Memorandum by the Association of the British
Pharmaceutical Industry (ABPI)
The Association of the British Pharmaceutical
Industry (forthwith referred to as the "Association"
or "ABPI") represents the majority of the companies
in the United Kingdom (UK) engaged in research, development, manufacturing
and supply of prescription medicines. The ABPI brings together
companies producing such medicines, whether branded or generic,
many smaller organisations involved in pharmaceutical and biopharmaceutical
research and development (R&D), and those with an interest
in the pharmaceutical industry in the UK. ABPI member companies
manufacture and supply more than 80 per cent of the medicines
prescribed through the National Health Service (NHS) and are major
exporters to countries all over the world.
In preparing its response to questions put forward
by the House of Lords' Science and Technology Sub-Committee on
Fighting Infection, the ABPI has drawn upon evidence provided
by member companies. The submission also makes use of the Anti-infectives
Research Mission to the USA 9-13 August 1999 report produced
by the Department of Trade and Industry and the ABPI, the ABPI's
written and oral evidence submitted to the House of Lords' Select
Committee on Science and Technology for the Resistance to Antibiotics
and Other Antimicrobial Agents Session (1997-98, 7th Report),
and the European Federation of Pharmaceutical Industries and Associations'
position paper (1999) on Containment of Antibacterial Resistance.
The ABPI strongly endorses the appropriate use
of anti-infective agents in fighting infection to benefit patients.
The ABPI supports the publication, Getting Ahead of the Curve
(GATC), in addressing the problem of infection. We support the
House of Lords in taking steps aimed at further strengthening
the UK's anti-infectives initiatives and are pleased to have been
invited to produce written evidence. Our aim in submitting evidence
is to put forward the pharmaceutical industry's view on how to
tackle infectious diseases in the UK most effectively, and to
identify policies which improve surveillance, diagnostics, prevention
and treatment of infectious diseases.
The UK benefits from medicines, in particular
those discovered and developed in the UK, not only for the health
benefits enjoyed by patient populations, but also in economic
terms. The ABPI believes that the most important contribution
the pharmaceutical industry can make in the fight against infectious
diseases is to continue its research efforts. Research areas covered
by UK-based pharmaceutical companies are identified in the ABPI's
A to Z of British Medicines Research (2002).
The ABPI welcomed the Pharmaceutical Industry Competitiveness
Task Force (PICTF) process and recommends that the Government
continue to take firm action to create a supportive environment
for pharmaceutical and biotechnology companies in the UK.
There needs to be significant investment in
a surveillance system within the NHS with links across regional
and national boundaries. Without a co-ordinated and effective
surveillance system, reliable information will not be available
to enable the development of appropriate treatment or prevention
strategies. With appropriate organisational structures, diagnostic
aids and information systems in place, incentives would serve
to ensure the effective use of a surveillance system.
Whilst the NHS can take overall responsibility
for surveillance, it cannot undertake prevention and treatment
by itself. The Government can most effectively continue the fight
against infection with a multifaceted approach embracing the health
services, industry and academia to ensure that surveillance information
is used to inform research programmes.
Modern prescribing practices and systems need
to be strengthened to enable UK general practitioners (GPs) to
implement prescribing guidelines and prescribe novel medicines.
Guidelines on appropriate prescribing of anti-microbials should
be coupled with procedures for correct usage. Ensuring take-up
of new medicines should serve to promote a positive environment
for the research and development into new vaccines and medicines.
Without treatments, the UK would be increasingly unable to fight
infection. Without prevention strategies, treatment would be overwhelmed
and surveillance would be irrelevant.
1. What are the main problems facing the
surveillance, treatment and prevention of human infectious disease
in the UK?
1. Historically, one of the main problems
has been a deficiency in Government expenditure on, and a lack
of co-ordination of, surveillance and reporting systems. The Public
Health Laboratory Service (PHLS) laboratories provide microbiology
services in the UK. With the ongoing reorganisation of the NHS,
there is a possibility that their operation and co-ordination
will be disrupted. It is considered that any such disturbance
should be minimised to ensure continuity of service. The prevention
and treatment of infectious diseases will be compromised if standardised
diagnostic procedures, and information technology (IT) systems
to facilitate coordination and communication of reliable, real-time
data are not developed. Without improvements in the implementation
of any new proposed surveillance procedures, expenditure on diagnostic
technologies and IT systems will be wasteful. Without co-ordinated
cross-boundary surveillance initiatives, regional surveillance
systems will be undermined.
2. In the UK, GPs are conservative in their
prescribing of novel therapeutics. Whether the underuse of novel
testing and treatment options is due to lack of availability,
lack of awareness of what is available, or budget constraints
undermining the concept of "Appropriate Prescribing",
this issue needs to be addressed.
