title: The rosiglitazone decision process at FDA and EMA. What should we learn?
abstract: In September 2010 the EMA decided to suspend the market authorisation of rosiglitazone, while the FDA decided to restrict the use of rosiglitazone. These actions were taken approximately 10 years after the introduction of rosiglitazone, because rosiglitazone might be associated with an increased risk of ischemic heart disease. It is often stated that the first signs of an increased risk of ischemic heart disease were noticed in 2004, however already in 2001 the FDA concluded, based on data available to the EMA at the time of initial approval, that rosiglitazone should not be used in combination with insulin, because this combination therapy was associated with an increased risk of cardiac failure and ischemic heart disease. Remarkably, in 2007, when the evidence against this combination therapy had increased, the EMA made a decision that encouraged the use of insulin in combination with rosiglitazone, while the FDA tried to restrict this combination therapy. Despite the publication of several studies, including a large randomized controlled study, the cardiovascular risk of rosiglitazone still has not been definitively established. The weight given to the benefits and the risks seems mainly a subjective decision. To prevent new cases like rosiglitazone, more attention should be given to evaluation of study protocols of safety trials prior to their starts. This paper gives a critical overview of the decision making process at the FDA and the EMA on the basis of public available information.
authors: University of Groningen, Department of Pharmacy, Division of Pharmacotherapy and Pharmaceutical Care, Groningen, The Netherlands.
authors: Koen B
authors: KB
authors: Pouwels
authors: Kees
authors: K
authors: van Grootheest
mesh_terms: D000075202:Contraindications; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D017277:Drug Approval; D004357:Drug Synergism; D004359:Drug Therapy, Combination / Q000009:adverse effects; D005060:Europe; D005062:European Union; D017408:Guidelines as Topic; D006333:Heart Failure / Q000139:chemically induced*; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects; D007328:Insulin / Q000009:adverse effects*; D015201:Meta-Analysis as Topic; D017202:Myocardial Ischemia / Q000139:chemically induced*; D018570:Risk Assessment; D000077154:Rosiglitazone; D056737:Safety-Based Drug Withdrawals; D045162:Thiazolidinediones / Q000009:adverse effects*; D014481:United States; D014486:United States Food and Drug Administration / Q000592:standards
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D045162:Thiazolidinediones; D000077154:Rosiglitazone