4. Types of Experimental Studies
| Site: | EUPATI Open Classroom |
| Course: | Epidemiology and Pharmacoepidemiology |
| Book: | 4. Types of Experimental Studies |
| Printed by: | Guest user |
| Date: | Tuesday, 3 June 2025, 3:15 AM |
1. Randomised controlled trials (RCT)
(This section is organised in the form of a book, please follow the blue arrows to navigate through the book or by following the navigation panel on the right side of the page.)
The randomised controlled trial (RCT) is considered as the most rigorous method of determining whether a cause-effect relationship exists between an intervention and outcome[1] and is the best design to explore if and how an intervention works. RCTs are trials that aim to evaluate the efficacy of an intervention in a well-defined and controlled setting. Usually, the intervention under examination is compared between two groups: the experimental group receiving the intervention and a comparison group (controls) which receives the standard treatment, no treatment or placebo. The study design aims to control for all known biases and confounders (e.g., by appropriate inclusion and exclusion criteria), so that the probability to observe an intervention's effect is maximized. Thus, groups should become as homogeneous as possible, and only one factor (also called the independent variable, in this case the IMP) that is relevant to the outcome varies. A strength of the RCT lies in randomisation that is unique to this type of study design. Generally, in an RCT, study participants are randomly assigned to either the experimental group or the control group. The groups are then followed prospectively according to the study protocol which is the set of rules by which the study is conducted.
Example: a trial of a new cancer treatment that randomly assigns patients to receive either the new treatment or the best existing treatment. The trial follows the patients to measure the risk or incidence proportion of recurrence (of cancer) and/or death among all patients.
[1] Kendall JM. Designing a research project: Randomised Controlled trials and their principles, Emerg Med J. 2003, March;20(2)164-168
2. Community intervention trials
Community trials are an extension of field trials. In community trials the study group is the entire community, rather than individuals. Conceptually, the difference is whether or not the intervention is implemented separately for each individual. If only two communities are involved in a study, one of which will receive the intervention and the other will not, random assignment of the community that receives the intervention is not required; differences in baseline characteristics will be the same whatever the method of assignment-only the direction of the differences will be affected.
Example: to study the efficacy of adding fluoride to the community water supply to prevent dental decay, two similar towns in New York State were studied in the Newburgh-Kingston water fluoridation trial (Ast et al, 1956[1]). In one town, fluoride was added to the water supply; nothing was done to the other town. Residents of both towns had dental examinations over a period of several years to measure the effect of the intervention. The outcome was that fluoride helped to prevent parodontids.
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)