Strasbourg, 3 April 2008

Dear Mrs M.,

On 27 June 2005, you submitted a complaint to the European Ombudsman against the European Commission concerning an alleged lack of transparency and information by the latter with regard to the review of medicines containing Paroxetine and of SSRIs(1). On 3 July 2005, you sent additional documents concerning your complaint.

On the same day you also submitted another complaint concerning the same matter against the European Medicines Agency with the same allegations. This complaint has been the subject of a separate inquiry under reference 2370/2005/OV which was closed by my decision of 5 December 2007.

On 18 July 2005, I forwarded your complaint to the President of the Commission.

On 25 July 2005, I received a letter dated 13 July 2005 from Mr Brian Crowley MEP who wrote to lend support to your complaint. I replied to Mr Crowley on 30 August 2005. A copy of the present decision will be sent to him for information.

The Commission sent its opinion on 16 November 2005. I forwarded it to you with an invitation to make observations, which you sent on 7 December 2005 and on 11 January 2006.

Afterwards, on a very regular basis, you continued to send voluminous e-mails to a varying list of between 20 and 40 addresses, including my Office. In these e-mails, you forwarded further reports, studies, articles as well as newspaper extracts concerning the issue of drug safety, and in particular Paroxetine and SSRIs. These e-mails were registered under the reference of both the present complaint and complaint 2370/2005/OV.

You sent these e-mails (more than 100 in total) on the following dates: on 11 March 2006, on 22 and 26 April 2006, on 6 (3 e-mails) 7, 13 and 16 (2 e-mails) May 2006, on 4, 8, 21, 25 and 27 (2 e-mails) June 2006, on 3, 4, 6, 8 (2 e-mails), 11, 19, 21, 22, 23, 25 and 29 July 2006, on 27 (3 e-mails), 28, 29 (2 e-mails) and 30 August 2006, on 7, 8, 12, 14, 20, 22, 23, 24, 28 and 30 September 2006, on 8, 13, 18 and 28 October 2006, on 6 (3 e-mails), 8, 24, 26, 27, 28 and 30 November 2006, on 5 (2 e-mails), 6 (2-mails), 9 (2 e-mails), 15, 16 and 18 (3 e-mails) December 2006, on 7 (3 e-mails), 8, 14, 19, 20, 21, 23 (2 e-mails), 24, 26, 28, 29 (4 e-mails) and 30 (3 e-mails) January 2007, on 1, 2, 5, 7, 15, 17, 24 and 27 February 2007, on 13, 18, 19, 22, 23 (2 e-mails) and 30 March 2007, and on 1, 2, 3 (2 e-mails), 4 (2 e-mails), 6, 30 April and 14 June 2007, and on 26 and 28 February 2008.

On 3 October 2007, my Office contacted you in order to explore the possibility of a friendly solution with regard to your complaint.

On 29 October 2007, I addressed a proposal for a friendly solution to the Commission. You were informed accordingly in a letter of the same day.

By letter of 13 November 2007, the Commission asked for an extension of the deadline for its reply to the friendly solution proposal until 31 December 2007. By letter of 4 December 2007, I accepted the Commission's request. I informed you in a letter of the same day. By letter of 19 December 2007, the Commission asked for an additional extension of the deadline for its reply until 31 January 2008. I accepted this request by letter of 20 December 2007 and informed you in a letter of the same day. The Commission sent its reply regarding the proposal for a friendly solution on 7 February 2008. I forwarded it to you with an invitation to make observations, which you sent on 15 February 2008.

I am writing now to let you know the results of the inquiries that have been made.

THE COMPLAINT

The complainant is an emergency nurse in Cork University Hospital. According to the complainant, the relevant facts of the case are, in summary, as follows:

On 26 December 2003, at the age of 39 years, the complainant's husband committed suicide, while taking Seroxat(2)/Paroxetine. According to the complainant, Seroxat caused her husband to commit suicide.

After the death of her husband, the complainant, by e-mails of 18 and 19 August 2004, contacted Commissioners Pavel Telicka and David Byrne respectively, with regard to the scientific opinion of the European Medicines Agency ("the Agency") on the review of medicines containing Paroxetine. The complainant believed that the above opinion had been sent to the Commission for approval and expressed her concerns about the failings in the proposed opinion. She also raised four questions/points and requested that the Commission intervene by referring the matter to the Agency for reconsideration.

On 20 September 2004, more than one month later and without providing an apology for the delay, Commissioner Olli Rehn, to whose cabinet the complainant's e-mail to Commissioner Telicka had been forwarded, replied to the complainant. The other Commissioners neither acknowledged receipt of, nor replied to, the complainant's e-mails. Commissioner Rehn attached to his reply a copy of the proposed opinion and the Summary of Product Characteristics for Paroxetine, which the Agency had not provided to the complainant, but failed to answer the complainant's questions and to address her concerns with regard to the failings of the warnings. Similarly, the complainant's request for the Commission to intervene and to reconsider the warnings was ignored.

The complainant then waited for the new Commission to take up office. On 25 November 2004, the complainant wrote a letter to Commissioner for Health and Consumer Protection, Markos Kyprianou, once again expressing her concerns and asking the Commission to intervene and to refer the text of the Agency's scientific opinion on the review of Paroxetine containing medicines to the Agency for its reconsideration. On 12 January 2005, the complainant sent further documents to the Commissioner. On 9 February 2005, that is, two and a half months after she wrote to Commissioner Kyprianou and without providing any apology for the delay, the Commissioner's cabinet replied that, as the issue fell within the competence of the Commissioner for Enterprise and Industry, her letter had been forwarded to Commissioner Verheugen.

On 8 March 2005, one month after receiving the reply from Commissioner Kyprianou's cabinet, again without an apology, Commissioner Verheugen wrote to the complainant, without, however, answering her concerns and ignoring her request for intervention by the Commission.

By letter of 21 April 2005, Mr B., the Acting Head of the Unit "Consumer goods/Pharmaceuticals" within the Commission's Directorate-General ("DG") for Enterprise and Industry, informed the complainant that the Agency's scientific opinion had become a binding Commission decision which had been sent to the Member States on 4 April 2005. However, the complainant did not receive an answer to her questions and concerns. According to the complainant, Mr B.'s letter, which reproduced the proposed warnings, was insulting and degrading. Also, the Commission did not give the complainant an opportunity to discuss and raise her concerns, namely, her personal evidence, about the warnings.

The complainant stated that she had very serious concerns regarding the Agency's/Commission's failings to protect the public and referred to concerns expressed by the Executive Director of the Agency in an e-mail of 28 January 2005. She further stated that the regulation of Selective Serotonin Reuptake Inhibitors ("SSRIs") and anti-depressants remains chaotic and misconceived. In this context, the complainant referred to a social audit complaint in the United Kingdom.

According to the complainant, there are different warnings for Paroxetine/SSRIs and on the risk of suicide in the United States and Canada, on the one hand, and, Europe, on the other. The complainant stated that in the United States and Canada black box warnings have been issued for all SSRIs and other anti-depressants regarding the higher risk of suicide, and these warnings relate to all ages. The complainant also stated that the National Institute of Clinical Excellence ("NICE") in the United Kingdom has given different advice for mildly depressed persons compared to the advice given by the Agency, namely, that such persons should not use any anti-depressant because the risk/benefit ratio is poor, whereas in the eyes of the Agency it remains positive.

The complainant referred to a parliamentary inquiry undertaken in the United Kindgom concerning the influence of the pharmaceutical industry, which recommended the overhaul of the Medicine and Healthcare Products Regulatory Agency ("MHRA") because of its failings in protecting the public. The complainant argued that a similar inquiry should take place with regard to the Agency.

The complainant stated that she has the right to expect the Commission to work properly, that is, it must protect her and her family from well-known drug-induced harm by ensuring that the information is not only publicly available but also acted upon promptly. Consumers have a right to expect full and impartial information about the potential risks and adverse effects of prescription medication. The Commission was set up to protect the public, but in the complainant's view it has ended up protecting the pharmaceutical companies.

On 27 June 2005, the complainant lodged the present complaint with the Ombudsman(3), pointing out that the Commission had not respected the European Code of Good Administrative Behaviour. Her allegations can be summarised as follows:

(1) there has been lack of transparency and information by the Commission with regard to the complainant's questions and requests relating to the decision on Paroxetine;

(2) there has been undue delay in the replies to the complainant's e-mail correspondence and letters;

(3) the complainant was not heard by the Commission with regard to the matter of the safety and suicide risks of Paroxetine and her opinion was not taken into account. Also, there was lack of action by the Commission regarding her concerns.

THE INQUIRY

The Commission's opinion

In its opinion, the Commission made, in summary, the following comments:

I. Background

On 9 May 2004, the Commission received an e-mail from the complainant regarding the warnings given in the Patient Leaflet and the Summary of Product Characteristics of SSRIs. In this communication, the complainant informed the Commission that her husband had committed suicide on 26 December 2003, that is, 13 days after first taking Paroxetine.