3. The UK policy climate does not provide
a sufficiently supportive environment for the development of anti-infectives
by companies. There is not enough Government support for collaboration
between the NHS, industry and research institutes to highlight
priorities for R&D.
4. Mixed results have followed previous
Government initiatives to impact prescribing behaviour and reduce
resistance to antibiotics. Within the UK, there is a conflict
between the adoption of advanced antibiotics with lower resistance
levels and other desirable attributes, and the economic constraints
of prescribing within the NHS. Use of inappropriate antibiotics
wastes time and money, extends the period of illness and may exacerbate
the emergence of resistance, endangering other patients. There
is inconsistency in the auditing amongst NHS Trusts and Primary
5. Current UK policy initiatives do not
serve to encourage investment in vaccine development programmes
by the pharmaceutical industry.
2. Will these problems be adequately addressed
by the Government's recent infectious disease strategy, Getting
Ahead of the Curve?
6. GATC recognises the weaknesses within
the structure of the NHS in enabling a co-ordinated surveillance
system. The ABPI supports the formation of a National Infection
Control and Health Protection Agency to oversee a national comprehensive
surveillance strategy, including the effective co-ordination of
the network of PHLS laboratories.
7. Variation exists in the use of IT to
support reporting and surveillance systems. GATC draws attention
to one of the roles of the proposed National Infection Control
and Health Protection Agency in developing information systems
to close surveillance gaps. We welcome this and discuss the IT
issue further under Question Three.
8. GATC recognises the importance of greater
alignment of national and European surveillance. However, GATC
deals primarily with surveillance systems in England. An efficient
surveillance system will require a surveillance system which links
across boundaries, for example, Scotland, Wales, Ireland and continental
9. Microbiologists should be enabled to
generate reliable, standardised resistance data supporting patients'
treatment and contributing to resistance surveillance needs, including
global standardised susceptibility sensitivity tests for whether
a bacterium is sensitive or resistant to an antibiotic. GATC recognises
the need for a fully accredited diagnostic and reference microbiology
service underpinning a strong system of surveillance and introduction
of standards for diagnosis and profiling of micro-organisms. The
ABPI strongly supports a mandatory system of evidence-based standard
operating procedures in diagnostic laboratories, together with
a mandatory accreditation system. Further diagnostics issues are
discussed under Question Three.
10. The current statutory reporting system
is inadequate and variably adhered to. To ensure high quality
surveillance, the ABPI recommends the implementation of incentive
systems to ensure that surveillance systems are used effectively.
This is not addressed in GATC.
11. The ABPI supports the sharing of surveillance
information in an appropriate and timely manner between health
services, industry and academia. This will serve to inform research
programmes on the demographics and epidemiology of disease, and
avoid potential delays in the development of new products for
the prevention and treatment of infectious diseases.
12. We recommend that the NHS support the
use of novel therapeutics and technologies. The ABPI supports
the establishment of best practice in prescription guidelines,
together with electronic prescribing capability and support systems
for implementation, for example recommendations put forward through
National Service Frameworks and the National Institute for Clinical
Excellence. This issue is not addressed in GATC. In addition to
patient benefits, we consider that higher levels of prescribing
of clinically effective novel medicines will have a positive impact
on the launch of new anti-microbials in the UK.
13. GATC recognises the need for R&D
in order to generate new therapeutics. The ABPI is of the opinion
that there is a lack of emphasis by the Government on fundamental
research in the treatment and prevention of emerging and re-emerging
diseases. New diseases are continuously arising and infectious
disease organisms mutating. More bacterial research needs to concentrate
on pathogens of importance to the UK, and additional research
should be dedicated to viruses, mycology and parasitology. We
do not consider that this issue is sufficiently addressed in GATC.
In supporting the co-ordination of NHS R&D programmes with
those of research councils, charities and pharmaceutical companies,
the ABPI recommends the development of a National Infectious Diseases
Research Network based on the recently established London model.
14. Physicians should be encouraged to prescribe
antibiotics at an appropriate dosage and for an appropriate length
of time. There should be increased public awareness around the
importance of completing the full course of prescribed antibiotics.
As noted in GATC, regular training and education should be provided
to healthcare professionals and patients on the proper use of
15. The ABPI supports the effective use
of information on the profiles of infectious diseases associated
with the shifting demographics in the UK population, for example,
the growing number of elderly people and immigrants, in order
that vaccination programmes be efficiently targeted.
3. Is the UK benefiting from advances in
surveillance and diagnostic technologies; if not, what are the
obstacles to its doing so?
16. The ABPI considers that the UK is not
sufficiently benefiting from advances in surveillance technologies.
