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The National Cancer Research Network is part of the National Institute for Health Research

NCRN Chemotherapy and Pharmacy Advisory Service

(CPAS) – 3 years on...

Stephen KellyOncology and Haematology Clinical Trials Pharmacist /

CPAS Committee Representative

Abbreviations for this presentation:

BSA

CCLG

CPAS

CTAAC

FSC

GCP

GFR

HTA

IRAS

MHRA

MRC

MREC

NCRN

NCRI

NCRN OSG

NIHR

NRES

OPCSC


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



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


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


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

• 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



• 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)


• CPAS currently have 19 Committee and 32 Panel members



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 - supply of drugs– dose capping/dose banding - safe administration of

chemotherapy– missing pharmacy information


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.


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.


Protocol Development Protocol Development TimelineTimeline

Application submitted to CTAAC/FSC/HTA

Approval letter issued by CTAAC/FSC/HTA *

Development of protocol and trial preparations

Submission to MREC

MREC approval

POSSIBLETIMELINE

(- 1 to 3 months)

0

0-12 months

12 months approx

14 months approx

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)


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 Liz Gardner, NCRN Portfolio Manager, in Leeds ([email protected])

mailto:[email protected]


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


• 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




• 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


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 sulphate and 20mmol posthydration bags insisted on by protocol

• (2mg/L = 0.008mmol Magnesium per litre)



• 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


• 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



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”


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

http://www.ncrn.org.uk/



Pharmacy Information Manual

• CPAS have produced a pharmacy information manual which will cover all the essential information required by pharmacy departments.

• This document can be located on the CPAS section of the NCRN website


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)


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 (once fully validated) and only continue with the enzymatic version if requested

• Once validated and approved the spreadsheet(s) will appear on the NCRN and MRC website to be used as an appendix in protocols


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

Chemotherapy and Pharmacy Advisory Service (CPAS) - NCRN Pharmacy Advisor

• The purpose of this post is to act as the main point of contact and liaison between researchers and the National Cancer Research Network (NCRN)’s 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)



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)


NCRN website www.ncrn.org.ukOn 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.

http://www.ncrn.org.uk/

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