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

#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.

 

References:

[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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#7 Practical RWE – Clinical Study Classification: Interventional or Non-Interventional?2024-02-01T14:57:36+00:00

#6 Practical RWE – Clinical Study Classification: Non-Interventional Study or Low Intervention Clinical Trial?

#6 Practical RWE – Clinical Study Classification: Non-Interventional Study or Low Intervention Clinical Trial?

 

Ideally, we would classify studies according to the level of intervention i.e., interventional, low intervention, and non-interventional.

However, although we assume clinical trials are the opposite of non-interventional studies and are therefore ‘interventional’, most regulators have been hesitant to define ‘intervention’ in their regulations.

In Europe, the EU Clinical Trials Regulation [ref 1], defines ‘clinical trials’, ‘low interventional clinical trials’, and ‘non-interventional studies’.

By definition [ref 1], a clinical trial is an investigation in humans that involves a medicinal product and the assignment of the patient to a therapeutic strategy is decided in advance  by the trial protocol i.e., protocol-defined healthcare intervention.

In a low intervention clinical trial (LICT), the assignment of the patient to a therapeutic strategy is still decided in advance  by the trial protocol, but the medicinal product is approved and used as per marketing authorisation.  So once again there is a protocol-defined healthcare intervention. In the case of a LICT, there are additional patient safety considerations i.e., any additional diagnostic or monitoring procedures that are implemented as part of the LICT must pose no more than minimal additional risk or burden to the safety of the trial participants compared to normal clinical practice.  Why?  If you increase the degree of risk to the patient above normal clinical practice…you have exceeded the ‘low risk’ threshold and the trial reverts to a ‘normal’ clinical trial.

Another consideration for LICT is that there is allowance for using medicinal products off-label (e.g., paediatric or oncology drugs), but their use in this context must be supported by “published scientific evidence on the safety and efficacy of those investigational medicinal products”…and again…the trial must meet the ‘low risk’ requirements such that any additional diagnostic or monitoring procedures applied to the patient poses no more than minimal additional risk or burden to the safety of the trial participants compared to normal clinical practice. 

Put simply, clinical trials and low intervention clinical trials involve protocol-defined healthcare interventions.

What about non-interventional studies?

By definition [ref 1], a non-interventional study is an investigation in humans that involves a medicinal product and the assignment of the patient to a therapeutic strategy is NOT decided in advance  by the trial protocol i.e., there is NO protocol-defined healthcare intervention. This means there are NO protocol-specified activities or procedures that alter the patients’ treatment regimens or plans i.e., there are no additional diagnostic or monitoring procedures applied to the patient that impact the patients’ treatment.

In summary, in Europe both low intervention clinical trials (LICT) and non-interventional studies (NIS) are investigations in humans that involves a medicinal product.  LICT involve protocol-defined healthcare interventions, whereas NIS do not.

 

References:

[1] 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.

Share this story...

#6 Practical RWE – Clinical Study Classification: Non-Interventional Study or Low Intervention Clinical Trial?2024-02-01T14:52:04+00:00
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