We consider it highly important that a sophisticated national
real time integrated electronic disease surveillance system be
established to deliver high quality information to improve the
nation's ability to identify and track outbreaks and emerging
infectious diseases, antibiotic resistance, and potential bioterrorism
attacks. A surveillance system should be able to transfer appropriate
public health, laboratory, and clinical data efficiently and securely
over the Internet. Information, organised in databases, linked
with mathematical models should be able to be analysed quickly
and accurately. We recommend significant cooperation between clinicians,
diagnostic laboratories, other relevant NHS departments, industry
and academia in ensuring that IT systems are user-friendly and
17. The ABPI considers that the UK is not
sufficiently benefiting from advances in diagnostic technologies.
Diagnostics underpin therapy and surveillance of resistance. Investment
in standardised, state of the art technologies is needed to bring
the UK back up to standard. The ABPI recognises that an impediment
to the use of advanced diagnostic technologies is the cost of
accommodating new technology. We propose evidence-based recommendations
on appropriate novel diagnostic tests, and justification to support
additional costs of testing, where appropriate.
4. Should the UK make greater use of vaccines
to combat infection and what problems exist for developing new,
more effective or safer vaccines?
18. The best way to deal with infectious
diseases is to prevent them. Vaccines and their use as part of
national immunisation programmes continue to rank among the most
important contributions to public health in the UK. The ABPI considers
that the Government should make greater use of vaccines to combat
infection, where appropriate. We support the UK Vaccine Industry
Group in its recommendation that by promoting greater access to
licensed vaccines, planning the introduction of new vaccines to
target previously unmanageable infectious diseases such as meningitis
B and rotavirus, and through more effective dialogue with stakeholders,
significantly more can be achieved as part of an overall programme
to fight infectious disease.
19. The science of vaccines is highly complex,
and clinical development may be lengthy and risky. The policy
environment in the UK which serves to determine pricing may result
in poor economics for vaccine R&D by UK-based pharmaceutical
companies. Clear demonstration of health economic arguments will
be critical in driving vaccine development by pharmaceutical companies,
as well as uptake by healthcare practitioners. Companies will
need to weigh the rewards of more directed therapies against the
drawbacks of reduced indications. As long as vaccines prove uneconomical
for pharmaceutical companies, they will be more focused on treatments
for infectious diseases, rather than prevention (DTI/ABPI, 1999).
20. The ABPI commends GATC's recommendation
for a programme of new vaccine development, though clarification
is sought regarding source of funds for R&D and responsibility
for undertaking vaccine R&D.
21. We recommend that the Government recognise
the possibility that despite the development of new, more effective
or safer vaccines, negative media coverage may undermine immunisation
programmes. Such media coverage may also frustrate attempts to
undertake clinical trials, especially as for many vaccines trials
have to be done in children. We consider that vaccination programmes
must be in the context of robust education of, and communication
to, the general public on the role of vaccination in the overall
public interest to avoid the difficulties arising from adverse
media campaigns on the use of the MMR (mumps, measles and rubella)
5. Which infectious diseases pose the biggest
threats in the foreseeable future?
The ABPI considers the following infectious
diseases to constitute the biggest threats:
|| Information|| Costs
|| Treatable||Vaccine Available
|Methicillin Resistant Staphylo- coccus aureus (MRSA)
||Hospital acquired infections, particularly due to organisms where resistance is rapidly emerging to commonly used agents (eg MRSA) are increasing in prevalence. Thus therapeutic options are diminishing thereby increasing costs of management.
||High (Due to hospitalisation, delay in hospital discharge and morbidity)
||Yes (MRSA is resistant to many antibiotics, but a few can still successfully cure infections)
|(Multi-resistant) Tuberculosis||TB is responsible for the greatest number of deaths. Antibiotic resistance affects a small, but growing, group. Multi-resistant tuberculosis is an important disease as communicability is high.
||High. (Due to treatment costs)||Yes
|Human Immuno- deficiency
Virus (HIV)/ Acquired Immune Deficiency Syndrome (AIDS)
|Chronic disease||(Due to direct and indirect costs).
|Increased infertility, especially with increase in chlamydia, increase in ectopic pregnancy, increase in cervical cancer
||High (If results in infertility and reduced population size)
|Gastric and duodenal|
ulcers and gastric cancer due to Helicobacter pylori
|H pylori is the most important factor in the aetiology of uncomplicated peptic ulcers. Evidence suggests that 73 per cent of gastric cancers are attributable to H pylori and 65 per cent of peptic ulcer deaths. It has been estimated that 1:35 men and 1:60 women will die from a complication of H pylori infection (Moayyedi and Axon, 1998).
||High (Due to treatment costs, morbidity and mortality).
|Influenza||Well covered for the elderly but insufficient funding for <65s target group
||High. (Due to treatment costs, morbidity and mortality)
|Infections in immuno- compromised populations
||Due to an increase in the susceptible patient population.
||Variable||Variable||Depends on the disease
|New and emerging infections||Due to uncertainty about natural history and diagnostic tests, long-term consequences and possible treatment modalities (eg new variant Creutzfeld Jacob Disease, nvCJD).
||Variable||Variable||Depends on the disease
|Imported infections||Due to lack of local knowledge
||Yes||Depends on the disease
22. A distinction may be made between threats to morbidity,
mortality and financial and economic costs of infectious disease.
