WC500165698

Summary of advice
The PRAC acknowledged that regarding the cancer signal, 3 reviews of mechanistic studies, one metaanalysis
of randomized trials and observational studies, 3 clinical trials and 8 observational studies had
been conducted. For insulin glargine in particular, publications of 2 non-clinical studies, one clinical trial
and 7 observational studies were assessed. Regarding the signal of cardiovascular morbidity, a series
of papers retrieved following a literature search were reviewed. Overall, 7 mechanistic studies, 11
randomized trials, 2 meta-analyses of randomized trials and 22 observational studies were assessed.
In addition to assessing these publications, the MHRA performed a Drug Utilisation Study using the
Clinical Practice Research Datalink to examine how insulin is being used to treat type 2 diabetes in the
UK, and compared this with recommendations for use of insulin described in national clinical guidance.
The PRAC stressed that the cancer risk associated with insulin use in the treatment of type 2 diabetes
is the focus of highly-active and fast-moving research. Nonetheless, the currently available studies of
relevance have too many methodological limitations to allow a conclusion to be reached on causality.
From the assessment of cardiovascular morbidity, although there is currently very little evidence that
use of insulin in type 2 diabetes leads to a reduction in MACE, there is also no consistent evidence of
cardiovascular harm from use of insulin in patients with type 2 diabetes, while acknowledging some
exceptions (ACCORD trial).
Overall, no regulatory action is considered necessary. The PRAC considered that at this stage, given
the limitations of the evidence currently available and in anticipation of the study results that will
become available from a range of studies, no revisions are required to the RMPs for insulin-containing
products.
12. Organisational, regulatory and methodological matters
12.1. Mandate and organisation of the PRAC
12.1.1. PRAC Rules of Procedure
Revision of the Rules of Procedure
The PRAC adopted a revised version of the rules of procedure following incorporation of Regulation
(EU) 1235/2010 and Directive 2010/84/EU into the Agreement on the European Economic Area (“the
EEA Agreement”). The PRAC Rules of Procedure have been amended to be in line with other EMA
Scientific Committees to reflect the involvement of Members nominated by the EEA-EFTA countries in
the PRAC. They will be published after receiving a favourable opinion from the Commission and the
EMA Management Board.
Post meeting note: the revised Rules of Procedure received a favourable opinion from the EMA
Management Board at its 20 March 2014 meeting and by the EC on 9 April 2014 and will be published
on the EMA website.
12.2. Pharmacovigilance audits and inspections
12.2.1. Pharmacovigilance Inspections
12.2.1.1. Union Procedure on Follow-up to Pharmacovigilance Inspections
Union procedure on the coordination of EU pharmacovigilance inspections
Union procedure on sharing of pharmacovigilance inspection information
Pharmacovigilance Risk Assessment Committee (PRAC)
EMA/PRAC/253432/2014 Page 38/64