What is a post-authorisation safety study (PASS)?
- A post-authorisation safety study is a study that is carried out after a medicinal product has been authorised. The aim of the study is to obtain further information on a medicine's safety, or to measure the effectiveness of risk-management measures. A PAS study can be either a clinical trial or a non-interventional study.
- PAS studies are either imposed or voluntary. In the case of CAR T-cell therapies MAHs are obligated to carry out imposed PAS studies. The EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) approves the study protocol and assesses the outcomes of these studies.
Is this a study that requires ethical approvals?
- The standard informed consent form and data collection procedures for the EBMT Registry do not require additional ethical approval and allow EBMT to share aggregated data with the MAHs and health authorities. However, EMA wants to receive patient level data. In addition we want to enhance data quality by source data verification of the reported data. As per GDPR, the patients need to give informed consent for these two new data processing purposes. That is why an updated consent form has been created.
- After the relevant authorities have approved the updated informed consent form, patients will need to (re-)consent to allow their data and their pseudonymised data to be monitored and shared with MAHs and the EMA in order to support regulatory decision making.
- In some countries only a local Data Protection Officer needs to review and approve the use of the updated Informed Consent Form. In other countries, the central and/or local ethical committees need to review the EBMT Registry Framework and related documents such as the informed consent form, contracts, etc.
- It is important to note when submitting the documents that this is a Registry that will share pseudonymised data with collaboration partners only if the patient consents to this.
I have heard people talking about an embargo, what does that mean?
The MAHs have negotiated, with EBMT, an embargo period for the release of the outcome data as defined in the PAS study protocol. This embargo prevents EBMT from publishing the outcome data within the specified period. However, this embargo does not prevent centres from using and publishing the data from their own patients.
How are patient rights protected?
- Patient consent is the legal basis and priority of the EBMT Registry. Therefore it is extremely important to ensure patients receive appropriate information, can ask questions and take their time to consider if they wish to share their data with the EBMT and EBMT collaboration partners.
The updated informed consent form allows patients to provide consent on if and how they wish to share their data. Explicit consent is requested from patients if they wish to share their data with EBMT’s collaboration partners by use of checkboxes.
- Patients are informed on how to exercise their rights in the informed consent form and this information is also publically available in the EBMT Patient Privacy Statement
Why is EBMT collaborating with pharmaceutical companies?
- Collaboration across stakeholders is key to solving the main challenges in the field of cellular therapies. In the context of the EMA-endorsed PAS studies it is important for EBMT to collaborate with the MAHs so we can ensure that the long-term follow-up data on CAR T-cell therapies is not siloed in private databases of MAHs but remains available to academic research and can further benefit patients. We believe in ‘collecting data once and using it often’. With a harmonised minimal data set we aim to support both regulatory decision making by authorities as well as scientific studies by EBMT members and our academic partners.
- EBMT supports further collaboration across stakeholders in the field of cellular therapies through the GoCART Coalition.
What should I do if I have a research proposal?
- If you have a research proposal you can present it to any of the EBMT Working Parties that discuss and select the best proposals. If your proposal is selected/accepted by a Working Party, you will not only have direct access to data from your centre but indirectly be able to access data from other centres in your country or the EBMT Registry as a whole. Working Parties have dedicated statisticians, data managers and study coordinators available that will support the conduct of the selected proposals.
- In addition GoCART has regular calls for research proposals that focus on multi-stakeholder collaboration. More information can be found on the webpage: https://www.ebmt.org/ebmt/gocart-coalition
Who can I contact if I have further questions?
EBMT has appointed both lead study coordinators and lead investigators for each country. Please refer to the list above in the “Find your country. Find your contact” section to identify the correct person to reach out to.
Why does EBMT need to collect minimal identifiable data including the date of birth?
- EBMT is committed to protecting patient privacy. We only collect personal data we actually need for our specified data processing purposes. This includes minimal identifiable data to ensure that patient data that is collected at different time points is accurately stored in the same patient record and that the correct reporting centres are provided access to the right records. Also, it allows for the identification and prevention of duplicate patient records within the system, which is essential to maintaining data integrity. The minimal identifiable data is not used to identify individual patients.
- All data in the EBMT Registry is reported pseudonymised. Full names of patients are never collected. The minimal data collected within the EBMT Registry is limited to the hospital UPN (Unique Patient Number), patient initials, date of birth (DD-MMM-YYYY), and gender. Without these minimal identifiable data, data integrity cannot be guaranteed.
- Privacy authorities explicitly recognise that a registry is a separate type of data collection. Consideration 157 of the GDPR states: “in order to facilitate scientific research, personal data can be processed for scientific research purposes, subject to appropriate conditions and safeguards set out in Union or Member State law.”
- Data subjects are asked to consent to the collection of their Date of Birth in the EBMT Registry database and are informed through the Patient Information Leaflet and Informed Consent Form for Sharing Data with the EBMT and EBMT collaboration partners and the patient privacy statement on the EBMT website (https://www.ebmt.org/patient-privacy-statement).
When does data collection start?
