Here you’ll find the steps required to update and add results to entries on the US clinical trials register, ClinicalTrials.gov, and to the EU Clinical Trials Register.
WHY DO THIS?
Researchers have an overriding set of ethical and legal obligations to report results from clinical trials. It should be a professional goal to ensure summary results are reported fully in a timely manner. Research funders and ethics committees are increasingly examining the track records of researchers to ensure past work has been reported before funding or approval decisions. Parliaments and Government bodies have now said that they will monitor reporting and ask institutions that don’t comply to explain why not. More and more groups are monitoring compliance with laws and rules.
It is in researchers’ professional interests to report results and also to ensure publicly available information on the clinical trials they are running is kept up to date and accurate. This is to ensure researchers and the public can know about trials being conducted and so that sanctions for non-reporting aren’t applied unfairly. In many circumstances it is mandatory under the rules that clinical trial register entries are complete and accurate. Ensuring register entries are accurate and results are reported should be part of the standard procedure for running any trial.
There is no barrier to uploading results and keeping information up to date – the steps here will be straightforward for anyone who has run a clinical trial and there is no charge for doing any of the following.
A BIT MORE ON LEGAL OBLIGATIONS
ClinicalTrials.gov is the US register. Any researcher from any country may register their trials there. Many interventional clinical trials of drugs and devices, and all clinical trials funded by the US National Institutes of Health, are required to be registered on ClinicalTrials.gov and to report results there under the FDAAA 2007 law and other related regulations. Read more about which specific clinical trials registered on ClinicalTrials.gov are required by law to report results onto the register here:
All trials carried out in the EU have been added to the European EU Clinical Trial Register since June 2004. These are all subject to the EU’s clinical trials reporting guidelines and legislation so all of them have to have their results recorded on the EU register.
The EU reporting requirements may also apply to certain trials conducted outside the EU (such as pediatric trials that will be part of a marketing authorization in the EU). The European Medicines Agency has published clear guidelines to reporting requirements, follow the link to read them in full.
The clinical trial laws in the US and EU both mandate that summary results for clinical trials are reported directly onto the register within 12 months of the end date of the trial.
WHO ULTIMATELY IS RESPONSIBLE FOR DOING THIS?
In both the EU and the US, a designated responsible party, usually referred to as the sponsor, is liable for ensuring information about a clinical trial on the register is accurate and up to date and that results are reported on time. Generally, the sponsor will be the company or institution which has oversight of the trial rather than the research funder or any individual researcher. There are some cases in which the Primary Investigator (PI) of the trial will act as a sponsor or accept some responsibility for the data on the registry entry.
Under US law the responsible party is the sponsor by default, but the sponsor can also designate a study PI as a responsible party. When this occurs, it is noted publicly on the trial record under “Information provided by (Responsible Party)”.
In the EU, the sponsor of the clinical trial is the designated responsible party. When trials have multiple sponsors, the EUCTR takes no stance on which is the responsible party – this is expected to be handled by the sponsors among themselves.
The Step-By-Step Guide to Updating Register Entries And Adding Results
This guide has been prepared by AllTrials in collaboration with experienced clinical trialists. We would appreciate any feedback from users at firstname.lastname@example.org
ADDING RESULTS TO AN ENTRY ON CLINICALTRIALS.GOV
Finding and accessing the trial entry
Each trial registered on ClinicalTrials.gov is linked to a specific sponsor. It should be clear on the register entry who the sponsor is and therefore who is responsible for maintaining the information. Generally, universities and companies will each have an institutional account in the Protocol Registration and Results System (PRS). Clinical trials will have been registered by someone using this account and therefore linked to the correct sponsor. Logging into an institutional account gives access to the register entries for all the sponsor institution’s trials.
Sponsor organisations tend to have nominated administrative staff who manage the institutional account. Your institutional administrators will probably be able to give you access to specific register entries to allow you to make updates, but in some cases may prefer that you work with compliance staff on edits to the entry and making your results available. Different organisations have different compliance workflows.
The ClinicalTrials.gov summary template asks for information on how the clinical trial was designed and carried out, the main results for the outcomes set out in the trial protocol, and the conclusions.
- Log in to the account used to register the trial
- Go to the Protocol Registration and Results System (PRS)
- The PRS User Guide is located here for any general queries about using the PRS system
- Ensure the protocol information for your trial is up to date and accurate. Changes/updates to information in the register entry can be submitted alongside results submissions.
- Enter results information into the defined fields. ClincialTrials.gov asks for results in four sections – Participant Flow; Baseline Characteristics; Outcome Measures and Statistical Analyses; and Adverse Events. It is important that submitted results remain internally consistent to pass the ClinicalTrials.gov review process.
- When all the results sections are completed submit the results to ClinicalTrials.gov for review. A staff member at the registry will check your submission for validity, logic and internal consistency, for the formatting of the results and the protocol.
