Conclusions and recommendations
1. The
industry's ability to compete internationally requires a legislative
and organisational framework for research that protects the interests
of all stakeholders - patients, researchers and pharmaceutical
companies. (Paragraph 43)
2. Priorities for
research into medicines inevitably reflect the interests of the
pharmaceutical companies and are not necessarily well aligned
with the medical needs of all patients. The industry will continue
to undertake the bulk of research in this area, but there are
improvements which could be made. We welcome Lord Warner's recognition
of this and look forward to his proposals to align more closely
the drug companies' research strategies with the public health
aims of the NHS. (Paragraph 189)
3. However it occurs,
the presence of many 'me-too' drugs on the market creates difficulties
for prescribers and the NHS. Although this is a considerable problem,
we were given no obvious solution. We expect that there will continue
to be a large number of me-too drugs. The National Prescribing
Centre and others should particularly consider issuing independent
advice in areas where many 'me-toos' exist. (Paragraph 190)
4. Much excellent
clinical science takes place within the industry and elsewhere,
but the current system of clinical testing provides ample opportunities
for bias. Too many of these problems appear to persist unnoticed
or unacknowledged by the organisations that are central to the
co-ordination, conduct and review of the clinical trials. There
is a need for more transparency and we welcome the contribution
that the proposed clinical trials register should make to this
approach. The regulators must check that research is designed
to provide objective evidence of a drug's efficacy and safety
at the time of licensing. (Paragraph 191)
5. The aggressive
promotion of medicines shortly after launch, the sheer volume
of information that is received in its many forms by prescribers
and the "promotional hospitality masquerading as education",
in the absence of effective countervailing forces, all contribute
to the inappropriate prescription of medicines. (Paragraph 232)
6. Ghost-writing,
in conjunction with suppression of negative trial results, is
harmful. If prescribers do not have access to fair and accurate
accounts of clinical trials they cannot be expected to make informed
prescribing decisions. The guidelines on the subject of authorship
and the role of professional medical writers quoted in Paragraph
199 must be followed. (Paragraph 233)
7. The blame for inadequate
or misinformed prescribing decisions does not only lie with the
pharmaceutical industry, but with doctors and other prescribers
who do not keep abreast of medicines information and are sometimes
too willing to accept hospitality from the industry and act uncritically
on the information supplied by the drug companies (Paragraph 234)
8. The pharmaceutical
industry's promotional efforts are relentless and pervasive. The
evidence presented showed the lengths to which the industry goes
to ensure that promotional messages reach their targets and that
these targets include not only prescribing groups, but patients
and the general public. (Paragraph 271)
9. There is an urgent
need for a comprehensive and informative PIL, preferably one which
indicates the role of the drug in overall management of the disease.
We were advised that patients themselves should be involved in
the process of developing such a PIL. The MHRA's Patient Information
Working Group is addressing this issue but the group is dominated
by professional interests. (Paragraph 272)
10. DTCA is inappropriate
and unnecessary in the UK. The evidence reviewed above on the
targeting of prospective patients, and the central emphasis on
emotional appeals, leads us to believe that great caution should
be exercised in any relaxation of the rules relating to provision
of consumer drug information by drug companies. (Paragraph 273)
11. The existing guidelines
on disease awareness campaigns are weak and unmonitored. Drawn
up after limited public consultation, they make no strict demands
apart from a requirement not to mention brand names. The effectiveness
of future guidelines will depend on interpretation, monitoring
and enforcement. (Paragraph 274)
12. We often do not
know what funds or support in kind patient groups receive from
pharmaceutical companies. Limiting or legislating against such
support is not appropriate; this would disadvantage both the charities
that rely on industry funding and the industry itself, by cutting
off a source of valuable feedback from the eventual consumers
of its products. Measures to limit the influence of industry on
patient groups are needed, however. Patient groups should declare
all significant funding and gifts in kind and the Government should
seek to make appropriate changes to charity law to ensure this.
