Download NECN dose banding guidelines version 2.0 Nov 15

GUIDELINES FOR THE DOSE BANDING OF
CANCER CHEMOTHERAPY
“Quality and safety for every patient every time”
Document Control
Prepared By
Issue Date
Approved By
S Williamson /
C Polwart
25/02/09
Chemotherapy
Group
29.6.11
C Polwart
20.02.13
C Polwart
3/11/15
Chemotherapy
Group
Chairs Action
Review
Date
Feb 2011
Version
Contributors
1.1 -1.3
Pharmacy
Group (NECN)
July 2013
1.4
Feb 2015
1.5
3/11/ 17
2.0
S Williamson
Comments/
Amendment
Updated title page format
and review date
Adjusted rounding limit to 6% to
facilitate logarithmic dose bands
Reviewed and updated noting
forthcoming national Dose
banding system added sections
6,4 & 6.5, updated section 9,
removed appendences,
For more information regarding this document, please contact:
North East Strategic Clinical Network
NHS England, Waterfront 4, Goldcrest Way,
Newcastle Upon Tyne, NE15 7NY
[email protected]
NECN dose banding guidelines version 2.0 Nov 15
Issue Date 03.11.15
Page 1 of 9
Expiry Date 03.11.17
Guidelines for the Dose Banding of Cancer Chemotherapy
Executive Summary
In order to meet the increasing demand for chemotherapy the North of England
Strategic Clinical Network (NESCN) and NHS England Commissioners recommend that
all Trusts introduce a system of standardised dose banding for prescribing and
dispensing selected chemotherapy drugs.
Dose banding should be undertaken before investing in staff and facilities to manage
capacity. Dose banding will allow use of commercially prepared/ stock items to
complement the individual aseptic dispensing by pharmacy used to prepare patient
ready chemotherapy.
This document gives guidelines for NESCN Trusts on introducing dose banding and
references a standardised system for dose banding for use in all Trusts in NESCN.
In 2015/16 NHS England is working to produce a National dose banded system with
standardised doses. Having an agreement national system could realise greater
benefits in terms of stock management and competitive tendering to manufacturers of
dose banded products. The new national system is expected to be put in place during
2016, at that point Trusts who have not implemented dose banding should adopt the
national system and those Trusts with alternative systems should, over time migrate to
the new system.
1
Background
1.1
What is dose banding?
Dose banding is a system whereby, through agreement with pharmacy and prescribers,
calculated doses of intravenous cytotoxic drugs are rounded up or down to predetermined standard doses. The maximum variation of the adjustment between the
prescribed dose and the banded dose issued to the patient will not be more than 6%. A
range of pre-filled syringes or infusions, manufactured by pharmacy staff or purchased
from commercial sources can then be used to administer the standard dose.
1.2
How accurate is dose banding?
As chemotherapy dosing based on body surface area BSA is not totally accurate 1, dose
banding to within approximately 6% of intended dose will not introduce additional
variance that could affect toxicity or clinical outcomes. The use of banded doses to give
doses within 5% of the prescribed dose was considered acceptable practice in a study
undertaken by UK oncology pharmacists and demonstrated acceptable in practice in
scotland2,3. However in guidance on logarithmic dose banding4 a 6% limit was agreed
as acceptable following a national project.
2
Benefits of Dose Banding
The benefits of dose banding and the use of pre-filled syringes are well documented
and include:

Reduction in waiting times for patients through improved pharmacy work flows,
e.g. facilitates preparation before blood results taken

Increased pharmacy capacity for chemotherapy

Facilitates pharmacy skill mix
NECN dose banding guidelines version 2.0 Nov 15
Issue Date 03.11.15
Page 2 of 9
Expiry Date 03.11.17

Allows external contractors to provide service

potential reduction of medicine waste by avoiding incomplete usage of the full
contents of a vial or ampoule when preparing individual doses

Reduces waste when treatments are deferred, due to ability to re-assign prefilled syringes if administration is cancelled
Dose banding must be undertaken before investing in staff and facilities to
manage capacity.
Dose banding of chemotherapy is already being implemented in a number of cancer
centres and units both within the NESCN and across the UK. Although there is a
common principle there can be variation in its application in practice, e.g. there are
various schemes using different ways of calculating bands. Ideally there should be
harmonisation of dose banding across the NESCN which would have benefits including:

For medical staff that travel between sites there will be consistency of dose banding
practice

Consensus on dose band nonograms will reduce the range of pre-filled syringe sizes
required. This provides an opportunity to improve cost-effectiveness through more
competitive pricing with the procurement of pre-filled syringes.

