Select Committee on Health Minutes of Evidence

Memorandum by Mind (PI27)


Introduction (1-6)
Drug innovation (7-13)
Conduct of medical research (14-25)
Provision of drug information and promotion (26-34)
Professional and patient education (35-38)
Regulatory review of drug safety and efficacy (39-64)
Product evaluation, including assessments of value for money (65-67)
Recommendations (68-78)


  Mind's contribution to this inquiry is based on the organisation's extensive information, policy and campaigning work on medication issues. The chief executive's recent participation in the Committee on Safety of Medicine's expert group on SSRI antidepressants provided an insight into the industry.

  Drug innovation: the innovation that takes place is not necessarily driven by health needs. Drugs are manufactured that differ very little from others on the market, and new conditions are defined that provide a new use for an existing drug thus extending its market and patent-life.

  Conduct of medical research: most published drugs research is industry funded, and recent analyses of clinical trials have shown how company-sponsored trials are more likely to produce results that favour the experimental drug. Companies are free not to publish trial results and some SSRI research has been shown to exaggerate the drugs' benefits and downplay the risks.

  Provision of drug information and promotion: information produced by pharmaceutical companies is mostly marketing, and the Medicines and Healthcare products Regulatory Agency (MHRA)'s information is generally aimed at professionals. Research with users of medication consistently shows a demand for information, which is often not met by prescribers.

  Professional and patient education: industry activities such as sponsorship of medical educational events and patient campaigns, and ghost-writing of clinical journal articles, promote particular drug treatments and also promote drug treatment over other approaches.

  Regulatory review of drug safety and efficacy: the ability of the MHRA to safeguard public health is compromised by its secrecy, industry links and its licensing role which is a service to industry. The review of SSRIs showed the MHRA slow to put important information into the public domain, and to act on information from clinical trials and consumers. It has little involvement with consumers and is only now about to accept consumer reports of drug side effects. From our recent involvement, the MHRA fails to understand basic elements of effective communication and involvement with consumer groups.

  Product evaluation, including assessments of value for money: shortcomings in drug regulation inevitably affect product evaluation. There is little or no consumer input to the process, and the basis on which licensing decisions are made are not public so that professionals and consumers can make informed decisions about marketed drugs.


    —  full publication of trial data and adverse drug reactions;

    —  comprehensive reform of the MHRA around consumer interests, with resources and powers to fulfil its responsibilities;

    —  separation of pharmacovigilance from licensing and independent testing of drugs;

    —  requirements for good practice in trial design and reporting;

    —  independent information service to consumers of medicines;

    —  national task force to develop a strategy for health research which involves the public, balances drug and other treatments and funds priority needs.


  1.  Mind is the leading mental health charity in England and Wales. We work for a better life for everyone with experience of mental distress by:

    —  advancing the views, needs and ambitions of people with experience of mental distress;

    —  promoting inclusion through challenging discrimination;

    —  influencing policy through campaigning and education;

    —  inspiring the development of quality services which reflect expressed need and diversity;

    —  achieving equal civil and legal rights through campaigning and education.

  2.  Mind's contribution to this inquiry is based on the organisation's extensive work on medication issues, and links with a wide-ranging network of individuals with experience of mental distress, Local Mind Associations and other local mental health organisations. The organisation believes in providing people with information with which to make their own decisions, and publishes information booklets about the drug treatments used for mental health problems. Through the organisation's information service we are in regular touch with the questions people have about medication. Enquiries about depression and antidepressants are the most frequent calls we receive. Drugs have a key role to play in alleviating serious mental distress; Mind's concern is that they are used in the safest, most effective way possible, alongside other options and on the basis of informed choice.

  3.  We have drawn attention over many years to the damage psychiatric drugs can do, and in the late 1990s ran a yellow card scheme for people to report the side effects they were experiencing. This was repeated in 2001 and was part of continuing efforts to have people's own accounts of side effects taken seriously. This work demonstrated the demand among people being prescribed drugs for impartial, accurate information about their effects. Mind carried out a similar survey with Panorama following their first programme on the antidepressant Seroxat, "Secrets of Seroxat" (October 2002). This highlighted serious side effects, including suicidal feelings, and withdrawal effects.

  4.  Richard Brook, Mind's chief executive, participated in the Committee on Safety of Medicines' (CSM) expert group reviewing the safety of SSRI antidepressants until he resigned in March 2004 because of the Medicines and Healthcare products Regulatory Agency's slowness to publicise important information about dosage. This experience provided an insight into the processes involved in medicines regulation and failures to protect public health. Mind is represented on the CSM's working groups on patient information and direct patient reporting of suspected adverse drug reactions. Mind has a policy of not accepting funds from the pharmaceutical industry.

