It’s a simple question. Actually…no it isn’t.

The EU defines a non-interventional study as a “clinical study other than a clinical  trial” 😳 [ref 1].  Whereas the US FDA talks about “non-interventional (observational) studies”[ref 2].

So…let’s simplify things…for the sake of your sanity and mine.

In Europe, by definition [ref 1], a non-interventional study must involve a drug.  If your clinical study does not involve a drug…then by regulatory definition it cannot be a non-interventional study. Meaning?  Any other type of study with a non-interventional design will be an observational study…which may or may not be defined at the local level.

The EMA list of metadata for the Real World Data catalogues (which go live in February 2024) [ref 3] define the drug study types as ‘clinical trial’ or ‘non-interventional study’.  The non-interventional study, study designs are defined as: cohort| case-control| case-only| cross-sectional| ecological| cluster design| systematic review and meta-analysis.  Note the absence of ‘observational’.

In the USA, the terms ‘non-interventional study’ and observational study are used interchangeably:

A non-interventional study (also referred to as an observational study) is a type of study in which patients received the marketed drug of interest during routine medical practice and are not assigned to an intervention according to a protocol (as per Section II of the FDA Guidance) [ref 2].

However, the FDA definition implies that a non-interventional study must involve a drug.

In summary, in both Europe and America, a non-interventional study must involve a drug.  If your clinical study does not involve a (marketed) drug…then by regulatory definition it cannot be a non-interventional study.

References:

[1] Article 2.2(4) of Regulation EU/536/2014: https://eur-lex.europa.eu/eli/reg/2014/536

[2] Section II 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

[3] Section 2.2(II) of the EMA List of Metadata for Real World Data Catalogues (May 2022): https://www.ema.europa.eu/en/documents/other/list-metadata-real-world-data-catalogues_en.pdf

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.