GUIDELINES FOR THE DOSE BANDING OF CANCER CHEMOTHERAPY

Transcription

1 GUIDELINES FOR THE DOSE BANDING OF CANCER CHEMOTHERAPY Quality and safety for every patient every time Document Control Prepared By Issue Date Approved By Review Date Version Contributors Comments/ Amendment S Williamson / C Polwart 25/02/09 Chemotherapy Group Feb Pharmacy Group (NECN) July Updated title page format and review date C Polwart Chemotherapy Group Feb Adjusted rounding limit to 6% to facilitate logarithmic dose bands C Polwart 3/11/15 Chairs Action 3/11/ S Williamson 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 england.nescn@nhs.net NECN dose banding guidelines version 2.0 Nov 15 Page 1 of 9

2 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 scotland 2,3. However in guidance on logarithmic dose banding 4 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 Page 2 of 9

3 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 Page 3 of 9

4 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 Page 4 of 9

5 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/m 2 for patient of 1.73 m 2, 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/m 2 for patient of 1.73 m 2, 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 mg. 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 Page 5 of 9

6 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 guidance 5 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 Page 6 of 9

7 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 Page 7 of 9

8 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 2.2m 2. Note pharmacists should check with prescriber when clinically verifying prescriptions where dosing is based on values greater than 2.0 m 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 Page 8 of 9

9 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 : 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, Dose Banding at the Edinburgh Cancer Centre. MacLean et Al Pharmaceutical Journal 17 May 03 p Toolkit: How to Implement Dose banding of Chemotherapy Andrew Gillian. Network Pharmacist (NELCN) on behalf of Cancer Network Pharmacists. Available at 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 Updated in NECN dose banding guidelines version 2.0 Nov 15 Page 9 of 9