(1) Paroxetine

The Commission first described in detail the anti-depressant Paroxetine, which is an SSRI. Paroxetine is indicated for the treatment of, among others, major depressive episodes, obsessive compulsive disorders, panic disorders with and without agoraphobia, as well as generalised anxiety disorders. In the EU, Paroxetine is authorised at the national level by the Member States.

In May 2003, the United Kingdom reviewed data from clinical trials involving Paroxetine in the treatment of paediatric obsessive compulsive disorder, social phobia/social anxiety disorder and major depressive disorder and concluded that these data provided evidence of an association between the use of Paroxetine and an increased risk of emotional instability including self-harm, hostility and suicidal behaviour in children and adolescents.

On 13 June 2003, the United Kingdom referred to the Agency, under Article 31 of Directive 2001/83/EC(4), a question concerning medicinal products containing Paroxetine. The question was based on the above data which concerned withdrawal reactions and suicidal behaviour. The Agency delivered an opinion on 22 April 2004, on the basis of the assessment of all data available at that time and concluded that the data had shown:

- an increased risk of suicide- and hostility-related behaviour in children and adolescents (7-17 years old);

- a possibility of an increased risk of suicide-related behaviour associated with Paroxetine in young adults (18-29 years), even though the increased risk was not statistically significant;

- in the older age groups no such increase was observed.

After the adoption of this opinion by the Agency, the United Kingdom informed the Commission about three studies (one published and two unpublished) that were based on the United Kingdom's General Practice Research Database ("GPRD") and that were of relevance to the question.

On 11 November 2004, the Commission asked the Agency to adopt a revised opinion including the evaluation of the new GPRD data. The Agency delivered a revised opinion on 8 December 2004 with the following conclusions:

"The Agency considered that efficacy has not been or has insufficiently been demonstrated in children and adolescents in most of the indications.

The Agency concluded that there are concerns in relation to the safety of Paroxetine containing medicinal products with an increased risk of suicidal and hostility related behaviours in the paediatric population (7-17 years old) and a possibility of an increased risk of suicidal related behaviours in young adults (18-29 years).

The Agency considered that Paroxetine containing medicinal products are effective in the treatment of adults and therefore considered the benefit/risk balance of Paroxetine to be favourable in adults.

As a consequence, the Agency recommended the maintenance of the Marketing Authorisation for Paroxetine containing medicinal products with amendments in the summary of products characteristics and the Package Leaflets related to its use in children and adolescents."

The Commission's decision based on the Agency's opinion was published on 29 March 2005 and Member States had to implement the decision by May 2005.

(2) SSRIs and SNRIs

SSRIs and Serotonin-Norepinephrine Reuptake Inhibitors ("SNRIs") are medicinal products which are authorised on the basis of national and centralised marketing authorisations. They are indicated for the treatment of, for example, major depression episodes. The warnings accompanying medicinal products falling within the class of SSRIs and SNRIs are not harmonised throughout Europe. These products are not authorised on a Europe-wide basis for the treatment of depression and for anxiety disorders in children or adolescents.

On 17 December 2004, the Commission presented to the Agency a referral under Article 31 of Directive 2001/83, requesting that the Agency undertake an assessment of the data on children and adolescents that were available to competent national authorities and in published literature. The Commission also asked the Agency to give its opinion on whether the marketing authorisation for medicinal products such as SSRIs/SNRIs should be maintained, varied, suspended or withdrawn.

On the basis of the data reviewed on SSRIs/SNRIs products and in particular as regards their use by children and adolescents, the Agency stated that an examination of suicide-related behaviour, namely, suicide attempts and suicidal thoughts, indicated that no suicide was reported in any of the reviewed studies. The Agency also noted that suicide-related behaviour and hostility (predominantly aggression, oppositional behaviour and anger) were more frequently observed among children and adolescents treated with anti-depressants as compared to those treated with a placebo. The Agency concluded that a warning to reflect this fact should be included in the relevant sections of the Summary of Product Characteristics and of the Package Leaflet.

The Agency recommended the maintenance of the Marketing Authorisations for the medicinal products containing SSRIs/SNRIs with the amendments to the relevant sections of the Summary of Product Characteristics and Package Leaflets.

The Commission's decision based on the Agency's opinion was published on 19 August 2005, and Member States had to implement the decision by September 2005.

(3) Conclusion

In the assessment of both referrals, the need to change the information contained in the Summary of Product Characteristics and Package Leaflet for the treatment of adult patients was discussed. No recommendations were proposed for a change of the risk/benefit evaluations of SSRIs/SNRIs for changes in relation to the information provided to patients. A warning regarding the use of SSRIs/SNRIs by adults was already included in the information of the Summary of Product Characteristics.

II. The Commission's comments on the complainant's arguments

The Commission made 11 points:

(1) As regards the e-mails sent to Commissioner Telicka on 18 August 2004 and to Commissioner Byrne on 19 August 2004, the Commission observed that a copy of the e-mails was received by the relevant service in DG Health and Consumer Protection on 23 August 2004. On 25 August 2004, after consideration of the above e-mails, the Commission transferred the e-mails to DG Enterprise and Industry, because the issues raised in them came within the latter DG's competence. DG Health and Consumer Protection then noted the transfer of the e-mail in the mail filing system on 25 August 2004.

As the e-mail to Commissioner Byrne of 19 August 2004 was identical to the e-mail sent to Commissioner Telicka on 18 August 2004, it was considered that there was no need for separate action and that the reply prepared by DG Enterprise and Industry would deal with the issues raised in both e-mails. It was regrettable, however, that no reply was sent to the complainant by DG Health and Consumer Protection informing her that the e-mails she had sent had been transferred to DG Enterprise and Industry. The Commission apologised for this oversight.

(2) As regards the letter from Commissioner Rehn, the complainant alleged that she received it one month after she had sent her e-mail and that the Commissioner's reply did not contain an apology or clear answers to her questions. In its reply, the Commission observed that, following the transfer of the e-mail to DG Enterprise and Industry on 25 August 2004, a draft answer was prepared including (i) a reference to the e-mail to Commissioner Telicka, and (ii) an explanation that the Commission did not have any justification for deviating from the draft Agency's opinion which had been prepared with the involvement of all relevant experts from all Member States.

The reply from Commissioner Rehn was dated 20 September and sent to the complainant on 21 September 2004. Bearing in mind the sensitivity of the issue and the need to contact other Commission services, as well as the Agency, the time taken to prepare a full response was not unreasonable. The Commission nevertheless regretted the delay and apologised for not acknowledging it in its reply to the complainant.

(3) As regards the letters of 25 November 2004 and 12 January 2005 to Commissioner Kyprianou, the complainant alleged that a response was received two and a half months later (on 9 February 2005) in the form of a holding letter. Furthermore, the complainant alleged that the only information contained in that reply was the statement that the case had been forwarded to Commissioner Verheugen. With respect to these letters, the Commission observed that the Head of Cabinet of Commissioner Kyprianou replied on 9 February 2005, explaining that the issues the complainant had raised came within the competence of the Commissioner responsible for DG Enterprise and Industry. Therefore, the letters were forwarded to the Head of the Cabinet of Vice-President Verheugen. It should, however, be noted that the complainant had already received replies from DG Enterprise and Industry in Commissioner Rehn's letter of 20 September 2004, which had attempted to respond to various points raised by her. Nonetheless, the Commission apologised for the delay in replying to the complainant's letters of 25 November 2004 and 12 January 2005.

(4) As regards the letter from Commissioner Verheugen, the complainant alleged that she received it one month after the referral by Commissioner Kyprianou, with no apology for the delay or any information or comments regarding her concerns. In this regard, the Commission observed that both letters were received by DG Enterprise and Industry on 14 February 2005. The reply was sent by Commissioner Verheugen on 8 March 2005. The Commission regretted this delay, but pointed out that it was nevertheless unavoidable, because of the need to contact other Commission services, as well as the Agency. As regards the substance of the matter, the reply did address the complainant's comments. It highlighted that the assessment of the safety issues concerning the use of SSRIs in adults undertaken by the Agency was not finalised and that further information would be provided by the Commission's services. The said information was provided to the complainant in the letter of 21 April 2005 from Mr B., Acting Head of the Unit "Consumer goods/Pharmaceuticals" within DG Enterprise and Industry.

(5) As regards Mr B.'s letter of 21 April 2005, the complainant alleged that it did not reply to her questions. In this regard, the Commission observed that the additional answer provided to the complainant by its services did address her questions, even though the request to refer the decision to the Agency for a second time was not granted, due to a lack of new evidence. After an in-depth analysis of all available data by European medical experts, the Agency concluded that the risk/benefit balance for Paroxetine remained positive in the treatment of adults and that no change in the Summary of Product Characteristics was needed with respect to the use of Paroxetine in adult patients and to the risk of suicide or suicide-related behaviour. As the complainant did not provide any new data or evidence, the Commission had no reason to refer the issue to the Agency again.

