Wednesday, September 14, 2011

Guest Blog: Mediator, symptom of a broken French system

Elena Pasca blogs at PharmaCritique, and is a member of the Fondation Sciences Citoyennes.  She discusses the pharmaceutical industry in France, and relationships among that industry and physicians and the government.  She demonstrates that the issues we discuss on Health Care Renewal are global.


A few weeks ago, the French health minister proposed a new law to improve pharmacovigilance, drug evaluation and transparency issues. It will be discussed in September by the Parliament. Let’s see what the actual situation is in France.

The Médiator (benfluorex) scandal raises not only pharmacovigilance issues. The first question that comes to one’s mind is how could the drugmaker Servier, who knew about its dangers, keep Médiator on the market for 30 years, despite the repeated alerts and the withdrawal of other amphetamines from the same drug class?

The answer goes far behind pharmacovigilance dysfunction. Médiator is not an isolated case, but an epiphenomenon of structural failures on every organisational level of the French health care, drug evaluation and health information system. The entire system is broken, and there still are dozens of defective and too risky drugs on the French market.

Most relevant for US readers is not to list all the alerts starting in the seventies with the fenfluramines. It’s to understand that the entire system was organised in order to be as industry friendly as possible. And the announced measures aren’t going far enough to change this fact.

Private profits before public health

In July 2009, president Nicolas Sarkozy decorated Jacques Servier with the Légion d’honneur and criticised again what he considered to be a huge amount of administrative regulations in the pharmaceutical branch. For him as the former business attorney of Servier, whose electoral program stipulated “cleaning business law”, too much regulation means less business, less competitive French drugmakers.

President Sarkozy’s health policy clearly favours the pharmaceutical industry, especially Sanofi-Aventis. His choice of Alzheimer disease as the first public health issue is not naïve. Sarkozy’s brothers have multiple conflicts of interests and ties with Sanofi-Aventis, the insurance industry and the organisations and institutions involved in the health care of the elderly, as I pointed out in an investigation published on Pharmacritique. And Sanofi hasn’t yet any me-too from the anticholinesterase drug class largely prescribed to Alzheimer patients, despite repeated proof of their ineffectiveness and of their side effects.

As a direct result of Sarkozy’s policy, publicly funded research will be exploited through public-private partnerships to produce immediate results – and neglecting fundamental research bringing new knowledge and thus real therapeutic progress. The intellectual property policy clearly favours private profits.

The European research policy has the same aims: the Innovative Medicines Initiative is clearly oriented toward “innovation” meant as competitive advantage for the pharmaceutical industry, not as an improvement in disease understanding and treatment. The exploitation of public research for private corporate profits has been criticised by the Helmholtz Gemeinschat (union of the German public research centres).

A few weeks ago, 98 European NGOs and organisations wrote an open letter criticising the Common Strategic Framework for EU Research and Innovation Funding and asking for a responsible European research policy: “Public Research should benefit Society, not Big Business”.

Conflicts of interests are everywhere, corrupting the entire health care system

In France, except for two journals (Prescrire and Pratiques), the entire medical press is completely dependent on drugmakers and their advertising. Especially family physicians receive such journals for free. They include no disclosures, so there’s no possibility to sort out advertising from information. Most of those journals are owned by a trust whose leader is Gérard Kouchner, brother of the former health minister Dr. Bernard Kouchner. (See this post on PharmaCritique.)

To this misinformation by the sponsored press has to be added another source of bias: continuing medical education [CME] is funded up to 98% by the pharmaceutical industry. And up to 97% of self-employed physicians still receive drug reps and consider them to be a comfortable, if not reliable, information source.

As long as I can go back, all health ministers have had conflicts of interest. In a hearing by the Parliament’s committee on Médiator, Gérard Kouchner was questioned about his journals’ silence about the risks of this drug and about the book written by the whistleblower Dr. Irène Frachon. He answered those journals are serious, no odd news, no sensationalism… As if informing physicians about severe side effects of a drug and experts’ conflicts of interests and drugmaker influence wouldn’t be serious enough…

The state can’t control conflicts of interest and implement oversight because the medical corporation is well organised (trade unions…) and opposes every reform or measure restricting its freedom. And the medical lobby knows how to use its political influence. Commercial interests, entrepreneurship, industrial funding (research, travel, professional activities, CME…) are organised and encouraged by the Order of Physicians. Despite of the 1994 law prohibiting gifts, dining, wining and lodging continues. Daily corruption is widely accepted, since it is approved by the Order of Physicians… Organised medicine’s unusually strong influence over France’s health care system is well described by Marc Rodwin in his book “Conflicts of Interest and the Future of Medicine. The United States, France, and Japan” (Oxford University Press 2011).

