Insulin Glulisine in Pregnancy - Experience from Clinical Trials and Post-marketing Surveillance.

Pregnancies complicated by gestational diabetes or pre-existing type 1 or type 2 diabetes mellitus are associated with a higher rate of adverse outcomes compared with pregnancies in the background population. These outcomes include miscarriage, pre-term delivery, pre-eclampsia, perinatal mortality and congenital malformations. Insulin glulisine (Apidra®, Sanofi) is a rapid-acting insulin analogue indicated for the treatment of adults, adolescents and children 6 years or older with diabetes mellitus where treatment with insulin is required. Here, all post-marketing and clinical trials safety data with insulin glulisine in pregnancy available to Sanofi up to June 2014 are summarised together with the findings of a comprehensive literature search. Cumulatively, a total of 303 pregnancy exposures to insulin glulisine were received. Of these 303 pregnancy exposures, there were 116 live births, 12 spontaneous abortions, two late foetal intra-uterine deaths (>28 weeks), three elective abortions and 170 cases without a known pregnancy outcome. There were six cases of congenital malformations; of these, there were five live births; in the other case a live birth was not confirmed. The congenital malformations reported to date do not reveal a pattern of defects. In conclusion, the evidence to date does not suggest a causal association between insulin glulisine and an increased risk of pregnancy complications or congenital malformations.

Planning and core analyses for periodic aggregate safety data reviews.

BACKGROUND: In 2009, the Safety Planning, Evaluation and Reporting Team gave detailed recommendations for a well-planned and systematic approach for safety data collection and analysis. Important aspects of this approach included regular reviews of aggregate data by a multidisciplinary team focusing on safety. PURPOSE: This article provides information to facilitate the planning and implementation of aggregate data reviews. METHODS: Our recommendations are based on experience of the authors and review of relevant literature. RESULTS: We present information regarding the planning of aggregate data reviews as well as examples of data displays that are useful for many different compounds. A subset of these data displays could form a set of 'core' analyses to be generated for aggregate data reviews.

Recommendations for safety planning, data collection, evaluation and reporting during drug, biologic and vaccine development: a report of the safety planning, evaluation, and reporting team.

BACKGROUND: The Safety Planning, Evaluation and Reporting Team (SPERT) was formed in 2006 by the Pharmaceutical Research and Manufacturers of America. PURPOSE: SPERT's goal was to propose a pharmaceutical industry standard for safety planning, data collection, evaluation, and reporting, beginning with planning first-in-human studies and continuing through the planning of the post-product-approval period. METHODS: SPERT's recommendations are based on our review of relevant literature and on consensus reached in our discussions. RESULTS: An important recommendation is that sponsors create a Program Safety Analysis Plan early in development. We also give recommendations for the planning of repeated, cumulative meta-analyses of the safety data obtained from the studies conducted within the development program. These include clear definitions of adverse events of special interest and standardization of many aspects of data collection and study design. We describe a 3-tier system for signal detection and analysis of adverse events and highlight proposals for reducing "false positive" safety findings. We recommend that sponsors review the aggregated safety data on a regular and ongoing basis throughout the development program, rather than waiting until the time of submission. LIMITATIONS: We recognize that there may be other valid approaches. CONCLUSIONS: The proactive approach we advocate has the potential to benefit patients and health care providers by providing more comprehensive safety information at the time of new product marketing and beyond.