Duration of the evaluation of additional risk minimization measures: the need for speed

Background: The evaluation of the effectiveness of additional risk minimization measures (aRMMs) has become an important element of risk management. In 2012, it became mandatory with amendments to the European Union’s (EU’s) pharmaceutical legislation and the Good pharmacovigilance practices (GVP) guidelines were released.

Objectives: The aim of this study is to assess the time needed for finalized aRMM evaluations with Pharmacovigilance Risk Assessment Committee (PRAC) conclusions for medicines licensed via the central authorization procedure in the EU.

Methods: A cohort that included medicines authorized through the EU centralized procedure between January 2005 and December 2017 was established using the European Public Assessment Report (EPAR) database of the European Medicines Agency. Generic, biosimilar and duplicate applications were excluded. Data on the presence of aRMMs at marketing authorization (MA) was extracted from the EPARs. For aRMMs implemented at MA, we were able to identify finalized evaluations between January 2017 and April 2021 using the PRAC minutes. Data on the time needed for the evaluation process was collected using clinical study reports and regulatory assessment reports via the Medicines Evaluation Board. The overall time as well as three consecutive time periods were calculated: aRMM implementation to start evaluation study, the evaluation study and assessment by PRAC.

Results: aRMMs were identified for 157 of the 615 (26%) medicines authorized between 2005 and 2017. Between 2017 and April 2021, 23 finalized aRMM evaluations of 21 unique medicines were identified, of which seven were authorized before 2012. The median time needed to complete the aRMM evaluation process was 5.3 years (IQR: 4.5-7.2). Specifically, the median time between aRMM implementation and start of data collection was 2.3 years (IQR: 1.6-5.0). Furthermore, the median duration of an aRMM evaluation study was 2.1 years (IQR: 1.5-2.8). More than half of the studies (n=13, 57%) were delayed for at least three months, mostly due to participant recruitment issues. Lastly, the median time needed for regulatory assessment by PRAC was 5.5 months (IQR: 2.1-7.0).

Conclusions: Approximately a quarter of the medicines authorized between 2005 and 2017 had aRMM(s) in place at time of MA. The time needed to complete the aRMM evaluation process for medicines authorized through the centralized procedure was about five years. Therefore, the feasibility of the draft GVP Module XVI rev 3 advice to measure effectiveness of aRMM at first 12 to 18 months after implementation has yet to be proven.