Long-Term Safety Evaluation of a Medicinal Product in Inherited Haematological Disorder in Europe


Non-Interventional Post-Authorisation Safety Study


The efficacy and long-term effectiveness of the test product in preventing painful crises and decreasing mortality and morbidity in patients suffering from an inherited disease affecting red blood cells, was previously established. Despite a first safety study, safety information regarding the use of the test product on long-term remains incomplete. An extension of the latter is proposed in this study aims to provide supplement data on specific safety concerns when using the test product in routine clinical practice in adult and paediatric patients and followed for up to 5 years.


Multicentre, prospective, non-interventional cohort study in adult and pediatric patients affected by the haematological condition and treated with the test product.



Long-term safety profile of the test product: poorly documented or unknown risks (not listed in the product information).


  • Changes in fertility status in males and females
  • Pregnancy outcomes
  • Potential barriers to the compliance to the prescription of the test product
  • Switch or combination with new treatments
  • Complications linked to the disease
  • Quality of life of adult patients


  • 2 Interim Clinical Study Reports (study ongoing)
  • 2 DSMB
  • Overall excellent client satisfaction

Key factors of success

  • ICTA’s expertise in site selection and management
  • ICTA’s responsiveness
  • ICTA’s expertise in Data Management

LESSONS LEARNED to speed up the start-up phase of the next study

  • Importance of close collaboration between ICTA and Sponsor and active involvement of Sponsor during the course of the study, in keeping the sites engaged
  • Due to the new GDPR regulation and the new French EC submission process, the site selection should be anticipated in order to collect CV in parallel of the protocol finalization, and the data flow should be described in a separate document for the EC submission
  • Implement an electronic signature system of the site financial contract to optimize its signature/collection
  • Adapt the study objectives according to the reality on the site (content of medical records and routine care visits)
  • Define the key data and PV requirements well beforehand.
  • Importance of setting up a steering committee to provide expert clinical guidance and a high standard of scientific quality.


Sites selection

Multicenter study carried out in several European countries
ICTA’s longstanding partners in European countries mandated for:

▪ Regulatory submissions
▪ Sites management in 4 European countries: France, Italy, Germany, Greece
▪ 120 contacted sites
▪ 88 selected sites
▪ 71 active sites
▪ 12 ready-to-include sites
► 69% of sites were willing to participate in the study.
Site contract management

▪ Several types of contract to be managed likely to lead to errors
▪ Follow-up of sites who agreed to finalize the financial contract

▪ Sound explanations to sites
▪ Close follow-up of site contacts and site reminders to obtain required documents and signature
. Management of physician data privacy
A total of 83 contracts were sent
▪ 83 financial contracts were in conformity with requirements and were signed (⇔ 100% of active sites)
Patients recruitment

N = 2,500 patients to be enrolled over a planned 5-year period
▪ Close follow-up of site (data collection visits, quality control visits, remote monitoring and close-out)
▪Close collaboration with the Sponsor who is actively involved with site coordination.
A total of 71 active sites recruited at least one patient
To date:
▪  1,738 patients recruited after 2.5 years of recruitment (⇔ 70% of the target sample size)
Discussion to reduce recruitment duration
Data collection and monitoring

▪ Study burden
▪ Lack of time and/or resource
▪ Keep the study simple and easy
▪ Focused on must-have data in the eCRF
▪ Data in accordance with routine care practice data
▪ ICTA resources provided to sites for data entry
Data quality ensured

▪ Monthly report of edit checks and posted queries (including status)
▪ Regular remote monitoring