  5.  Whilst a mental health charity, we believe our experience, past and recent makes us able to determine some common aspects of drug regulation which we believe are wider than just our specific interest.

  6.  In addition to the references in the text of this submission we should like to draw the Committee's attention to the important work by Dr David Healy in identifying and exposing the links between SSRI antidepressants and suicidality, and to the work of Charles Medawar of Social Audit in describing and challenging the operations of the industry and regulator, most recently in his book "Medicines out of control?".

Drug innovation

  7.  Drug innovation is clearly an important role for the pharmaceutical industry but the innovation that takes place is not necessarily driven by health needs. Drugs are manufactured which differ very little from others on the market, and new conditions are defined that provide a new use for an existing drug thus extending its market and patent-life. In her paper "Is psychiatry for sale?" Joanna Moncrieff shows how Smith Kline Beecham (now GSK—GlaxoSmithKline) identified a new use for its antidepressant paroxetine (sold as Seroxat in the UK, Paxil in the US). The manufacturer created a market for Seroxat as a treatment for social anxiety disorder or social phobia by shaping public and medical opinion through a disease awareness campaign. Roche ran a similar campaign about its antidepressant moclobemide (Moncrieff, 2003).

  8.  As evidence for these strategies, we are taking the unusual step of submitting the internal fact file of Seroxat, sourced from the Panorama programme in the research it has done for a pending third programme. Unlike our other references, this document is not in the public domain. Such types of documents are rarely available to the general public or consumer groups, although we suppose that regulatory agencies do see them. (They could be submitted to the agency or seen by appointees to bodies such as the Committee on Safety of Medicines because of their own pharmaceutical interests.) Initially produced in 1998 and subsequently updated, it is an internal document relating to the marketing of Seroxat.

  9.  GlaxoSmithKline (GSK), manufacturers of this heavily marketed and promoted blockbuster antidepressant drug, revealingly title a major section (section 1) of it as "Towards the second billion—all SSRI's are not the same". The driver is obvious—greater profitability—and the strategy involves making the case that the drug fits a whole new number of "diseases" and providing arguments why Seroxat should be used as the "anti-depressant of first choice".

  10.  These industry strategies make the case, in Mind's view, for a stronger, and better resourced, regulatory framework that is transparent and in turn requires openness from the industry. Greater transparency of industry research would make it harder for misleading claims to be made or to go unchallenged. There is also a case for improved provision of information and education to the professions and public which is independent of the industry. Recommendations on medicines regulation, and other relevant sections of the evidence, are set out below.

  11.  Drug innovation is important but should be seen in the wider context of health and medicines research, and led by need. A discussion paper published by the Kings Fund (Harrison, 2003) points out that the pharmaceutical industry is the active driver in an implicit public-private partnership, in which the industry develops the products that it considers likely to be profitable and the Government is generally a passive purchaser. The weaknesses identified in this situation are that research areas other than new medicines are neglected, the needs of some groups of people—particularly children and older people—are not sufficiently taken into account, and the public is not involved.

  12.  Consideration should be given to setting up a task force as set out in the paper which would address pharmaceutical research, within a broader strategy for health research generally, and include independent reviewers, consumers and other research users. For example through the process of reviewing clinical evidence for National Institute for Clinical Excellence (NICE) guidelines and treatment appraisals, research needs are identified. NICE should equally be able to specify at an earlier stage in the development of treatments what kind of data is needed in order to assess effectiveness in clinical practice.

  13.  Involving citizens and service users in the governance of pharmaceutical research could result in significant changes in priorities. This approach could also be a way to create equality between the opportunities for researching different therapies, not only medicines. Setting priorities in this way could provide a basis for expanding and/or redirecting the funds available for health research.

Conduct of medical research

  14.  The pharmaceutical industry is a massive part of the UK economy and exerts a pervasive influence over the research into and use of medicines. Virtually all research on drugs—70% of trials reported in major medical journals—is funded by the industry (Smith, 2004). By virtue of doing most of the research, the industry has a hugely disproportionate effect on what gets researched, and also how it is researched, how the results are interpreted, and how—and crucially whether—the results are reported.

