Transcript Document

NCRN Chemotherapy and
Pharmacy Advisory Service
(CPAS) – 3 years on...
Stephen Kelly
Oncology and Haematology Clinical Trials Pharmacist /
CPAS Committee Representative
The National Cancer Research Network is part of the National Institute for Health Research
Abbreviations for
this presentation:
BSA
CCLG
CPAS
CTAAC
FSC
GCP
GFR
HTA
IRAS
MHRA
The National Cancer Research Network is part of the National Institute for Health Research
BSA
– Body Surface Area
CCLG – Childrens Cancer and Leukaemia Group
CPAS – Chemotherapy and Pharmacy Advisory Service
CTAAC – Clinical Trials Awards and Advisory Committee
FSC
– Feasibility Study Committee
GCP
– Good Clinical Practice
GFR
– Glomerular Filtration Rate
HTA
– Health Technology Assessment
IRAS
– Integrated Research Application System
MHRA – Medicines and Healthcare products Regulatory Agency
MRC
– Medical Research Council
MREC – Multicentre Research Ethics Committee
NCRN – National Cancer Research Network
NCRI
– National Cancer Research Institute
NCRN OSG - National Cancer Research Network Operational Steering Group
NIHR
– National Institute for Health Research
NRES – National Research Ethics Service
OPCSC – Oncology, Pharmacy and Chemotherapy Standardisation Committee
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Chemotherapy and Pharmacy
Advisory Service (CPAS)
• Background
• Why and how to use the service
• The review process, some findings and responses
• Guidelines
• Examples
• The future of CPAS
The National Cancer Research Network is part of the National Institute for Health Research
The National Cancer Research Network is part of the National Institute for Health Research
Background
• Pharmacists frequently reported practical and
organisational issues in clinical trials
– many put patients at unnecessary risk of errors and
increased workload for pharmacy and nursing staff.
• NCRN and NCRI recognised drug
management as an important aspect of clinical
trial protocols and noted many inconsistencies
• An ad hoc group formed to review oncology
protocols
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Background
• OPCSC established in Dec 2003
– Oncology Pharmacy and Chemotherapy
Standardisation Committee
– Chair: Professor Mahesh (Max) Parmar with
support provided by NCRN Coordinating Centre
(Leeds and London).
– Open membership
• OPCSC report to the NCRN Operational
Steering Group (OSG)
• Originally 12 core members
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• The remit of the Committee is to:
– Consider trials to be adopted by the NCRN and
review draft/near final versions of protocols
– Provide support to investigators and others about
medicines related issues in oncology trials.
– Review published evidence to help standardise
chemotherapy administration in clinical trials
• particularly addressing generic issues such as dosage
modifications in organ dysfunction, calculations of body
surface area, modifications for obesity etc
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• Protocol reviews were initially on a voluntary basis
• Mandatory for a pilot period of 12 months
– (1 Sept 2007 to 31 Aug 2008)
• Oct 2008 it was agreed that CPAS would continue to
review protocols, due to the very positive feedback
received, on a mandatory basis for another 2 years
with a less formal interim review at 1 year.
• CRUK had been very supportive of CPAS and NIHR
CRN (formerly UKCRN) are interested in developing
the process beyond cancer protocols.
• Foster links with the CCLG (Childrens Cancer and
Leukaemia Group)
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Chemotherapy and Pharmacy
Advisory Service (CPAS)
• CPAS currently have 19 Committee and 32
Panel members
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CPAS - Why use it?
• The aim of the service is to help trials across
the whole NCRN portfolio run as smoothly and
safely as possible.
• There are issues which make trials difficult to
implement at local level and which lead to
delays in set up:
–
–
–
–
dose adjustments
dose capping/dose banding
inconsistent hydration schedules
missing pharmacy information
- supply of drugs
- safe administration of
chemotherapy
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CPAS - Why use it?
• CPAS aims to help investigators through these
problems also achieving some consistency.
• Investigators who have had protocols
reviewed in this way have reported that it was
a helpful and constructive process which
reduced the number of protocol amendments
that were required during the trial.
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CPAS - When to submit the
protocol?
• A protocol can be submitted any time after approval for
funding and no later than 2 months prior to MREC
submission.
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Protocol Development
Timeline
POSSIBLE
TIMELINE
(- 1 to 3
months)
Application submitted to
CTAAC/FSC/HTA
0
Approval letter issued by
CTAAC/FSC/HTA *
0-12 months
Development of protocol
and trial preparations
}
12 months
approx
Submission to MREC
14 months
approx
MREC approval
At any stage during
this period of
approx. 12 months,
the protocol is
submitted to the
Advisory Service.
Comments will be
returned to the
Investigator within
6 weeks.
* (containing guidance on submitting the protocol to the Chemotherapy and Pharmacy Advisory Service)
The National Cancer Research Network is part of the National Institute for Health Research
CPAS - When to submit the
protocol?
• A protocol can be submitted any time after approval for
funding and no later than 2 months prior to MREC
submission.
• A protocol can be reviewed once the drug treatment
section is more or less complete, or the trial team can
approach CPAS prior to the protocol being finalised in
order to get their advice
• Protocols are submitted to the NCRN Clinical Trials
Liaison Officer in Leeds
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CPAS - Review Process
• Each protocol is reviewed by at least one
pharmacist, one nurse and usually one
medical oncologist
• Reviewers are given 2 weeks to review each
protocol, the lead reviewer has to return the
completed review within 6 weeks of
submission
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CPAS - Review Process
• Protocols are reviews against
template/checklist of questions.
• 12 sections with a total of 110 questions
– topics include nomenclature, supportive
medications, monitoring, supply (inc funding
implications), administration, accountability etc.