(6) As regards the allegedly different standards of information with respect to Paroxetine/SSRIs and the risk of suicide in the United States/Canada and Europe, the Commission stated that the complainant's view was not correct. The content of the information regarding Paroxetine and the risk of suicide/suicidal behaviour is the same in all regions. The only difference concerns the way in which this information is presented. The common practice in the United States is to include information in so-called eye-catching black boxes. This tool is not available in the EU in a harmonised manner, due to the implementation of different medicinal product legislation at the national level.

The Commission referred to the text of the recommendations published by the United States Food and Drug Administration ("FDA") on 1 July 2005, and of the recommendations contained in the Summary of Product Characteristics for Paroxetine in the EU. It stated that these recommendations were consistent with warnings already present in approved labelling for anti-depressants used by adults. The Commission also stated that it is important to inform the patient and the prescriber so as to make it possible to evaluate the treatment's benefits and risks. Overestimating the risk might prevent the patient from taking a useful and necessary medicinal product for the treatment of a serious disease.

The Commission also stated that there was an ongoing discussion between patient-organisations and the Agency designed to improve the information in the Package Leaflet. Patient-organisations request better and more balanced information with respect to the benefit of the medicinal product in the treatment of a disease and not to extend the information regarding warnings and adverse reactions.

(7) As regards the complainant's argument that the Agency provided the public with a relaxed risk/benefit analysis, the Commission observed that the Agency's scientific opinions are developed and decided on the basis of justified and sound scientific risk/benefit analysis undertaken in the Agency's scientific committees. In these opinions, not only the age of the patient has been taken into consideration, but also the warnings that accompany the relevant products. These have to be reflected in a correct manner in the advice and information given to the prescriber and the patient. The treatment of mild depression with anti-depressants, to the extent that it is not recommended in the Summary of Product Characteristics, is a misuse or has to be seen in the context of the freedom of prescription by the prescriber who is responsible for the treatment of his/her patient.

(8) As regards the complainant's statement that NICE in the United Kingdom has given different advice for mildly depressed persons compared to the advice given by the Agency, the Commission pointed out that NICE and the Agency work in a completely different context so that there is no conflict between these recommendations. Scientific decisions are taken by the Agency with a view to issuing marketing authorisations. They are based on the quality, safety and efficacy data of the medicinal product presented by the applicant/marketing authorisation holder and, if available, other scientific publications. By contrast, NICE gives recommendations, not with regard to marketing authorisations, but with regard to price and reimbursement as well as with regard to the use of a medicinal product, such as Paroxetine, for mild to moderate depression. Mild or moderate depression is not part of the warnings that accompany Paroxetine in the marketing authorisation of that product. Therefore the Agency cannot give any advice for such warnings. Therefore it might be possible that, under certain circumstances, the recommendations for the use of a medicinal product might slightly differ between the scientific recommendations given by the Agency and NICE.

(9) As regards the complainant's argument that there are different criteria for the authorisation and withdrawal of medicinal products, the Commission stated that a marketing authorisation is granted only when the applicant has demonstrated the medicinal product's quality, safety and efficacy and its positive risk/benefit balance. Equally, the same criteria apply for the decision as to whether an existing marketing authorisation shall be maintained or withdrawn.

(10) The complainant referred to the harmful influence of the industry on the Agency. In this regard, the Commission stated that the Agency is required to provide the Member States and the Community institutions with the best possible scientific advice on any question relating to the evaluation of the quality, safety and efficacy of medicinal products for human use, which is referred to it. To this end, the Agency, acting particularly through its committees, shall co-ordinate the scientific evaluation of the quality, safety and efficacy of medicinal products which are subject to Community marketing authorisation. The pharmaceutical industry is not represented in the Management Board or in the committees of the Agency. The Agency also receives EU subventions in order to ensure financial independence.

(11) As regards the complainant's allegation that she was not heard personally before a decision was taken, the Commission observed that the complainant's comments had been fully considered by the Commission and also by the Agency. Several informal discussions between the Commission and the Agency took place over the year 2005 based on the information provided by the complainant. This resulted, for example, in a request for the Agency's Pharmacovigilance Working Group to review the available data also with respect to patients older than 30 years of age. While the Commission's Code of Good Administrative Behaviour requires that the Commission answer inquiries in an appropriate manner and as quickly as possible, it does not require the Commission to hear personally each individual making an inquiry.

III. Conclusions

On the basis of the above, the Commission came to the following conclusions:

(1) As regards the allegation concerning the delays in the replies to the complainant's e-mails and letters, the Commission stated that it had answered all of her complaints. Her complaints were taken into account at all stages of the Commission’s inquiry, as part of an overall assessment of the issue. The Commission regretted any delays in its replies, which were however necessary and reasonable in light of the need to co-ordinate its different services and the Agency.

(2) As regards the allegation of lack of transparency and information, and of inappropriate scientific evaluation of data, the Commission stated that all available data were taken into account when taking the relevant scientific decisions. Information relating to these decisions has been made publicly available by the Agency and on the Commission's website(5) which contains information for medicinal products authorised by the Commission and also information regarding decisions taken in referral procedures.

(3) As regards the allegation that the complainant was not heard and her opinion was not taken into account before a decision was taken, the Commission stated that the complainant's comments had been fully considered by the Commission and the Agency.

The complainant's observations

The complainant presented 22 pages of observations on the various points in the Commission's opinion, and on the enclosures. These observations can be summarised as follows:

(1) Comments on the points raised in the Commission's opinion

First of all, the complainant wished to praise the Commission for providing her with more thorough information and having attempted to address more issues than the Agency had.

The complainant, however, did not find it acceptable that the Commission stated that the Agency delivered its opinion on the basis of the assessment of all data available at the time. According to the complainant, the statement that no increase of suicide-related behaviour associated with Paroxetine in the older age groups was observed was not acceptable, because the available data were extremely limited, since it was not possible to examine raw data collected in clinical trials. The complainant wondered how many people needed to die before the risk became statistically significant. According to the complainant, 90% of the anecdotal evidence was unavailable.

With regard to the Commission's statement that the Agency considered the risk/benefit balance of medicines containing Paroxetine to be favourable for adults, the complainant pointed out that the fact that this product might be effective for some patients did not mean that there were no risks for other patients.

As regards the Commission's comments on the complainant's arguments, contained in point II of the Commission's opinion, the complainant stated that she accepted the Commission's apology concerning points (1), (2) and (3), but wondered why, with respect to point (4), the Commission regretted the delay but did not apologise for it.

As regards point (5), the complainant disagreed with the Commission's statement that all the issues she raised in her letter of 25 November 2004 to Commissioner Kyprianou had been addressed in the letter sent by Mr B. on 21 April 2005. She more particularly referred to the issue raised in her letter concerning a lawsuit brought by the New York State Attorney against GlaxoSmithKline ("GSK") for withholding safety data on Paroxetine with respect to children and adolescents and pointed out that the Commission had not addressed it. The complainant stated that she would also like to receive the Commission's opinion on the lack of implementation of the law concerning GSK's failure to comply with its obligation to report safety data to the Agency within 15 days. With respect to the Commission's comment that she did not provide any new evidence, the complainant replied that this was correct as she had no access to GSK's archives, but neither did the Commission or the Agency. Therefore, according to the complainant, the Commission and the Agency had reached decisions without being cognisant of all the data, which were withheld by the pharmaceutical industry.

As regards point (6) of the Commission's opinion, the complainant highlighted various warnings contained in the product characteristics issued in the United States, by the FDA, on 22 March 2004 and asked where similar statements were made in the EU warnings. The complainant pointed out that the Commission had, however, chosen to refer to the preliminary warning which the FDA issued on 1 July 2005 and which more closely resembled the EU warning. The complainant invited the Ombudsman to compare the text of the FDA warnings with that of the EU warnings.

Similarly, the complainant referred to warnings in Canada (the Health Canada Important Safety Information on Paroxetine, "Health Canada") and asked again where similar warnings were made in the EU warnings. The complainant concluded that the Commission's position that she was wrong as regards her allegation of different information standards was false.

The complainant also referred to the Commission's statement that, "[b]y overestimating the risk it might prevent the patient from taking a useful and necessary medicinal product for the treatment of a serious disease". The complainant stated that the Commission was choosing selectively to report certain information. The Commission overestimated the benefits of SSRIs and underestimated the risks, thereby causing more harm. The complainant then referred to the statement in the Commission's opinion that "[p]atient organisations [are] requesting better and more balanced information in [sic] respect to the benefit of the medicinal product in the treatment of a disease and not to extend the information regarding warnings and adverse reactions". The complainant found it hard to believe that any patient organisation which had as its goal the promotion of the best interests of the patient would request more information about the benefits of a medicinal product but not its risks. The complainant stated that she would like an explanation from the Commission on this, as well as an opinion from the Commission on the United Kingdom parliamentary inquiry into the pharmaceutical influence report.

As regards the Commission's comments concerning the allegedly relaxed risk/benefit analysis (point (7) of the Commission's opinion), the complainant again observed that the Agency and the Commission do not listen to individuals and do not examine raw data and data on unavailable adverse drug reactions (90% of data on adverse drug reactions is unavailable). The complainant also pointed out that, among the committees' members are individuals who have conflicts of interest and who, therefore, should leave the meetings when a product such as Paroxetine is being discussed. In relation to conflicts of interest, the complainant mentioned one member who had GSK shares.

