Ten years too long: strontium ranelate, cardiac events, and the European Medicines Agency
BMJ 2016; 354 doi: https://doi.org/10.1136/bmj.i5109 (Published 30 September 2016) Cite this as: BMJ 2016;354:i5109
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Bolland and Grey showed robust evidence of European Medicines Agency (EMA) regulatory failures with strontium ranelate.(1) Their conclusion “strontium ranelate should not be registered for clinical use” is right but in vain. Indeed, there is too much evidence that the EMA is under pressure from the drug industry: it has chosen to accelerate approval of new drugs.(2) Moreover, re-evaluation in case of gross errors or withdrawal of the so numerous drugs to avoid is not its motto yet.(3-5) If a train runs off the track, it stops but the EMA doesn't.
The regulatory failure is not only about the EMA. Why are regulatory agencies in charge of assessment for price and reimbursement such as the National Institute for Health and Clinical Excellence (NICE) also failing to do their job properly? Since 1 August 2016, strontium ranelate has been available in Australia as a private prescription only. This means that doctors are still able to prescribe it, but it costs more to the patient as the government is no longer paying (subsidising) some of the cost (http://www.nps.org.au/publications/consumer/medicinewise-living/2016/str...). Accordingly, doctors will prescribe safer alternatives to their patients.
1 Bolland, MJ and Grey A. Ten years too long: strontium ranelate, cardiac events, and the European Medicines Agency. BMJ 2016;354:i5109.
2 Davis C, Lexchin J, Jefferson T, et al. "Adaptive pathways" to drug authorisation: adapting to industry? BMJ 2016;354:i4437.
3 Braillon A. Nalmefene in alcohol misuse: junk evaluation by the European Medicines Agency. BMJ 2014;348:g2017.
4 Fitzgerald N, Angus K, Elders A, et al. Weak evidence on nalmefene creates dilemmas for clinicians and poses questions for regulators and researchers. Addiction 2016;111:1477-87.
5 Toussaint B. Prescrire: France's Choosing Wisely initiative. BMJ. 2015 Jun 24;350:h3325.
Competing interests: No competing interests
Cessation of strontium ranelate supply
To our knowledge, there has been no response to our article1 from the European Medicines Agency (EMA), the manufacturer of strontium ranelate, Servier, or the academics involved in the phase 3 trials of strontium.
However, a news release on the Servier website dated 14 March 2017 states that Servier sent a letter on 10 February 2017 to the EMA notifying them that worldwide marketing and distribution of strontium ranelate will cease permanently in August 2017 for commercial reasons.2 Similar letters were sent to all countries worldwide where strontium is marketed.2 At least one Servier website states that the decision “is not related to a quality or safety issue”,3 although the Servier news release cites the restricted indication/limited use of strontium as a contributing factor.2 These prescribing restrictions were imposed because of safety concerns.1
On 2 May 2017, we were unable to find any information about the upcoming cessation of strontium distribution in broad searches of the internet nor on all websites we specifically searched: the EMA website, and the websites of national regulatory bodies for the UK, Ireland, France, Germany, Italy, Denmark, Sweden, the Netherlands, Hong Kong or Australia. Therefore, the imminent cessation of strontium supply may come as a surprise to many clinicians and patients. Regulatory bodies that have not yet done so should notify practitioners as soon as possible of this development, so that patients can consider other management options.
Given the manufacturer will be no longer distributing strontium ranelate, and that any benefit of strontium in fracture prevention is outweighed by the risks of cardiovascular events and venous thromboembolism,1 it seems timely and appropriate that the registration for strontium ranelate be withdrawn.
1. Bolland MJ, Grey A. Ten years too long: strontium ranelate, cardiac events, and the European Medicines Agency. BMJ 2016;354:i5109.
2. http://www.servier.com/content/cessation-marketing-protelososseor-extrac...
3. http://www.servier.com.au/products/protosdiscontinuation
Competing interests: No competing interests