To determine which infectious diseases pose the biggest threats,
we recommend that attention be given to cost of illness and cost-effectiveness
studies, and where information
is lacking, further studies be undertaken.
6. What policy interventions would have the greatest impact
on preventing outbreaks of, and damage caused by, infectious disease
in the UK?
23. In this issue, it is important to acknowledge the
roles played by academic and government research institutions,
and pharmaceutical and biotechnology companies in discovering
and developing those anti-microbials which have served to improve
outcomes for patients and reduce the costs of disease.
24. We consider that with the backing of the Government,
the UK has the opportunity to take a lead internationally in anti-infectives
research, in particular, where clear preventative strategies are
already evident, such as in the case of HIV, AIDS, MRSA, multidrug
resistant tuberculosis, genital chlamydia, and food borne infections.
25. The ABPI recommends unequivocal Government support
for UK-based biotechnology and pharmaceutical companies. Policies
which support commercial R&D activities and dispersal of products
to patient populations should serve to contribute to prevention.
The ABPI recommends that the Government assist companies through
providing additional marketing exclusivity for pharmaceutical
companies, for example, for medicines developed in children upon
Government request. We urge the Government to continue its support
for proposals to improve the efficiency of clinical research laid
out in the PICTF report. These include a reduction in licensing
times and bureaucracy for animal testing and clinical development,
and co-ordinated action to deter animal rights activists and to
educate the public in the importance of animal testing.
26. The ABPI supports policies which promote a partnership
approach between companies and healthcare professionals to provide
an appropriate environment for the development of new medicines,
vaccines, diagnostics, and drug delivery tools.
27. We urge the Government to encourage those involved
in anti-infectives research including academia, industry and health
services, to play a greater role in emphasising to the public
the importance of biotechnology and new life-saving medicines.
28. We continue to impress on the Government the importance
of ensuring improvements in education in science, engineering
and technology. This will require significantly increased funding
of, and emphasis on, scientific study on infectious diseases in
academic and research centres of excellence, and related infrastructure.
29. The ABPI welcomes the outcome of further legislation
in Section 60 of the Health and Social Care Act enabling the continuation
of surveillance of non-statutory communicable diseases.
SUPPLEMENTARY INFORMATION RELATED TO THE INQUIRY
1. What are the main problems facing the surveillance,
treatment and prevention of human infectious disease in the UK?
1. Inadequate accreditation systems for laboratories,
hospitals and community care facilities.
2. A shift in healthcare provision from hospitals to
the community means that more healthcare related infections are
within the public arena, such as nursing and residential homes.
This poses a greater challenge for traditional surveillance methods.
3. Insufficient communication with the public in terms
of communication at times of crisis. Also, there is an irregular
system of reporting by individual physicians and microbiology
4. The several hundreds of marketed antibiotic formulations
represent only nine separate drug types with only five distinct
modes of action. Evolution or acquisition of resistance to even
one class of antibiotics significantly reduces the choice of treatments
available to the physician (DTI/ABPI, 1999).
5. We note that previous reports on resistance to antibiotics
and other anti-microbial agents produced by the House of Lords'
Select Committee on Science and Technology have drawn attention
to the growing problem of infectious diseases and antibiotic resistance.
We consider that there has been a mixed outcome as a result of
these reports' recommendations. For example, whilst there has
been a reduction in the use of antibiotics overall, there has
been a growth in expenditure on antibiotics in some disease areas,
for example, lower respiratory tract infection (LRTI), due to
the rise in use of parental antibiotics.
6. The ABPI questions whether the level of NHS expenditure
on anti-infective treatment is targeted properly. Treatment decisions
may not be made on the basis of an infection being established.
Cost pressures may cause treatments to be inappropriately applied
to patients, which may induce greater sickness. For instance,
from 1997 to 2000 hospital admissions for LRTI increased by 68
per cent; this coincided with a decline in community prescribing
for LRTI by 26 per cent. The campaign to reduce inappropriate
antibiotic prescribing for upper respiratory tract infection may
have produced important consequences for the management of LRTI
in terms of outcomes and resource use.
