Register clinical trials in CTIS
All clinical trials are registered in the EU-joint web portal Clinical Trials Information System (CTIS). Everything regarding your clinical trial is managed within the portal; applications to the Medical Products Agency (Läkemedelsverket) and the Swedish Ethical Review Authority (Etikprövningsmyndigheten), continuous contact between Principal Investigator (PI) and regulatory authorities as well as reporting of results.
A clinical trial, according to the EU-regulation 536/2014, refers to an investigation in relation to humans intended to e.g. discover or verify the clinical, pharmacological or pharmacodynamic effects of a medicinal product as well as ascertaining the safety and efficacy.
From the 31 January 2023, all new clinical trials shall be registered in the European web portal CTIS. CTIS is replacing the old web portal EudraCT. Compared to the previous procedure for clinical trials applications, everything regarding the clinical trial is now managed in one system. One single clinical trial application is submitted to CTIS, where Läkemedelsverket and Etikprövningsmyndigheten will have access to the application. The regulatory authorities will review the application and provide feedback and decisions to the applicant directly in the CTIS portal.
Karolinska Institutet (KI) uses an ”Organization-centric approach” in CTIS, meaning that we at Compliance & Data Office (CDO) have an administrator account where we have an overview of all clinical trials registered through CTIS with KI as sponsor. We can also manage the KI-users’ different user roles in the system.
Create an account in CTIS
- In order to log in to CTIS you would first need to create an account with the European Medicines Agency (EMA). You can create an EMA account on their webpage.
- Once you have an EMA account, you can log in to CTIS.
- When you have entered the system, you need to double check that Karolinska Institutet is listed as your Employer. You do that by clicking on your name in the upper right corner and choose ”Personal profile”. Under ”My employer” it should say ”Karolinska Institute” and the address should be either ”Nobels vag 6, Solna” or ” Alfred Nobels Alle 8, Huddinge”.
Register a new clinical trial
To initiate a new clinical trial application, you need an EUCT-number (study number). Please contact firstname.lastname@example.org in order to get the EUCT-number and in the email please provide us with:
- Name of Principal Investigator
- EMA username of Principal Investigator
- Email address to Principal Investigator (should be the same email that’s used for the EMA-account)
- Title of the clinical trial
We at CDO will create a blank application for you and assign you the roles ”CT Admin for a specific trial” and ”ASR Submitter”. After this, you will get access to your application and the EUCT-number, and you can then begin working on your application in the system.
If more than one person needs access to the same trial, the PI can provide access for the other researchers by assigning roles to the specific trial.
A clinical trial application in CTIS consists by two parts:
- Part I contains study specific information (the same for the entire EU in case the study is a multinational study), e.g. study protocol and information about the investigational medicinal product. Part I can be written in English or Swedish. However, protocol and patient-related information should be in Swedish.
- Part II contains national information, e.g. trial site, recruitment arrangements, informed consent form and suitability of investigator. Part II should be written in Swedish.
More information on how to apply for a clinical trial in CTIS can be found on Läkemedelsverket’s webpage. There you can also find Swedish templates for Part II.
Once the application has been submitted, Läkemedelsverket and Etikprövningsmyndigheten will review the application in parallel. The decision will then be provided within the CTIS portal. During the review process Läkemedelsverket and Etikprövningsmyndigheten can send so called RFI’s (Request For Information) to the PI if adjustments are needed for the application. Please note that no email notifications are sent out, so you as a PI need to log in to CTIS on a regular basis in order to take part of the decisions and notifications!
The application review process normally takes up to 60 days but including potential RFI’s the process can be extended to a total of 106 days. For each RFI, you as a submitter have up to 10–12 days to reply. If you don’t reply before the deadline, the application will lapse, and you will then need to submit a new application. If you suspect you won’t be able to meet the deadline of the RFI or the application requires substantial adjustments, it might be beneficial to withdraw your application and resubmitting at a later timepoint, instead of risking the application to lapse or be rejected.
EMA has created a guide about timelines in CTIS where you will find more details around different deadlines.
Once the application is approved, it is important to regularly update the information about your trial in CTIS, e.g., report recruitment start date and study start. This should be reported within 15 days from the recruitment/study start has occurred. In CTIS, this is reported under the tab ”Notifications”.
In case any major changes are made to the protocol or any unexpected events occur during the course of the study, this should be reported as a ”substantial modification” or a ”non-substantial modification”. This should be reported within 15 days in case of an unexpected event and 7 days for an urgent safety measure or a serious breach. For examples, see EudraLex Volume 10 chapter 5, the Q&A document about the Regulation.
As long as the trial is ongoing, the PI must yearly upload an Annual Safety Report (ASR) in CTIS. Unfortunately, the ASR function in CTIS doesn’t allow you to save and continue later, so please make sure to have all documentation ready at hand when submitting the ASR. The ASR document should be in PDF format.
Reporting of results
According to the EU-regulation 536/2014 the sponsor should, regardless of the outcome of the trial (negative or positive results), report a summary of the trial results within 1 year after study completion (6 months if it is a pediatric trial). In Annex IV of the regulation you will find a description of what should be included in this summary. You should also include a layperson summary. The content of that summary is set out in Annex V of the EU-regulation.
Even if the results have already been published in a scientific journal, results must still be reported in CTIS.
PI:s with ongoing trials already registered in EudraCT and where the trial is expected to be completed after 31 January 2025, need to transfer these trials to CTIS. These trials must be submitted to CTIS by the 31 August 2024 the latest to ensure sufficient processing time, otherwise you risk having to register the trial as a completely new clinical trial application. Unfortunately, there is no simple function that auto-populates structured data from EudraCT into CTIS, this needs to be entered manually. However, EMA has agreed on an exception from some of the documents that are mandatory in the regulation but weren’t mandatory in the directive. If you have clinical trials that need to be transferred, please reach out to email@example.com and then we can help you get started.
The Medical Products Agency has decided to consider a transitional trial as a new application, which therefore requires a new application fee. If the application, however, is identical to a previously approved application (submitted via EudraCT), you could apply for a reduction of the fee.
For information on which documents in CTIS that are reviewed by Etikprövningsmyndigheten, please visit Etikprövningsmyndigheten's webpage on CTR.
Trials that have an ongoing application or amendment in EudraCT cannot be transferred to CTIS until the review of the application/amendment is completed.
Clinical trials that include biobank samples
A clinical trial that includes biobank samples requires an approved biobank application. A biobank application is submitted separately to the Regional Biobank Centre (Regionalt biobankscentrum) on the same day as the CTIS application is submitted. The biobank application will be reviewed in parallel to the clinical trial application but cannot be approved until the clinical trial application has been approved. At Biobank Sverige’s webpage you will find more information on clinical trials with biobank samples. Biobank applications are sent to firstname.lastname@example.org.
Clinical trials funded by the Swedish Research Council (Vetenskapsrådet)
The Swedish Research Council (Vetenskapsrådet) has new guidelines from 2022 stating that all clinical studies/trials funded by the Swedish Research Council must be registered in a public clinical trial registry.
It is Karolinska Institutet’s responsibility to make sure the PI of the study is registering and updating the study. Affected researchers will therefore be contacted by CDO with information and guidance.
Read more on the Swedish Research Council’s webpage.