Paving: Gene therapy in haemophilia

Haemophilia is a rare genetic bleeding disorder occurring in 1 of 10 000 births. Haemophilia A is caused by an error in the gene for coagulation factor VIII (FVIII) and haemophilia B is caused by an error in the gene for coagulation factor IX (FIX). These errors cause patients to bleed for a longer time compared to people with the correct gene.

Bleeds can occur after injuries in mild and moderate haemophilia, but can also occur spontaneously in severe haemophilia. Bleeding can also occur in joints, where it causes joint swelling, pain, stiffness and immobility. Today, haemophilia treatment is based on increasing coagulation factor concentrations through factor replacement therapy to prevent and treat bleeds.

The invasiveness of intravenous injection and the high administration frequency results in a high burden of treatment. Recently, gene therapy for the treatment of haemophilia has been developed. Clinical trial results are promising and gene therapy may be able to cure patients. However, multiple challenges remain. These challenges mainly relate to the fact that it is currently still unknown whether the therapeutic effect of gene therapy will be maintained throughout the full lifespan of patients, and what side effects may occur in the long run.

In the Patient preferences to Assess Value IN Gene therapies (PAVING) case study, we had a look at how features of the standard therapy and gene therapy influence patients’ choices between these therapies.


Woollacott, I, Morgan, G, Chowdary, P, et al. Examining patient and professional perspectives in the UK for gene therapy in haemophilia. Haemophilia. 2022; 1- 22.

van Overbeeke, Eline; Hauber, Brett; Michelsen, Sissel; Peerlinck, Kathelijne et al. Patient preferences for gene therapy in haemophilia: Results from the PAVING threshold technique survey. Haemophilia. 2021; 1-11.

van Overbeeke E, Hauber B, Michelsen S, Goldman M et al. Patient Preferences to Assess Value IN Gene Therapies: Protocol Development for the PAVING Study in Hemophilia, Frontiers in Medicine, 9 March 2021

Van Overbeeke E, PAVING the way: Patient preferences to Assess Value in Gene therapies, PhD thesis, KU Leuven

Van Overbeeke E, Michelsen S, Hauber B, Peerlinck K, Harmans C, Lambert C, Goldman M, Simoens S, Huys I, Patient perspectives regarding gene therapy in haemophilia: Interviews from the PAVING study, Haemophilia, 2020;00:1–8.

Lay language summary of qualitiative work

De meeste hemofiliepatiënten staan positief tegenover gentherapieën, Vereining van hemofilie- von Willebrandpatiënten en andere stollingsstoornissen (AHVH)


Therapeutic area: Haemophilia

Study led by: KU Leuven

PREFER leads team: Eline van Overbeeke, Isabelle Huys

MPLC decision point of interest: Post-marketing, Pre-marketing: future developments

PREFER case study acronym: MSD

Clinical objectives: To compare patient preferences for antithrombotic treatment attributes for patients with an acute MI and patients with chronic disease. To assess preference heterogeneity in other relevant subgroups.

Patients from: United Kingdom, Acute MI patients recruited by NHS clinical sites,
Chronic patients recruited via patient panels

Methods in Qualitative study: Semi-structured interviews

Methods in Quantitative study:Discrete Choice Experiment (DCE), Best-worst Scaling Case 1

End-date qualitative data collection: June 2018

End-date quantitative data collection: Target: May 2020

Therapeutic area: Haemophilia
Study led by: KU Leuven
Prefer leads team: Eline van Overbeeke, Isabelle Huys
MPLC decision point of interest: HTA/reimbursement
PREFER case study acronym: KUL - PAV
Clinical objectives: Identify attributes of gene therapy and standard of care that are important to patients, Understand trade-offs that patients make when choosing between gene therapy and standard of care
Patients from: Belgium
Methods in Qualitative Study: Semi-structured interviews
Methods in Quantitative study: Threshold technique
End-date qualitative data collection: September 2019
End-date quantitative data collection: May 2020






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The Patient Preferences in Benefit-Risk Assessments during the Drug Life Cycle (PREFER) project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 115966. This Joint Undertaking receives support from the European Union's Horizon 2020 research and innovation programme and the European Federation of Pharmaceutical Industries and Associations (EFPIA).