• Reviews are encouraged to add any
relevant comments not covered by
standard checklist
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CPAS - Review Process
• Whether or not the recommendations are
incorporated into the final protocol is at the
Chief Investigator’s discretion.
• Recommendations will be classed as either
major or minor, depending on their significance
– CPAS reserves the right to negotiate about any
initial non-acceptance of major recommendations
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CPAS - Summary of Findings
• Some major findings:
– Dose banding table of gemcitabine with doses expected to be
measured to 2 decimal places – not very practical
– Depocyte® stated as a brand of cytarabine for iv injection,
however this brand is for intrathecal use only (this occurred in
more than one protocol)
– 2mg/L Magnesium and 20mmol /L Potassium in the
posthydration bags insisted on by protocol
• (2mg/L = 0.008mmol Magnesium per litre)
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CPAS - Summary of Findings
• Common findings:
– No information on which drugs are IMP’s and therefore which need
accountability
– Information missing on infusion times, stability of a product, diluents,
use of non-PVC infusion bags and giving sets
– Information missing on what to do if a patient vomits following a
dose or misses a dose
– No advice given for supportive medicines e.g. pre-meds,
antiemetics, hydration etc
– No information on frequency of re-calculation of BSA or formula to
use, re-calculation of GFR and method of GFR calculation
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CPAS - Summary of Findings
• Common findings (cont):
– Use of brand names instead of generic
– Use of drugs not available in the UK e.g. Acetaminophen
– No reference to dose banding
– Information missing on haematological and biochemical
monitoring
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CPAS - Feedback
• Comments back from investigators following CPAS
reviews:
– “Thank you for the comprehensive review. We do appreciate the
effort that went in to this and would like to thank the reviewers.”
– “As with any protocol, several rounds of review had already taken
place but the [CPAS] review did highlight several points/issues that
had not been mentioned previously....I would recommend the
[CPAS] review to my colleagues for other chemotherapy trials in the
future.”
– “We found the review process useful and were appreciative of the
speed it took the committee to review the protocol. ”
– “Thank you very much for your excellent, and indeed highly
comprehensive notes on the study protocol”
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CPAS - Standard Protocol
Template
• CPAS was asked to produce a
standard protocol template to
help investigators with the
pharmaceutical contents of trial
protocols.
• This document is now available
on the NCRN website
(www.ncrn.org.uk) entitled
“Guidance on the drug-related
content of clinical trial protocols”
version 2.0
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Chemotherapy and Pharmacy Advisory
Service (CPAS)
Pharmacy Information Manual
• CPAS have produced a
pharmacy information
manual
– covering all the essential
information required by
pharmacy departments.
• This document can be
located on the CPAS
section of the NCRN
website
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Chemotherapy and Pharmacy Advisory
Service (CPAS) - Wright Formula
Background
• CTAAC now requires all its new trials containing
Carboplatin to use the Wright Formula rather than
the Cockcroft-Gault equation to calculate GFR.
• CPAS asked to produce validated spreadsheet(s) for
using the Wright Formula and CTAAC would then
encourage it’s inclusion as an appendix in future
protocols involving carboplatin.
• There are 4 different formulae
– after discussions CPAS will produce validated spreadsheets
for both ‘without CK’ (Jaffe and enzymatic)
The National Cancer Research Network is part of the National Institute for Health Research
The National Cancer Research Network is part of the National Institute for Health Research
Chemotherapy and Pharmacy Advisory
Service (CPAS) - Wright Formula
Current status
• The spreadsheet(s) were developed and the Jaffe serum version
has been validated
• Currently no data has been forwarded to validate the enzymatic
serum version, therefore it has been agreed to go ahead with
implementing the Jaffe
• Spreadsheet(s) will appear on the NCRN and MRC website to be
used as an appendix in protocols
– Appearing in some newer protocols e.g. TNT
• CPAS has liased with manufacturers of computerised prescribing
systems (Chemocare and Varian) to adopt the Wright Formula
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Chemotherapy and Pharmacy
Advisory Service (CPAS) - Queries
• Any pharmacy related queries, or requests for advice,
in relation to NCRN portfolio studies, are forwarded to
the CPAS Pharmacy Advisor.
• The queries range from specific study related
questions to trial questions in general e.g.:
– Use of electronic signatures on prescriptions
– Use of the Wright Formula in specific trials
– Carmustine being discontinued
– Monitoring visits and archiving by Clinical Trial Units
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Chemotherapy and Pharmacy Advisory
Service (CPAS) - NCRN Pharmacy Advisor
• Main point of contact and liaison between researchers and the
NCRN Chemotherapy and Pharmacy Advisory Service.
• Responsible for providing professional secretarial support to
review team leaders and their teams, and to the Advisory Service
as a whole.
• Ideal opportunity for a motivated individual with an interest in
clinical trials who wishes to extend their pharmacy expertise to
this national initiative
• Agenda for Change Band 7 (0.5wte)
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The Future of CPAS
• Demonstrate effectiveness of the service through audit
of CPAS intervention
• Ultimate goal of CPAS is to become redundant through
the implementation of detailed guidance documents to
Investigators and by creating a system of national
‘experts’ available to answer ‘ad hoc’ questions
• Please encourage your local researchers to make use
of the help and guidance that has been made available
by CPAS (www.ncrn.org.uk)
The National Cancer Research Network is part of the National Institute for Health Research
NCRN website www.ncrn.org.uk
On the home page select CPAS and this will open our page, half-way down you will see the documents previously
mentioned, that can be download as either word or PDF files.
The National Cancer Research Network is part of the National Institute for Health Research