7. The shift in healthcare provision to the community
will result in a greater challenge for establishing preventative
measures for infectious diseases. One solution to improve the
situation would be the development of a community infection nursing
8. There is an absence of good evidence concerning what
is cost-effective in terms of different prevention programmes
and reducing the emergence of antimicrobial resistance (Wilton
et al., 2002).
9. Lack of guidelines on hygiene, which are central to
reducing the spread of disease.
10. Using the wrong antibiotic, sub-optimal dosage and
duration of treatment along with reduced patient compliance can
lead to the selection of bacterial populations with reduced susceptibility
and thus trigger the development of bacterial resistance. This
is recognized in GATC.
11. Overuse of antibiotics in agriculture is also considered
to be a significant contributor to antibiotic resistance.
2. Will these problems be adequately addressed by the
government's recent infectious disease strategy, "Getting
Ahead of the Curve?"
12. The ABPI considers that there is a need to effectively
move the existing predominant diagnostic role of microbiology
laboratories to a wider public health function, in effect to become
specialists in public health for communities served rather than
routine diagnostic processing centres.
13. The ABPI has concerns regarding how public health
surveillance of food and water, for example, will fit in the overall
14. The ABPI recommends that therapeutic and economic
impacts of continuous versus intermittent surveillance be assessed
to assist in the development of meaningful health policy decisions
15. The ABPI recommends improvements in surveillance
methods and procedures, such as those suggested by the ABPI (see
Appendix One for a list of recommendations on surveillance procedures),
and in GATC.
16. GATC addresses the issue of mandatory accreditation
of laboratories. The ABPI considers it important for all healthcare
facilities to be accredited including hospitals and community
17. A shift in healthcare provision from hospitals to
the community poses a greater challenge for traditional surveillance
methods. The ABPI recommends that the Government should outline
its strategy for surveillance in community settings.
18. There is an irregular system of reporting by individual
physicians and microbiology laboratories. The issues around communication
of changes in surveillance and reporting systems to health care
professionals and the wider public are not adequately dealt with
in GATC. The Association recommends that the Government outlines
its policy in this regard. Similarly, the ABPI recommends that
the Government outlines its policy on communication at times of
19. In considering policies which would serve to prevent
outbreaks of and damage caused by infectious disease in the UK,
the ABPI recommends a simple, universal, robust reporting and
surveillance system with:
Clear guidelines for inclusion/exclusion of infections.
Rapid identification of clusters/outbreaks of
infections and provision of appropriate alerts.
The ability to provide data on antimicrobial susceptibility
at international, national and local level in response to enquiries.
The ability to monitor outcomes on both a short
term and long term basis.
20. We welcome the Government instructions that NICE
recommendations are taken up by the Trusts, especially as there
have been recommendations by NICE and further appraisals are underway.
21. In order to treat patients, it is important to have
available the appropriate therapeutics. Currently, although there
is investment in R&D by pharmaceutical companies, there is
a lack of treatment alternatives. This needs to be tackled through
greater investment in R&D, on for example new antibiotics
with characteristics that facilitate patient compliance, for example,
simple dosage regimen and reduced side effects. GATC recognizes
the need for R&D in order to generate new therapeutics. There
appears to be little emphasis attached by UK Public Health policy
on the fundamental role of research in the treatment and prevention
of emerging and re-emerging infectious disease. The ABPI recommends
that the House of Lords urge the Government to make explicit,
at an appropriate point in time, its R&D investment strategy
and methodologies and justifications in the decision-making process
22. Bacterial research needs to concentrate on pathogens
of importance to the UK, ie Gram positive, including MRSA, Tuberculosis,
vancomycin (or glycopeptide)-resistant enterococci, and also Gram
negative bacteria such as Pseudomonas aeruginosa. Alternatives
to antimicrobials, for example, use of bacteriophages, also need
to be developed.
23. The majority of research is on bacteria (see Appendix
Two for recommended research on the organism's response to antimicrobials).
More research is also needed on viruses, mycology and parasitology.
There is a need for more work on STDs.
24. Whilst closer collaboration between therapeutics
companies and research institutes should serve to highlight priorities
for R&D, there are difficulties associated with encouraging
UK centres to collaborate with pharmaceutical companies in anti-infectives
research due to cost issues, particularly large overhead costs
imposed by some university and academic institutions.
25. More needs to be done to address social inequalities
which fuel the spread of infection. There is a disproportionate
burden which some infections place on certain social groups. For
example, tuberculosis disproportionately affects certain minority
ethnic groups, and HIV affects Black Africans and gay men more
than other groups in society. Ways need to be found to ensure
that prevention messages and health services are accessible to
different social groups. Unless this is accomplished, there is
the risk that the health gap will widen. Immunisation programmes
should be implemented where appropriate.