Concerning point (9) of the Commission's comments, the complainant wondered how the applicant for the authorisation of a medicinal product could demonstrate beyond any reasonable doubt its quality, safety and efficacy when the raw data which the applicant has analysed could not be examined by anyone else. The complainant added that the pharmaceutical companies were also able to arrange clinical trials repeatedly until they achieved the necessary standard for obtaining a license. In the end, it was the responsibility of the patients, doctors and independent scientists to demonstrate that the safety of the drug was problematic.

Regarding point (10) of the Commission's comments, the complainant stated that she would like the Commission to provide her with a list of the members of the scientific committees of the Agency and their affiliations with, and sponsorship by, the pharmaceutical industry. The complainant did not agree with the Commission's statement that it could be excluded that the industry had a harmful influence on the decisions taken by the Agency or other competent authorities in the EU.

With regard to point (11) of the Commission's opinion, the complainant welcomed the informal discussions undertaken between the Commission and the Agency based on her information. The complainant expressed her concern that the issues of safety and efficacy in adults (suicidal behaviour, withdrawal reactions and effects of dose) were not put on the agenda because of her comments. The complainant also wondered how long it would take for the Commission/the Agency to release a warning comparable to that issued by the FDA or Health Canada. The complainant also mentioned that the Commission and the Agency had discussions concerning her information but that they did not answer her scientific questions. With regard to the Commission's reference that the Code of Good Administrative Behaviour does not require the Commission to hear personally every individual who makes an inquiry, the complainant stated that there was something fundamentally wrong when the bodies that were supposed to protect patients did not have an obligation to listen to them. The complainant stated that no SSRI had been proven to prevent suicide, but that instead they were causing more harm than good because of their adverse reactions, as the tablets were inducing what they were supposed to prevent. The Patient Leaflets were misleading and should be changed. In order to make informed decisions about their health, members of the general public needed to have access to the full facts, and the complainant wondered whether the Agency and the Commission were going to provide the people with those facts.

(2) Comments on the attachments enclosed with the Commission's opinion

The complainant made very detailed comments with respect to pages 2 to 12 of the annexes of the Commission's opinion, starting with comments on the substance of the Agency's scientific conclusions on medicines containing Paroxetine (attachment (1) to the Commission's opinion). More particularly, the complainant made comments on the Agency's conclusions regarding the efficacy and the safety of the drug for adults in relation to (i) Major Depressive Episode (MDM), (ii) Obsessive Compulsive Disorder (OCD), (iii) Panic Disorder, (iv) Social Anxiety Disorder/Social Phobia, (v) Post-Traumatic Stress Disorder, (vi) Suicidal Behaviour, Self-Harm and Hostility, (vii) Withdrawal Reactions, and (viii) Akathisia. With regard to these different aspects, the complainant stated that the Agency's conclusions did not mention how many studies were conducted in order to come to the above conclusions (the Agency’s conclusions referred to "numerous" trials and "some" studies) or what the outcome of these studies was (positive/negative). The complainant also underlined the shortcomings of the trials, and the lack of information or reduced information about certain conclusions in the Patient Leaflet or the Agency's warnings (for instance, with regard to Post-Traumatic Stress Disorder and Withdrawal Reactions). Also, some information was only contained in the Summary of Product Characteristics which patients were not allowed to access and doctors rarely checked. The Patient Leaflet therefore became unclear and misleading.

With regard more particularly to the assessment of Paroxetine in relation to Suicidal Behaviour, Self-Harm and Hostility, the complainant wondered how the Agency or the Commission could come to conclusions which were statistically significant when (i) "individuals" had no right to be heard and (ii) only 10% of the factual adverse effects were taken into consideration.

As regards the Agency's conclusions regarding the review of SSRIs (attachment (2) to the Commission opinion), the complainant stated that the Committee for Medicinal Products for Human Use ("CHMP") had decided by a majority of 24 out of 22 votes (sic) in favour of the maintenance of the Marketing Authorisations. The complainant wondered how a majority of 24 out of 22 votes was possible. With regard to the same attachment, the complainant stated that the CHMP mentioned that suicide-related behaviour and hostility were more frequently observed in trials among children and adolescents treated with anti-depressants as compared to those treated with a placebo. The CHMP had thus recommended that such a risk should be included in the summaries of product characteristics and the relevant section of the Package Leaflets of medicines containing SSRIs. The complainant pointed out, however, that some copies of Patient Leaflets she had obtained from the Irish Medicines Board did not contain such a warning, and stated that she would like to have the Commission's opinion on these issues.

With regard to the Summary of Product Characteristics on Paroxetine (attachment (4) to the Commission's opinion), the complainant pointed out that this document was not available to the public and doctors hardly ever referred to it. The complainant wanted to know, therefore, what the Commission was going to do in order to remedy the lack of communication between the Agency, the Commission and doctors in Ireland. With regard to the section "posology and method of administration" (section 4.2 of the Summary of Product Characteristics), the complainant stated that the possibility that the drug does not work was not raised. The complainant further made comments on the suggestion made in the Summary of Product Characteristics gradually to increase the dose in case of insufficient response within three or four weeks, pointing out the dangers of adverse reactions and suicide.

With regard to the section "Special warnings and special precautions for use" (section 4.4. of the Summary of Product Characteristics), the complainant stated that not all depressions carry an intrinsic risk of suicide.

With regard to the section "Undesirable effects" (section 4.8 of the Summary), the complainant indicated that she had a problem with the warnings that accompanied the relevant products, to the extent that certain symptoms might also be due to an underlying disease.

With regard to the section "Pharmacodynamic properties" (section 5.1 of the Summary), the complainant again made comments with regard to the dangers of increasing the dose of certain medicines.

Further correspondence from the complainant

After having sent her observations, the complainant sent more than 100 e-mails to the Ombudsman's Office and other addressees, and, in addition, forwarded further reports, studies, articles as well as newspaper extracts concerning the issue of drug safety, and in particular SSRIs and Paroxetine.

THE OMBUDSMAN'S EFFORTS TO ACHIEVE A FRIENDLY SOLUTION

After careful consideration of the Commission's opinion and the complainant's observations, the Ombudsman was not satisfied that the Commission had responded adequately to the complainant's allegations.

1 Preliminary remark and scope of the Ombudsman's inquiry

1.1 The European Ombudsman notes that the present complaint, in which the complainant made three allegations against the Commission about the way it had reacted to her various requests and e-mails and to her concerns, originates in the suicide, at a young age, of her husband, who was also the father of her three children, on 26 December 2003.

The Ombudsman realises that the complainant has, over the past four years, gone through an extremely difficult time in her life and that, unfortunately, whatever the outcome of the present inquiry into her complaint, the complainant's personal situation resulting from that tragic event cannot be undone. The Ombudsman wishes to convey to the complainant his deepest sympathy for her loss and his sincere wishes for her future and that of her family.

1.2 The Ombudsman notes that, in her complaint and in her observations, the complainant often refers at the same time to the Commission and to the Agency. The Ombudsman would like to point out, however, that the Agency is the subject of another ongoing inquiry (2370/2005/OV) and that the present inquiry will therefore only deal with the allegations against the Commission.

1.3 The Ombudsman further notes that, in her observations, the complainant raised numerous new points and questions, asking the Commission to provide an opinion on these issues. For instance, the complainant asked the Commission for an explanation as regards its statement that patient organisations request more information about the benefits than about the risks of medicines. She also requested that the Commission provide her with a list of the members of the scientific committees of the Agency and their affiliations with, and sponsorship by, the pharmaceutical industry. In connection with this request, the complainant also presented a new allegation in her observations, namely, that certain members of the committees within the Agency had a conflict of interest. In addition to her observations on the Commission's opinion, the complainant also made detailed comments on the substance of the scientific conclusions reached by the Agency, raising further questions (for instance, concerning the reaching of a majority vote in the Committee for Medicinal Products for Human Use). These conclusions were attached to the Commission's opinion.

The Ombudsman would like to underline that, as it stands, the complaint is already very voluminous and complex. In order not to delay and complicate further the inquiry into the present complaint, the Ombudsman finds it appropriate to limit the present inquiry to an analysis of the allegations as set out in the complainant's original complaint of 27 June 2005. Should the complainant wish for the Ombudsman to deal with new allegations against either the Agency or the Commission, she could consider making first the appropriate prior administrative approaches to the Agency and/or the Commission, before lodging a new complaint with the Ombudsman. The allegation relating to the conflict of interest, for instance, concerns the Agency and the complainant should therefore first complain to it about this issue.

1.4 The Ombudsman notes that, in her complaint, the complainant referred also to shortcomings in the United Kingdom's Medicine and Healthcare Products Regulatory Agency and to a parliamentary inquiry into its functioning. The Ombudsman would like to underline that he can only investigate alleged instances of maladministration by Community institutions and bodies, and that he has no power to investigate alleged maladministration by national authorities of the Member States. The present inquiry will therefore deal only with the alleged maladministration by the Commission.

