LAUSR

Zeukeng et al. compared characteristics of approvals by the Food and Drug Administration (FDA), the European Medicine Agency (EMA), and Swissmedic (SMC): (a) indications approved for the same drugs were similar in content for only 23% drugs; (b) 66% of the drugs were first approved by the FDA vs 3% by SMC [1]. This deserved comment. First, obviously, approvals by regulatory agencies are not only based upon evidence when considering discrepancies in indications [2]. Second, the FDA, thanks to its new expedited review pathways (e.g., accelerated approval, priority review, fast track ...), won the race, although the time lag between the FDA and SMC is only 9 months [1]. Finding a prudent middle ground to protect patient interests represents an immense tension for drug regulators and the present race for approvals which is not only about less bureaucracy but also mainly about more reliance on surrogate endpoints. This may have serious backlashes: drugs can turn out to be ineffective or harmful [2]. Kim and Prasad robustly documented the tenuous or unknown links of surrogates with overall survival for cancer drugs [3]. This is a most critical issue as required post-marketing studies are performed in only two thirds of cases, and with a median delay of 4 years [4]. I hope Zeukeng et al. could provide us a review about the other side of the coin: market withdrawals. Indeed, withdrawals are often unreasonably delayed, even in the case of drug-related deaths [5]. For lack of efficacy, it is even slower: 10 years for drotrecogin alfa and almost 4 for bevacizumab approved with an accelerated program for metastatic breast cancer. Last, withdrawals for financial reasons are more frequent than those prompted by harms or inefficacy [6]. The FDA did not approve strontium ranelate while the European Agency did it and has been flying in the face of the robust evidence of its devastating harms for a decade [7]. Zeukeng et al. were rightly concerned by Binternational harmonization^ [1]; however, beginning by an Binternal harmonization^ of the speed for approvals and for withdrawals is as important. The French independent drug bulletin Prescrire yearly publishes a list of Bdrugs to avoid^, i.e., drugs with adverse effects that are disproportionate to their benefits or drugs superseded by others with a better harm-benefit balance. The 2018 list identified 90 drugs authorized in the European Union [8]. Year after year, the list is growing as regulators are too slow to act. Practitioners and patients should not overlook this list.