It would in any case be greatly preferable if patient groups were
funded by companies' charitable arms, rather than by companies
themselves. (Paragraph 275)
13. Post-marketing
surveillance in the UK is inadequate. This has several causes:
the lack of effective post-marketing investigation of drug benefits
and harms in real life situations, and institutional indifference
to the experience and reports of medicine users. In addition,
the focus on drug licensing and on the safety profiles of individual
drugs has contributed to a dearth of information about the overall
impact of drug-induced illness in the community. (Paragraph 312)
14. The reputation
and credibility of the MHRA depends on its ability to communicate
uniformly with its different stakeholders. These diverging messages
contribute to confusion between health and trade priorities (Paragraph
313)
15. Areas of research
that are not of direct interest to the pharmaceutical industry
but may significantly benefit patients, such as non-pharmacological
treatments, should be funded by Government. (Paragraph 328)
16. The interests
of patients, the NHS and industry can be at odds and we have no
confidence that the Department is capable of achieving the balance
required. The 'cross-dressing' role of the Department in this
regard does not serve the public as well as it should (Paragraph
335)
17. Prescribers must
take their share of the blame for the problems that have resulted
from the prescribing of SSRI antidepressants and COX-2 inhibitors.
There is no doubt that these medicines have been indiscriminately
prescribed on a grand scale. This is partly attributable to intensive
promotional activity, especially around the time of drug launch,
but also the consequence of data secrecy and uncritical acceptance
of drug company views. It seems that intensive marketing has worked
to persuade too many professionals that they can prescribe with
impunity. There is a huge variation in prescribing, even within
a limited area. That many acted cautiously makes those who did
not more open to criticism. There is a lack of any effective mechanism
for tempering the prescribing explosion often seen in the months
following a product launch. We have been told time and again that
this is the most important period in drug promotion terms, but
is also the time when least is known about the product. (Paragraph
348)
18. We recommend that
the clinical trials register be maintained by an independent body
and the results of all clinical trials data, containing full trials
information, be put on the register at launch as a condition of
the marketing licence. (Paragraph 355)
19. Clinical trials
have significant limitations. We recommend that the MHRA work
with the pharmaceutical industry and outside experts to design
clinical trials that establish the real therapeutic value of new
medicines using measures that are relevant to patients and public
health. Trials should be designed to more accurately predict the
performance of drugs in routine clinical settings. We recommend
that research ethics committees encourage where appropriate the
inclusion of comparator drugs and non-drug approaches in the evaluation
of proposed clinical trials. Ethics committees should also require
applicants to prove that the trial does not duplicate previous
research and that results will be published in full. (Paragraph
356)
20. We recommend that
the NHS take further steps to facilitate the conduct of clinical
trials, with each Trust having a single point of contact for the
pharmaceutical industry to approach when considering a trial.
(Paragraph 357)
21. We recommend that
limits be set as to the quantity of material prescribers receive,
particularly in the first six months after launch. Less experienced
and non-specialist doctors are ill-equipped to cope effectively
with the promotional material. The pressure on nurses and pharmacists
is likely to intensify as their prescribing powers are further
extended. Stricter controls are needed in respect of drug company
representatives' promotion of their products to junior doctors
and to nurses or pharmacists with new prescribing powers. (Paragraph
358)
22. Marketing practices
that appear to be illegal should be reported by the pharmaceutical
industry and others to the MHRA. (Paragraph 359)
23. We recommend a
major review of the investigation of complaints (of marketing
and advertising practices) to ensure the process is far quicker
and effective sanctions are enforced. (Paragraph 360)
24. The PPRS should
be used more effectively to influence the actions of the pharmaceutical
industry in the public's interest. When companies are found to
be in breach of advertising regulations or to have published misleading
findings the allowance for promotion and research, respectively,
provided under the Scheme should be reduced. In addition, rewards
for innovation should be limited to those drugs that are proven
to offer clinical advantage. (Paragraph 361)
25. We recommend that
the MHRA publishes, in some form of useable database, the material
it receives from drug companies and the assessments it sends to
advisory bodies at the time it sends them. We welcome the MHRA's
plans to include lay members on every MHRA advisory committee,
and recommend that these members receive sufficient training
and support to allow them to fully contribute to decision making.
