Non-Interventional Studies (NIS)
- Non-Interventional Studies (NIS)
- Observational Study
- Non-IND Study
- Disease Registry
- Product Registry
- Post-Authorisation Safety Study (PASS)
- Real World Evidence
- Are non-interventional studies regulated?
- What are the regulatory requirements for my study?
- What GxPs are applicable to NIS?
- Do we need informed consent?
- Is my research interventional or non-interventional?
- If my study requires questionnaires that are not standard of care, does this make it interventional?
What is a Non-Interventional Study?
According to the official regulatory definitions:
“Non-Interventional Study or Non-Interventional Trial is 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 (as per Article 2(c) of 2001/20/EC)”
- In these studies, interviews, questionnaires, blood samples and patient follow-up may be performed as part of normal clinical practice (as per Section VIII.A of GVP Module VIII)
Non-interventional studies are defined by the methodological approach used and not by its scientific objectives. Non-interventional studies include database research or review of records where all the events of interest have already happened (this may include case-control, cross-sectional, cohort or other study designs making secondary use of data). Non-interventional studies also include those involving primary data collection (e.g. prospective observational studies and registries in which the data collected derive from routine clinical care), provided that the conditions set out above are met. In these studies, interviews, questionnaires, blood samples and patient follow-up may be performed as part of normal clinical practice (as per Section VIII.A of GVP Module VIII)
A More Practical NIS Definition?
A more practical definition, based on our experience, is:
- A study that involves a medicinal product
- The protocol does not dictate which medicinal product the patient receives, this is decided by the treating Physician in advance of inclusion of the patient into the study (i.e., there is no treatment intervention)
- Physical interventions, such as study-specific blood draws, additional questionnaires and diagnostic procedures may be allowed. This is country-dependent
- Countries where extra blood draws are not allowed include, for example, France and Austria
Critical Factors for NIS in Europe:
- NIS not covered by the Clinical Trials Directive (2001/20/EC) or Clinical Trials Regulation (EU/536/2014)
- As a result, GCP does not apply…
- NIS covered by country-level regulations and guidelines
How do Non-Interventional Studies Differ from Clinical Trials?
Interventional or Non-Interventional?
We are often asked about what makes a non-interventional study, interventional. This is a seemingly logical question given that there is a regulatory definition for “non-intervention” and “low intervention”. What might surprise you is that in 99% of countries there is no regulatory (legal clinical research) definition for “intervention”. With France being an exception.
From a regulatory perspective, a more appropriate question would be – “Is my research a clinical trial? If not, what is it?”
Do physical interventions make my non-interventional study interventional?
- Interventional or Non-Interventional Study?
- Non-Interventional + Blood Sample = Interventional?
- Non-Interventional + Diagnostic Test = Interventional?
- No Drug = Non-Interventional Study?
- No Drug + Blood Sample = Interventional?
- No Drug + PRO = Interventional?
- Not Interventional = Non-Interventional?
Are we asking the right questions?
- Interventional or Non-Interventional?
- Clinical trial or not a clinical trial?
- Not a clinical trial?Then what is it?
Regulatory Framework for Clinical Studies
In essence, simplicity comes from unraveling the regulatory complexity of non-interventional studies = the complex simplicity of NIS.