For medicines intended for chronic use, the number of patients studied before regulatory approval in the European Union (EU) is insufficient to properly evaluate safety and long-term efficacy, and this points to a need for new EU legislation, say researchers writing in this week's PLOS Medicine.Current EU guidelines specify that, in order to fully evaluate the safety of medicines being developed for long-term treatment of non-life-threatening diseases, at least 1,000 patients should take the new drug and that 300 and 100 patients must use the product for six and 12 months, respectively, before approval by the European Medicines Agency (EMA).
In an analysis led by Ruben Duijnhoven from Utrecht University, the Netherlands, the authors used information from the European Commission about 200 medicines approved between 2000 and 2010 to investigate whether the number of patients included was in compliance with the International Conference on Harmonisation (ICH) E1 guidelines.
They found that the average number of patients studied before approval was 1,708 for standard medicines and 438 for orphan drugs. On average, medicines for chronic use, such as asthma medications, were studied in more patients - 2,338 - than those for intermediate use such as anti-cancer drugs - 878 - or short-term use such as antibiotics - 1,315.
They also reported that the safety and efficacy of chronic use was studied in fewer than 1,000 patients for at least six and 12 months in 46.4% and 58.3% of new medicines, respectively. In addition, they discovered that, among the 84 medicines intended for chronic use, 69 were studied in at least 300 patients for six months and 67 were studied in at least 100 patients for 12 months.
Commenting on their findings, the authors say they show that, for medicines intended for chronic use, the number of patients studied before marketing is insufficient to evaluate safety and long-term efficacy, and that both safety and efficacy require continued study after approval.
"In light of new scientific and legislative tools to monitor benefits and risks in clinical use, discussion of the long-term exposure requirements for approval of medicines, particularly for medicines for chronic use, seems warranted," they say, adding: "such a discussion should involve healthcare providers, patients and academia, as well as industry and regulators, and should include debate on the level of acceptable uncertainty, especially for adverse events and the long-term outcomes for chronic medication."