Introduction

Obesity

Approximately two-thirds of the United States' population is overweight or obese, defined as having a body mass index (BMI) of 25 kg/m² and above. In Europe, there is also a high prevalence of overweight, estimated to affect approximately 50% of adults, and obesity, estimated to affect up to 30% of adults. As obesity is strongly associated with an increased risk of type two diabetes mellitus (T2DM), cardiovascular diseases, and premature mortality, itis a major public health concern. With around 2.5 million deaths worldwide due to medical complications associated with obesity, there is a large unmet medical need for safe and effective treatments. The prevalence of obesity is increasing not only in the US but also in other countries, in adults as well as children.As diet and exercise have demonstrated limited success in weight reduction, alternative approaches to treat obesity are necessary.

Rimonabant

Rimonabant (Acomplia/Zimulti) is a new drug, the first in its class, indicated for weight loss in obese or overweight patients with co-morbidities. Different trials have also shown that it could improve HbA1c and lipid profiles (increased HDL and reduced triglyceride) in overweight or obese patients. Its use was associated with occurrence of psychiatric adverse events, although most of the patients with various kinds of depressive symptoms did eventually recover with or without anti-depressants drugs. Other common adverse events were anxiety, insomnia, mood alterations with depressive symptoms, depressive disorders, dizziness, nausea, diarrhoea, vomiting, and asthenia/fatigue.

Rimonabant was approved in Europe and was first marketed in the UK in 2006. In July 2007, the Committee for Medicinal Products for Human Use (CHMP) recommended some changes to the prescribing information. CHMP recommended that rimonabant not be prescribed in patients with ongoing major depression or in patients taking antidepressants. CHMP also warned that treatment with rimonabant should be stopped if a patient develops depression, including additional information on the psychiatric safety of rimonabant.In November 2008, the marketing authorisation of rimonabant was suspended in all the Member States in which the product was being marketed; and in December 2008, the marketing authorisation holder (MAH) responsible for rimonabant, Sanofi-Aventis, voluntarily withdrew its marketing authorisation. In January 2009, the European Commission withdrew the marketing authorisation for rimonabant on the ground of negative benefit-risk balance based on post-marketing data.

The scope of the case study

In this case study, we tested different benefit-risk methods using rimonabantagainst comparators. In the first wave the case study, only placebo was used as the comparator.However, in real life, multiple comparators exist and therefore make decision analysis more complex. We extended the rimonabant case study to include two active comparators (alternatives) sibutramine and orlistat; and further tested methodologies that could address the added level of complexity. In all analyses, we only used publically available data.

The full rimonabant case study reports are available for download.