26. In assessing cost-effective approaches to reducing
antibiotic resistance, Wilton et al. (2002) recommend further
validating intermediate or surrogate outcome measures
to enable better use to be made of the literature on intermediate
development and evaluation of "macro"
empirical and methodological research concerning
the economic evaluation of interventions.
27. As recommended in GATC, isolation and hand hygiene
are central to reducing the spread of disease. We recommend that
such a programme targets high-risk areas: intensive care and surgical
units, in particular. Community-wide public health strategies,
such as home hygiene, must also be given a much higher profile.
(See Appendix Three.) Also, community-based institutions need
to be more aware of cross-infection. This would be aided by the
development of a community-infection nursing service.
28. As part of local health improvement programmes, local
antibiotics have been more readily formulated as part of clinical
29. An audit approach for managing antibiotic prescribing
to reduce the need for antimicrobials is recommended for further
30. Antibiotics should be used only when indicated in
individual infected animals for a targeted pathogen and prescribed
by a veterinarian. The use of certain drugs that have important
uses in humans should be restricted in animals.
3. Is the UK benefiting from advances in surveillance
and diagnostic technologies; if not, what are the obstacles to
its doing so?
The ABPI considers that the UK is not sufficiently benefiting
from advances in surveillance and diagnostic technologies, as
31. Despite several initiatives, no broad based real
time systems are available in the UK to deliver high quality local
surveillance information. This is in part due to:
failure to standardise IT reporting and surveillance
costs of introducing new IT systems to support
excessive complexity of existing reporting systems;
lack of incentives for reporting; and
lack of understanding of purpose and importance
of technology developments and where and how they could improve
32. Strengthening IT in the NHS is addressed in GATC
and the DH's 2002 report Delivering 21st Century IT support
for the NHS: National Strategic Programme. We recommend significant
cooperation between NHS departments in ensuring that IT systems
are well coordinated.
33. Diagnostics have the potential to underpin therapy
and surveillance of resistance:
Isolation of infecting organisms from clinical
Determination of antibiotic susceptibility test
results through in vitro testing.
Guidance of the correct choice of antibiotic.
Provision of more accurate data for the purposes
of hospital prescribing policy, control of prevention, surveillance
34. There have been several improvements in rapid and
accurate diagnostic tools for anti-infectives including molecular
diagnostic technologies, and near patient testing. Novel diagnostic
technology products, eg biochips, biosensors, and high-density
deoxyribonucleic acid (DNA) arrays represent more rapid and accurate
tools. Novel approaches using ultramodern molecular techniques
such as DNA microarray analysis can identify genes whose expression
is up or down regulated under different environmental stresses
and whose products can then be targeted. Genetic tests for bacterial
resistance give faster, more accurate microbiology, ensuring that
the patient gets the right antibiotic sooner. Sequencing whole
pathogen genomes such as Salmonella spp. has already reaped
rewards with the production of a Polymerase Chain Reaction-based
system for detecting multi-drug resistance in S. typhi.
Rapid bedside tests will distinguish patients with bacterial infections
who need antibiotics from those with viruses who do not (DTI/ABPI,
35. Further improvements in molecular diagnostic methods
are needed for:
detection of resistance markers;
development and evaluation of rapid detection
rapid screening methods for patient isolation;
rapid typing methods for the epidemiology and
control of resistant organisms.
36. Several recommendations are made in GATC:
a strong system of surveillance should be supported
by fully accredited diagnostic and reference microbiology services;
proper diagnostic and treatment facilities should
be made available for people with infections (including isolation
facilities for those with highly infectious diseases).
37. To benefit from novel diagnostic tools, the Government
needs to be proactive in two areas: funding research and increasing
38. Pressure on budgets has led to a reduction in the
quality of UK microbiology with bacteria incompletely identified
and with few antibiotics tested. UK laboratories cannot afford
the costs of precise identification and high quality sensitivity
testing. Consequently, the quality and quantity of microbiological
testing in the UK is behind that of the US and most of Europe.
GATC highlights the significant gaps which exist in specialist
and reference diagnostic microbiological testing; as well as the
variety of management arrangements for microbiology laboratories
and lack of standard diagnostic criteria in their operations.
Investment in standardized, state of the art technologies which
underpin detection and surveillance of resistance is needed to
bring the UK back up to standard.
39. Antimicrobial resistance is continually evolving.
To keep up with this pace of change in resistance requires new
diagnostic tests. R&D activity is expensive and mainly funded
by companies. To encourage investment in diagnostic technologies,
the ABPI recommends that the Government outline its strategy for:
using diagnostics in combating infectious diseases and the resistance
problem; funding diagnostics R&D; and coordinating its diagnostic
R&D activity with that of the pharmaceutical companies.
