#7 Practical RWE – Clinical Study Classification: Interventional or Non-Interventional?


And so…we come to the most painful, controversial, and confusing of the definitions… ”intervention” and “interventional”.

Ideally, we would classify studies according to the level of intervention i.e., interventional, low intervention, and non-interventional. However, most regulators have been hesitant to define ‘intervention’ in their regulations. Only a few countries (e.g., USA, France, and South Africa) [refs 1 to 3] have defined “intervention” in the context of clinical trials.

If ‘intervention’ isn’t defined in the regulations of the region of interest it becomes difficult (impossible) to define what is, and is not, an intervention, and therefore what is, and is not, a clinical trial.

There is a simple solution.  Most countries define a ‘clinical trial’.

For example, in Europe:  ‘Clinical trial’ means a clinical study which fulfils any of the following conditions [ref 4]:

(a)  the assignment of the subject to a particular therapeutic strategy is decided in advance and does not fall within normal clinical practice of the Member State concerned;

(b)  the decision to prescribe the investigational medicinal products is taken together with the decision to include the subject in the clinical study; or

(c)  diagnostic or monitoring procedures in addition to normal clinical practice are applied to the subjects

So…when classifying a clinical study, the recommendation is to determine whether the proposed study is a clinical trial.

If the study isn’t a clinical trial, then what is it?

In Europe, a ‘non-interventional study’ is a clinical study other than a clinical trial [ref 4].

Therefore, in Europe both clinical trials and non-interventional studies (NIS) are investigations in humans that involves a medicinal product.  Whereas, clinical trials involve protocol-defined healthcare interventions, and NIS do not.



[1] Section III.A of the FDA Guidance – Considerations for the Use of Real-World Data and Real-World Evidence to Support Regulatory Decision-Making for Drug and Biological Products (August 2023): https://www.fda.gov/media/171667/download

[2] Article L1121-1 of the Public Health Code (CSP): https://www.legifrance.gouv.fr/codes/article_lc/LEGIARTI000032722870/

[3] Glossary of the Department of Health – Ethics in Health Research Guidelines: Principles, Processes and Structures (2015): https://www.health.gov.za/wp-content/uploads/2022/05/NHREC-DoH-2015-Ethics-in-Health-Research-Guidelines-1.pdf

[4] Article 2 of the EU Clinical Trials Regulation (Regulation EU/536/2014): https://eur-lex.europa.eu/legal-content/EN/TXT/?uri=CELEX%3A02014R0536-20221205

In essence, definitions lay the groundwork for accurate, consistent, and meaningful research, especially in areas where the data and its sources are as diverse and complex as in RWD and RWE.

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