  15.  There is bias in research design. Several reviews of trials have shown that results are more likely to show a positive result for the experimental drug if the trial is funded by the company (Smith, 2004, Kjaergard and Als-Nielsen, 2002, Wahlbeck and Adams, 1999). Experts in the subject have shown how aspects of clinical trial design can favour the experimental drug. These include:

    —  comparison with placebo rather than other drugs;

    —  comparison with other drugs that are prescribed at ineffective or excessive doses;

    —  trials that are too small;

    —  using "categorical outcomes" which can exaggerate small differences between groups (eg two points in a depression rating scale can make the difference between "response" and "non-response" to a treatment). (Smith, 2004, Moncrieff and Double, 2003, Jureidini et al, 2004.)

  16.  Selection of people for clinical trials who are most likely to benefit from the drug, or least likely to have adverse reactions, can also present a more favourable picture than when the drug is in general use and prescribed more widely. This is one factor in the better results obtained for SSRIs than for tricyclic drugs in older trials.

  17.  The way trial results are interpreted and reported may also exaggerate the drug's benefits and play down the size of the placebo effect and/or the adverse reactions. A case in point is that of the SSRI class of antidepressants as used in children and adolescents (Jureidini, 2004). We are also aware of research in progress that shows atypical antipsychotic drugs may have been oversold.

  18.  Pharmaceutical companies and others conducting clinical trials are free not to publish the results at all. The recent controversy over the safety of SSRI antidepressants for children and young people centred on the results of unpublished trials. A review (Whittington et al, 2004) of published and unpublished trials of SSRIs in children and young people shows that the published trials suggested that the drugs were effective, but once the unpublished data were built into the analysis the indications were that risks outweighed the benefits. In developing a guideline on depression in children for the National Institute for Clinical Excellence (NICE) reviewers had contacted all pharmaceutical companies that made antidepressants requesting unpublished data, but none were forthcoming. NICE was able to access the information obtained by the MHRA for its review, but without this NICE would be likely to have issued harmful guidance.

  19.  An internal GSK paper that was dated 1998 and revealed by the press in February 2004, indicated that trials of the antidepressant Seroxat (generic name paroxetine) in children showed this drug was no better than placebo in alleviating children's depression. The report stated "it would be commercially unacceptable to include a statement that the efficacy had not been demonstrated, as this would undermine the profile [of Seroxat]". When the company pooled the trial data it also discovered a "safety signal"—more of the children on the real drug than the dummy drug had suicidal thoughts. The Medicines and Healthcare products Regulatory Agency issued guidance effectively banning the drug (along with other SSRI antidepressants) for under 18s in the UK in September 2003 (other antidepressants in February 2004).

  20.  The New York State attorney Elliot Spitzer has taken this issue to the courts, suing GSK (GlaxoSmithKline) and claiming that by "concealing critically important scientific studies on Paxil [US brand name of paroxetine], GSK impaired doctors' ability to make appropriate prescribing decision for their patients and may have jeopardized their health and safety". GSK subsequently announced that it would publish summaries of all its clinical trials of a new product once it has been launched. However this is still a voluntary arrangement and leaves control in the hands of the company. Regulatory agencies at least need full data before that point.

  21.  Under the EU Clinical Trials Directive, which came into force in May this year, all clinical trials must be registered on an EU database. However, only national regulatory agencies have access to this information, and although the conclusion of a trial must be notified, including reasons for early termination where relevant, this does not include the results.

  22.  The degree of control exercised by the industry in determining what research is carried out as part of product development is also illustrated by the SSRI expert group's work. In the course of the group's work, Richard Brook was struck by the number of times that it was acknowledged more research was needed on the issues under consideration. On several occasions of raising the issue, it was clear that whilst there was almost universal agreement work was needed, sometimes of an urgent nature, there was no way of making pharmaceutical companies undertake or fund it, and neither was it possible to find an accessible independent source of funds that could do this. It was thus accepted that on the issues identified, there were unlikely to be any useful additional facts coming forward, and nothing further could be done.

  23.  The interpretation and evaluation of research would be greatly assisted if all clinical trials, whether sponsored by pharmaceutical companies or not, complied with CONSORT guidelines (consolidated standards of reporting trials, CONSORT is a research tool, developed by international collaboration and continually evolving, that provides a checklist and flowchart on what to include in trial reports. For example there is guidance on reporting the eligibility criteria for trial participants, methods for random allocation, and the reporting of adverse events experienced by trial participants.

