43703 ABPI clinical brief

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43703 ABPI clinical brief Powered By Docstoc
					        Clinical trials
           - developing
             new medicines
   In the search to understand, prevent and treat    The prime sponsor of medicines research in
   disease, clinical trials involving healthy        the UK is the pharmaceutical industry, but
   volunteers and patients play an essential role.   research charities, Research Councils and the
   Their aim is to evaluate new medicines or a       NHS also undertake medicines research.
   combination of medicines, as well as other
                                                     A new medicine has to demonstrate its safety,
   types of therapies, to determine their
                                                     quality and efficacy through a series of
   potential benefits and safety.
                                                     rigorous clinical trials in order to obtain a
   •   Nearly a quarter of the world’s top 100       licence (called a marketing authorisation)
       medicines were developed in the UK.           and be available to the general public.
   •   Attracting clinical trials to the UK is       Clinical trials consist of four phases – the first
       important for patients, for the NHS,          three occur before a licence is granted and
       for academia and for the nation’s             the last is conducted as a post-licensing
       economy.                                      phase. Each phase varies in size, character
   •   Studies have demonstrated that                and focus:
       patients taking part in clinical trials           Phase 1 primarily determines how a
       have better health outcomes than
                                                         medicine works in humans and helps to
       those not involved in a trial.
                                                         predict the dosage range for the
   •   Clinical trials mean that NHS patients            medicine, and involves healthy
       have potential early access to the                volunteers.
       newest forms of treatment together
       with the highest standards of medical         •   Phase 2 tests efficacy as well as safety
       care.                                             among a small group of patients (100-300)
                                                         with the condition for which the medicine
   •   Clinical trial participants must have             has been developed.
       given their informed consent and
       confirmed they have received and               •   Phase 3 involves a much larger group
       understood fully information before               (1000-5000) of these patients which will
       they can take part in a trial.                    help determine if the medicine can be
                                                         considered both safe and effective.
   •   A company must provide all results
       from the trials when applying for a
       licence for a new medicine.                   DEVELOPING A PROTOCOL
                                                     Having decided clinical development is
The Association of the                               justified, clinical researchers will need to
British Pharmaceutical Industry                      develop protocols for the necessary trials. A
12 Whitehall, London SW1A 2DY                        protocol is a study plan which is not only
Telephone: +44 (0)20 7930 3477                       designed to answer specific research
Fax: +44 (0)20 7747 1411                             questions but also has the safety of
E-mail:                             participants in mind. Used as the basis for all
Website:                             clinical trials, protocols determine:
ABPI Scotland
                                                     •   Who can participate.
9 Queen Street, Edinburgh EH2 1JQ
Telephone: 0131 247 3688                             •   The schedule for tests, dosages and other
Fax: 0131 225 4865                                       details of the study.
ABPI Cymru Wales                                     •   The trial duration.
Floor 4, Caspian Point 2, Pierhead Street,
Cardiff Bay, Cardiff CF10 4DQ
Telephone: 02920 454297
Fax: 02920 454298
THE BENEFITS OF CLINICAL RESEARCH TO                expertise in the clinical area under
THE UK                                              investigation; they are directly approached by
Nearly a quarter of the world’s top 100             a sponsor or have expressed an interest in
medicines were developed in the UK,                 being involved.
which is a leading centre for clinical trials.      Any NHS clinical researcher who acts as an
However, trials are increasingly conducted          investigator for a pharmaceutical company-
around the world, in order that greater
                                                    sponsored clinical trial will receive payment
numbers of patients and different ethnic
                                                    from the company, via their NHS trust, for
groups can be included in a study.
                                                    the work they have done – much as with
Attracting clinical trials to the UK is             government-sponsored Medical Research
important for patients, for the NHS, for            Council trials, where a research grant will
academia and for the nation’s economy.              cover the cost of paying for staff and for the
Their presence means that NHS patients
have potential early access to the newest           In the UK, under the Research Governance
forms of treatment, together with the highest       Framework, all receipts go through an NHS
standards of medical care. But these studies        or primary care trust and any benefits of
are also important because they bring               more than £25 must be declared.
investment into academic research centres in
the UK. Researchers are provided with the
opportunity to be at the centre of the
development of the latest medicines,                TRIAL APPROVAL
benefiting the quality and depth of science          With doctors appointed, clinical trial sponsors
research in this country.                           must meet strict regulatory requirements.
