Non-Randomized Controlled Trials

Discover what a Non-Randomized Controlled Trial is. Understand its purpose, how it differs from a randomized controlled trial, and when it's used.

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Reviewed by Nam Tram, PharmD

Published 14 April 2024

There are many types of clinical trials, including randomized and non-randomized controlled trials, referring to how participants are chosen to take part. In this article, we will discuss what a non-randomized controlled trial is, how it differs from randomized trials, and the different types of non-randomized clinical studies.

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What is a non-randomized controlled trial?

A non-randomized controlled trial is a clinical trial where participants are selected specifically to a treatment group, unlike randomized clinical trials when individuals are chosen arbitrarily. Typically referring to quasi-experimental studies, participants can choose a treatment group that meets their requirements.

An example of a non-randomized controlled trial would be a cohort study that looks into the link between smoking and lung cancer. Researchers may handpick individuals based on how many cigarettes they smoke per day and their age or gender, and compare them to a control group - a group that is not exposed to smoking. The trial may last for several years, monitoring any adverse changes and if lung cancer develops.

This provides valuable insights into whether smokers are more prone to lung cancer and can also help to identify signs of cancer in patients earlier than before.

What is the difference between randomized and non-randomized trials?

The obvious difference between a randomized trial and a non-randomized one is that in randomized clinical trials the participants are allocated to a study group randomly, while in non-randomized trials they are allocated by the researchers conducting the trial.

Benefits of non-randomized trials

Non-randomized trials have a number of key benefits over randomized trials that make them preferable for certain studies.

  • Typically, non-randomized controlled trials cost less per participant, allowing for larger studies, or more frequent studies.
  • When compared to randomized trials, less planning and management may be required.
  • Non-randomized trials can be considered more ethical in terms of providing treatment that could be potentially harmful. Physicians who are convinced that a specific treatment is better than another for a certain patient cannot ethically choose at random which treatment to give.
  • They can provide measurable evidence of any effects caused by medical intervention.

Disadvantages of non-randomized trials

Like any form of clinical study, non-randomized controlled trials also have a couple of drawbacks that need to be outlined to participants.

  • As these types of trials often have more specific inclusion and exclusion criteria, it can limit the ability to apply the results to a broader population. The participants in these trials may not accurately represent the wider population, so it's difficult to say if the results would be the same for other groups.
  • There may be some bias when selecting participants which could impact the overall results of the trial, making any insights less valuable.

Different types of non-randomized controlled trials

There are a number of different types of non-randomized controlled trials, with different techniques used to assess the effectiveness of medical intervention. The type of trial used may also depend on a range of factors such as patient type, geographical location, timeframes, and expected outcome.

A standard NRCT involves participants being assigned to different intervention groups following a selection process. To be selected, a participant would usually need to meet certain requirements, such as them being based near a specific geographical location, their treatment preferences, and their availability. Each separate group would then be compared, assessing the various results of the different treatments administered.

Example: An example of an NRCT would be two different surgical procedures being administered, with one group receiving surgery A, which is the standard-of-care, and the other surgery B, which is the procedure being studied. The outcomes of the surgery will then be assessed to determine which has a higher success rate, a faster recovery time, or fewer side effects.

Types of non-randomized controlled trials include observational, quasi experimental - also known as “before and after studies”, case-control, and cross sectional studies.

Observational cohort study

This type of study focuses on a group of individuals over a period of time, allowing researchers to study the effects of interventions and treatment outcomes. Non-randomized participants are usually separated into two groups, exposed and unexposed, relating to their exposure to medical intervention. The comparison groups are formed based on variations in intervention usage that happen independently of the study. The data that is compiled over time is then compared to analyze the outcomes.

Example: This type of study could assess the long-term effects of a type of cardiovascular medication that is issued to participants who suffer from hypertension. Participants may be monitored in a medical facility, evaluating the effects of the exposure. Participants may then return for checkups over the next few years to determine the outcomes.

Quasi-experimental study (before and after study)

Quasi-experimental studies are similar to a randomized controlled trial but without the random selection of participants. In these types of studies, the study investigator has some degree of control over the allocation of interventions, as opposed to observational or cohort studies. These trials involve an intervention group and a non-intervention comparison group, allowing researchers to assess the effectiveness of the intervention.

Example: Smokers are also commonly assessed using this type of study. One group may continue to smoke regularly, while the second group may have quit or are in the process of quitting with the help of nicotine supplements. This helps researchers to assess the effects of smoking and its connection with a range of diseases.

Case-control study

A case-control is an observational study, examining natural variations that would have occurred regardless of the study. The study begins with individuals who have a particular medical case, in addition to a control group that does not have any known cases. These two groups are then compared to determine if there is any connection between exposures and the outcome.

Example: A case-control study may examine the connection between exposures to medication, such as a painkiller, and a rare, unexpected event such as an increase in liver toxicity. The evaluation that is conducted explores whether exposures (e.g., to the medication) are disproportionately distributed between the disease cases and the controls, thus potentially identifying a risk factor.

Cross-sectional study

A cross-sectional study helps to provide a snapshot of the population at a certain point in time. By doing so, researchers can highlight certain conditions, characteristics, or exposures that may be prevalent in the population, allowing necessary vaccinations to be rolled out.

Example: An example of this type of study could be an observational study that determines how common high blood pressure (hypertension) is among adults belonging to a certain demographic or community. 

The bottom line

Non-randomized controlled trials (NRCT) involve participants being allocated into treatment and control groups by the investigator, differing from randomized trials where candidates are selected by chance. They have a number of benefits over randomized trials, such as lower costs, less planning and management, and more ethics in some cases. However, there are some drawbacks in terms of comparing the outcomes, sometimes resulting in less valuable insights.

Common NRCTs include observational cohort studies, case-control studies, and cross-sectional studies.

If you would like to learn more about participating in non-randomized controlled trials, or any other type of clinical trial then you can find out more here.

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