Following complaints made by the London-based health consumer group, Social Audit Ltd, the company (GSK) was judged in breach of three clauses of the marketing code of the Prescriptions Medicines Code of Practice Authority (PMCOPA), the semi-autonomous self-regulatory scheme operating under the aegis of the Association of the British Pharmaceutical Industry (ABPI). Following a three-hour hearing on October 10th, The Authoritys Appeal Board upheld Social Audits complaints under the following provisions of the Code:
Information, claims and comparisons must be accurate, balanced, fair, objective and unambiguous and must be based on an up-to-date evaluation of all evidence and reflect that evidence clearly. They must not mislead either directly or by implication. (ABPI Code, clause 7.2)
Information and claims about side-effects must reflect available clinical evidence or be capable of substantiation by clinical experience. It must not be stated that a product has no side effects, toxic hazards or risks of addiction. The word safe must not be used without qualification. (ABPI Code, clause 7.9)
Information about medicines made available to the public ... must be presented in a balanced way and must not be misleading with respect to the safety of the product (ABPI Code, clause 20.2)
Social Audit had another complaint upheld about GSKs promotion of paroxetine (Paxil) one year ago. On both that and this occasion, the complaint was originally rejected but then won on Appeal. The Appeal is heard by a board comprising 12 members from the pharmaceutical industry and 6 independent members, including the Chairman (Mr Nicholas Browne QC). One member of the Appeal Board (Mrs Mary Baker MBE) represents patients interests.
The complaints were brought by Mr Charles Medawar, Director of Social Audit Ltd. Three other experts attended the Appeal helped to present Social Audits case. They were: Dr Andrew Herxheimer (Emeritus Follow, The Cochrane Centres, and founder editor of Drug & Therapeutics Bulletin); Dr David Healy (Consultant psychiatrist and psychopharmacologist, historian of psychiatry); Ms Anne Winyard (Solicitor with Leigh Day & Co, acting pro-bono publico). Following news of the ruling by the PMCOPA, Mr Medawar said:
This is an important ruling which casts serious doubt on GSKs claims that paroxetine is not addictive or habit forming and by extension applies to all manufacturers of antidepressant drugs of this kind. It also discredits the regulatory response to the problem of severe withdrawal reactions on antidepressants and raises basic questions about the effectiveness of such drugs in long-term use. This ruling should cause the UK Committee on Safety of Medicines/Medicines Control Agency, the US Food & Drug Administration and the European Medicines Evaluation Agency, to fundamentally rethink their warnings policies which to date have been lamentable.
The absurdity of the UK regulators position is underlined by the PMCOPAs ruling that GSK was in breach of Clause 7.9, which says that manufacturers should not claim a drug carries no risk of addiction because the current Patient Information Leaflet, approved by the MCA/CSM, positively emphasises just that: These tablets are not addictive remember that you cannot become addicted to Seroxat, and that the withdrawal symptoms some people experience when stopping paroxetine are not common and (they) are not a sign of addiction.
Social Audits allegations are set out in detail in the correspondence shown below. Briefly, Social Audits had complained that, in promoting paroxetine (Seroxat/Paxil) GlaxoSmithKline had consistently understated the risk of withdrawal reactions and dependence, obfuscating the truth by using definitions and terms wholly unfamiliar to consumers and probably many doctors as well. Social Audit argued that GSK should be using terminology consistent with the central idea in World Health Organisation statements:
The simplest definition of drug dependence given by WHO (1994) is 'a need for repeated doses of the drug to feel good or to avoid feeling bad.' When the patient needs to take repeated doses of the drug to avoid bad feelings caused by withdrawal reactions, the person is dependent on the drug. (WHO, Lexicon of alcohol and drug terms, 1994, and WHO bulletin, Drug Information, 1998, 12, 3, 136-138.)
Social Audit accused GSK of inviting patients to infer that the government enquiries had established there was no risk of dependence when this was not true. In fact, the jury is still out and it is misleading to represent a tentative verdict of non-proven as not guilty. The continuing risk is underlined by the recent announcement by the UK regulators (responding to a request from Social Audit) that the Committee on Safety of Medicines will conduct a further review of SSRI dependence at its meeting on 21 November.
This PMCOPA Appeal Board rejected Social Audits complaints under Clause 3.2, a decision Medawar described as inexplicable other than as a reflection on the pitiful state of government regulation. This clause in effect says that promotional materials should be in line with the information made available to health professionals (in the data sheet or Summary of Product Characteristics) and to consumers (in the Patient Information Leaflet):
The promotion of a medicine must be in accordance with the terms of the marketing authorization and must not be inconsistent with the particulars listed in its summary of product characteristics (Clause 3.2)
Mr Medawar said that the Appeal Board had ample evidence before it of several breaches of this requirement, including a letter to Social Audit from Dr June Raine of the Medicines Control Agency, confirming that persistent misdescription of drug withdrawal symptoms as discontinuation symptoms was inconsistent with both UK and European regulatory requirements. Medawar confirmed that Social Audit would be writing to the Medicines Control Agency asking them to take action against GlaxoSmithKline in relation to this and several other obvious violations and to advise the PMCOPA accordingly.
Social Audit had also sought a judgment against GSK for a breach of Clause 2 of the ABPI Code: promotion must never be such as to bring discredit upon, or reduce confidence in, the pharmaceutical industry Mr Medawar said, We believe GlaxoSmithKline has behaved disgracefully, causing many patients much distress. It is hard to imagine what more a company needs to do to be in breach of this requirement - though we knew our chances were slim, since a ruling of a breach of this clause is a particular sign of censure and is reserved for such circumstances. Medawar added:
its pretty depressing to learn that the other companies represented on the Appeal Board consider that public confidence in GSKs would not be badly shaken. True, this would have been a very hard decision for the Appeal Board - though I expect that, with further disclosure and in time, they will come to regret they could not rise to this occasion
The Appeal Boards detailed findings will be published
at a later date. Meanwhile, the basic documentation on the detail of the complaints
and the companys response has been posted on the Social Audit website
at www.socialaudit.org.uk. The Social Audit website now attracts over 250,000
visitors/year and includes well over 1,000 messages from disappointed
and often very distressed users of paroxetine and similar drugs. The Social
Audit website is one of several websites dedicated to reporting evidence not
only of the benefits, but also the risks of antidepressant drugs.