The French FDA – AFSSAPS - is financed up to 80% by the pharmaceutical industry, via taxes. Up to 70% of the AFSSAPS experts have conflicts of interest. But the real percentage must be higher, because the recently introduced disclosures aren’t verified, and omissions or false declarations aren’t prosecuted. In a 2007 report, AFSSAPS officials had to acknowledge their strategy of “managing” conflicts of interests wasn’t a success...

The more drugs the agency approves, the more money it gets. Drugmakers exploit competition existing among European agencies to earn more money, and they also know which country will easily approve their drugs, opening the door for a homologation by the EMA (European Medicines Agency). When a drugmaker knows this or that drug is defective, approval is not even attempted in the US, but only in certain European countries. Why risk a defeat that could damage its image?

For example, during the swine flu epidemics, some vaccine makers haven’t asked for approval in the USA, because their vaccines contain new technologies (MDCK cells, adjuvants such as squalen) they wanted to “test” on European people first, before submitting them to the FDA. The German independent journal Arznei-Telegramm revealed the existence of a market analysis counselling this strategy (2009; 40: 85-7).

None of the swine flu vaccines commercialised in Europe were approved in the US. The same laboratories produced different vaccines, and new technologies were used instead of the classical ones, in the name of the… emergency. Since then, hundreds of cases of narcolepsy were reported, especially among children and teen-agers, as a side effect of GSK’s Pandemrix (containing squalen).  (See this post on PharmaCritique.)

Complete lack of information about drugs and their adverse reactions

Pharmacovigilance in France is rather pharmacosomnolence: the AFSSAPS reacts late after others western countries when it comes to puttin a defective drug off the market. On the opposite, it easily accepts homologation demands. If you compare the drugs available in France and the USA, you’ll find lots of drugs rapidly withdrawn or rejected by the FDA, or even unknown in the US: etoricoxib (Arcoxia), nimesulid, rimonabant (Acomplia), lots of progestagens, veraliprid (Agréal)… After the FDA decision, it took 11 years to take Distilbene (DES) off the French market. Vioxx continued for years on the French market after its withdrawal in the US. Mediator was withdrawn 1997 in the US, 2010 in France. And so on.

In a 2008 article, Donald Light highlighted “Europeans are kept in ignorance about dangerous drugs” (Rev Prescrire 2008;28(297):553). He gave several examples of drugs such as aprotinin, olanzapine, etoricoxib, sleeping drugs… where safety alerts have been made public by the FDA and relayed by the US media, and compared this information with the silence in France. Before the Médiator scandal, the French media weren’t interested in drug safety, conflicts of interest, corruption, bias in the medical research…

But it’s even worse. The public has no access to the official prescribing information, reserved to physicians paying for the Vidal (equivalent of the Physicians’ Desk Reference), edited by a private company… I compared the prescribing information of lots for drugs available in the US and in France, produced by the same drug companies, approved in the same indications. The information is so different, as if they weren’t the same drugs…

France has few relevant regulations and laws, so the country is a paradise for the pharmaceutical industry, and for industries, lobbies and business in general. There’s no FOIA, no way for watchdogs – even for official watchdog agencies – to get real information. In a 2007 report, the IGAS (General Inspection of Social Affairs, France’s OIG) only could give estimations, based on extrapolations, about lobbying and marketing expenses of the pharmaceutical industry.

Consumers International published the results of a 2008 conducted inquiry about drugmakers’ legal obligations in the US compared to Europe. 12 drugmakers answered and all agreed the requirements aren’t at all the same, in regard of transparency and disclosures, in regard of complete information about drugs, and so on.

So why would drugmakers give an information no one requires and no one wants?

Pharmacovigilance is subordinated to drug approval, and until recently, patients couldn’t report side effects. A pharmacovigilance official told me that even now, adverse reaction reports without documentation and follow-up aren’t always counted. The regional pharmacovigilance centres don’t forward them to the AFSSAPS.

There’s no transparency about the specific phases of the drug evaluation system, in terms of risk/benefits, and there’s no evaluation at all in terms of cost/effectiveness and economic efficiency. The Haute Autorité de Santé was created for this kind of quality and economic efficiency evaluation, like the German IQWIG and the British NICE. But everything it does is officialise drugmaker marketing claims and “assess” the improvement in the actual benefit. But it’s only a formal assessment, and I don’t remember of a drug dismissed by this agency because of insufficient improvement…

In January 2011, president Sarkozy appointed Pr. Jean-Luc Harousseau as the head of the Haute Autorité de Santé, despite all the recent promises to reform the system and fight against the conflicts of interest of experts and officials. Pr. Harousseau is the perfect example of French opinion leaders with political and industrial interests that become experts and leaders of national institutions: he was politically involved in Sarkozy’s party (UMP); he and his research teams earned more than 200.000 euros in the 3 years before his nomination.  (See this post on PharmaCritique.)