1.5 The Ombudsman notes that, after having sent her observations on the Commission's opinion, the complainant sent a considerable number of further e-mails. The Ombudsman has carefully analysed this correspondence. However, it appears that these e-mails do not contain information that would be relevant for the purposes of the inquiry into the complainant's allegations. The complainant's correspondence has, however, been added to the file, for information.

2 The alleged lack of transparency and lack of information

2.1 In order to deal with the complainant's allegation of lack of transparency and lack of information, the Ombudsman considers it necessary to examine the complainant's correspondence with the Commission and the Commission's replies.

2.2 The Ombudsman notes that, in her identical e-mails of 18 and 19 August 2004 to Commissioners Telicka and Byrne respectively, the complainant (i) described her personal situation referring to her husband’s suicide, and (ii) referred to the Agency's warning concerning Selective Serotonin Reuptake Inhibitors ("SSRIs") and Paroxetine which had to be approved by the Commission. The complainant raised serious concerns about the failings of the proposed warnings, more particularly with regard to the safety and suicide risks for patients who are 30 years and older. In this context, the complainant also referred to stronger warnings that exist in the United States and Canada. The complainant raised the following four points/questions, which she quoted again in her complaint to the Ombudsman:

(1) "Why the EU warning does not go far enough to protect the European citizens as much as the Americans and Canadians are protecting theirs?"

(2) "Don't we deserve to be protected as much as any other citizen about the same drug or are we going to allow this tragedy to continue to strike the adult population of Europe?"

(3) "I am asking you to intervene, show leadership and courage to request the EMEA(6) /CHMP(7) to look into the latest developments again to protect the European population as the Americans and the Canadians protect theirs. Empower the patient, their families and health practitioners with all the information and this problem could be reduced in Europe saving lives".

(4) "I would request you before this happens to reconsider for the health and safety of the patient who would be using this drug in the future in European Soil [sic]".

2.3 In its reply of 20 September 2004(8), the Commission informed the complainant that

"the Committee for Human Medicinal Products (...), made up of medicines experts from all the EU Member States, carefully considered all the relevant data on the safety and efficacy of Paroxetine, including all the relevant clinical trials, reports received spontaneously from health professionals and additional information received from manufacturers and a patient group. The Committee particularly focussed its attention on the safety of Paroxetine with regard to withdrawal reactions and suicide. The Committee's conclusions are set out in the attachment to this letter and are reflected in the Summary of Product Characteristics, also attached to this letter. The Summary of Product Characteristics contains clear and explicit warnings about the risk of suicide during therapy and the consequent need for vigilance during therapy. There is additional information regarding suicide risk in different age groups and this additional information is based on detailed assessment of the data available in those age groups. A Commission Decision on medicinal products containing Paroxetine implementing the conclusions of the Committee will be prepared. This will lead to new product information in all EU Member States with clear warnings regarding the risks of suicide during therapy".

2.4 In her letter of 25 November 2004 to Commissioner Kyprianou, the complainant referred in detail to the suicide of her husband. She reiterated her concerns with regard to the safety and suicide risks of Paroxetine for patients aged 30 years and older. The complainant referred in length to GSK's practice of not releasing all clinical trial data and to a lawsuit against GSK brought by the New York State Attorney and its settlement. The complainant wondered how much of these data the Agency had seen before reaching its conclusions. She pointed out that the Agency listens to GSK but not to anecdotal evidence from patients. The complainant asked the Commission to intervene with regard to her concerns by again referring the Agency's opinion to the Agency for further consideration about an appropriately strong warning concerning Paroxetine that would apply to all ages. On 12 January 2005, the complainant sent further documents recently released in the United States.

2.5 The Commission replied to the complainant's letter on 8 March and on 21 April 2005. In his reply of 8 March 2005, Commissioner Verheugen stated the following:

"[p]lease let me assure you that the intention of the Commission has always been and is to improve the information on medicinal products for the patients. The recently amended pharmaceutical legislation sets out that by November 2005 a public database shall be in place to assist the public in searching information on authorised medicinal products. On the subject of Paroxetine, let me point out that the European Medicines Agency recommended that safety issues concerning the use of Serotonin-Selective Reuptake Inhibitors in adults should be re-assessed by the scientific working party evaluating marketed medicinal products. This assessment is on-going. Detailed information will be sent to you in a letter by my services".

2.6 In the additional reply of 21 April 2005 of the Acting Head of the Unit "Consumer goods/Pharmaceuticals" within the Commission's DG for Enterprise and Industry, the Commission provided the complainant with more detailed information on the ongoing scientific review of Paroxetine and SSRIs. With regard to medicines containing Paroxetine, the Commission explained that the matter had been referred to the Agency for review by the MHRA of the United Kingdom with regard to safety concerns in the use of these medicines, namely, increased risk of suicidal behaviour and hostility in children and adolescents treated with Paroxetine. The Commission explained that, following this referral, the Agency conducted a review of the benefits and risks of medicines containing Paroxetine, during which all available data were taken into account, and confirmed its initial conclusion that the risk/benefit balance of Paroxetine remained positive as concerns the treatment of adults. The Agency also reaffirmed its previous conclusion that changes to the product information should be introduced, especially with regard to warnings concerning suicide-related behaviour in children and adolescents. The Commission attached an annex containing details on the Agency's conclusions and also referred the complainant to a press release published by the Agency. The Commission further explained that the scientific opinion of the Agency had been transformed into a binding Commission Decision which was sent to the Member States on 4 April 2005 and indicated to the complainant where this decision could be found on the Internet. With regard to SSRIs, the Commission explained that it referred the matter for review to the Agency in December 2004, especially for a review of the use of these products in children. The Commission indicated that this evaluation was ongoing.

2.7 On the basis of the above correspondence between the complainant and the Commission, the Ombudsman comes to the following conclusions with regard to the complainant's allegation of lack of transparency and information. It appears that, in its three replies of 20 September 2004, 8 March and 21 April 2005, as well as in the framework of the present inquiry, the Commission provided the complainant with detailed and relevant information concerning the review of Paroxetine and SSRIs. The Ombudsman more particularly notes that, in these replies, the complainant was provided with a copy of the CHMP's conclusions on the said review and with a copy of the Summary of Product Characteristics. The Commission also referred the complainant to a press release issued by the Agency which contained further details on the said review and for which the Commission gave the Internet link. The Commission also indicated to the complainant where on the Internet she could find the Commission’s Decision on the review of Paroxetine. Finally, in the framework of the present inquiry, the Commission provided the complainant with copies of both the final Commission Decisions of 29 March 2005 (concerning Paroxetine) and of 19 August 2005 concerning SSRIs and SNRIs(9) and of their annexes which included the scientific conclusions of the Agency and the Summary of Product Characteristics.

2.8 The Ombudsman also notes that, in her observations, the complainant praised the Commission for having provided her with more thorough information than the Agency had. On the basis of the above considerations, the Ombudsman concludes that, with regard to the general information concerning the review of Paroxetine and SSRIs, there has been no lack of transparency or lack of information by the Commission.

2.9 With regard to the specific points or questions raised by the complainant, the Ombudsman notes that the complainant alleged in her complaint to the Ombudsman that, in its reply of 20 September 2004, the Commission failed to answer her (four) questions and to address her concerns. The complainant also alleged that the Commission's replies of 8 March and 21 April 2005 did not answer her concerns and ignored her request for intervention.

2.10 The Ombudsman notes that, with the four questions/points raised in her e-mails of 18 and 19 August 2004 which overlap somewhat, the complainant sought, in fact, to raise three points: (i) to draw the Commission's attention to her concern that the EU warnings were not as strong as the warnings given in the United States and in Canada; (ii) to express, in particular, concerns with regard to the warnings for patients aged 30 years and older; and (iii) to request that the Commission intervene by asking the Agency to consider the matter again on the basis of all available information. The Ombudsman notes that, in its reply of 20 September 2004, the Commission did not answer these specific concerns raised by the complainant, but informed her in general terms about the Agency's review of medicines containing Paroxetine.

2.11 In her letter of 25 November 2004 addressed to Commissioner Kyprianou, the complainant raised her concerns again with regard to warnings for adults and again asked the Commission to refer the matter to the Agency. Additionally, the complainant raised at length a fourth issue, which concerned GSK's behaviour as regards the release of information about clinical trials and referred to a lawsuit against GSK by the New York State Attorney. The complainant asked how much of these data the Agency had seen before reaching its conclusions. The Ombudsman notes that, in its reply of 8 March 2005, the Commission only partially replied to her concern by informing her that the Agency recommended that safety issues concerning the use of SSRI’s in adults should be reassessed and that this assessment was ongoing. In its reply of 21 April 2005, the Commission informed the complainant about the outcome of this reassessment by the Agency. Although the Ombudsman does not consider this reply to be insulting or degrading, as suggested by the complainant in her complaint, it is true that the Commission's letter of 21 April 2005, as well as its previous letter of 20 September 2004, provided the complainant with general information about the Agency's review of medicines containing Paroxetine and SSRI's/SNRIs rather than address her specific concerns.

