Transcript Clinical Trials - Amazon Web Services

Janyne Afseth
Research Network Manager
Scottish Cancer Research
Network
Describe the drug development process
Review the ethical framework that
underpins clinical research
Discuss current trends in cancer research
– and where we are going
Discuss the role of the nurse in clinical
trials
Behind the scenes
Trial management
team
Statistician
Ethics Committees
Sponsors, Funding
Sources
Lab scientists
Patient
Regulatory Groups
Regulation,
Management
and approval
Clinic
Doctors, Nurses
NHS Laboratory
Staff
 Research
study
 Conducted
 Designed
 Uses
in human volunteers
to answer specific questions
scientifically controlled methods
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Evaluate the efficacy of new drug therapies and
drug side effects (combinations of drugs, new ways of
giving treatment, new types of treatment)
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Evaluate the use and effectiveness of
interventions, i.e.. surgical or diagnostic
procedures (Scans, screening tests,surgical procedures)
Evaluate programs of cancer prevention and
control (vitamins,foods, drugs)
Evaluate the psychological impact of treatment on
patients (quality of life studies)
 Quest
to advance knowledge often benefits
research subjects.
 Patients may directly benefit from advanced
therapies or indirectly from the satisfaction
of contributing to society
 Research benefits society as a whole
 Safe ways of new drug/novel agent
development
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Lind (1747) comparative study using citrus in the
treatment of scurvy (6 arms)
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19th century utilized basic trial concepts in the
development of of drugs and vaccines
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Early 20th century studies focused on the prophylaxis
and treatment of infectious diseases
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1948 first placebo, controlled randomised trial
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1960’s – present over 50 new drugs have been
developed for treatment of cancer
 Gold
standard for evaluating new
practices and therapeutic agents in
medicine
 The reason is that investigators
could introduce bias and invalidate
conclusions by the manner that
they assigned patients to
treatment groups
 Question
to be answered needs to be
defined
 Study endpoints
 Study then designed to test this
hypothesis using statistical methods
 Investigators must evaluation also
evaluate what is clinically significant (i.e
likely to change practice)
Ensure consistency
 Define a specific plan of action
 Contain the following elements:
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 Introduction
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Eligibility Criteria
Schedule of events
Toxicity evaluation/dose reduction
Kinetic sampling information
Drug storage and admixture information
Evaluation of response/follow up
 Phase
I maximum tolerated dose
 Phase II determines drug
activity/response
 Phase III compared to standard therapy
 Phase IV post marketing studies
 Medicines
and Health Care Products
Regulatory Agency (UK) (MHRA)/FDA
(USA)
• Must give authorisation for trials
• Can inspect sites for compliance with research
legislation
• Ultimately decide if the evidence for usage in
an indication can be licensed
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1948 NHS committee set up to look at limiting prescriptions
1960s Thalidomide sparked the formation of the Committee on
the Safety of Drugs
1968 Medicines Act provided for a comprehensive system of
licensing affecting manufacture, sale, supply and importation of
medicinal products.
MHRA also controls clinical trials, advertising, quality control,
manufacture of unlicensed products and control of imports
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Nuremberg Code (1947) basic moral, ethical, and legal
concepts for experimentation. Developed as a result
of experiments done in the Nazi concentration camps.
Helsinki Declaration (1964) Recommendations to
guide the physician in biomedical research involving
human subjects. Includes basic principles, medical
research combined with professional care, and nontherapeutic biomedical research guidelines
 10-12
years and £550 million to develop
a new medicine
 20% of world’s top medicines were
discovered and developed in UK
 £9 million invested in UK R&D daily
-www.abpi.org.uk
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Drug Companies
• £500 million annually
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International/national Trial Organizations
• EORTC
• NCRI
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Government Funding
• Medical research council (MRC)
• Department of Health (England)/CSO (Scotland)
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Cancer Charities
• Cancer Research UK (largest cancer research organisation
outside US)
• The Leukaemia Research Fund
•
 All
will have ‘patient selection criteria’
 Doctors and nurses identify patients
through multidisciplinary meetings and
by screening clinic lists
 Some patients will self refer
 Must pass all eligibility criteria to go on
(i.e. bloods, scans etc.