Pharmacy manufacturing units within NESCN will be able to offer a single set of
dose bands to Trusts.

A new national dose banding system is expected to be put in place during 2016, at
that point Trusts who have not implemented dose banding should adopt the national
system and those Trusts with alternative systems should, over time migrate to the
new system.
3
Drugs most suitable for dose banding
Not all cytotoxic drugs are suitable for preparation as pre-filled syringes, infusion bags
or infuser devices. The key determinant is extended stability, usually an expiry of 30
days or more. Drugs that are currently available with extended expiry include:

Cyclophosphamide syringes

Carboplatin Infusions

Doxorubicin syringes

5-Fluorouracil infusors

Epirubicin syringes

Gemcitabine Infusions

5-Fluorouracil syringe

Oxaliplatin Infusions

Methotrexate syringes

Irinotecan Infusions
These drugs compromise some common chemotherapy regimens used in NESCN e.g.
weekly/ Mayo 5-FU, FOLFOX and FOLFIRI, for colorectal; FEC and AC for Breast;
CHOP/ RCHOP for lymphoma; CE and Gem Carbo for Lung.
Dose banding has also been applied to other intravenous drugs such as paclitaxel,
rituximab and trastuzumab and can also be used for oral preparations e.g. capecitabine.
The national project is also looking at fixed doses to use for banding for commonly used
monoclonal antibodies, i.e. bevacizumab, rituximab based on their pharmacokinetics.
NECN dose banding guidelines version 2.0 Nov 15
Issue Date 03.11.15
Page 3 of 9
Expiry Date 03.11.17
4
Cost Implications
It is estimated that introducing dose banding will have minimal impact on the overall
cost of the Trust's oncology medicine spend. There is potentially a mark up in price for
drugs that have relatively cheap raw materials costs, e.g. 5-FU, Methotrexate. The
percentage increase in price is very small with drugs that have a high raw material cost,
e.g. gemcitabine, epirubicin. The ready made doses of these drugs are often
competitively priced against the raw material cost paid by Trusts.
In some instances the high cost drugs can be cheaper when purchased as dose bands
due to the buying power of the manufacturerer to negotiate discounted prices on raw
materials. Trusts in NESCN are advised to contact the leading manufacturers of dose
banded products and undertake a budget impact assessment based on quoted prices.
This is a competitive commercial area, use of local pharmacist contracting expertise is
strongly recommended, e.g. the regional specialist purchasing pharmacist David Cook.
There is an on-going (2015/16) regional tender which Trusts are advised to access
when complete.
Investment in dose banding, were appropriate, is likely to be cheaper in the first
instance than investing in new facilities or additional staff. It is however acknowledged
that investment may be necessary in some units.
Dose banding is beneficial to commissioners as it reduces the on-cost paid to Trust to
prepare ready-made doses, hence commissioners are willing to invest in dose banding
as a means of saving the health economy money. Commissioners will potentially be
able to negotiate incentives to introduce dose banding.
5
Suppliers
Some of the main manufacturers of pre-filled syringes for dose banding are listed below.
It is noted there are both commercial suppliers and NHS suppliers. Trusts must
undertake contracting as described above, however the NESCN strategy is to
recommend local NHS suppliers.
NHS suppliers
 Newcastle Hospitals NHS Trust Pharmacy
 Leeds Teaching Hospitals
 James Cook University Hospitals
Commercial suppliers
 Baxter Healthcare
 Calea UK Limited
 Dabour Healthcare
 Hospira (formerly Mayne Pharma)
 Qualsept UK
Disclaimer:
This does not represent a comprehensive list of suppliers nor does it in anyway
constitute an endorsement of any of the commercial suppliers.
NECN dose banding guidelines version 2.0 Nov 15
Issue Date 03.11.15
Page 4 of 9
Expiry Date 03.11.17
6.
Choice of Dose Banding Scheme
6.1
There are four types of dose banding schemes that can be used:
BSA Centred Dose Banding
 Bands are set in increments of body surface area, e.g. patient’s body surface
area is rounded up or down to one decimal place and a set dose band given for
that BSA, e.g. doxorubicin 50mg/m2 for patient of 1.73 m2, the BSA is rounded to
1.7 and a dose of 85mg given.
Drug Centred Dose Banding or ‘Target Dose’ Banding.
 The patient’s dose is prescribed as per BSA and then rounded up or down to the
nearest band e.g. doxorubicin 50mg/m2 for patient of 1.73 m2, the calculated
dose is 86.5mg. This falls in the 82.6mg to 87.5mg range for which a dose of
85mg is given.
Logarithmic dose banding
 Uses a logarithmic scale to achieve a consistent relationship between doses, i.e.
when doses are reduced by a consistent amount, e.g. 10% of previous dose to
allow precise dose adjustments to be made if required. The disadvantage is that
doses can be impractical to measure/prepare, e.g. 157.8mg.
Modified Logarithmic dose banding
 Uses a logarithmic scale to achieve a consistent relationship between doses, i.e.
when doses are reduced by a consistent amount, e.g. 10% of previous dose to
allow precise dose adjustments to be made if required, but the logarithmic doses
have been rounded to give practical doses that can be measured.
In practical terms it makes no difference to the patient which of these methods is used
to dose band. Within the NECN prescriber’s clinical practice is to round BSA to one
decimal place, therefore the first method was been chosen as it was perceived to be
most compatible with existing clinical practice.
6.2
Risk of double rounding
It is recognised that when adopting either dose banding scheme here is potential for
‘double rounding’. With the BSA centred scheme many of the bands chosen for each
BSA have been rounded and hence there is double rounding, rounding up or down of
BSA then rounding to the band. Similarly if adopting the Drug centred scheme double
rounding can occur if the prescriber has rounded BSA to give a dose higher/ lower than
the one based on exact BSA which is then rounded once more to the band.
The key to managing this risk is to validate the dose banding tables used and measure
the maximum percentage variance from the exact dose. The aim is to ensure doses
always fall within 5% of the original intended dose. The dose bands selected below will
always deliver a dose with 5% of the intended dose per BSA. There will be certain
occasions when a patients BSA falls exactly between the BSA bands that the variance
will be between 5% and 7.5%.
NECN dose banding guidelines version 2.0 Nov 15
Issue Date 03.11.15
Page 5 of 9
Expiry Date 03.11.17
6.3
Dose Adjustments and reductions for banded doses.
When a dose banded product is dose is reduced, e.g. for toxicity, there are a number of
approaches to changing the dose.