Philippe Lamoureux, the former head of INPES (National Institute for Prevention and Health Education) went over to the LEEM (French PhRMA), without any “cooling off” period. (See this post on PharmCritique.)

The revolving doors turn very easily in France, as well as in Europe. ALTER-EU (Alliance for Lobbying Transparency and Ethics Regulation) reported about EMA’s former director, Thomas Löngrenn, who took a job as a lobbyist for the pharmaceutical industry, just like other European commissioners. And Guido Rasi, the next EMA director, said at a colloquium in Bologna that an expert without conflicts of interest is not interesting, because drug companies only work with the best…

Some other points in brief:

- there’s no Sunshine Act or any similar obligation in France;

- the 2002 law requiring a disclosure for health professionals talking publicly about a drug is not applied;

- no whistleblower protection (so that libel law is used all the time against them in SLAPP’s: strategic lawsuits against public participation);

- there are no specific laws (like the US False Claims Act or RICO) allowing trials for defective drugs or other abuses; no possibility for a qui tam lawsuit;

- no law to prosecute corruption and its consequences (like the US Federal Anti Kickback Statute);

- no law enabling class actions;

- no specific qualifications for victims of defective drugs (“injury”, “aggravated deception” are those used by Médiator victims and their families…);

- taxpayers pay for the victims (if ever they can get recognition and damages);

- no physician liability for prescriptions and their consequences, or for conflicts of interest and corruption;

- no FOIA; a minimalist law called CADA (« accès aux documents administratifs ») preserves secrecy of data and of conflicts of interests in the name of industrial property and private life protection);

- no corporate integrity agreement;

- no attorney general asset redistribution programs (well, without trials, there’s no need for such frameworks…);

- no disclosure in scientific publications.

Direct-to-consumer advertising is prohibited by law. A good point. But this prohibition is by-passed all the time. Pharmaceutical firms sponsor “health education campaigns” organised together with public institutions, medical societies and/or patient associations tied to drugmakers. For example, a public campaign whose official goal is to raise awareness about the “dangers” of cholesterol is meant to transform a risk factor in a disease, medicalise more and more people who will look for the statins commercialised by the sponsor Pfizer. Not to speak about the repeated attempts of the European Commission to impose the “pharmaceutical package” wanted by EFPIA (European Federation of Pharmaceutical Industry Associations), i.e. enable drugmakers to have a direct access to patients and provide “information”, and weaken pharmacovigilance through several regulations exposed in this text by Prescrire International.

Worst of both socialised medicine and market logic

The French system allies the worst side of socialised medicine and of the market and competition-based system.

Co-payments were introduced a few years ago, but cost reimbursement is still good. Everyone has a public insurance (“régime général”) that covers about 65% of the costs, for a quite large list of drugs and procedures. For the remaining 35%, each individual has to pay for a private insurance. There is a public “universal” insurance for people earning less than 650 euros a month. Nevertheless, about 23% give up health care, because of the costs, and especially because of excessive charges exceeding the statutory fees. This rate is much higher in dental and optical care, where public coverage is almost inexistent.

So what’s the problem, compared with countries without universal health insurance? The problem is lack of organisation, poor economic efficiency and quality, in regard of the high costs. Primary care isn’t organised as it should be in a socialised system. Most of it consists of self-employed physicians working alone, and the same applies for self-employed specialists outside hospitals. They work without coordination and oversight. More and more for-profit hospitals are founded, to treat lucrative, acute diseases, leaving the chronic ones and all complications to public hospitals that still do a good job, but are chronically deficient, because of inappropriate activity-based payment model and budget distribution, and because of budgetary restrictions as a result of an irrational policy of economic management and accountable cost containment.

This lack of organisation originates in organised medicine’s resistance to any restriction and oversight. It hinders every evaluation in terms of quality and leads to specific forms of conflicts of interest and global poor quality. The recent introduction of some pay-for-performance measures worsens the problem; incentives are paid by the social security for objectives that aren’t subjected to any evaluation. Family physicians get up to 9.000 euros extra a year if they obtain the wanted percentages of regular breast screening, influenza vaccines in elderly, and so on. It’s not prevention, but overmedicalisation and aggressive preventive medicine as described by David Sackett.