  24.  Improvements in reporting should have an effect on the conduct of the research itself; if information has to be reported it has to be collected. However, Mind's view is that more requirements about the conduct of research should be built into the drug licensing process. Individuals' own assessment of the treatment they have received, its efficacy and adverse effects are rarely included in clinical research, but should be. Research in the field of ECT (electroconvulsive therapy) shows how research by clinicians and research by consumers comes to different conclusions (Rose, 2003). Improvements to clinical trials should include user, and where appropriate carer, assessments of treatment efficacy and adverse effects, optimal doses of comparator drugs, and better collection of data on adverse effects.

  25.  Biased reporting of drug trials may unfairly advantage drug treatments in relation to safer non-drug approaches, not just one drug over another. However, simply by virtue of its size and economic power the pharmaceutical industry advantages drug treatments over other types of treatment. Clearly drug treatments are the industry's business, and pharmaceutical companies are not responsible for other sectors. There is a need for a national strategy for health research that balances drugs with other treatments, with public funds directed to non-pharmaceutical treatments research (see 11-13).

Provision of drug information and promotion

  26.  There are several problems with drug information as provided or influenced by the pharmaceutical industry. As shown above it may be partial, and potentially harmfully so. The foundation for information about drugs is the clinical trial data; it provides the basis for licensing medicines, advice to prescribers, the development of clinical guidelines, and information to consumers. The lack of independent research and the biases in the system make it more likely that this information will be partial or inaccurate. This in turn means that people will not be able to make properly informed choices, and prescribing may be at best less than optimal, and a worst harmful. It may also lead to distorted allocation of NHS funds.

  27.  Much information from pharmaceutical companies is in fact marketing. Pharmaceutical companies exert extensive influence through promotional activities including:

    —  highly visible sponsorship and products;

    —  sponsoring conferences and other medical training;

    —  payments to speakers and opinion leaders;

    —  ghost-writing clinical journal articles;

    —  sponsoring patient groups/campaigns to support and market medicines;

    —  creating new, and expanding existing, problems to treat;

    —  pressing for direct to consumer advertising;

    —  heavy marketing of new products/uses despite the caution that is needed before a full side effect profile begins to emerge.

  28.  The Seroxat file is highly illustrative of using marketing information as facts, in particular in relation to the arguments over discontinuation. Prozac manufacturer, Eli Lilly, raised the issues of discontinuation and Seroxat's relatively short half-life as a issue to try and defend its falling market share in 1998. The Seroxat fact-file sets out strong arguments about why Eli Lilly's arguments are wrong and how the half-life is a major advantage even allowing "treatment holidays". Original trial data submitted to the UK regulators from the licensing of Seroxat show at best this was naive and at worst, seriously misleading. It was clearly an emerging theme in the SSRI working group prior to Richard Brook's departure that discontinuation of Seroxat was probably influenced by its short-half life and was likely to be the major reason why it has been experienced as the most problematic of the SSRI's. The fact file minimises the therapeutic considerations and maximises those of commercial success to the detriment of the consumer.

  29.  Another example of this approach is the failure of GSK to issue a "dear doctor" letter to physicians in the US warning about paroxetine use in children at the time that it did amend labelling in the UK in line with the MHRA's requirement.

  30.  Again, these strategies reinforce the case for a strong regulator (see 39-64). Full publication of trial results could also strengthen the capacity of the Prescription Medicines Code of Practice Authority to challenge misleading claims by companies.

  31.  There is a real gap in independent specialist information provision for the public. Research with users of medication consistently shows a demand for information, which is often not met by the prescriber. For example, 61% of respondents to Mind's Yellow Card survey about drug side effects (Cobb, 2001) said they did not receive enough information when they were prescribed medication. People wanted information about what drugs do (benefits and risks), withdrawal effects, alternatives, and new ways of using drugs. They identified numerous ways in which information could be improved, including its independence; more detail; clearer, more understandable language and large print; information based on others' experience; and information as of right.

  32.  In a more recent survey by the Scottish Association for Mental Health (Bradstreet and Norris, 2004) 29% of respondents had not been given written information at the time when a drug was prescribed. The report comments, "This is of some concern given that a Patient Information Leaflet (PIL) should be included with every prescription. While our findings may demonstrate inadequacies in prescribing practice they may also be due, in part, to survey respondents not being aware of a PIL." The authors also comment that patients may not be given PILs and that the issue requires investigation. For example people may not have been given a PIL on receiving a generic drug, a depot injection of antipsychotic medication, or when they are in hospital.

  33.  In the course of the SSRI review the MHRA has provided more information for consumers, for example question and answer sheets, but most of the Agency's communication is with prescribers.

