How to apply for a clinical trial including eligibility, phases, model IMPDs, costs and how to make changes to your application.
To apply, you must be the sponsor of the trial, or someone authorised by them. If you are not established in the European Community then your legal representative must make the application.
When a clinical trial authorisation (CTA) is needed
Use the MHRA’s online algorithmto find out if your study needs MHRA authorisation.
The algorithm is a set of questions that determine:
- whether the substance you’re testing counts as a medicinal product
- whether your trial counts as a clinical trial within the scope of the relevant EU directive
You can also read theto help you decide if your study needs a CTA.
If you are still unsure, email a copy of the protocol (the document describing the objectives, design and methodology) to email@example.com, with ‘Scope - protocol review’ as the subject line.
You’ll need a EudraCT number.
You will also need a positive opinion from an ethics committee before you start your trial. You can get this before, at the same time or after you have made your submission to MHRA.
Clinical trial application form
You must create XML and PDF versions, save and sign them electronically, and submit them on a CD with the rest of the required documents.
Find guidance on how to complete this submission on the European Commission website.
Clinical trial phases
There are 4 phases of a clinical trial and a product can only go to the next phase if it has passed the safety and effectiveness tests of the previous one. Your application must specify the phase.
Phase I trials, sometimes called first-in-human trials, test a small number of subjects to find out how the treatment works in the body. This type of trial aims to find the lowest dose at which the treatment is effective (the minimum therapeutic dose) and the highest dose at which it can be taken without causing harm.
Phase II trials test the treatment in several hundred people with a given disease or condition. They aim to find out how well the treatment works in larger numbers, identify common side effects, and refine the dose and length of treatment.
Phase III trials typically compare the treatment across several thousand patients to gather more detailed information on how well it works in groups of patients and its safety. The results influence the prescribing and patient information of a medicine once it is marketed.
Trials are carried out after a medicine has been licensed and put on the market. These trials are designed to find out more about the long term harms and benefits of a medicine and to discover new uses for it.
Documents to send with your application
Your submission package must include:
- a covering letter (when applicable, the subject line should state that the submission is for a Phase I trial and is eligible for a shortened assessment time, or if it is submitted as part of the notification scheme)
- a clinical trial application form in PDF and XML versions
- a protocol document
- an investigator’s brochure (IB) or document replacing the IB
- an investigational medical product dossier (IMPD) or a simplified IMPD
- a non-investigational medicinal product dossier (if required)
- a summary of scientific advice from any Member State or the European Medicines Agency (EMA), if available
- manufacturer’s authorisation, including the importer’s authorisation and Qualified Person declaration on good manufacturing practice for each manufacturing site if the product is manufactured outside the EU
- a copy of the EMA’s decision on the paediatric investigation plan and the opinion of the paediatric committee, if applicable
- the content of the labelling of the investigational medicinal product (IMP) (or justification for its absence)
- proof of payment (not required for applications made under the notification scheme)
All documents must have copy and paste functionality. You must provide a file for each section of the submission, even if you don’t have to provide the documents as part of your application. If you do not need to include documents in a section, you must insert a document which gives an explanation for why the document has not been supplied.
The information you provide in the submission package will be used to validate your application. Incomplete applications will be rejected. You can submit your applications using the Common European Submission Platform (CESP). Alternatively you can send submissions on a CD to:
Information Processing Unit
Medicines and Healthcare products Regulatory Agency
151 Buckingham Palace Road
All documents must have copy and paste functionality and the CD must be clearly marked with:
- the EudraCT number
- a description of contents eg
- initial application
- response to remarks from an initial application
- amendment to a CTA
- the company name
- the date sent
We have produced guidance on.
Example investigational medical product dossiers (IMPDs)
If you are carrying out a trial using modified established medicines, MHRA has produced some mock examples of completed IMPDs which set out our minimum requirements:
Assessment of your submission
The initial assessment will be completed within 30 days of being submitted. Applications for healthy volunteer trials and sponsor-determined phase I trials in non-oncology patients may qualify for a shortened assessment time (average 14 days). You should state on your covering letter if you think your trial is eligible.
We will tell you the outcome of your submission, which could be:
- acceptance of the request for a clinical trial authorisation
- acceptance of the request for a clinical trial authorisation subject to conditions
- grounds for non-acceptance of the request for a clinical trial authorisation
If we do not accept your submission you will be told why and will usually have to amend your application and resubmit.
Change your application before or during assessment
You can submit further supporting documentation before assessors begin their assessment of the application. You can’t send additional documents once we have begun assessment.
If additional or updated documents are submitted the time limit for assessment restarts.
To submit updated or additional documentation you should notify us by email outlining the changes you intend to make.
The email must be sent by the contact person listed in the application form and must be entitled:
‘Changes to submitted documentation/additional documentation to CTA (Number XXXXX/XXXX/XXX-XXXX) - EudraCT Number XXXX-XXXXXX-XX.’
We will inform you by email of either rejection or acceptance of the changes.
If the request is accepted, you should submit the documentation on CD to the address above. This must be received no later than day 23 from receipt of a valid application. This date will be on your acknowledgement letter.
Withdraw your request before the final decision
You may withdraw your request at any point before a decision on authorisation is reached. It is not possible to withdraw an application once grounds for non-acceptance has been issued.
To withdraw an application you must send an email entitled ‘Withdrawal of CTA – EudraCT Number XXXX-XXXXXX-XX.’ The email must be sent by the contact person listed in Section C.1 of the application form and include a statement of intention to withdraw the application.
You must also send a signed, formal letter on company-headed paper including:
- the EudraCT number, CTA number (if available) and protocol number of the application to be withdrawn
- a brief description of the reasons for withdrawing the application
Once we receive the formal letter, it will be processed within 5 days and an acknowledgement email will be sent to you to confirm that the application has been withdrawn.
If you want to resubmit your application after withdrawing it, you must state that it is a re-submission in the covering letter and on the application form.
We provide a notification scheme for certain lower-risk trials, defined as ‘Type A’ trials. In these cases, the risk to the patient from the IMP is considered to be no greater than that of standard medical care.
Trials under the notification scheme also have simplified requirements for conducting the trial. Our guidance documentgives more information about these requirements.
These are trials involving medicinal products licensed in any EU Member State if:
- the trial relates to the licensed range of indications, dosage and form of the product
- the trial involves off-label use (such as in paediatrics and oncology) that is established practice and supported by enough published evidence and/or guidelines
|Applications with an IMPD||£3,400|
|Applications without an IMPD||£250|
|Clinical trial variation/amendment||£250|
|Phase IV notification||£0|
For the purposes of fee determination, an application supported by quality data for blinding purposes (for example placebo comparator or over-encapsulation) remains within the category of applications without an IMPD.
When paying please quote your EudraCT number.
You must pay before you submit your application. Proof of payment must be stated in the covering letter or included as a separate document (eg photocopy of cheque/confirmation of bank transfer).
You can contact MHRA Cashiers Department on 020 3080 6069/6671 or email firstname.lastname@example.org for more information on how to pay fees.
To get further information about your submission contact the clinical trials helpline on 020 3080 6456 (Monday to Friday 8:30am to 4.30pm) or email email@example.com.
For status and tracking enquiries you should call the Regualtory Information Service on 020 3080 7400 or email firstname.lastname@example.org.