4. Types of Experimental Studies

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3. Pragmatic clinical trials

The term pragmatic was used for trials designed to test the effectiveness of an intervention in broad routine clinical practice in order to maximize applicability and generalisability. The research question is whether an intervention actually works in real life. The GetReal Institute defines a pragmatic clinical trial as ‘a study comparing several health interventions among a randomised, diverse population representing clinical practice, and measuring a broad range of health outcomes’. Pragmatic clinical trials are focused on evaluating benefits and risks of treatments in patient populations and settings that are more representative of routine clinical practice. To ensure generalisability, pragmatic trials should represent the patients to whom the treatment will be applied, for instance, inclusion criteria may be broader (e.g., allowing co-morbidity, co-medication, wider age range), and the follow-up may be minimised and allow for treatment switching.
In order to overcome the inherited heterogeneity, which leads to dilution of the effect, pragmatic trials must be large enough (to increase power to detect small effects) and simple in their design. Simple trials are easier to plan, perform, and follow.

Example: Monitoring safety in a phase III real-world effectiveness trial: use of novel methodology in the Salford Lung Study[2] describes the model of a phase III pragmatic clinical trial where patients were enrolled through primary care practices using minimal exclusion criteria and without extensive diagnostic testing, and where potential safety events were captured through patients’ electronic health records and triggered review by the specialist safety team. While a classical RCT is looking at the causal relationship and the mechanism of action, this kind of pragmatic trial design is still an RCT but with a focus on the effectiveness and less the mechanism behind.


[1] Homepage - GetReal Institute (getreal-institute.org)
Launched in October 2013, GetReal was a three-year project of the Innovative Medicines Initiative (IMI), a EU public-private consortium consisting of pharmaceutical companies, academia, HTA agencies and regulators (e.g., NICE, HAS, EMA and ZIN), patient organisations and SMEs). In June 2018 the follow up project 'GetReal Initiative' was launched.

[2]  The Salford Lung Study: a pioneering comparative effectiveness approach to COPD and asthma in clinical trials - PMC (nih.gov)
The Salford Lung Study: a pioneering comparative effectiveness approach to COPD and asthma in clinical trials (Pharmacoepidemiol Drug Saf 2017;26(3):344-352)