  34.  Therefore there is a real need for a consumer information resource about medication. There is a useful helpline providing information on psychiatric medication to consumers, which is run by the UKPPG (UK Psychiatric Pharmacists Group) with funding from the National Institute for Mental Health in England. However we believe that a service that can meet wide scale demand needs to be developed and publicised.

Professional and patient education

  35.  Several of the activities listed in the section above relate to professional and patient education. These activities not only favour one drug over another, they also have the effect of promoting drug treatment over other approaches.

  36.  The predominance of pharmaceutical company research means that other treatment options do not get comparable resources, and the position of medicines as the effective treatment is reinforced (11-13).

  37.  There is also a responsibility on the medical professions to examine their links with the pharmaceutical industry and the use of industry funding. However aware a doctor is of their exposure to marketing, the volume of material and the blurring of clinical and promotional information mean it is difficult to believe that doctors and other health care professionals are not influenced in their day-to-day practice.

  38.  However this evidence is most concerned with the statutory regulation of the companies and their products.

Regulatory review of drug safety and efficacy

  39.  This section summarises concerns arising from the SSRI review, and then looks at the regulatory process in more detail, drawing on the SSRI review for evidence.

  40.  SSRI review: The Committee on Safety of Medicines' review of the safety of SSRI antidepressants revealed major failings in the regulatory process, relating to the two sets of guidance issued so far as a result of the group's work.

  41.  Children and young people: As discussed above (18-20) there was a failure either to obtain full trial data, or to interpret and act on information received, such that some 10,000 under 18s in the UK were prescribed paroxetine before it was eventually warned against in 2003. The European Agency for the Evaluation of Medicines has recommended that paroxetine (Seroxat) be prescribed with extra caution to people aged under 30 because of a possibility of increased risk of suicide-related behaviour in young adults. However the MHRA has not significantly publicised this warning to doctors and the public.

  42.  Dosage: as a result of the review group's work, guidance was issued in March 2004 reminding doctors that the maximum effective dose of paroxetine for depression is 20mg. However the information on which this guidance was based formed part of the manufacturer's licence application and was therefore held by the regulator. As recently as 2003 an estimated 17,000 people were started on doses above that at which there is no additional benefit although the risk of side effects continues to increase. Either the Agency did not understand the full implications of the data when the drug was licensed, or it did understand but failed to act. In Mind's view this is extremely negligent and a dereliction of duty and has led to many individuals suffering side effects or worse that they did not need to experience. It is also Mind's view the current advice still falls short of what the Companies' own trial data warrants.

  43.  Medicines regulation: The pharmaceutical industry's relationship with the Medicines and Healthcare products Regulatory Agency includes:

    —  controlling the data supplied to the MHRA;

    —  funding the MHRA through fees;

    —  financial and employment links with MHRA and Committee on Safety of Medicines personnel;

    —  commercial confidentiality assured by the MHRA (at least until the Freedom of Information Act comes into force).

  44.  Other limitations on the MHRA to provide an adequate safeguard are:

    —  lack of research that is independent of the industry;

    —  lack of consumer input;

    —  lack of public profile;

    —  possibly inadequate powers and resources;

    —  organisational culture that fails to recognise the importance and centrality of the consumer;

    —  a legal framework that prevents full and frank disclosure.

  45.  The next paragraphs look at these links and limitations in more detail.

  46.  Reliance on company data: When it is deciding whether to license a drug for sale in the UK, the MHRA depends on the company's own dossier on the drug. It does not analyse the raw data independently and only in recent times has had in-house statistical staff able to undertake such reviews of the data. The SSRI review shows there was at least one occasion in the past when the Agency either failed to interpret the "top-level" data a company submitted or else failed to communicate its meaning effectively to prescribers (see 42). This failure, as far as Richard Brook knows, remains unacknowledged and no action has been taken on it or considered for other drugs where the same situation may apply.

  47.  Lack of independent research: Clinical research is largely what the pharmaceutical companies want to fund, rather than what serves a wider interest. The MHRA does not in general commission research apart from limited research it carries out through its General Practice Research Database. It has no powers or funds to have specific work done as might be indicated by, say, adverse effects reports.

  48.  No duty to report new efficacy data: Although they must report adverse drug reactions within 15 days, and supply periodic safety reports, there is no obligation on pharmaceutical companies to provide new efficacy data once a drug has been marketed, other than in the five yearly licence renewal applications. It appears from the SSRI review that companies would not report a trial that showed no efficacy to the Regulator, often explaining away adverse effects or safety issues arising in trials as not relevant in their view. The Regulator has no access (or capacity) to examine these types of events.

