Memorandum by Mind (PI27)
THE INFLUENCE
OF THE
PHARMACEUTICAL INDUSTRY:
SUMMARY
Contents
Summary
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)
References
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.
Recommendations
— 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.
INTRODUCTION
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, www.consort-statement.org).
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.
RECOMMENDATIONS
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, www.consort-statement.org).
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
REFERENCES
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.
Moncrieff, J (2003) Is psychiatry for sale?
Maudsley Discussion Paper. Institute of Psychiatry.
Moncrieff, J and Double, D (2003) Double blind
random bluff, Mental Health Today, November 2003.
National Audit Office (2003) Safety, quality,
efficacy: regulating medicines in the UK: report by the Comptroller
and Auditor General, HC 255 Session 2002-2003. The Stationery
Office.
Rose, D, Fleischmann, P et al (2003) Patients'
perspectives on electroconvulsive therapy: systematic review,
British Medical Journal 326: 1363-0.
Smith, R (2004) Foregone conclusions, Guardian
14 January 2004.
Wahlbeck, K and Adams, C (1999) British Medical
Journal 318:465.
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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