Consultation outcome

Appendix 3: Risk-adapted approaches to the management of clinical trials of investigational medicinal product

Updated 16 December 2021

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The current regulatory framework in the UK/EU allows for a range of risk-adapted approaches that may simplify the processes for initiating and conducting some clinical trials. These adaptations are largely related to how much is known about the investigational medicinal product (IMP). A simple risk categorisation is proposed, based on the marketing status of the IMP and standard medical care.

The potential risks should be balanced against the level of risk that a trial participant would be exposed to outside of the trial. We propose a three-level categorisation, based on the classification put forward by Brosteanu and colleagues in the ADAMON Project[footnote 1].

  • Type A = No higher than the risk of standard medical care
  • Type B = Somewhat higher than the risk of standard medical care
  • Type C = Markedly higher than the risk of standard medical care

A pragmatic approach to achieving this would be to use the marketing authorisation status of the medicines being investigated, as proposed below.

0.1 Trial category based upon potential risk associated with the IMP

Type A: no higher than that of standard medical care

Examples of types of clinical trial

Trials involving medicinal products licensed in any EU member state if:

  • they relate to the licensed range of indications, dosage and form or
  • they involve off-label use (such as in paediatrics and in oncology, etc) if this off-label use is established practice and supported by sufficient published evidence and/or guidelines
Type B: somewhat higher than that of standard medical care.

Examples of types of clinical trial

Trials involving medicinal products licensed in any EU member state if:

  • such products are used for a new indications (different patient population/disease group) or
  • substantial dosage modifications are made for the licensed indication or
  • if they are used in combinations for which interactions are suspected

Trials involving medicinal products not licensed in any EU Member State if:

  • the active substance is part of a medicinal product licensed in the EU

(A grading of TYPE A may be justified if there is extensive clinical experience with the product and no reason to suspect a different safety profile in the trial population.)

Type C: markedly higher than that of standard medical care

Examples of types of clinical trial

Trials involving a medicinal product not licensed in any EU member state.

(A grading other than TYPE C may be justified if there is extensive class data or pre=clinical and clinical evidence.)

  1. Brosteanu et al. “Risk analysis and risk adapted on-site monitoring in non-commercial clinical trials.” Clinical Trials 2009: 585-596 ↩

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