RWE – Definitions

Authorised Investigational Medicinal Product

‘Authorised investigational medicinal product’ means a medicinal product authorised in accordance with Regulation (EC) No 726/2004 or in any Member State concerned in accordance with Directive 2001/83/EC, irrespective of changes to the labelling of the medicinal product, which is used as an investigational medicinal product.

(Article 2.2.9 of Regulation EU/2014/536)


 

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.

(Article 2.2.1 of Regulation EU/2014/536)


 

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.

(Article 2.2.2 of Regulation EU/2014/536)


 

Cluster Sampling

A sampling method in which each unit selected in a group of persons (all persons in a city block, a family etc) rather than an individual.

(A Dictionary of Epidemiology, Sixth Edition, 2014. Ed. Miquel Porta. Oxford University Press)


 

Cluster Trial/ Cluster Randomised Controlled Trial

A form of randomised controlled trial in which entire groups of participants (i.e., clusters), instead of individual participants are randomised. It is used to reduce the risk of contamination between participants receiving the experimental and control intervention.

(A Dictionary of Epidemiology, Sixth Edition, 2014. Ed. Miquel Porta. Oxford University Press)


 

Explanatory Trial/ Study

A study whose main objective is to ascertain some preliminary facts or to familiarize researchers with a problem or technology, often without a clear or precise hypothesis; or, sometimes, to screen several hypotheses at once in a preliminary fashion.

(A Dictionary of Epidemiology, Sixth Edition, 2014. Ed. Miquel Porta. Oxford University Press)


 

Low-Intervention Clinical Trial (LICT)

‘Low-intervention clinical trial’ means a clinical trial which fulfils all of the following conditions:

(a) the investigational medicinal products, excluding placebos, are authorised;

(b)  according to the protocol of the clinical trial,

(i)  the investigational medicinal products are used in accordance with the terms of the marketing authorisation; or

(ii)  the use of the investigational medicinal products is evidence-based and supported by published scientific evidence on the safety and efficacy of those investigational medicinal products in any of the Member States concerned; and

(c) the additional diagnostic or monitoring procedures do not pose more than minimal additional risk or burden to the safety of the subjects compared to normal clinical practice in any Member State concerned;

(Article 2.2.3 of Regulation EU/2014/536)


 

Non-Interventional Study (NIS)

‘Non-interventional study’ means a clinical study other than a clinical trial.

(Article 2.2.4 of Regulation EU/2014/536)


 

Non-Interventional Trial/ Study

Non-Interventional Study or Non-Interventional Trial: a study where the medicinal product(s) is (are) prescribed in the usual manner in accordance with the terms of the marketing authorisation. The assignment of the patient to a particular therapeutic strategy is not decided in advance by a trial protocol but falls within current practice and the prescription of the medicine is clearly separated from the decision to include the patient in the study. No additional diagnostic or monitoring procedures shall be applied to the patients and epidemiological methods shall be used for the analysis of collected data.

(Article 2(c) of 2001/20/EC – The EU Clinical Trials Directive)


 

Normal Clinical Practice

‘Normal clinical practice’ means the treatment regime typically followed to treat, prevent, or diagnose a disease or a disorder.

(Article 2.2.6 of Regulation EU/2014/536)


 

Observational Study

Refer to ‘Non-Interventional Study (NIS)’


 

Pragmatic Clinical Trial (PCT)

A study (including randomized clinical trials) whose aim is to determine the effects of an intervention under the usual conditions in which it will be applied. By contrast with an EXPLANATORY STUDY, the focus is on guiding decision e.g., about healthcare.

(A Dictionary of Epidemiology, Sixth Edition, 2014. Ed. Miquel Porta. Oxford University Press)


 

Pragmatic Clinical Trial – New Definition?

Califf et al., (2015) propose three key attributes of PCT s:

  1. 1)  An intent to inform decision-makers (patients, clinicians, administrators, and policy-makers), as opposed to elucidating a biological or social mechanism;
  2. 2)  An intent to enroll a population relevant to the decision in practice and representative of the patients or populations and clinical settings for whom the decision is relevant; and
  3. 3)  Either an intent to:
    1. streamline procedures and data collection so that the trial can focus on adequate power for informing the clinical and policy decisions targeted by the trial, or
    2. measure a broad range of outcomes

Given these attributes, a common-sense definition for a PCT would thus be as follows:

“Designed for the primary purpose of informing decision-makers regarding the comparative balance of benefits, burdens and risks of a biomedical or behavioral health intervention at the individual or population level” (Califf et al., 2015)