French govt promises "culture shock" in drug regulation, while price cuts and levies loom
This article was originally published in SRA
The French drug regulatory sector is in for a "culture shock", says the government, as the parliament prepares to vote on a reform bill addressing the drug safety and other issues raised by the Mediator affair1-3.
Meanwhile, the pharmaceutical industry could be hit by the social security financing bill (PLFSS) for 2012, which was presented to parliament last week. If approved in its present form, the bill will bring several more years of downward pressure on drug spending, with price and reimbursement cuts as well as higher taxes in prospect. While industry goes along with most of the reform measures, it is furious at the proposals laid out in the PLFSS4.
Regulatory reform
The regulatory reform bill is heavily influenced by the Mediator drug scandal. It is intended not simply to make technical changes but to provoke "a true culture shock", says health minister Xavier Bertrand. Parliament examined the bill on 27 and 28 September, and is due to vote on it on 4 October.
The key themes of the bill are increasing responsibility, maximising transparency and putting patient safety at the centre of the drug regulatory system. The government says all must play their part in achieving these aims. Doctors must make more effort to control off-label prescribing and notify side-effects, companies must be "exemplary" in putting in place internal pharmacovigilance systems, and the authorities must be more reactive and have more resources at their disposal.
The bill, which has just come out of the parliament's social affairs committee in an amended form, contains a raft of measures intended to help guarantee the safety of medicines. Among them are actions to extend the conflict of interest rules beyond committee members and experts to members of working groups; introduce the recording of committee meetings and the publication of full transcripts; improve the pharmacovigilance system and safety reporting; and curb the activities of company sales reps.
On this last issue, the bill says that while sales reps can play a positive role in providing technical information on health products, the system must be changed to avoid the "misguided behaviour" that was seen in the Mediator affair.
Mediator, which contained benfluorex, was associated with cases of heart valve damage and was belatedly withdrawn from the market. While it was registered as an antidiabetic, it was widely prescribed as a diet drug, a fact that the government suggests was at least partly down to the behaviour of its manufacturer, Servier. "It is difficult to completely exonerate the Servier sales reps of all responsibility for the fact that benfluorex [the active ingredient in Mediator] was in 78% of cases prescribed outside its official therapeutic indications," says the bill.
The bill proposes to introduce a pilot system where reps visiting hospitals and other healthcare establishments must present to a group of doctors, rather than just one, and with the hospital pharmacist present, the idea being to ensure that misleading messages are not imparted.
As an added precaution, writing the INN (international nonproprietary name) of a product on the prescription form would become obligatory for doctors for all products from 1 January 2015. The government notes that if Mediator had been prescribed as benfluorex, healthcare professionals and patients might have been able to recognise its "anorectic character".
Added therapeutic value
The bill also suggests that proof of added therapeutic value compared with existing treatments should be a requirement for marketing authorisation purposes. This question frequently crops up – most recently in an article in the BMJ calling for comparative efficacy to have a formal place in the drug approval procedure5.
The French government says that its room for manoeuvre here is quite limited because EU Directive 2001/83/EC on medicinal products for human use does not provide for a systematic requirement for comparative trials. However, Mr Bertrand is championing the cause, and has held talks with European health commissioner John Dalli on changing the rules.
Addressing the social affairs committee on 13 September, he said new medicines "should not be just a little better than nothing" and that he was "fighting at European level" for added therapeutic value to be a criterion – although he noted that "EU processes are sometimes slow".
In the meantime, he said he would take action in France so that products with inadequate therapeutic value were not reimbursed, and that complementary safety and efficacy studies on authorised medicines could be demanded "at any moment" if there was the slightest suspicion that a product's risk benefit profile had changed.
Other proposals
Other proposals in the bill include a French version of the US Sunshine Act, with companies to declare all agreements with health professionals, students, patient bodies, private and public health establishments, foundations and specialised press; the creation of a new medicines regulatory body (ANSM) with wider powers and tasks than the present Afssap, and a better balance between its pharmacovigilance and marketing authorisation departments.
There would be more systematic re-evaluation of medicines after marketing, and a requirement on companies to inform the ANSM of any information regarding a potential change in the risk-benefit of a product, or any bans or restrictions imposed on a product in any country. The ANSM would at any time be able to ask a company to provide data showing that the risk-benefit of its product was still favourable.
