The growing tendency for drugs to be marketed prematurely, without adequate assessment, is particularly troubling, but not, apparently, for the drug licensing authorities. The losers are the patients who are exposed to drugs that are no better than existing options and that may be more harmful.

Waivers mean faster profits but more risks for patients The European Union offers drug companies a variety of waivers that help them get their products on the market more rapidly: conditional marketing authorisation, exceptional marketing authorisation and accelerated assessment (Prescrire International 99).

An American study has shown that more rapid processing of marketing authorisation applications, either as a result of pressure from drug companies or from patients demanding early access to certain treatments, is associated with more frequent major post-marketing alerts and with more drug withdrawals for safety reasons (la revue Prescrire 297 p. 535).

Thus, among the 6 drugs granted waivers to the standard authorisation procedure by the EMEA that we examined in 2008, we considered three to be “Not acceptable”: panitumumab (conditional marketing authorisation), idursulfase (exceptional marketing authorisation) and trabectedin (exceptional marketing authorisation). Only one drug, raltegravir (conditional marketing authorisation), was useful for patients.

Public trial registries are needed More transparency is needed in clinical evaluation of drugs, whether the results are positive or negative, in order to assess the risk-benefit balance of new products. Mandatory inscription of all drug trials, and their results, in a public registry is one means of achieving this goal. This would also limit data massaging and manipulation, as in the celecoxib scandal in the early 2000s (la revue Prescrire 297 p. 536-541).

It is better to refuse marketing authorisation in the first place It is better not to license a product rather than see it withdrawn later for safety reasons. In 2008 the European Medicines Agency demanded the market suspension of rimonabant only 2 years after authorising its use in obesity, despite an unfavourable risk-benefit balance (la revue Prescrire 302 p. 885, 897 and 909). The Agency also demanded the market suspension of Ionsys°, an iontophoretic transdermal system delivering fentanyl, which had been authorised despite evidence of unreliable drug delivery (la revue Prescrire 303 p. 19). Marketing authorisation of inhaled insulin was also withdrawn, at the company’s request; here too, the data submitted for marketing authorisation were clearly negative at the time of approval (la revue Prescrire 291 p. 16). If the Agency had refused to approve these three products in the first place, it would have prevented the unnecessary exposure of patients to a risk of serious adverse effects.

We were relieved to see the withdrawal of marketing applications for the psychotropics desvenlafaxine (in hot flashes associated with menopause) and duloxetine (in fibromyalgia), after the European Committee for Medicinal Products for Human Use (CHMP) issued negative opinions (la revue Prescrire 300 p. 737-738; la revue Prescrire 303 p. 15).

Withdrawals of marketing authorisation: too rare The above examples show that the Committee for Medicinal Products for Human Use (CHMP) is capable of “doing the right thing”. Hopefully, national agencies will follow their lead. Unfortunately, some drugs are still marketed in France despite a clearly unfavourable risk-benefit balance. These drugs include: benfluorex, an amphetamine used as an adjuvant to dietary measures in diabetic patients (la revue Prescrire 291 p. 19); celecoxib, a NSAID used in rheumatology (la revue Prescrire 291 p. 13); and meprobamate, a psychotropic used in alcohol withdrawal (la revue Prescrire 292 p. 100).

In September 2007 we asked the CHMP to arbitrate in the case of the analgesic combination containing dextroproxyphene and paracetamol, which had already been banned in several European countries. On 2 January 2009, the CHMP’s conclusions had still not been made public (la revue Prescrire 294 p. 259).

If this situation is to improve, patients and healthcare professionals will have to take it upon themselves to counteract the excessive influence of Big Pharma.

©Prescrire April 2009

Source: Prescrire Int 2009; 18 (100): 84-88.