Organised medicine dominates and shapes France’s medical economy and health care organisation. It also blocks the development of not-for-profit hospitals, created by mutual insurers, as well as any form of medical centres employing physicians. Every attempt to regulate charges exceeding the statutory fees is blocked.

The Order of Physicians is the only “judge” in cases of misconduct, and it rarely forwards the proof to the public watchdogs or to prosecutors. Self-regulation through voluntary codes of conduct is the rule, for the medical corporation as well as for the pharmaceutical industry.

This can’t be called “socialised medicine” and contradicts the republican principles originating in the French revolution, fought to put a stop to corporations and their influence on public decision, on politics and on economy.

Medical consumerism and physician financial interests complete themselves, and “socialised medicine” isn’t appropriate anymore to describe the French system. The dangers for public health care and coverage were pointed out in a paper written by the former medical director of social security, Pr. Claude Béraud.  (See this post on PharmaCritique.)

Of course, such a system isn’t affordable in the long term. And this is exactly what ultra-capitalists and right-wing politicians want, in order to demolish socialised medicine and public health care and promote private health maintenance organisations and insurances.

Passivity, no awareness, no criticism

Another consequence of a deformed conception of socialised medicine is patients’ lack of health education, of healthy skepticism, of criticism and of action. Before the Médiator scandal, patients were too confident in what they thought to be state protection on every level : an approved drug was thought to be sure and useful, an opinion leader’s discourse promoting some new drug was thought to express the highest technical standards, and so on. There was no awareness at all about conflicts of interest.

Physicians’ awareness wasn’t much better. For example, Arnold Relman wrote his paper about “The new medical-industrial complex” in 1980. In France, it took 25 years until Jean-Claude Salomon wrote “The medical-financial complex”…

The only resistance comes from a few organisations, such as the independent medical journal Prescrire and the grassroots NGO Fondation Sciences Citoyennes, and from a few personalities such as senator François Autain, Pr. Claude Béraud and a few others, mentioned by Marc Rodwin in his book “Conflicts of Interest and the Future of Medicine. The United States, France, and Japan”.

The Fondation Sciences Citoyennes and the European Alliance for Lobbying Transparency and Ethic Regulation regularly protest and start actions and proposals about revolving doors, lobbying, conflicts of interests and corruption in all areas, as well as law proposals about expertise deontology and whistleblower protection.

Lots of reports without consequences

The left-wing representatives in the two parliament chambers have put in place hearings about the Mediator scandal, but no enquiry that could enable them to investigate the structural causes of repeated drug and conflicts of interest problems and take concrete measures. Some of the representatives are members of the “Club Hippocrate”, sponsored by Glaxo Smith Kline…

The congressman Bernard Debré and the former medicine professor Philippe Even, known for his longstanding criticism, have written a vehement report about the drug evaluation system. Without consequences. The Inspector General for Social Affairs (IGAS) has published a report on Médiator that clearly points out the responsibilities: every single institution has failed, from the drug agency to the political instances and the medical organisations. The last report of the same IGAS, published in June, contains concrete and pragmatic proposals on how to deeply reform the entire pharmacovigilance and drug evaluation system.

The assessment process initiated by the health minister Xavier Bertrand – Assises du Médicament – has nothing to do with a trial assessing facts (“assises” means a trial with jurors). The working groups were clearly dominated by LEEM (the French PhRMA) representatives and by opinion leaders tied to drugmakers. Most of the independent organisations and critiques were not allowed to participate, “in order to respect a balance” between different interests. Fondation Sciences Citoyennes was excluded and described the situation in this detailed press release, asking independent NGOs to organise counter-Assises. 

The law proposal presented on the 1st August by Xavier Bertrand contains some long due measures, but no real progress.

The pharmaceutical industry’s interests won’t be endangered by any measures and laws arising from the Médiator scandal.

Elena Pasca
Pharmacritique, Fondation Sciences Citoyennes

ADDENDUM - Elena Pasca asked me to insert her thanks that we published her guest post.  But we owe her considerable thanks for her efforts to explain the French situation, and show how the issues we discuss on Health Care Renewal are truly global. 

1 comment:

braillon said...

Elena provide us with a brilliant but sad summary of the Mediator/benfluorex scandal, another french scandal in health, another french exception. Incomptence + corruption is a tragic mix with devastating consequences. Below are 3 short pieces published in leading medical journal which evidenced that the Mediator/benfluorex scandal was not an accident.