4. Should the UK make greater use of vaccines to combat
infection and what problems exist for developing new, more effective
or safer vaccines?
40. The previously immense burden of morbidity and mortality
associated with "common" childhood diseases such as
diphtheria and pertussis is now rare. However, as acknowledged
in GATC more can be done. Taking preventative measures when managing
public health has benefits for the individual, the population
as a whole, and for the NHS through effective use of health care
41. The ABPI supports GATC in recognizing the need for
a carefully managed relationship with the research community and
the vaccine industry. We suggest that this relationship encompasses
the medical profession, Wellcome Trust, Government Research Councils,
patients, pharmaceutical industry, researchers, health authorities,
and the general public.
5. Which infectious diseases pose the biggest threats
in the foreseeable future?
42. In considering which diseases pose the biggest threat,
the ABPI suggests that the Government take note of whether screening
and prevention measures are currently available which are not
widely used. There are cost of illness and cost-effectiveness
studies available which provide information on economic and clinical
costs and benefits associated with different screening, prevention
and treatment measures. For example, a conservative crude estimate
suggests that the cost of dyspepsia in the UK is £525 million
each year. Any eradication programme for H pylori would be expensive
but would be partially offset by over £50 million each year
saved (Moayyedi and Axon, 1998).
43. Insufficient collaboration between industry and academic/healthcare
institutions in establishing national priorities for infectious
disease management and prevention.
6. What policy interventions would have the greatest impact
on preventing outbreaks of and damage caused by infectious disease
in the UK?
44. There is a huge medical need for anti-infectives
at global level. However, commercial organizations will inevitably
focus finite R&D resources on therapeutic areas where they
can reasonably expect to generate a return on their investment.
Equally, commercial organizations will look at the market situation
in individual countries to assess whether or not to embark upon
the approval process to launch the product at a local level. The
ABPI considers that policies which support commercial institutions
in R&D activities and product launch will help to address
the issue of prevention of outbreaks and damage caused by infectious
disease in the UK.
45. Biotechnology, which is undertaken in both pharmaceutical
and biotechnology companies, continues to offer new approaches
to the discovery, design and production of drugs, vaccines, diagnostics,
and drug delivery tools (for example, liposomal formulations)
making it possible to:
anticipate and prevent infectious disease rather
than just react to symptoms;
treat and cure more infectious diseases with more
precise and effective medicines with fewer side effects;
eliminate contamination risks for infectious pathogens
by avoiding the use of human and animal sources for raw material;
apply novel control methods once the mechanisms
by which antibiotic resistance genes emerge and spread are understood.
46. There is a need for highly coordinated research on
the epidemiology and genetics of antibiotic resistance with regards
to the impact of usage of antibiotics in human and veterinary
medicine (Hawkey and Thomson,1999).
47. Further basic research in anti-infectives in academia
need to be stimulated. Academics in the UK, as compared to the
US, are not encouraged to be as enthusiastic about the application
of their research to the treatment and prevention of infectious
48. In the UK grant support for research in anti-infectives
and antibiotic resistance is diverse and needs greater coordination
and strategic direction (DTI/ABPI, 1999). All avenues should be
explored to encourage effective multi-stream funding of research
in academia (industry research councils, medical charities and
the NHS) and barriers to such collaborations removed (DTI/ABPI,
49. Academic scientists in UK university and governmental
laboratories are neither as well informed about pharmaceutical
research in anti-infectives nor as receptive to collaborating
with the large pharmaceutical companies, as their US counterparts.
Increased collaboration between industry and academia in this
field needs to be encouraged to help establish national priorities
for infectious disease management and prevention. Policies need
to encourage collaboration with and investment by industry.
50. The ABPI considers the Government should establish
mechanisms which encourage the commercialization of innovation
within academic and healthcare institutions.
51. UK Public Health policy places insufficient emphasis
on the fundamental role of research in the prevention of emerging
and re-emerging infectious disease (DTI/ABPI, 1999). Funding ongoing
research into the mechanisms and spread of resistance needs to
be a priority for the Government.
52. Another key step in the development of biopharmaceutical
products is testing their efficacy and safety in clinical trials.
The efficiency and effectiveness of this process is constrained
through bureaucracy in initiating the trials, cost, access to
patients and number and quality of investigators.
53. A key stumbling block for companies in the UK is
the bureaucracy around getting clinical trials started. A survey
of 19 countries showed that only the UK and Hungary have four
regulatory and ethical approval steps compared with only two for
the majority (11/19) of the countries. Under the EU clinical trials
directive introduced in April 2001 and to be implemented by member
states by 2004, a 60 day timeline is given for regulatory activity.