- ClinicalTrials.gov staff may contact the responsible party for clarifications. Generally this will happen within 28 calendar days. You are then required, by law, to address these comments and resubmit within 28 days.
- After passing review ClinicalTrials.gov will make the results tables public.
ADDING RESULTS TO AN ENTRY ON THE EU CLINICAL TRIALS REGISTER
Results can be added retrospectively. The steps to follow are the same whether the trial ended 10 years ago or one year ago.
Finding and accessing the trial entry
Entries on the EU clinical trial register are made up of information submitted to the National Competent Authority that originally gave the researcher permission to run the clinical trial. Results information is the only information a researcher can add to EU CTR directly. For everything else the information must go through the national authority.
- Sponsors of clinical trials should apply for a secure sponsor account. Check with your institution, as they may already have an account and can designate access to you.
- Log in using this account and ‘claim’ the trial as belonging to the sponsor.
- A template results form is generated by EudraCT system and will be displayed in the secure area after log in with the secure account. The form has:
- fixed fields generated from information in the trial protocol that results must be reported against
- free text fields to be used if the fixed fields do not accommodate all the results you want to report.
- In some circumstances it is possible to upload results in the form of a document produced for some other reason, for example a journal article or the synopsis section of a Clinical Study Report. This is only possible for trials that ended on or before 21 July 2013, for more recent trials you’ll need to fill in the full table of results information. The EMA will supply the list of acceptable results documentation.
- Fill in the fields on the results form.
- Submit the results form.
- Staff at EudraCT will review the information. They may ask the researcher for clarifications or to resolve conflicting or questionable information.
- Once validated, the EMA’s system will make most results information public, according to the regulations set out here.
Note – when the new EU Clinical Trials Regulation begins to apply, expected towards the end of 2019, a new trial portal will be launched. The new database will contain basically the same information as the current register but has been designed to be more user friendly. We will update this guide with the equivalent steps for the new register once it is live. There will be a transition period when both registers will be usable. It is unclear whether there are any plans to migrate trial information from the EU CTR to the new trial portal at any point.
UPDATING AN ENTRY ON CLINCIALTRIALS.GOV
ClinicalTrials.gov entries covered by the FDAAA 2007 law are required to update their entries once every 12 months, and if no changes are required, the researcher must make a declaration that the current information is accurate. Certain fields must be updated within 30 days for any changes including the trial’s recruitment status and completion dates. Section 11.64 of the Final Rule and the ClinicalTrials.gov FAQ covers these requirements in detail.
While the subset of trials covered under the FDAAA 2007 law have precise guidance on how and when they must update fields, even if your trial is not covered by the relevant law, your funder, sponsor, or institution may require that you keep trial information reasonably up to date. Regardless of any requirements, ensuring that information on the registry is accurate is both ethically sound and valuable to the research community, medical professionals, and interested members of the public.
Sponsors/researchers will need to log in with the account details used to register the trial. This will probably be an institutional account overseen by a member of the institution’s staff.
- Log in to the account
- Go to the Protocol Registration and Results System (PRS) of ClinicalTrials.gov
- Click on “Edit Record”and make the edits needed.
- After making the changes, submit the entry to ClinicalTrials.gov for review and acceptance. If no issues are found, updates usually post within a few days.
UPDATING AN ENTRY ON THE EU CTR
Entries on the EU CTR are made up of information uploaded by the National Competent Authority (NCA) in EU member states. (When a researcher receives ethical permission to run a clinical trial, they then apply to the competent authority for authorisation, and this body forwards the trial information to the EMA if the trial receives permission to proceed. For example, in the UK the competent authority is the MHRA, in France it is l’ANSM. (See the list of authorities in all EU countries and their contact details here) This means that if your trial is of a medicinal product covered by EU law, your trial will automatically be registered onto the EU CTR upon acceptance by the NCA.
Unlike adding results information, which a researcher or representative of the sponsor can do directly onto the register entry, updates to register entries need to be done through the national competent authority which originally authorized the clinical trial. Researchers should have the EudraCT number of the specific trial on hand to allow the authority to locate and identify the record. It is important to note that EudraCT records can be made up of a number of protocols for each EU country in which the trial takes place. Global or country specific changes to the protocol may require you to contact multiple national authorities.
Amendments can be submitted to authorities using the EU CTR Substantial Amendment Form, which is available here.
EU law defines a substantial amendment as one that will create a significant difference to the scientific value of the trial or to the safety or wellbeing of the trial participants, and it is up to the sponsor of the trial to assess whether amendments are substantial or not.
End dates of the clinical trial or changes to these should be notified to the national competent authority using an EU Declaration of the End of Trial form (available to download here) and the National Competent Authority will amend the information on the status of the trial on the database. Use the same form to notify the NCA that the trial failed to recruit any participants so they can add a note to the register entry to say that no results are expected.