The pharmacovigilance system itself is to be strengthened, with the ANSM having a new, stronger national pharmacovigilance committee.
While industry accepts most of the reforms as necessary, it says that some measures in the bill, such as the restrictions on hospital promotional activity, are unrelated to the facts of the Mediator case.
Healthcare spending
On the healthcare spending front, the government is certainly showing its determination to get tough, and it has the pharma industry firmly in its sights. Mr Bertrand says that hospitals and medicines are the main contributors to the growth in consumption of healthcare and medical products, and that things will only get worse as the population ages.
Although it concedes that growth in medicines consumption is stabilising, the government wants to ensure that this trend continues, and so has set the annual rate of growth in healthcare expenditure (ONDAM) at 2.8%, not only for 2012 but for each year through to 2015. Without this target, growth in spending would be 4%. Overall, the government is seeking healthcare savings of €2.2 billion in 2012.
The targets are set out in the draft PLFSS for 2012. In the pharmaceutical area, actions proposed for next year include drug price and reimbursement cuts, and additional contributions from the industry. The price cuts on medicines are expected to save the government some €620 million next year, according to the industry association Leem, while the removal from reimbursement of some 600 products, currently reimbursed at 15%, will cut a further €40 million from the drugs bill.
On top of this, the industry will be called on to contribute an additional €40 million to the future regulatory body ANSM (the successor to the current Afssaps), and an extra €150 million in the form of levies on industry turnover, Leem says.
Also in prospect are actions to increase the use of generics, and a greater emphasis on the use of medico-economic studies in making reimbursement decisions on new and existing drugs. The medico-economic role of the higher health authority (HAS) will be strengthened: it will have a specialised committee in medico-economic evaluation whose opinions will be taken into account when setting prices and deciding whether or not to reimburse products.
Industry reaction
While industry goes along with most of the reform measures, it is furious at the proposals laid out in the bill. It says the government is exploiting the decline in public trust in the industry following the Mediator affair in order to introduce draconian measures that have nothing to do with the issues raised by the Servier drug and everything to do with making quick and easy healthcare savings.
Leem claims the government is using the Mediator affair as an excuse to batter the industry6. It points out the levies on its turnover already amount to more than €850 million or almost 4% of total turnover. The additional €150 million in levies are supposed to help finance the training of health professionals, but it says that industry will have no say in how this is done.
This abundance of taxation is "totally incomprehensible", says Leem, and comes at a time when turnover is already expected to fall next year. The levies and price cuts come at a time when even the government concedes that medicines spending is under control. As for the reimbursement cuts, they are "useless and unjustified", and will hit medicines of long standing therapeutic value, resulting in job losses among small and medium enterprises, Leem argues.
The entire bill, in its view, is a short-term piece of work that will "seriously hinder" French industrial competitiveness. Even though the government claims to distinguish between the practices brought to light in Mediator and the actions of the drug industry overall, "these measures can only be viewed as a collective penalty", it declares.
The move will also be eyed warily by GlaxoSmithKline CEO Andrew Witty, who said recently that European governments might be overstating their economic woes and warned that the pharmaceutical industry in Europe might not be able to absorb many more price cuts7.
References
1. Regulatory reform bill as amended by social affairs committee, website accessed 30 September 2011,
www.assemblee-nationale.fr/13/dossiers/renforcement_securite_sanitaire_medicament.asp
2. Xavier Bertrand, address to the social affairs committee, 13 September 2011,
3. French bill tightens up on safety and conflicts of interest, but not drug approval criteria, Scrip Regulatory Affairs, 11 August 2011
4. Draft social security financing bill (PLFSS), website accessed 30 September 2011,
www.assemblee-nationale.fr/13/dossiers/loi_finances_2012.asp
5. Comparative efficacy should have a formal role in EU drug licensing, researchers say, Scrip Regulatory Affairs, 9 September 2011
6. Leem, 22 September 2011,
www.leem.org/plfss-2012-les-entreprises-du-medicament-denoncent-une-sanction-collective
7. Scrip Intelligence, 28 September 2011