As a result of PICTF, the UK Government has agreed not to wait
until 2004 but is already taking steps to implement some of the
requirements, such as parallel review of research protocols. The
goal is that the UK will be an attractive place for clinical research
in Europe. In the UK there has been an agreement that all regulatory
processes and protocols reviewed would be done in parallel within
60 days by: 1) Medicines Control Agency, 2) MRECs (Multi Research
Ethics Committees), 3) LRECs (Local Research Ethics Committees)
and 4) local hospital R&D committees. As part of the PICTF
agreement, the ABPI is benchmarking clinical research start-up
times and patient recruitment. Early results are encouraging in
that 60 per cent of multi-centred trials are able to begin 60
days after the ethics committee application and more than 80 per
cent of local studies. This compares with less than 40 per cent
before the PICTF process began. It is recommended that the Government
continue to support the 60 day review procedure, as well as review
the need for LREC involvement in multi-centre research.
54. Companies require large numbers of subjects for clinical
trials but recruitment in the UK is low. Thirty per cent of sites
in the UK fail to recruit a single patient compared with 10 per
cent in the US. Currently recruitment is being benchmarked by
the industry. The NHS R&D Directorate and ABPI are developing
a clinical trial agreement that should enhance recruitment to
industry organised trials in the UK.
55. The UK is one of the most expensive countries in
the world for clinical research, and over the past decade growth
in costs have risen at a higher rate relative to continental European
countries (Continental Europe:UK=60-70:100). The ABPI welcomes
the recently announced DH's review of its guidance on the relationship
between prices charged and the cost of studies with the intention
of greater transparency and consistency in pricing.
56. The ABPI considers that more and better trained investigators
are needed for clinical research. The ABPI is working with the
Research Ethics Committees to develop a joint training programme
for companies in improving Ethics Committees' applications. We
recommend that the Council of Heads of Medical Schools introduce
good clinical research practice into the undergraduate curriculum.
57. The ABPI considers that taking part in clinical research
is of benefit to participants.
58. The ABPI and NHS R&D Directorate launched a partnership
agreement for collaborative clinical research in England and Wales
In the surveillance of resistant organisms, the ABPI recommends
undertaking the following research:
Molecular epidemiology of resistant isolates.
Current levels of resistance in both the hospital
and community settings.
Reasons for the current increase in antibiotic
resistance, eg if related to level of prescribing.
Dynamics of the spread of resistance.
Public health impact from rise in resistance.
Relation between rise in resistance and particular
Impact of resistance levels following a reduction
in use of specific antibiotics.
Proportion of the population who consults the
GP with specified syndromes.
Reasons GPs send samples.
Surveillance of near-patients testing data on
organisms and resistance.
Propensity for emergence of resistance.
Impact of antibacterials on clinical outcomes.
Impacts of controlling antibacterial usage.
Effect of antibacterial usage on the carriage
rates of resistant organisms in the hospital and community.
Clinical outcome in infections with resistant
versus sensitive organisms.
Routinely generated susceptibility data research needs:
Informed population denominator.
Standardization of laboratory methods.
Link resistance and prescribing data.
Reservoirs of resistance in the normal flora and
Linkage to specific disease syndromes.
Focus on problem environments, such as day care
and nursing homes.
Link outcome data, ie response to treatment.
Recommended research on the organism's response to antimicrobials:
Impact of anti-microbial resistance on microbiological
Population biology, including the effect of resistance
Basic cellular processes in bacterial model systems.
Molecular genetic basis of resistance mechanisms.
Detection of novel resistance genes.
Evolutionary biology, eg origin of resistance.
Mechanisms for the emergence of resistance.
Molecular genetic basis of biosynthesis.
Efflux mechanisms, particularly environmental
Regulation of anti-microbial resistance.
Mechanism of resistance transfer and subsequent
maintenance of resistance (including plasmid replication).
In monitoring infection control, the following issues should
Determine the relationship between antibiotic
prescribing, hospital hygiene and performance in infection control.
Show how to improve control of infection with
antibiotic-resistant organisms association with invasive devices.
Evidence-based practice of even basic measures
such as hand washing, barrier nursing, patient isolation, etc.
Mode of action of disinfectants.
Mechanisms and genetics of resistance to disinfectants.
Association of disinfectants with antibiotic resistance
(shared targets, etc).
Comparison of disinfectants.
Impact of handwashing on the transmission of resistant
Improve effectiveness and adherence of handwashing
Environmental effects of hospital hygiene.
Effects of inadequate ward cleaning and poor hospital
environmental hygiene on the emergence and spread of antibiotic
Validated evidence for the impact of staffing
levels, patient movement, patient isolation, hospital design etc
on the spread of antibiotic resistance.
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