  49.  Overt relationship with the industry: Facilitating the development of a successful pharmaceutical industry in Britain was until recently an objective of the Agency. Licensing medicines is a service to the industry, as well as a safeguard for the public; it is an inherently reactive process and the MHRA is funded by industry fees. It can be argued that this makes too close a relationship with the industry (at least for pharmacovigilance work), or that it is right that this successful industry—and not the public—should bear the costs of regulating it. With respect to new licence applications, centralisation and mutual recognition in Europe mean that there is more competition between regulators for less work. Essentially the scale, size and status of the MHRA's work, including pharmacovigilance, is determined by the level of industry activity funding it and to some extent the "general" view of how successful it is.

  50.  Other industry links: The approach to the holding of pharmaceutical interests by those involved in medicines regulation is in urgent need of review. It is quite untenable that regulatory advice and decision-making should be the responsibility of people with close links with the industry. Many members of the MHRA's committees have extensive interests in the pharmaceutical industry, such as shares, consultancies and fees (details of which are published in the Medicines Act 1968 Advisory Bodies Annual Reports). These interests have to be declared, and depending on their status—personal or non-personal (eg funding for the member's research department), specific to a product under discussion or not—the member may or may not take part in proceedings. A proposal to stop members of committees holding interests is part of the MHRA`s recent consultation on its advisory committees.

  51.  The extent of company interests inevitably raises concerns about the independence of decision-making. It also raises questions about the effectiveness of committees where several members are disqualified from a discussion (for example in the 2001 annual report six out of 36 members of the Committee on Safety of Medicines had a personal interest in GlaxoSmithKline and a further seven had a non-personal interest.). This is especially heightened if such members have any involvement or contact with material such as that in the Seroxat Fact File.

  52.  Lack of consumer input: There is lay representation on the Committee on Safety of Medicines which advises the MHRA and runs the Yellow Card scheme for reporting suspected adverse drug reactions. Indirect consumer reporting of adverse drug reactions—via NHS Direct—was piloted in 2003, and the Government has now announced that direct consumer reporting is to be piloted. However consumer representation and championing of robust consumer rights are not built into the MHRA's structures and processes. Indeed the MHRA appears to be extremely inept at handling consumer involvement. Some examples from many from Richard Brook's involvement in the SSRI expert group are:

    —  Seating arrangements at meetings that are intimidating and conflictual.

    —  Undermining comments from MHRA staff about the usefulness and expertise of consumer representation.

    —  Suggestions by a working group member—unchallenged by MHRA staff/officials—that a few consumers may have made up the 1,600 plus Panorama emails following their most recent programme on Seroxat.

    —  Use of email for numerous and extensive papers, making participation harder for a consumer representative.

  53.  A further concern is that despite pressure from Mind and other groups and parties for Richard Brook's place on the group to be filled, to date we are not aware that an additional consumer representative has been announced or appointed.

  54.  Whilst undoubtedly, there have been recent efforts to improve communication with patients and health professionals much is still needed to be done as a matter of urgency. During the SSRI review, some of these changes occurred—such as giving more raw data, simple Q&A sheets, etc. However, the handling of consumer involvement in the release of information about the dosage of Seroxat suggests a lack of expertise and knowledge within the MHRA over communicating with the public and users of medication. It clearly has never been a major strand to their work and despite recent attempts to improve this area they remain at a very fundamental stage of development.

  55.  Lack of public profile and impact: In its report on the then Medicines Control Agency, the National Audit Office stated that the Agency needed to strengthen its public profile in order to fulfil its mission to provide information to contribute to the safe and effective use of medicines (National Audit Office, 2003). The Agency does not for example have a high public profile as the Food and Drug Administration in the USA does. This limits its ability to get safety messages across to the public, and to engage with the public as a source of information on the effects of medicines.

  56.  Despite recent announcements that the MHRA is addressing this, it still remains a low priority in terms of action. For instance, the MHRA does not comment or present its view of events such as the controversy over the SSRI issues. It places a low priority on communicating with the public and even health care professionals. One example of this is the very limited publicity over the EMEA (European regulator) decision to advise that Seroxat use in people aged under 30 should be undertaken with extra caution despite this being European advice to which the UK contributed.