The first is to apply the dose adjustment to the mg/m 2 intended dose, recalculate
drug dose and then apply the dose band.
The second is to apply the percentage dose reduction to the original intended
calculated dose, before dose banding, recalculate drug dose and then apply the
dose band.
The third is to apply the percentage dose reduction to the banded dose,
recalculate and select new dose band.
The final approach is, if using a logarithmic based system, to move down one or
two bands to achieve a dose reduction that is approximately 20%.
In clinical practice it is probably most appropriate to dose reduce using the actual dose
the patient has received as the starting point for percentage dose reduction as this is
the dose that is causing toxicity to the patient, i.e. methods 3 or 4 above.
It is acknowledged that it is technically more accurate to calculate dose reduction based
on intended original dose, i.e. methods 1 or 2 above, and some clinical trials may
specify this. However in practical terms the method of dose reduction applied should be
that which is most meets the needs of a reduced dose for the patient, i.e. reduction in
toxicity whilst maintaining suitable dose intensity.’
6.4
Validation of dose bands chosen.
NECN has prepared an excel spreadsheet to validate the dose bands, the spreadsheet
calculates the range of variance from the original intended dose and demonstrates that
the 5% rule is intact for the majority of doses in the scheme (86%). The spreadsheet
highlights BSA dose where there is potential for a variance between 5% and 7.5% as
’amber’. 14% of doses in the scheme have potential for amber variance. At the
extremes of the dose band range there are 3 (1%) doses where the variance is between
7.5% and 10% highlighted as red. Banding should be avoided for these three doses.
6.5
Banding of monoclonal antibodies.
Work is on-going looking at the pharmacokinetics of monoclonal antibodies, with the
rational being that these can be dose banded with greater variation between bands,
10% rather than 5%. The 2015 Scottish dose banding guidance5 states
‘the link between therapeutic outcomes and reproducible dosing strategies for monoclonal
antibodies is difficult as classical tests of maximum tolerated dose may have no relationship to
activity as the targets for the antibodies may well have overwhelmed targets at much lower
doses. In addition in a number of clinical situations doses of monoclonal antibodies are fixed
without any adjustment for BSA or weight. The fact that there was greater uncertainty around
the dosing of monoclonal antibodies helped support agreement for a move to dose banding to a
10% variance with these agents across NHS Scotland’.
The NECN guidance does not currently include tables for monoclonal antibodies, but if
Trusts wish to dose band, 10% would seem acceptable variance.
NECN dose banding guidelines version 2.0 Nov 15
Issue Date 03.11.15
Page 6 of 9
Expiry Date 03.11.17
7
When is Dose Banding not recommended?
7.1
Children:
Advice of specialists within Paediatric Oncology and Haematology must be sought if
considering dose banding. Dose banding is not prohibited in paediatrics but it is rarely
used for a number of reasons. For example:
 Dosing in children is difficult up to 30kg/8-10 years. UKCCLG recommends a
range of dose reductions to BSA calculated doses for children < 12 months old.
 A 10kg child could be a large 9 month old or an underweight 14 month old.
 Most treatment is within clinical trials, banding is not approved in the protocols and
methods of drug administration have not been consistent between trials
 Impractically small dose increments may be needed between bands
 Sites preparing batches of dose banded chemotherapy for use in clinical trials
would need an IMP license
 Banding across the whole paediatric age range would result in an impractically
large number of dose bands
7.2