(Paragraph 363)
26. We are concerned
that the MHRA is not permitted to routinely inspect audit reports
for compliance with standards of Good Clinical Practice (GCP).
The Department of Health should reconsider its agreement to waive
powers to inspect, on a routine basis, audit reports of compliance
with GCP standards, including standards of patient care. The Department
should review all current and proposed standards developed by
the International Conference on Harmonisation that impose restrictions
on MHRA staff relating to inspection of company-held data and
records (Paragraph 364)
27. The MHRA should
put in place systematic procedures to randomly audit raw data.
The results of such audits should be published. We also recommend
that, like the US Food and Drug Administration, the MHRA play
a greater role during the early stages of drug development. Guidance
should be provided by the MHRA to the industry as to the types
of clinical trial likely to prove the degree of therapeutic gain.
NICE should also be involved in this process to provide advice
on the type of data more likely to lead to the drug being included
in NICE guidance. (Paragraph 365)
28. The adverse drug
reactions reported in the clinical trials that are considered
in the medicines licensing process typically prove unreliable
as a guide to routine clinical practice. Moreover, the adverse
effects that may be linked to stopping treatment are insufficiently
investigated. The MHRA should focus more intensely on updating
drug benefit:risk profiles in the Summary of Product Characteristics,
following systematic post-marketing review. (Paragraph 366)
29. We recommend that
the MHRA employ sufficient numbers of staff to monitor effectively
drugs which have been recently licensed. Given the limited value
of clinical trials in predicting drug impact in naturalistic settings,
the MHRA should investigate options for the development of more
effective post-marketing surveillance systems. Consideration should
be given to the establishment of post-marketing surveillance and
drug safety monitoring systems independently of the Licensing
Authority. We also recommend that the MHRA enhances its relicensing
procedures five years after launch. During the renewal procedure,
the MHRA should again assess in detail the product's efficacy,
safety and quality. (Paragraph 367)
30. We recommend that
the MHRA is given the same authority to propose restrictions on
drug use as it has when approving them. (Paragraph 369)
31. We recommend that:
the system of patient reporting to the Yellow Card Scheme country-wide
be put in place as soon as possible; that steps be taken to improve
rates of healthcare professional reporting of adverse drug reactions;
that greater efforts be made to investigate signals of possible
problems; and that maximum transparency be combined with concerted
efforts to explain the uncertainties of risk. (Paragraph 370)
32. We recommend that
there should be a public inquiry whenever a drug is withdrawn
on health grounds. (Paragraph 371)
33. The intensive
marketing which encourages inappropriate prescribing of drugs
must be curbed. Present methods of supplying independent information,
as described by Lord Warner, are inadequate. We recommend that
all the promotional material for a new product be pre-vetted by
the MHRA prior to publication, and that consideration be given
to limiting those who can prescribe a new drug in the two years
following launch. Drug and Therapeutics Committees would be well-placed
to implement this. Wider prescribing rights would be permitted
once comparative studies, and trials investigating the potential
adverse effects of the medicine in large populations, had been
undertaken and after formal evaluation of the value of the product
in clinical practice had been confirmed by the Licensing Authority
and/or NICE. (Paragraph 372)
34. We recommend that
the MHRA and the PMCPA better co-ordinate their work relating
to the promotion of medicines to avoid duplication. Complaints
should be investigated swiftly, particularly when claims for new
drugs are involved. When the PMCPA has evidence that a company
has breached the regulations it should inform the MHRA of its
findings. When companies are found to be in breach of advertising
or marketing regulations by the MHRA, we recommend that corrective
statements always be required and that such statements are given
as much prominence as the original promotional piece. The publication
of misleading promotional material is a criminal offence and the
punishment should befit such a status. (Paragraph 373)
35. A healthy generics
market is important for the NHS and patients. We recommend a systematic
review of so-called evergreening and other practices that impede
the entry of generic drugs on to the market. (Paragraph 374)
36. We recommend that
there be an independent review of the MHRA. The earlier review
by the National Audit Office was designed expressly to assess
the public expenditure aspects of the work of the agency; a more
wide-reaching and in-depth review needs to be carried out to determine
whether the processes now used for decision-making are adequate
and reflect patients' health needs and society's expectations.
