Objective: This study aims to i) evaluate the association between EU regulatory measures and national market access measures and ii) assess the impact of regulatory measures on the rate of and time to reimbursement of centrally authorised medicines in Belgium.
Methods: Included medicines were granted a European centralised marketing authorization between 2015 and 2020, excluding generic products/biosimilars. The association between the application of regulatory measures and market access measures is assessed in a logistic regression model (i) and the impact of regulatory measures on the time to and rate of reimbursement was tested via cox regressions (ii). 
Results: A total of 322 medicines were selected for inclusion of which the time to and rate of availability were calculated and the impact of regulatory measures assessed. Included regulatory measures were installed at the European level and relied on the unmet medical need concept as eligibility criterium. Analysis resulted in 79 (24.4%) medicines with orphan designation, 11 (3.4%) included in the PRIME scheme, 25 (7.7%) accelerated assessed, 22 (6.8%) conditionally authorized, and 11 (3.4%) authorized under exceptional circumstance, with some medicines applied a combination of these regulatory measures. Of all include medicines, 282 (88%) were submitted a dossier for reimbursement in Belgium, and 167 (52%) were reimbursed at the time of analysis, leaving 155 (48%) not reimbursed. (i) Logistic regression showed a positive association between the application of any regulatory measure and the application of any market access measure (i.e. compassionate use program, medical need program, managed entry agreement, or early temporary reimbursement) (p<.001). For individual regulatory measures, no significant association was found with the application of any market access measure, except for the accelerated assessment (p<.001). (ii) Two cox regression analyses were performed with varying survival intervals; a) the interval between marketing authorization application and reimbursement and b) the interval between submission of the reimbursement dossier and reimbursement. Predictors are the identified regulatory measures. No significant impact was reported of any regulatory measure on both a) the time and rate to reimbursement starting from MA application and b) the P&R assessment time.
Conclusion: Inclusion in expediting regulatory pathways often implicates a higher acceptance of uncertainties which can be justified considering the high need for those medicines. However, if the national payer/regulator does not agree upon the relative pressing nature of the respective need, the remaining uncertainties can be unacceptable, impacting pricing and reimbursement decisions. This study found that medicines that obtained any regulatory measure by the EMA are more likely to also obtain any included market access measure in Belgium, possibly indicating alignment in prioritization between the EMA and the Belgian HTA body/payer. Nevertheless, there is no (positive) significant impact of these regulatory measures on the time to and rate of availability in Belgium. However, there is also no (negative) significant impact of any regulatory measure on the P&R assessment time, as one might expect due to the limited available data package. More alignment between the EMA and the national HTA body/payer on eligibility criteria for medicines to be included in expediting pathways and the underlying required evidence to support regulatory and HTA/payer decision-making could ensure that medicines for which there is an important unmet medical need reach patients earlier, not only in theory but also in practice.

**Objective:** This study aims to i) evaluate the association between EU regulatory measures and national market access measures and ii) assess the impact of regulatory measures on the rate of and time to reimbursement of centrally authorised medicines in Belgium.
**Methods**: Included medicines were granted a European centralised marketing authorization between 2015 and 2020, excluding generic products/biosimilars. The association between the application of regulatory measures and market access measures is assessed in a logistic regression model (i) and the impact of regulatory measures on the time to and rate of reimbursement was tested via cox regressions (ii). 
**Results**: A total of 322 medicines were selected for inclusion of which the time to and rate of availability were calculated and the impact of regulatory measures assessed. Included regulatory measures were installed at the European level and relied on the unmet medical need concept as eligibility criterium. Analysis resulted in 79 (24.4%) medicines with orphan designation, 11 (3.4%) included in the PRIME scheme, 25 (7.7%) accelerated assessed, 22 (6.8%) conditionally authorized, and 11 (3.4%) authorized under exceptional circumstance, with some medicines applied a combination of these regulatory measures. Of all include medicines, 282 (88%) were submitted a dossier for reimbursement in Belgium, and 167 (52%) were reimbursed at the time of analysis, leaving 155 (48%) not reimbursed. (i) Logistic regression showed a positive association between the application of any regulatory measure and the application of any market access measure (i.e. compassionate use program, medical need program, managed entry agreement, or early temporary reimbursement) (p<.001). For individual regulatory measures, no significant association was found with the application of any market access measure, except for the accelerated assessment (p<.001). (ii) Two cox regression analyses were performed with varying survival intervals; a) the interval between marketing authorization application and reimbursement and b) the interval between submission of the reimbursement dossier and reimbursement. Predictors are the identified regulatory measures. No significant impact was reported of any regulatory measure on both a) the time and rate to reimbursement starting from MA application and b) the P&R assessment time.
**Conclusion**: Inclusion in expediting regulatory pathways often implicates a higher acceptance of uncertainties which can be justified considering the high need for those medicines. However, if the national payer/regulator does not agree upon the relative pressing nature of the respective need, the remaining uncertainties can be unacceptable, impacting pricing and reimbursement decisions. This study found that medicines that obtained any regulatory measure by the EMA are more likely to also obtain any included market access measure in Belgium, possibly indicating alignment in prioritization between the EMA and the Belgian HTA body/payer. Nevertheless, there is no (positive) significant impact of these regulatory measures on the time to and rate of availability in Belgium. However, there is also no (negative) significant impact of any regulatory measure on the P&R assessment time, as one might expect due to the limited available data package. More alignment between the EMA and the national HTA body/payer on eligibility criteria for medicines to be included in expediting pathways and the underlying required evidence to support regulatory and HTA/payer decision-making could ensure that medicines for which there is an important unmet medical need reach patients earlier, not only in theory but also in practice.

IMPACT OF EXPEDITING UNMET MEDICAL NEED REGULATORY MEASURES ON REIMBURSEMENT OF MEDICINES IN BELGIUM 

For it's 35th anniversary, DIA Europe is back in Basel, where all thought leaders meet in person to discuss, inspire, and network.

Join us in Basel: March 22-24, 2023

DIA Europe 2023 is designed to drive insights into action by connecting key policy discussions to real-world knowledge that you need for your everyday job. Your participation will accelerate your growth and your organization's performance in the drug development ecosystem.

Gathering innovative thought leaders from the entire life science landscape, DIA always has the aspiration to be ahead of current developments, reflected by 4 new content tracks in 2023:

- Artificial Intelligence and Data Science
- EU Health Policy and Regulatory Strategy
- Medical Devices and Combination Products
- Professional Development

DIA Europe 2023

A global, member-driven non-profit organization mobilizing life sciences and healthcare. DIA fosters innovation to improve health and well-being worldwide. Professionals from 80 countries continue to engage with DIA through our unparalleled membership network, educational offerings, and professional development opportunities.