Cachexia and obesity:
Methods of individualised dose calculation may be more appropriate in severe cases.
7.3
Clinical Trials:
Dose banding can only be used in clinical trials with prior agreement of the trial chief
investigator and sponsor (preferably discussed during protocol development). With the
exception of pharmacokinetic trials, there is no sound reason to exclude dose banding
from trials which use BSA based dose regimens, provided effects on dose-limiting
toxicities are considered.
Pharmacy departments are advised to check with trial protocol and /or investigator if
dose banding is acceptable for each trial that is opened.
NECN dose banding guidelines version 2.0 Nov 15
Issue Date 03.11.15
Page 7 of 9
Expiry Date 03.11.17
8
Procedure for Dose Banding based on dose rounding
8.1
For the purpose of dose banding BSA shall be calculated to one decimal place
only. The range of BSAs of the nomograms will be from 1.4m 2 to 2.2m2. Note
pharmacists should check with prescriber when clinically verifying prescriptions
where dosing is based on values greater than 2.0 m2.
8.2
The pharmacist undertaking clinical verification of chemotherapy prescription
identifies drug suitable for dose banding, by consulting appropriate approved
dose banding tables.
8.3
If not already banded by the prescriber the prescription is amended and dose is
banded by the pharmacist according to the agreed table.
8.4
The pharmacist endorses any amendments to original prescription, e.g. doses
rounded for dose banding, with the date and their initials.
8.5
Drugs are supplied to the ward as combination of pre-filled syringes or infusion
bags for administration. Doses in syringes will often be supplied as a
combination of 2 to 3 syringes each containing a proportion of the total dose.
8.6
No more than 3 syringes should be supplied per dose. It must be noted that it is
actually easier fro nursing staff to administer smaller volume (less than 30mls)
syringe sizes, so there may be some instances where it is preferable to give
more than 3 syringes for one dose. Check with local nursing staff on their
preferences.
8.7
Stocks of dose banded products come pre-labelled with drug, strength, expiry
date and batch number. Pharmacy departments issuing dose banded products
will need to label the products with the patient name, ward, consultant and date
issued. Ideally this will be on the product and its outer wrap.
8.8
The dose banded drugs are issued to the ward for administration in the usual
fashion. There may be prescriptions where some products are banded and
some are aseptically prepared.
8.9
It is acceptable round doses that will be aseptically prepared to the suggested
bands within the scheme in the absence of stocks of prefilled syringes. It is
recognised that this reduces waste and increases chance of doses being reused
should patients not be fit to proceed with chemotherapy.
9
Implementation and Audit.
9.1
Out-sourced dose banded syringes/ infusion bags are unlicensed products
known as ‘specials’. As a result there is a need to undertake significant Quality
Checks on the product. There is no national standard for this process and
different trusts perform Quality Checks with different grades of staff at different
stages in the process. Those trusts that undertake the majority of the quality
check as part of the dispensing process report that they are making staff time
(and grade) savings compared to those who undertake an assessment at the
point of receipt of every batch
NECN dose banding guidelines version 2.0 Nov 15
Issue Date 03.11.15
Page 8 of 9
Expiry Date 03.11.17
9.2
It is therefore recommended that pharmacies using pre-filled syringes/ infusion
bags for the purpose of dose banding should complete accountability records for
the receipt and dispensing of syringes and ensure good practice for handling
unlicensed medicines. Factors to go consider include:

Involvement of local Quality Assurance QA advice on processes

Need for increased fridge space for storage of prefills

The range of syringe sizes should be chosen to ensure that all dose bands
can be delivered using no more than three syringes

Need to specify labelling requirements, light protective packaging, fill volume
limits and closure type for syringes, delivery schedule.

Cold chain integrity (both from supplier and on delivery within Trust as cold
chain needs to be maintained if unused doses are to be recycled)
9.3
It is recommended that Trusts undertake a review/ audit of prescribing of drugs
suitable for dose banding. Some regimens may be used in such low volume to
make dose banding not feasible. There needs to be regular use, i.e. more than
once per week prescribing to ensure that stocks will be used.
9.4
Trusts are also advised to monitor wastage of prefills used for dose banding.
Due to relatively short expiry date of the products careful attention needs to be
given to stock levels and stock turnaround.
9.5
The electronic prescribing system used in the network, chemocare, has a facility
to automatically dose band when prescribing. The method chemocare uses to
calculate the final is target dose based, rather than BSA based but is the
resulting recommended doses are consistent with the tables described above.
References
1
Body Surface Area as a basis for dosing of anti-cancer agents science, myth or
habit; Ratain MJ. J Clin Oncol. 1998. 16: 2297-9 Editorial
2
Dose- Banding of cytotoxic drugs: A new concept in cancer chemotherapy.
Plumridge RJ & Sewell G.J. Am J Health-Syst Pharm Vol 58 sep 15, 2001
3
Dose Banding at the Edinburgh Cancer Centre. MacLean et Al Pharmaceutical
Journal 17 May 03 p691-693
4
Toolkit: How to Implement Dose banding of Chemotherapy. 2008. Andrew
Gillian. Network Pharmacist (NELCN) on behalf of Cancer Network Pharmacists.
Available at http://www.bopawebsite.org/contentimages/publications/Toolkit_Ver_3.0_FINAL.pdf
5
SCOTTISH ONCOLOGY PHARMACY PRACTICE GROUP, Guidelines for Dose
Banding of Systemic Anti-Cancer Therapy Development and Governance
Framework, June 2015
Acknowledgements
With Thanks to Mary Maclean, Regional Cancer Care Pharmacist, West of
Scotland Cancer Network for permission to adopt parts of the Scottish Cancer
Pharmacy Group :Guidelines For Dose Banding of Cancer Chemotherapy June
2005. Updated in 2015.
NECN dose banding guidelines version 2.0 Nov 15
Issue Date 03.11.15
Page 9 of 9
Expiry Date 03.11.17