2.12 It appears, however, that, ultimately, three of the four points raised by the complainant have been addressed by the Commission in its opinion on the complaint:

(i) the Commission commented on the issue of the different warnings existing in the EU and the United States and Canada (as regards the substance of this issue, see point 4.10 below);

(ii) as regards the warnings for patients aged 30 years and older, the Commission pointed out in its opinion that, in the assessment of both referrals, the need to change the information in the Summary of Product Characteristics and in the Package Leaflet for the treatment of adult patients was discussed, but that no recommendations were proposed for a change of the risk/benefit evaluations of SSRIs/SNRIs or changes in relation to the information provided to patients. The Commission pointed out, however, that a warning regarding the use of SSRIs/SNRIs by adults was already included in the information of the Summary of Product Characteristics;

(iii) as regards the complainant's request to the Commission to intervene by referring the matter for review to the Agency for a second time, the Ombudsman notes that, in its opinion, the Commission explained that it did not grant this request as the complainant did not provide new data or evidence. On the basis of the above considerations, the Ombudsman considers that no further inquiries are needed into this aspect of the allegation.

2.13 In her letter of 25 November 2004 to Commissioner Kyprianou, the complainant raised her concerns with regard to GSK's failure to release all clinical data and asked a question concerning how much of these data the Agency's CHMP had seen before reaching its conclusions. In this regard, the Ombudsman notes that these concerns were not addressed by the Commission in its replies of 8 March and 21 April 2005. The Ombudsman's provisional conclusion is therefore that the Commission's failure to address these concerns constitutes an instance of maladministration. The Ombudsman therefore makes the proposal for a friendly solution below.

3 The alleged undue delay

3.1 The complainant alleged that there had been undue delay in replying to her e-mail correspondence and letters.

3.2 The Ombudsman notes that, in this section, he will deal only with the allegation of undue delay and not with the substance of the replies which were sent to the complainant. The substance of these replies forms the subject of the complainant's first and third allegations, which are dealt with in points 2 above and 4 below.

3.3 Principles of good administration require that the institutions reply to correspondence from citizens within a reasonable deadline. The Ombudsman notes that the Commission's Code of Good Administrative Behaviour ("the Code") foresees that a reply to a letter or e-mail (when, by its nature, it is equivalent to a letter) should be sent within 15 working days from the date of receipt of the letter/e-mail. Also, if a reply cannot be sent within this deadline or requires more work on it, a holding reply should be sent(10). Principles of good administration also require the institutions to apologise where doing so is appropriate(11).

3.4 The Ombudsman notes that the complainant's allegation of undue delay concerns in fact three alleged delays, namely, (i) the Commission's reply of 20 September 2004 to the complainant's e-mails of 18 and 19 August 2004 to Commissioners Telicka and Byrne respectively; (ii) the Commission's holding reply of 9 February 2005 to her letters of 25 November 2004 and 12 January 2005 to Commissioner Kyprianou; and (iii) the Commission's reply of 8 March 2005 to the above letters of 25 November 2004 and 12 January 2005.

3.5 The Ombudsman notes that, in its opinion, the Commission has apologised for the delays concerning its replies of 20 September 2004 and 9 February 2005 and that the complainant has accepted the Commission's apology. However, with regard to the Commission's reply of 8 March 2005, the Ombudsman notes that the Commission has regretted the additional delay, but has not apologised for it. The Ombudsman would therefore welcome it if, when replying to his proposal for a friendly solution (see point 2.13 above), the Commission were also to consider apologising to the complainant for the further delay in replying to her letter of 25 November 2004, which occurred after the Commission had sent its holding letter of 9 February 2005.

4 The allegation that the complainant was not heard and that there was lack of action by the Commission with regard to her concerns

4.1 The complainant alleges that she was not heard by the Commission with regard to the matter of the safety and suicide risks of Paroxetine and that her opinion was not taken into account. The complainant also stated that there was lack of action by the Commission regarding her concerns. As regards the latter, the complainant expressed grave concerns about the Commission's failure to protect the public (page 3 of her complaint). She also stated that she expected the Commission to work properly and that this meant that it should protect her and her family from well-known drug-induced harm (page 5). In the complaint form, the complainant also referred to the lack of appropriate warnings, which, in her view, was likely to induce avoidable harm.

4.2 The Ombudsman notes that the complainant's allegation that she was not heard by the Commission with regard to the matter of safety and the suicide risks of Paroxetine has to be considered from the point of view of the procedure foreseen for the adoption of medicine marketing authorisations. In this regard, the Ombudsman notes that it is the responsibility of the CHMP within the Agency to prepare the Agency's opinions on all questions concerning the evaluation of medicinal products for human use. The relevant procedure in this regard is described in Directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001 on the Community Code relating to medicinal products for human use(12) ("Directive 2001/83") and the CHMP's Rules of Procedure . Following the opinions prepared by the Agency, it is, however, the Commission which takes the final decision on the marketing authorisation.

4.3 As regards the corresponding allegation that was directed against the Agency, the Ombudsman observed the following, in his friendly solution proposal of 26 July 2007 concerning the complaint that the complainant had submitted against the Agency (complaint 2370/2005/OV):

(i) the CHMP's Rules of Procedure do not foresee the possibility for an individual patient or his/her representative to be heard;

(ii) the CHMP organised a meeting with representatives from a group of patients who were given the possibility to describe their personal experiences concerning the undesirable effects of treatment with Paroxetine;

(iii) the Agency informed the complainant about recent developments concerning the evaluation of Paroxetine by the CHMP and the meeting with the patient group; and

(iv) the CHMP appeared to have considered the complainant's arguments.

On the basis of these considerations, the Ombudsman came to the conclusion that there had been no maladministration by the Agency with regard to the complainant's allegation that she was not heard.

4.4 As regards the allegation against the Commission, the Ombudsman notes that Directive 2001/83 does not foresee the possibility for an individual patient or his/her representative to be heard by the Commission. The Directive foresees, in Article 33, that

"[w]ithin 15 days of the receipt of the opinion [from the Agency], the Commission shall prepare a draft of the decision to be taken in respect of the application, taking into account Community law (...). The draft decision shall be forwarded to the Member States and the applicant or the marketing authorisation holder.

Article 34 foresees that "[t]he Commission shall take a final decision in accordance with, and within 15 days after the end of, the procedure referred to in Article 121(3)".

4.5 Although the procedure in question does not provide for a right of an individual patient or his/her representative to be heard, the Ombudsman notes that it appears that, in 2005, several informal discussions between the Commission and the Agency took place on the basis of the information provided by the complainant, and that the complainant has welcomed this in her observations. More particularly, it appears from the minutes of the meeting of the Pharmacovigilance working party of the CHMP of 18-19 April 2005 that the safety and efficacy of SSRIs in adults from the point of view of suicidal behaviour, withdrawal reactions and the effects of dose were considered. The Ombudsman considers that the complainant has not established that the Commission would have been obliged to hear her in person. Considering furthermore that it appears that the Commission has acted in accordance with the applicable procedures, the Ombudsman finds no instance of maladministration by the Commission with regard to the complainant's allegation that she was not heard.

4.6 As regards the complainant's allegation that there was a lack of action by the Commission with regard to her concerns, the Ombudsman notes that, by "lack of action", the complainant was in fact referring to the alleged failure of the Commission to protect the public from drug-induced harm and to provide appropriate warnings. The complainant appeared to object to the outcome of the review of medicines containing Paroxetine and SSRIs/SNRIs, more particularly with regard to the warnings formulated for adult patients (aged 30 years or older). The complainant referred in this context also to stronger warnings which exist in Canada and the United States.

4.7 The Ombudsman notes that, as regards the review of medicines containing Paroxetine, the Commission adopted a decision on 29 March 2005 on the basis of the Agency's (the CHMP's) opinion of 8 December 2004. In this opinion, the CHMP reaffirmed the conclusion it had reached in its earlier opinion of 22 April 2004 that the risk/benefit assessment remained positive for medicines containing Paroxetine when used in the treatment of adults. In the same opinion, the CHMP confirmed the previously recommended changes to the product information for Paroxetine on an EU-wide basis(13). As regards the review of SSRIs/SNRIs, the Commission adopted a decision on 19 August 2005 on the basis of the Agency's (the CHMP's) opinion of 21 April 2005. In this opinion, the CHMP recommended the maintenance of the Marketing Authorisations for the relevant medicines with amendments to the relevant sections of the "Summary of Product Characteristics and Package Leaflets". The CHMP's proposed amendments included the addition of a warning to reflect the finding that suicide-related behaviour (suicide attempts and suicidal thoughts) was more frequently observed in clinical trials among children and adolescents treated with anti-depressants compared to those treated with a placebo.

4.8 As regards the complainant's allegation of a lack of action on the part of the Commission, the Ombudsman would first like to note that the expert EU body in the field of medicines is the Agency, which provides opinions to the Commission. In turn, the latter takes the final decisions on the basis of these opinions. The Ombudsman does not have the necessary specialised expertise in the field concerned and thus cannot (and should not) substitute his own views for those of the Agency and, ultimately, the Commission. The Ombudsman's role is to examine whether there has been maladministration. In the present case this means, in view of the above, that he should examine whether the Commission has taken into account all relevant information and whether it has made a manifest error as regards the assessment of these facts.