The following principles should govern the review: the need for
greater independence from Government; the need for greater independence
from the pharmaceutical industry; the need for policies of greater
transparency and accountability in light of recent freedom of
information legislation; the effectiveness of the post-licensing
department and the need for the MHRA to become pro-active rather
than re-active; scrutiny of the regulatory standards underpinning
clinical and non-clinical new drug review; the reporting and evaluation
of adverse drug reactions; the prioritisation of new marketing
applications; and inclusion of the public in policy-making and
implementation (Paragraph 376)
37. We recommend that
all medical students be taught how to judge clinical trial results
effectively, recognise adverse drug reactions and deal with drug
company representatives. There should be mandatory post-graduate
training for all prescribers to keep up-to-date with prescribing
changes. In addition, stricter regulation of individual prescriber's
practices is required. (Paragraph 378)
38. There is a lack
of consistent and reliable independent advice, information and
oversight of prescribers. We recommend that the Department of
Health look into ways of making Use of Medicines Committees/Drug
and Therapeutics Committees of a uniformly high standard, so that
they can reliably carry out this vital educational role. Wherever
possible, clinical pharmacologists and specialist pharmacists
should be included on such Committees, as should lay representatives.
Formularies established in hospital Trusts should be shared with
affiliated PCTs with a view to adoption by the entire local health
community. Ideally, new drugs should not be prescribed until they
have been approved by such a committee. New drugs that might represent
significant advances should be fast-tracked through these committees.
(Paragraph 380)
39. We recommend that
a register of interests be maintained by the relevant professional
body (General Medical Council, Royal College of Nursing, Royal
Pharmaceutical Society of Great Britain etc), detailing all substantial
gifts, hospitality and honoraria received by members. The register
should be made available for public inspection. Individual practitioners
should be responsible for maintaining their entry on the register.
Professional bodies should provide advice to their members about
the levels of hospitality and payments that are acceptable. (Paragraph
381)
40. We recommend that
the current guidelines on disease awareness campaigns be strengthened.
When a campaign is sponsored by a company that is developing or
marketing a product to treat the condition that is the subject
of the campaign, any related literature should carry a statement
to this effect. (Paragraph 382)
41. We recommend that
patient groups be required to declare all substantial sources
of funding, including support given in kind, and make such declarations
accessible to the public. (Paragraph 383)
42. We recommend increased
funding of NICE to allow it to evaluate more medicines more quickly.
Consequent improvement in prescribing standards should make such
investment cost-effective. (Paragraph 384)
43. The Government
should look at the levels and range of expertise required by the
pharmaceutical industry and, with universities, take action to
ensure that appropriate numbers and quality of staff are trained.
(Paragraph 385)
44. We recommend that
the Government fund: a multi-disciplinary investigation of existing
medicines, combinations of medicines and medicines use where there
is a reluctance of the industry to fund such research; research
into the adverse health effects of medicalisation; and trials
of non-drug approaches to treatment. (Paragraph 388.)
45. We recommend that
the extent, cost and implications of illness resulting from the
use of medicines be systematically investigated by the Department
of Health in conjunction with the MHRA. (Paragraph 389)
46. We recommend that
the Government adopt a National Drugs Policy to encourage the
availability of medicines to all types of patients, the safety
and efficacy of these medicines and their rational use and to
ensure that medicines are compared to non-drug approaches. (Paragraph
390)
47. We recommend that
the NHS adopt a policy regarding the role of drug treatment in
relation to non-drug treatment, emphasising the importance of
both approaches. (Paragraph 391)
48. We recommend that
responsibility for representing the interests of the pharmaceutical
industry should move into the remit of the Department of Trade
and Industry to enable the Department of Health to concentrate
solely on medicines regulation and the promotion of health. (Paragraph
392)
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