The cost of developing a new medicine is            This means they need to demonstrate to the
about £500 million – 60 per cent of which is        regulatory authority – the UK Medicines and
spent in clinical trials – and the full             Healthcare products Regulatory Agency
development process takes 10-12 years.              (MHRA) – that they have a reasonable
                                                    hypothesis upon which to base the study and
New medicines are selected from a range of
                                                    that pre-clinical results warrant further
many thousands of substances with the
potential to treat the targeted condition.
Fewer than one or two compounds in 10,000           Details of all trials conducted within the UK
tested actually make it through the process         must also be approved by independent
and are eventually authorised for use in            research ethics committees before work
patients – a potential new medicine may be          starts. Additionally, sponsors must receive
rejected at various stages in the development       approval from the NHS trust in which the
process on safety, efficacy or quality grounds.      trial is being conducted.
A new medicine arises from a series of              Ethics committees review and advise on
pre-clinical tests – using techniques which         whether proposals for research studies meet
identify potentially beneficial new                  required ethical and scientific standards.
compounds, like computer modelling, high-           These reviews are designed to protect people
speed computer technology and tissue                participating in studies.
culture studies. It is then tested in a series of   Ethics committees are completely
scientific studies using animals before any          independent of industry and are at
trials involving humans.                            liberty to reject a clinical trial. They are
                                                    established and funded by the NHS, while
                                                    remaining health authority based. Typically
FINDING AN INVESTIGATOR                             consisting of between 12 and 18 members,
Once the protocol has been established, a           they include lay people, medical
trial then needs investigators (clinical            professionals, and scientists.
researchers) to carry out the study.
Investigators are doctors who work with a
team to monitor and care for the patients           SELECTING VOLUNTEERS
involved in the studies.
                                                    The first stage in which humans are used in
They usually come from universities or from         the study of a new medicine is Phase 1.
within the NHS – including GPs – and                Participants in these trials are usually healthy
become involved because they have specific           volunteers under 45 years.
Participants in Phases 2 and 3 are patients         Throughout the process, data is collected and
with the medical condition for which the new        recorded for analysis to evaluate the patient’s
medicine is being tested. However, like Phase       response. However, only the investigator and
1 participants, they can only take part in a        his team will know the identity of the patient;
clinical trial on a voluntary basis.                the sponsoring company will have only a
                                                    patient code number to bring all the
Additionally, these volunteers – whether
                                                    individual patient data together.
they are healthy participants or patients
– can only participate in clinical trials if
they have given their informed consent              CONTROL GROUPS
and have confirmed they have received                Most trials will involve some sort of
and fully understood information about              comparison for the medicine being tested.
the trial. They are also free to withdraw           This means that in many clinical trials, while
from a trial at any time without                    one group of patients will be given an
prejudice to their continuing care.                 experimental medicine or treatment, a
A number of studies have demonstrated               control group is given either an existing
that patients taking part in clinical trials        standard treatment (comparator) for the
have better outcomes than equivalent                illness or a placebo – a dose that looks like
patients not involved in a trial. This is           the medicine being tested but, in fact,
because the trial patients are receiving            contains no medical ingredients.
close and ongoing medical care.                     Regulatory authorities have complete power
Guidelines have been set on the processes           to require a comparison to be carried out and
involved in clinical trials on medicines by the     suggest either a placebo or specific
International Committee on Harmonisation            comparator product.
(ICH) – a series of joint agreements between        It is more common for such a control group to
the regulatory authorities and the                  use a standard existing treatment for the
representative pharmaceutical industry              studied condition as its comparator substance.
groups in Japan, Europe and the US. The             However, as many trials are multinational, it
principles of these guidelines, known as Good       may be that the comparator is not always the
Clinical Practice (GCP), will be enshrined in       most commonly used treatment in all of the
UK law for implementation from May 2004.            countries involved in the trial. The choice of
Patients taking part in Phases 2 and 3 are          which medicine to use as a comparator can
invited to participate in three main ways:          be influenced by many factors, including the
                                                    comparative sizes of the different countries’
1. Advertising is mostly placed at a local
                                                    trials groups, the location of the medicine’s
level – using both newspapers and radio
                                                    pre-clinical development or the intended
stations or through hospital and GP surgery
                                                    location for a licensing application.
notice boards.