- Data collection per the regular data collection forms and procedures does not require additional contracts and regulatory approvals. Consequently this data collection is already ongoing. You are requested to provide all data available on patients treated with CAR T-cell therapies within one month of treatment or the follow up visits.
- The contracts EBMT has sent you define the reimbursement and additional product specific requirements for reporting. The regulatory submissions are meant to update the EBMT informed consent form to obtain patient consent to share their data with the MAHs. Until the approval of the updated consent form and subsequent patient reconsent have been obtained, data will only be shared in aggregate reports. As indicated above, finalising the contracts and obtaining approvals for the updated informed consent do not need to be completed before the data collection per the EBMT Registry standard procedures.
Why do I have to report data to multiple registries?
EBMT works together with many national registries to harmonise data collection and reduce data management efforts for centres. Despite this effort, in some countries, centres may be required by national health authorities to report data on patients treated with CAR T-cell therapies to other registries as well. EBMT cannot control this and emphasises that this is separate from your EBMT commitments.
Who will have access to the data of my patients?
- EBMT’s access to the EBMT Registry is restricted to EBMT research staff. Working Party (WP) members can submit proposals for studies to the WP, which – upon approval by the WP – will be run by the dedicated EBMT research staff who have access to the Registry data.
- A member centre, as joint controller together with the EBMT, has continuous access to data of their patients. Personal, non-transferable usernames and passwords are given to individuals who are authorised by the principal investigator of the member centre where they work. In each case, access is awarded at different levels.
- Upon request from a member centre, the EBMT may grant national registries, those in the field of HSCT and IEC therapy and/or specific diseases, direct access to the EBMT Registry data of said member centre. The aim is to facilitate data registration and minimise duplication of data management activities for member centres that need to submit similar data to these registries. Yet, national registries are only given access to the data of patients within their own country and, if applicable, to only those patients with the concerned disease. The EBMT has contracts governing the processing and usage of data in line with GDPR requirements with all national registries that have access to the EBMT Registry.
How do I report my data?
We request you to report data on all patients treated with CAR T-cell therapies that have consented to sharing their data with the EBMT. Data can be reported on the cellular therapy form in ProMISe as you are used to (Login to ProMISe). Moreover, we kindly ask you to comply with additional data requests to ensure completeness and quality of the data.
When do I report data?
- Data on patients treated with CAR T-cell therapies needs to be reported at the following time points: baseline, 100 days, 6 months and then yearly up until 15 years have passed and at that time a 15 year follow up will be conducted.
- We ask you to report data on all patients treated with CAR T-cell therapy within one month of treatment or the follow up visits.
Can I use my own data?
Yes, we encourage you to use your own data that has already been entered in ProMISe in the past.
European Medicines Agency FAQs
What is the role of the EMA?
- The European Medicines Agency (EMA) is responsible for the scientific evaluation of centralised marketing authorisation applications for all advanced therapy medicinal products (ATMPs). The EMA advises the European Commission on final product approval. The Pharmacovigilance Risk Assessment Committee (PRAC) is the EMA committee responsible for assessing and monitoring the safety of human medicines.
- For ATMPs a post-authorisation study to monitor the product’s safety and efficacy profiles in the long term may be imposed. For the currently marketed CAR T-cell therapies, the PRAC approved study protocols that are based on secondary use of EBMT Registry data.
What is the EMA positive qualification opinion of the EBMT Registry?
- The EMA has issued a positive qualification opinion of the Cellular Therapy Module of the EBMT Registry. This means that the EMA Committee for Medicinal Products for Human Use (CHMP) considers that “the current status of the cellular therapy module of the EBMT Registry (coverage, core dataset, governance, quality assurance approaches, and completeness of core variables), may allow its use as a data source for regulatory purposes in the context of drug utilisation studies, drug efficacy/effectiveness studies and drug safety evaluation studies concerning CAR T-cell therapies authorised for haematological malignancies”.
- View the EMA's qualification opinion
Data Collection Initiative FAQs
What is the difference between the Post Authorisation Safety (PAS) study and the data collection initiative?
Marketing Authorisation Holders (MAHs) of a CAR T-cell product are legally obliged to conduct a PAS study. The Pharmacovigilance Risk Assessment Committee (PRAC) of the EMA approved the secondary use of registry data in the PAS studies. EBMT has the leading European registry and is providing data to MAHs to support their PAS studies. EBMT only shares the data that the MAHs require to perform their PAS studies. MAHs cannot use the data for other purposes. EBMT performs a data collection initiative (DCI) to ensure data accuracy and completeness in support of the PAS studies.
Who else participates in the data collection initiative?
All European centres that treat patients with CAR T-cell therapies have been invited.
How is the data collection initiative different from the normal data contribution to EBMT?
This data collection initiative to support regulatory decision making is based on the standard cellular therapy data collection forms and Registry procedures. The difference with the normal data contribution is that in addition to sharing data with EBMT’s regular collaboration partners, we now ask patients to consent to sharing their data with MAHs and health authorities. This requires (re-)consent on the updated informed consent form. Also, in order to ensure the quality of the data, your centre may be selected for a monitoring visit. This requires a clinical research associate to visit your centre and verify the collected data within patient files (source data).