4.9 The Ombudsman notes that, according to the Agency's website, a ssessments conducted by the CHMP are based on purely scientific criteria and are meant to determine whether or not the products concerned meet the necessary quality, safety and efficacy requirements, in accordance with EU legislation, in particular, Directive 2001/83. These assessments are intended to ensure that, once they are put on the market, medicinal products have a positive risk/benefit balance in favour of patients/users of these products. The Ombudsman considers that, in order to fulfil this task, the Agency needs to take into account all relevant facts. In the present case, the Ombudsman notes that the CHMP considered the available data on suicide, suicide attempts, suicidal thoughts from clinical trials, as well as data derived from reports and the published literature. The Agency also heard a group of Paroxetine users. On the basis of these considerations, the Ombudsman concluded, in his friendly solution proposal of 26 July 2007 concerning the complainant’s complaint against the Agency (complaint 2370/2005/OV), that there was no maladministration by the Agency with regard to her allegation of lack of action. As the Commission's decisions concerning the placing on the market of medicines are based on the opinions delivered by the Agency, it would therefore appear that this conclusion also applies as regards the allegation of lack of action against the Commission. In this context, the Ombudsman would, nevertheless, like to note that, in its reply of 20 September 2004, the Commission stated that the Agency had considered all the relevant data on the safety and efficacy of Paroxetine, including all the relevant clinical trials, reports received from health professionals and additional information received from manufacturers and a patient group. In its reply of 21 April 2005 to the complainant, the Commission reiterated this view.

4.10 With regard to the complainant's argument that more explicit warnings apply in the United States and Canada than in the EU with regard to medicines containing Paroxetine, the Ombudsman notes that the Commission has submitted that this argument is not correct. According to the Commission, the content of the information regarding Paroxetine and the risk of suicide/suicide behaviour is the same in all countries concerned, and the only difference is to be found in the way in which this information is presented. For instance, it is common practice in the United States to include such information in so-called black boxes. This method is not available in the EU in a harmonised manner due to the implementation of different medicinal product legislation at the national level. Also, the European legislation does not require that certain information/warnings have to be presented in a specifically "eye catching" way, such as the "black box warning" which is used in the United States or Canada. The Ombudsman notes that, in her observations, the complainant rejected this argument. She referred to several extracts from earlier warnings issued in the United States by the FDA on 22 March 2004 which, according to the complainant, were more explicit than the relevant EU warnings(14). The complainant made the same remarks with regard to warnings which exist in Canada. The complainant suggested that the Ombudsman compare the wording and contents of the above-mentioned warnings. As stated in point 4.8 above, the Ombudsman would like to recall that he does not have the necessary expertise to compare the level of the warnings that exist in, on the one hand, the EU and, on the other hand, the United States and Canada. The Ombudsman also recalls that the Agency is the EU's specialised body in this field.

4.11 The Ombudsman furthermore considers that the complainant has not established that the Commission committed a manifest error as regards the assessment of the relevant facts. It is clear from the complaint and from the complainant's observations that she is not satisfied with the outcome of the review by the Agency of medicines containing Paroxetine and SSRIs/SNRIs and with the Commission's final decisions. The Ombudsman would, however, like to point out that it is the essence of a decision-making process that there will always be different views as regards the merits of the final decision adopted. However, this does not necessarily mean that there has been maladministration in the adoption of these decisions.

The possibility of a friendly solution

Article 3(5) of his Statute directs the Ombudsman to seek, as far as possible, a solution with the institution concerned to eliminate the instance of maladministration and satisfy the complainant.

With regard to the Commission's failure to react to two of the complainant's concerns, as expressed in her letter of 25 November 2004, on 29 October 2007, the Ombudsman made the following proposal for a friendly solution to the Commission:

The Commission could consider addressing the concerns raised by the complainant in this letter, which relate to her allegation that GSK did not release all clinical data and to her question as to how much of these data the Agency had seen before reaching its conclusion.

In his proposal for a friendly solution, the Ombudsman also pointed out that he would welcome it if the Commission could also consider apologising to the complainant for the further delay in replying to her letter of 25 November 2004 that occurred after the Commission had sent its holding letter of 9 February 2005.

The Commission's reply to the Ombudsman's proposal

The Commission's opinion consisted of a copy of a letter of apology which the Director-General of DG Enterprise and Industry sent to the complainant on 28 January 2008 following the Ombudsman's proposal for a friendly solution.

In its letter, the Commission first offered its apologies for the delay in replying to the complainant's letters of 25 November 2004 and 12 January 2005. The Commission pointed out that the complainant had complained that, in its previous correspondence, the Commission had only indicated its regret but did not apologise for the fact that its response was considerably delayed. The Commission therefore explicitly expressed its apologies for the general delay as well as for the further delay in replying to her letter of 25 November 2004 that occurred after the Commission had sent its holding letter of 9 February 2005.

The Commission then referred to the Ombudsman's suggestion that it could consider addressing the concerns raised by the complainant in her letter of 25 November 2004, namely, that GSK did not release all clinical data in its possession and the issue of how much of these data the Agency had seen before reaching its conclusion in the framework of the referral procedure initiated under Article 31 of Directive 2001/83/EC. The Commission acknowledged that these questions had not been addressed specifically in its answers and welcomed the possibility to address them at this stage.

In relation to clinical data from GSK, the Commission stated that it did not possess any evidence that GSK withheld data concerning clinical trials.

In relation to the data available to and actually seen by the Agency before reaching its conclusion, the Commission referred in the first place to the answer provided by the Agency in its letter of 1 October 2007. In that letter, the Agency stated that its Committee for Medicinal Products for Human Use (CHMP) "considered the available scientific data relevant to the safety and efficacy of Paroxetine treatment including data from clinical trials, spontaneous adverse reaction reports, epidemiological studies and published literature". It also added that the Committee "requested all Marketing Authorisation Holders for Paroxetine containing medicinal products in the European Union, including GSK, to provide «[a]11 data relating to the risk of self-harm, hostility and suicidal behaviour with Paroxetine from all data sources including clinical trials, spontaneous reporting, observational studies, healthy volunteer studies and consumer reports»".

Second, the Commission noted that the Agency had informed it of the following:

As part of its answers to the CHMP's "List of Questions", GSK provided data from clinical trials, spontaneous adverse reaction reports, epidemiological studies and published literature. As regards clinical trials, data from all studies included in the company's aggregated database were provided. This included data from healthy volunteer studies, adult placebo-controlled trials, adult active-controlled trials and paediatric placebo-controlled trials. Furthermore, GSK performed several analyses on the clinical trial dataset, including adverse events.

The Commission concluded by stating that it remained at the complainant's disposal for any further clarification that would be helpful.

The complainant's observations

In her observations, the complainant first of all wholeheartedly welcomed the apology from the Commission. She praised the Commission's attempt to address her concerns regarding GSK's failure to release all clinical data in its possession to the Agency. The complainant pointed out that the Commission acknowledged that her concerns had not been addressed specifically in its previous answers, but unfortunately did not throw more light on them in its latest response to her. She submitted that the Commission had quoted a paragraph from the Agency's response to her in an attempt to bridge the gap and chosen not to provide her with a specific answer to the concerns mentioned. The complainant stated that her remaining concerns on the use of prescription medications and SSRIs in particular, were as follows:

The available scientific data provided by GSK to the Agency about Paroxetine was lacking as it had been challenged in the courts in the US on many occasions and much of this evidence remained confidential as a consequence of those court proceedings. The complainant wondered why the Commission and the Agency did not take action similar to that of the New York State Attorney. She referred to the latest evidence stemming from a court procedure in the US in 2007. The complainant also reiterated her view that published literature was influenced by the pharmaceutical industry before and after it was published and that the same was the case with clinical trial reports. The negative results were however not published.

The complainant concluded by quoting James Baldwin: "Not everything that is faced can be changed but nothing can be changed until it is faced". The complainant expressed the hope that the Commission would, in the near future, face this issue and change it so that humanity could prevail over profit margins.

THE DECISION

1 The alleged lack of transparency and lack of information, the alleged undue delay and the allegation that the complainant was not heard and that there was lack of action by the Commission

1.1 The complainant is an emergency nurse in Cork University Hospital. According to the complainant, her husband committed suicide because he was taking Seroxat/Paroxetine. After the death of her husband, the complainant sent e-mails to the Commission on 18 and 19 August 2004, as well as two letters on 25 November 2004 and 12 January 2005 in which she raised several questions and expressed her concerns with regard to the safety and suicide risk of Paroxetine and Selective Serotonin Reuptake Inhibitors ("SSRIs"). In her complaint to the Ombudsman, the complainant made the following three allegations: (1) there has been lack of transparency and information by the Commission with regard to the complainant's questions and requests relating to the decision on Paroxetine; (2) there has been undue delay in the replies to the complainant's e-mail correspondence and letters; and (3) the complainant was not heard by the Commission with regard to the matter of the safety and suicide risks of Paroxetine and her opinion was not taken into account. Also, there was lack of action by the Commission regarding her concerns.

