There are a number of steps to follow before a trial can commence. The first step is to confirm whether it falls within the scope of the European Directive (2001/20/EC) (PDF, 152 KB). This Directive was transposed into UK law by means of The Medicines for Human Use (Clinical Trials) Regulations 2004, which together with its amendments are referred to as the Clinical Trials Regulations within this Toolkit.
The Clinical Trials Regulations cover only investigations/studies which are undertaken to ascertain the efficacy or safety of a medicine in human subjects. Non-interventional trials are excluded from the Regulations. To classify a trial as non-interventional, it must meet all of the following criteria:
- involves products with a marketing authorisation that are prescribed in the usual manner and used in accordance with the authorisation;
- when the patient is assigned to a therapeutic strategy within current practice and not according to a protocol;
- the diagnostic or monitoring procedures are only those ordinarily applied to the therapeutic strategy;
- and epidemiological methods are used to analyse the data.
(defined in full in column E of the MHRA algorithm linked below).
If a study is not for the purpose of ascertaining the effects of or reactions to a product and the product is simply being used as an aid or tool in the study, it is not a clinical trial covered by the Regulations. For example, in the case of the study of blood flow involving the infusion of vasoactive substances, if the purpose of the study is to monitor the effects of a particular substance to see if it is effective in achieving a particular physiological effect, then it is not a clinical trial. If the infusion is for the purpose of modifying the rate of flow for a therapeutic indication such as claudication, it would be deemed a trial under the Directive as the purpose of the study is to establish the efficacy of a particular medicine.
A Clinical Trials Regulations Flowchart (pdf, 76.83 KB) has been developed which describes the relationship between the EU Directive and UK regulation including a brief description of each regulation. Any trial that falls within the scope of Directive 2001/20/EC is known as a Clinical Trial of an Investigational Medicinal Product (CTIMP).
The Medicines and Healthcare Regulatory Agency (MHRA) is the competent authority that regulates CTIMPs in the UK. The MHRA web pages describe the difference between Investigational Medicinal Products (IMPs) and Non-Investigational Products (NIMPs) and contains an algorithm (PDF) designed to help researchers determine if their trial is a CTIMP.
Researchers planning a CTIMP should be familiar with the MHRA Clinical Trials Pages to help ensure all legal requirements are considered.
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- Trial Planning & Design
- Within the scope of the Clinical Trial Regulations?
- Risk Assessment
- Protocol Development
- GCP & Serious Breach Reporting
- Trial Management & Monitoring
- Trial Documentation
- Trial Supplies
- R&D Consultation
- Funding Proposal
- Peer Review
- Funding Secured
- Trial Master File
- Unique Trial Number
- EudraCT Number
- Confirm Sponsor
- Feasibility & Investigator Selection
- Contracts & Agreements
- Final Protocol
- CI Checklist Before Seeking Approval
- CTA Submission
- Ethics Submission
- R&D Submission
- Permissions & Approvals Obtained
- Final Trial Management Documentation
- Trial is Abandoned
- Trial Begins
- Informed Consent
- Safety Reporting
- Progress Reporting
- Ongoing Management & Monitoring
- MHRA Inspection
- Addition of New Sites & Investigators
- Substantial Amendments
- Urgent Safety Measures
- Temporary Halt or Early Termination
- Trial does not Recommence
- End of Trial Declaration
- Statistical Data Analysis
- Clinical Trial Summary Report
- Dissemination of Results
Key to Symbols
Demonstrates processes that can be done in parallel
Demonstrates that not all processes will apply to all trials
|Standard Process||Legal Requirement||Good Practice|
|Specific for trials within Directive's scope|
|Relevant to all trials|