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New treatment may work, drug not available outside
of trial
Improving cancer treatment for other patients
Close monitoring
Patients treated in a centre where clinical trials are
done do better than people with a similar stage and
type of cancer
 Altruism
 Family
pressure
 Unwillingness to “give up”
 Hope of benefit
 Input into care
 They think the treatments may be better
 Fear
of being allocated to control group
 Too far to travel
 Desire to have Dr. choose treatment
 Guinea Pigs
 Complex Consent process
 Disliked focusing on disease
 Participation
is voluntary
 No coercion or inducement
 Information verbally and in writing
 Time to consider
 Support and communication
 1940-50s
the effect of mustard gas as
therapeutic agent investigated.
 50-60s combination chemotherapy
 Bone marrow transplant, hormonal agents
(Tamoxifen – 1970s)
 Biological agents
 Allows
selectivity with less toxicity
 As the understanding of how cancer cells
survive, thrive and spread can allow
researchers to target these mechanisms.
 Vascular
Epithelial Growth Factor (VEGF)
inhibitors
• Avastin, Thalidomide
 PARP
inhibitors
 Epidermal Growth Factor Receptor
(EGFR) inhibitors
• Herceptin, cetuximab, Iressa
 Proteasome
• velcade
Inhibitors
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Angiogenesis is the formation of new blood vessels from
pre-existing vasculature
Angiogenesis is highly dependent on the VEGF signalling
pathway
• VEGFR-2 is the most important VEGF signalling
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pathway for angiogenesis
VEGF is frequently overexpressed in cancer and is
associated with poor prognosis
Without a blood supply, tumours do not grow larger than
1–2mm
As tumours grow they become hypoxic, which leads to
the up-regulation of angiogenic factors such as VEGF
• Stimulates the production of new vasculature
PlGF
VEGF-A
VEGF-B
VEGF-A
VEGF-C
VEGF-D
VEGF-C
VEGF-D
Blood vascular
endothelial cell
VEGFR-1
VEGFR-2
VEGFR-3
Lymphatic
vascular
endothelial
cell
Proliferation, vascular permeability, migration, survival
PlGF, placental growth factor
VEGFR, vascular endothelial growth factor receptor
Ligands
Monoclonal
antibody
VEGF-A
VEGF-B
VEGF-C
VEGF-D
Anti-VEGF
antibodies
Blood vascular
endothelial cell
Lymphatic
vascular
endothelial
cell
VEGFR-1
VEGFR-2
VEGFR-3
Ligands
VEGF-A
VEGF-B
VEGF-C
VEGF-D
VEGFR-TKIs
Lymphatic
vascular
endothelial
cell
Blood vascular
endothelial cell
VEGFR-TKI
VEGFR-1
Inhibition
X
X
VEGFR-2
X
Angiogenesis
VEGFR-3
X
Lymphangiogenesis
VEGFR-TKI, vascular endothelial growth factor receptor-tyrosine kinase inhibitor
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Inhibiting VEGF signalling
• inhibits growth of new tumour vessels
• decreases vascular density, diameter and
permeability
• may induce regression of recently developed tumour
microvessels
Therapeutic inhibition of tumour angiogenesis should be
effective in a broad range of solid malignancies
Target tissue is in direct contact with blood, facilitating
drug delivery
 Patient
advocate
 Patient educator
 Direct care provider
 Coordinator
 Administrator
 Data manager
The potential for unexpected side effects is
high with the pattern not yet established
 Supportive care – what works with
chemotherapy may not be the same for newer
agent
 Synergy of drugs is often unknown
 Information of to larger multidisciplinary team
is essential
 Patient involvement and time commitment
often may be much greater with the associated
education needs
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Scientific discovery
 New drug development
 Improved procedures
 Benefits to patients
 Economic development
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