1.2 On the basis of his analysis of the file in his proposal for a friendly solution of 29 October 2007, the Ombudsman found no instance of maladministration with regard to the complainant's third allegation.

1.3 With regard to the first and second allegations of lack of information and undue delay, on 29 October 2007, the Ombudsman addressed a proposal for a friendly solution to the Commission, suggesting that it could consider (i) addressing the concerns raised by the complainant in her letter of 25 November 2004, which related to her allegation that GlaxoSmithKline ("GSK") failed to release all clinical data and to her question with respect to how much of these data the European Medicines Agency ("the Agency") had seen before reaching its conclusion and (ii) apologising to the complainant for the further delay in replying to this letter that occurred after the Commission had sent its holding letter of 9 February 2005.

1.4 In its reply of 7 February 2008, the Commission attached a copy of a letter of apology which the Director-General of the Directorate-General ("DG") for Enterprise and Industry sent to the complainant on 28 January 2008 following the Ombudsman's proposal for a friendly solution. In this letter, the Commission explicitly expressed its apologies for the general delay as well as the further delay in replying to her letter of 25 November 2004 that occurred after the Commission had sent its holding letter of 9 February 2005. The Commission further acknowledged that the questions concerning GSK had not been addressed specifically in its answers and welcomed the possibility to address them at this stage. In relation to clinical data from GSK, the Commission stated that it did not possess any evidence that GSK withheld data concerning clinical trials. In relation to the data available to and actually seen by the Agency before reaching its conclusion, the Commission referred in the first place to the answer provided by the Agency in its letter of 1 October 2007. The Commission further stated that the Agency had informed it that, as part of their answers to the CHMP's "List of Questions", GSK provided data from clinical trials, spontaneous adverse reaction reports, epidemiological studies and published literature.

1.5 In her observations, the complainant first of all wholeheartedly welcomed the apology from the Commission. She praised the Commission's attempt to address her concerns regarding GSK's failure to release all clinical data in its possession to the Agency. The complainant however pointed out that the Commission acknowledged that her concerns had not been addressed specifically in their previous answers, but unfortunately did not shed more light on them in its latest response to her. More particularly, the complainant submitted that the Commission had quoted a paragraph from the Agency's response to her in an attempt to bridge the gap and chosen not to provide her with a specific answer to the concerns mentioned. The complainant stated that she still had concerns as regards the use of prescription medications and SSRIs in particular. More particularly, she stated that the available scientific data provided by GSK to the Agency about Paroxetine was lacking as it had been challenged in the courts in the US on many occasions and much of this evidence remains confidential as a consequence of those court proceedings. The complainant wondered why the Commission and the Agency did not take action similar to that of the New York State Attorney. The complainant referred to the latest evidence stemming from a court procedure in the US in 2007. The complainant also reiterated her view that published literature was influenced by the pharmaceutical industry before and after it was published and so were clinical trial reports. The negative results were not published.

1.6 The Ombudsman notes that the Commission has accepted his proposal for a friendly solution. The Ombudsman notes in particular that, in its letter of 28 January 2008, the Director-General of DG Enterprise and Industry explicitly apologised to the complainant for the general delay and the further delay in its reply to her letter of 25 November 2004 that occurred after the Commission had sent its holding letter of 9 February 2005. The Ombudsman further notes that the Commission also acknowledged that the questions concerning GSK were not addressed specifically in its previous answers.

1.7 The Ombudsman very much welcomes the fact that the Commission has accepted his proposal for a friendly solution. However, given the fact that the complainant has made it clear that she remains dissatisfied, more particularly with regard to the substance of the Commission's answer with regard to her concerns about GSK releasing all the relevant data, the Ombudsman concludes that no friendly solution could be achieved in the present case. The Ombudsman nevertheless notes that the Commission has, in its letter of 28 January 2008, addressed the issues that he considered to constitute possible instances of maladministration. He further considers that the action taken by the Commission was sufficient to remove his concerns. The Ombudsman therefore takes the view that, bearing in mind the letter addressed to the complainant by the Commission on 28 January 2008, there is no longer any maladministration on the part of the Commission.

2 Conclusion

The Ombudsman concludes that there is no longer any maladministration on the part of the Commission. The Ombudsman therefore closes the case.

The Ombudsman would finally like sincerely to express his regret for the fact that he cannot be of further assistance to the complainant. As already pointed out when he made his proposal for a friendly solution on 29 October 2007, the Ombudsman realises that the complainant has gone through an extremely difficult time in her life due to the suicide of her husband. The Ombudsman also realises that the assistance he could provide to the complainant in the framework of the present inquiry was very marginal in comparison to the tragedy she suffered. The Ombudsman would however like to reiterate to the complainant his deepest sympathy for her loss and his kind wishes for her future and that of her family.

The President of the Commission and Mr Brian Crowley MEP will also be informed of this decision.

Yours sincerely,

 

P. Nikiforos DIAMANDOUROS

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(1) Serotonin-Selective Reuptake Inhibitors.

(2) Seroxat is a medicine containing Paroxetine.

(3) The complainant also submitted a complaint against the Agency (2370/2005/OV) in relation to the same subject-matter as the present case. The Ombudsman's inquiries into this case were closed by a decision adopted on 5 December 2007.

(4) Directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001 on the Community Code relating to medicinal products for human use, as amended, OJ 2001 L 311, p. 67.

(5) This information is available on the Eudra website (http://ec.europa.eu/enterprise/pharmaceuticals/eudralex/homev1.htm).

(6) That is, the European Medicines Agency.

(7) That is, the Committee for Medicinal Products for Human Use.

(8) The Ombudsman notes that the allegation of the various delays is dealt with below in point 3 of the decision.

(9) Serotonin Norepinephrine Reuptake Inhibitors.

(10) "Electronic mail

(...) where the e- mail message is, by its nature, the equivalent of a letter, it shall be handled according to the guidelines for handling correspondence and shall be subject to the same deadlines.

Correspondence

A reply to a letter addressed to the Commission shall be sent within fifteen working days from the date of receipt of the letter by the responsible Commission department. The reply should identify the person responsible for the matter and state how he or she may be contacted.

If a reply cannot be sent within the deadline mentioned above, and in all cases where the reply requires other work on it, such as interdepartmental consultation or translation, the member of staff responsible should send a holding reply, indicating a date by which the addressee may expect to be sent a reply in the light of this additional work, taking into account the relative urgency and complexity of the matter.

If the reply is to be drawn up by a department other than the one to which the initial correspondence is addressed, the person making the enquiry should be informed of the name and address of the person to whom the letter has been passed". (Emphasis added).

The Code can be consulted on the Europa website (http://ec.europa.eu/civil_society/code/index_en.htm).

(11) Article 12(3) of the European Code of Good Administrative Behaviour.

(12) OJ 2001 L 311, p. 67, as amended. The consolidated version of Directive 2001/83 is available on the Europa website: (http://ec.europa.eu/enterprise/pharmaceuticals/eudralex/homev1.htm). The Ombudsman notes that the procedure which was followed in the present case with regard to, on the one hand, Paroxetine and, on the other hand, SSRIs and SNRIs, was the "referral" procedure foreseen in Articles 31 to 34 of the Directive.

(13) "The changes included:

- A warning to reflect that Paroxetine should not be used in children and adolescents. In the EU Paroxetine is not authorised for use in this population. Data from clinical trials raised concerns regarding suicidal behaviour and hostility. In addition, data from clinical trials have not adequately demonstrated efficacy in these age groups.

- A warning to prescribers recommending close monitoring of patients at high risk of suicidal behaviour. These include patients with a known history of suicidal behaviour or suicidal thoughts prior to starting treatment and possibly also young adults.

- Prescribers and patients should be warned regarding the occurrence of withdrawal reactions upon stopping treatment. Generally these are mild to moderate and self-limiting. However, in some patients they may be severe and/or prolonged".

(14) The Ombudsman notes that the Summary of Product Characteristics for Paroxetine in the EU contains the following warning under the title "Special warnings and Special Precaution for use":

"Suicide/suicidal

Depression is associated with an increased risk of suicidal thoughts, self harm and suicide. This risk persists until significant remission occurs. As improvement may not occur during the first few weeks or more of treatment, patients should be closely monitored until such improvement occurs. It is general clinical experience with all anti-depressant therapies that the risk of suicide may increase in the early stages of recovery.

Other psychiatric conditions for which Paroxetine is prescribed can also be associated with an increased risk of suicidal behaviour. In addition, these conditions may be co-morbid with major depressive disorder. The same precautions observed when treating patients with major depressive disorder should therefore be observed when treating patients with other psychiatric disorders.

Patients with a history of suicidal behaviour of [sic] thoughts, or those exhibiting a significant degree of suicidal ideation prior to commencement of treatment, are at a greater risk of suicidal thoughts or suicide attempts, and should receive careful monitoring during treatment (...)."