Clinical Trial vs Clinical Study – Synonyms or Significant Differences
According to ICH GCP, the terms CLINICAL TRIAL and CLINICAL STUDY are synonymous (Section 1.12 of ICH E6(R2)). If you run clinical trials this will probably have little or no impact on you. However, consider those of us who support and manage clinical studies that are not clinical trials e.g., observational studies and non-interventional studies (also known as Real World Research – RWR). Our studies are NOT the same or even similar to clinical trials, especially when it comes to the regulatory requirements we need to comply with. For a start, we aren’t governed by regulations that have their basis in ICH GCP. So…why add terminology to clinical trials guidance document that impacts observational studies and causes confusion, misdirection and horror(!) to those of us who already have our hands full trying to address the regulatory complexity of ‘not clinical trials’.
CLINICAL TRIAL/ STUDY
Any investigation in human subjects intended to discover or verify the clinical, pharmacological and/or other pharmacodynamic effects of an investigational product(s), and/or to identify any adverse reactions to an investigational product(s), and/or to study absorption, distribution, metabolism, and excretion of an investigational product(s) with the object of ascertaining its safety and/or efficacy. The terms clinical trial and clinical study are synonymous (as per Section 1.12 of ICH E6(R2)).

Are the Terms Clinical Trial and Clinical Study Really Synonymous?
Not according to FDA and EMA regulatory definitions!
According to the FDA, an observational study is a non-interventional clinical study design that is not considered a clinical trial (as per Glossary of Framework for FDA’s Real-World Evidence Program – Dec 2018); and according to the EU Clinical Trials Regulation, a non-interventional study is a clinical study other than a clinical trial (as per Article 2.2(4) of Regulation EU/536/2014 – See Table below).
The terms ‘clinical study’ and ‘clinical trial’ are not the same. The impact of grouping them together is far reaching and deconstructive. It causes confusion at the study design, approvals/submissions, conduct, and reporting levels. According to Albert Einstein, the definition of insanity is doing the same thing over and over and expecting different results. As someone who provides regulatory guidance for clinical studies that are not clinical trials, I know from first-hand experience that we can submit the same study type to IRBs/RECs and competent authorities and get different results. Insanity? If the regulatory definitions are unclear or without regulatory context/ guidance, it’s just as difficult for the regulators to implement as for the researcher to understand.
Take Home Point = The terms ‘Clinical Trial‘ and ‘Clinical Study‘ are not synonymous.
Term | Definition | Context |
---|---|---|
Clinical Study | ‘Clinical study’ means any investigation in relation to humans intended:
(a) to discover or verify the clinical, pharmacological or other pharmacodynamic effects of one or more medicinal products; (b) to identify any adverse reactions to one or more medicinal products; or (c) to study the absorption, distribution, metabolism and excretion of one or more medicinal products; with the objective of ascertaining the safety and/or efficacy of those medicinal products >>as per Article 2.2(1) of Regulation EU/536/2014 |
There must be a medicinal product for this to be a clinical study in the context of this regulation.
So, we know that this regulatory definition does not cover clinical research where there is no medicinal product e.g., disease registry studies. |
Clinical Trial | ‘Clinical trial’ means a clinical study which fulfils any of the following conditions:
(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. >>as per Article 2.2(2) of Regulation EU/536/2014 |
There must be a medicinal product for this to be a clinical trial in the context of this regulation.
So, think about this…what is a clinical research study in which patients are subjected to liver biopsies (physical interventions) and which does not involve a medicinal product? Is it a clinical trial in the context of this definition? |
Non-Interventional Study | ‘Non-interventional study’ means a clinical study other than a clinical trial
>>as per Article 2.2(4) of Regulation EU/536/2014 |
There must be a medicinal product for this to be a non-interventional study in the context of this regulation.
Oh…but don’t forget that the regulation that defines what a non-interventional study is, also derogates any responsibility to governing the clinical study type that they’ve just defined with an ‘anti-definition’ i.e., the regulations tells us what it is not, rather than what it is…err…thanks, I think. “This Regulation applies to all clinical trials conducted in the Union. It does not apply to non-interventional studies.” >>as per Article 1 of Regulation EU/536/2014 |