  57.  Secrecy: There are legal constraints set out in the Medicines Act 1968 on what information the MHRA can make public. Pharmaceutical companies are free to withhold unpublished data from such bodies as the National Institute for Clinical Excellence, which is responsible for developing guidance for the NHS on effective treatments. This prevents independent scrutiny of MHRA decisions, and undermines public safety. The legal basis for giving and withholding information by the MHRA will change with implementation of the Freedom of Information Act but any attempts to thwart the thrust of this Act must be prevented.

  58.  The other issue is that any consumer groups or representatives involved in regulatory processes are restricted by the legislation and the MHRA's view of the legislation. During Richard Brook's involvement with the SSRI Expert Group there was an ongoing emphasis on this legal framework which seemed to work against consumer's interests and in favour of the pharmaceutical companies.

  Examples are:

    —  Concerns of litigation if certain public health decisions were made and announced;

    —  Due process potentially allowing facts about pharmaceutical companies being hidden or never exposed;

    —  Requiring consumer representatives to forgo any level of moral or ethical responsibility to their stakeholders whilst involved in drug regulatory processes.

  59.  Resources: The capacity of the MHRA to properly evaluate the risks and benefits of medicines, both pre-and post-licensing, and to act promptly on the outcome, depends on its being adequately resourced. In its report the National Audit Office stated that the Agency needed more resources for its pharmacovigilance strategy and that with more resources it could make fuller use of the General Practice Research Database which it holds. It also remarked on the amount of information with which the Agency has to deal. The amount of available information will increase with the recently established EU-wide clinical trials database and adverse drug reactions database. There is also a pressure to carry out the licensing process within specific timeframes. Mind considers that a greater amount of audit work by the MHRA is also needed with more active visiting of companies.

  60.  There is clearly, in terms of at least the SSRI work, an inability to effectively predict work-load, resources required and work-plans that match the two. Despite receiving absolute assurances in September 2003 from the Chairman and the Acting CEO of the MHRA that there was no resource issue in terms of the SSRI review work, the work has consistently been behind schedule and additional staff were recruited to match the ever increasing demands on a few key staff.

  61.  Need for reform: Mind considers that consumers have a right to expect full and impartial information about the potential risks and side effects of prescription medicines. This requires a robust regulatory framework to ensure that this information is not only publicly available but also acted upon promptly.

  62.  We need a drug regulatory system:

    —  that puts consumer safety before commercial pressures and cost;

    —  whose membership and operation is transparent and accountable;

    —  that has sufficient legal powers to ensure access to all drug trial information and adequate funding to verify the accuracy of this information;

    —  that gives comparable weighting to consumer experience of drugs as it does to information from drug trials.

  63.  Public views obtained in an NOP poll carried out in March 2004, support a shift in the balance in favour of legal powers and regulatory action:

    —  The majority of the public thought the following people ought to be able to see the findings of pharmaceutical companies' research: Government bodies responsible for medicines safety (79%), doctors and other health professionals (84%), independent health researchers (72%), patients and the general public (76%).

    —  Only one third of the public trusted pharmaceutical companies to pass the information on voluntarily. Indeed 17% of the public did not trust the companies to pass the information on even if legally required to do so.

    —  Only 13% of the public believed that companies themselves should be in charge of deciding how they carry out research into the safety and effectiveness of medicines and how they report the findings. Fifty per cent thought this should be the responsibility of Government bodies responsible for medicines safety, and 33% thought it should be independent health researchers.

  64.  Recommendations for reform of the MHRA are made in more detail in the recommendations section, but in summary, Mind considers that the agency should be reformed around consumer interests with strong consumer representation and a commitment to make full use of consumer intelligence. The MHRA should have access to all clinical trial results in full and be able to make this available to independent reviewers. Pharmacovigilance should be separated from the licensing process. The MHRA should have the powers and resources it needs to safeguard public health. Its operation should be transparent and accountable with key personnel free of industry interests.

Product evaluation, including assessments of value for money

  65.  The industry's influence on research and the shortcomings in drug regulation inevitably affect product evaluation. The yellow card scheme and other pharmacovigilance activity need to be strengthened, and recipients' own assessments of treatments' effectiveness measured. Drop-out from clinical trials is a useful indicator but it is hardly an adequate measure of a drug's acceptability to the person taking it, yet is generally the only one available.

