Paris, 12 December 2014

Prescrire's response to a European Medicines Agency (EMA) consultation on the evaluation of medicinal products used in weight control. A transitory weight loss of a few kilograms does not justify exposing patients to a disproportionate risk of adverse drug reactions.

> Click here to download Prescrire's response (pdf, 196 Ko)

Key points of Prescrire's response

• The draft guideline on evaluation of the harm-benefit balance of medicinal products used in weight control, released for consultation by the EMA in July 2014, contains a number of improvements over the existing version, adopted in 2007, in particular the recommendation to systematically assess the neuropsychiatric and cardiovascular adverse effects of drugs that act on the central nervous system.
• However, in the draft guideline, the Committee for Medicinal Products for Human Use (CHMP) accepts that evaluation of the efficacy of weight-control drugs can be based on modest weight loss alone after one year only, a surrogate endpoint that has not been demonstrated to translate into a reduction in morbidity and mortality. Instead, Prescrire argues that in order to determine whether treatment effects are maintained, it is essential to conduct clinical trials with a follow-up of at least several years prior to submission of the marketing authorisation (MA) application.
• In addition, the draft guideline recommends "actively-controlled" trials but does not specify that non-pharmacological therapies should be preferred (dietary and/or psychological/behavioural support, gastric banding or the use of another established medical device). Moreover, based on numerous disasters with amphetamine anorectics, these drugs should be avoided due to their foreseeable unfavourable harm-benefit balance.
• Regarding the evaluation of adverse effects, Prescrire urges the EMA to broaden its recommendation to assess neuropsychiatric and cardiovascular adverse effects to include all medicinal products used in weight control, regardless of their mechanism of action, and also to systematically evaluate:
  • the adverse effects of rapid weight loss, including increased fracture risk;
  • the adverse effects already known to occur with other weight-control drugs;
  • the risk of interaction with other drugs likely to be used by overweight patients (antidiabetic drugs, antidepressants);
  • the risk of addiction to weight-control medicines, since they are often prescribed for patients who would be particularly susceptible (eating disorders).
• In order to take on board the lessons learnt from past public health disasters caused by appetite suppressants, Prescrire also insists that enhanced surveillance of the adverse effects of weight-control medicines is necessary for at least 5 years post-authorisation, but that these post-authorisation "safety" studies must not be used as a pretext for approving dangerous, under-evaluated medicines, nor to keep dangerous medicines on the market pending the results of these studies.

©Prescrire December 2014

> Click here to download Prescrire's response (pdf, 196 Ko)