decisions are made; the treatments are administered as they would be in normal clinical practice, and information is collected regarding the outcomes of those treatments. This means that switching therapies midway through the treatment can be common – patients are not restricted to a particular drug therapy. Some observational studies are carried out retrospectively using existing databases of patient data, but the most robust and useful type of study is carried out prospectively; i.e. the study design is decided, then the patients are enrolled.

Observational studies can also collect data on outcomes important to patients that may not be included in RCTs, for example:

  • quality of life;
  • satisfaction with treatment;
  • out-of-pocket expenses;
  • activities of daily living/independence;
  • employment status/time off work;
  • social inclusion;
  • impact on careers; and
  • longer term outcomes (can be over many years).

Patients and their concerns are central to the study, and unlike RCTs, patients are active partners in both their treatments and the study. Typically, patient reported outcomes (PROs) are integral to the study design.

The table below shows where observational studies tend to fit on the hierarchy of evidence established by Bandolier.

Levels of evidence

Level 1 is the highest; i.e. considered the most robust. Levels of evidence system adapted from Bandolier.


While RCTS answer questions such as “Is medicine efficacious?” or “Is a treatment safe and tolerable?” these answers are often provided in highly controlled settings, which may mean that the findings are not easily translated to actual clinical practice.

So while RCTs can provide definitive answers in specific circumstances and populations, other evidence is required to answer more far-reaching questions now posed by healthcare authorities, such as

  • How will this treatment work in actual clinical practice?
  • What happens if the patient has co-existing conditions?
  • Will treatment be taken according to the dosage regimen prescribed?

Large, well-designed prospective observational studies help provide answers to these all-important questions about medicine use in the real world.