                                                    Placebo trials tend to be most common in the
2. Patient groups may also be a means
                                                    US, which uses them more than the UK. The
through which patients learn about clinical
                                                    Food and Drug Administration (FDA), the US
trials. These groups are often well informed
                                                    regulatory authority, prefers the use of placebos
about research being conducted in their area
                                                    to comparator substances because it is often a
of interest.
                                                    more rigorous way of determining the
3. An invitation is the most common                 difference between results. In Europe, however,
method of recruitment – usually through             most ethics committees favour the use of
doctors who are involved in, or aware of, a         comparators, which they see as more ethical.
trial that would be of relevance to, and in the
interest of, a patient.
                                                    REGULATION AND MONITORING
Before a participant enters a trial, a trial team
                                                    All trials must be performed in line with ICH
will check and record his/her health. Each
                                                    GCP principles or they will be rejected by the
participant will then be closely monitored
                                                    regulators. Clinical trials in the UK are also
throughout the study and will continue to
                                                    conducted according to a series of guidelines
have some contact from the research team
                                                    and regulations laid down by government
after the trial is finished.
                                                    authorities, including the NHS Research
A potential treatment will be constantly            Governance Framework and the guidance
monitored in an attempt to optimise its             provided by ethics committees – all of which
effectiveness and reduce any side-effects.          are underpinned by the Declaration of Helsinki.
If a patient has concerns about any aspect of     When a licence application is submitted, a
a trial, they have numerous avenues through       company must provide all results – both
which they can lodge a complaint. These           positive and negative – from the trials. A
include ethics committees; the research           summary of this information is available to
centre’s administration; their GP; patient        the public through European Public
groups; the research sponsor; and the ABPI.       Assessment Reports (EPARs), produced by
                                                  the European Medicines Evaluation Agency
TRIALS AFTER A LICENCE                            (EMEA) on the granting of a licence.

Phase 4 trials are conducted after a medicine     In line with this, the ABPI has established a
has been granted a licence. In these studies a    special website for companies to publish
medicine is prescribed in an everyday             information about clinical trials conducted
healthcare environment which allows results       for licensed medicines. The website provides
to be developed using a much larger group of      a readily accessible list and information
participants. Phase 4 trials are performed to:    about which trials have been carried out and
                                                  in which therapeutic areas. The site is not
•   Develop new treatment uses for the            only intended for healthcare professionals,
    medicine.                                     but will also be of use to patient organisations
•   Compare with other treatments for the         and the public.
    condition.                                    Details are supplied on a voluntary basis by
•   Determine the clinical effectiveness of the   companies and can be found at
    medicine in a much wider variety of 
    patient types in conditions of “real life”.
Safety is a major part of Phase 4 trials, which   CONCLUSION
often involve several thousand patients so        The UK has traditionally been a leading
that more rare side effects, if any, may be       nation in medicines development and clinical
detected.                                         research, largely by providing the highest
In addition, because larger numbers of            standards of scientific research and medical
patients can be studied, doctors are able to      care. The treatments discovered and
monitor quality of life issues, and other         developed are vital because they have helped
benefits of the medicine may become evident.       save lives, reduced suffering and improved
                                                  the quality of life for millions of people all
As with all phases of UK clinical trials,         over the world.
there are strict rules regarding the way
in which Phase 4 studies are conducted.
In particular, this means they cannot be
used for anything other than a scientific
purpose – for example, as a promotional
tool for the product.

After a trial is complete, doctors will seek to
publish the information in a medical journal.
This is primarily so that other doctors and
scientists can benefit from the research findings
and be aware of potential new treatments.
When a trial fails to show positive
results, it normally does not make
interesting news and medical journals
often do not publish them. The industry
believes that these ‘negative’ data should
be made available and so the majority of
the trials not accepted in peer reviewed
medical journals are published in other
ways through supplements to journals,
clinical reports, conference posters,
abstracts and on the internet.                                                       BSC Print 4k Oct 03

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