  66.  Work on the safety of SSRIs has underlined the importance of consumer reporting of suspected adverse drug reactions. There was a huge public response to Panorama's "Secrets of Seroxat" programme and analysis of emails sent to the BBC revealed patterns of experience of side effects which are not identified by the filtered and coded data collected through the yellow card scheme (Medawar et al, 2002). Consumer reports are to be accepted through the yellow card scheme and Mind welcomes this, having argued the case for some time. However this analysis indicates that narrative reports give a quality of information that it is essential to capture, and we believe the MHRA needs to make fullest use of consumer intelligence through the extended yellow card scheme and other methods.

  67.  The authorities' decision-making on the balance of effectiveness and risk needs to be transparent —for example on what basis is fluoxetine tacitly approved for under 18s when there is only limited evidence of efficacy and this is for a short-term only? Despite requests from the SSRI Expert Working Group to the MHRA to emphasise this, it has not occurred. It is also extremely worrying to learn from journalists that Eli Lilly's press office confirmed they were directly approached by the MHRA to seek a licence for Prozac (fluoxetine) without any need for further trial data. If this is correct, it is another example of the inappropriate relationship of the MHRA and pharmaceutical companies.


  68.  A minimum level of safety requires access by the MHRA to all trial results, in full, regardless of whether they have been published and whether the results are negative, equivocal or positive. It in turn should be able to put such information into the domain of researchers and reviewers, and once a drug has been licensed, make the information available in suitable format to all.

  69.  The quality of research and its interpretation would be improved if all clinical trials, whether sponsored by pharmaceutical companies or not, complied with CONSORT guidelines (consolidated standards of reporting trials,

  70.  There should be more requirements on companies as part of the licensing process. This should include that user, and where appropriate carer, assessments of treatment efficacy and adverse effects are built into trials, that optimal doses of comparator drugs are given, and that there is better collection of data on adverse effects.

  71.  Pharmacovigilance work should be separated from the licensing process, and there should be independent testing of drugs, not just reliance on companies' own data.

  72.  The MHRA should make a commitment to full use of consumer intelligence in its pharmacovigilance work, and do this through the yellow card scheme and other approaches. It should proactively engage with the public both to get intelligence in and send information out.

  73.  The MHRA should have all necessary legal powers and resources to obtain the information it needs in order to safeguard public health and the resources to audit companies, use the information fully, act promptly on it, and publicise any safety messages effectively.

  74.  The MHRA should champion consumer safety and have strong consumer representation. There should be a well-supported consumer committee on a par with other MHRA committees, as well as a "critical mass" of lay people in those other committees, including consumer representatives, and legal and ethical expertise.

  75.  The operation of the MHRA should be transparent and accountable. Members as well as chairs of advisory groups should hold no personal interests, and preferably no interests at all, and the most senior personnel should have a complete break from the industry.

  76.  The MHRA should only keep confidential information that absolutely needs to be—confidentiality should be an active and justifiable decision. There needs to be a clear process for putting full trials data into the domain of researchers/reviewers both pre-and post-marketing and making it publicly available in suitable format after licensing.

  77.  An independent information service to consumers about medication should be developed.

  78.  There should be a national task force to develop a strategy for health research which involves the public, balances drug and other treatments and directs funding towards priority needs.

August 2004


  Bradstreet, S and Norris, R eds (2004) "All you need to know?" Scottish survey of people's experience of psychiatric drugs. Scottish Association of Mental Health.

  Cobb, A, Darton, K and Juttla, K (2001) Mind's Yellow Card for reporting drug side effects: a report of users' experiences. Mind.

  Doerry, U and Kent, L (2003) Prescribing practices of community child and adolescent psychiatrists, Psychiatric Bulletin, 27, 407-410.

  Harrison, A (2003) Getting the right medicines? Putting public interests at the heart of health-related research. Kings Fund.

  Jureidini, J N et al (2004) Efficacy and safety of antidepressants for children and adolescents, British Medical Journal, 328:879.

  Kjaergard, L and Als-Nielsen, B (2002) British Medical Journal 325:249 quoted in P Thomas and P Bracken (2003) Marketing science or the science of marketing? Openmind 122, 10-11.

  Medawar, C, Herxheimer, A, Bell, A and Jofre, S (2002) Paroxetine, Panorama and user reporting of ADRs: consumer intelligence matters in clinical practice and post-marketing drug surveillance, International Journal of Risk and Safety in Medicine, 15, 161-169.

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  Smith, R (2004) Foregone conclusions, Guardian 14 January 2004.

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  Whittington, C J et al (2004) Selective serotonin reuputake inhibitors in childhood depression: systematic review of published versus unpublished data, The Lancet, 363, 1341-1345.

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