Background

The UK’s ageing population is likely to see the number of new cancers being diagnosed rise by 20% in 2021, from 318,000 seen in 2010 and the total cost of treating these cancers, to the National Health Service (NHS), the private and voluntary sector is predicted to be GBP 15.3 billion [1].

There has been a huge increase in the number and complexity of novel agents being introduced into clinical practice to treat cancer over the last 10 years. An analysis published by the Pharmaceutical Research and Manufacturers of America notes that there are over 981 new cancer therapies, which are either in clinical trials or under review by Food and Drug Administration (FDA) in the US, including 121 for lung cancer, 117 for lymphoma and 111 for breast cancer [2]. These new medicines come at a cost, but it is not clear if spending more on health care may even increase the five-year survival [3, 4].

In times of austerity (particularly in the NHS) [5], it is important that there is a clear evidence base for introduction of new medicines.

Health Technology Assessment

The use of Health Technology Assessment (HTA) to inform the managed entry of new medicines is rising in the UK and internationally. HTA is a multidisciplinary field of policy analysis that examines the medical, economic, social and ethical implications of the incremental value, diffusion and use of medical technology in health care [6]. HTA is intended to provide a bridge between the world of research and the world of decision-making.

In England and Wales, the National Institute for Health and Clinical Excellence (NICE) provides advice to commissioners and clinicians alike by producing guidance documents and HTA, many of which apply to cancer medicines. Commissioners in England are mandated to fund NICE technology appraisals, with a positive NICE opinion, within three months of publication. However, to date, NICE guidance has not been timed to coincide with the time many cancer medicines have gained their marketing authorisation in the UK. This has led to a situation referred to as ‘NICE blight’, which describes the time delay between licensing and NICE approval, where no funding is in place to use these cancer medicines [7, 8].

The London Cancer New Drugs Group (LCNDG), has provided guidance for cancer medicines, but funding has not been in place for implementation of their recommendations [9].

The overall aim of the LCNDG [10] is to facilitate consistency of approach in London, UK, by informing the managed entry of new drugs in cancer treatments and to promote the cost-effective and equitable provision of all medicines used in cancer management. With objectives to make recommendations on new cancer drugs taking account of evidence for clinical effectiveness, cost, likely service impact and to identify and prioritize new drugs and new indications for existing drugs to be considered by the group. The pan-London prioritization exercise for new cancer regimens is used as the main resource for prioritizing the treatments to be included in the work programme of the group.

LCNDG publishes reviews providing for each one a critical appraisal of available literature, a summary of clinical data, clinical outcome in relation to current UK standard of care, a toxicity assessment, financial impact and a summary of issues for local consideration.

Prioritization of cancer medicines

In 2007, commissioners in primary care trusts (PCTs) in the South East London Cancer Network (SELCN) recognised there was no process in place to inform their commissioning of new cancer medicines. Consultants would apply to PCTs for individual patients for whom they would need access to new ‘unfunded’ medicines, as this appeared to be the only mechanism to gain funding. These applications are called independent funding requests (IFRs). IFR panels have to make difficult decisions on funding as often the resources available are insufficient to meet legitimate calls on their use [10]. This has led to reporting of ‘post code lottery’ stories in national and local media. In 2007, the number of IFR applications to PCTs was rising rapidly in SELCN. Commissioners approached the SELCN management team to devise a process for prioritization of new cancer regimens for 2008–09.

A working group was set up and chaired by the SELCN medical director—a consultant in public health medicine. The group consisted of a medical oncologist, a haemato-oncologist and a network pharmacist and developed a scoring tool to be used to prioritize cancer medicines and tested it using drugs that had already been appraised by NICE, those with both positive and negative decisions, to ensure that the criteria and scoring within the tool would differentiate effectively, by the score assigned, between those medicines which would be likely to be approved or declined by NICE.

The scoring tool

The scoring tool, see Figure 1, was split into two domains, where a numerical score was assigned for clinical effectiveness and a letter to indicate the strength of the evidence that demonstrated the clinical benefit.

*Figure 1 pending to upload.

The domain of effectiveness included: the magnitude of benefit–outcome measures including, for example, overall survival or progression free survival, quality of life, unmet need and cost-effectiveness expressed as quality-adjusted life-years.

The strength of evidence was assigned as follows:
A: ≥ 2 good quality randomised controlled trials
B: 1 good quality randomised controlled trial
C: comparative phase 2 data
D: non-comparative data
U: unpublished data

The highest score possible was 20A, good evidence which demonstrated good clinical benefit over and above current standard treatment and lowest score 0A, good evidence to demonstrate poor clinical benefit.

The prioritization process

The following sequence of events took place in order to develop a list of medicines, ranked in order of the scores assigned:

• Lead oncologists and haemato-oncologists were invited to identify medicines on the horizon, likely to be licensed over the coming 18 months.
• Assessment panels chaired by the public health consultant were held where oncologists, pharmacists and lay representatives scored each application, using the most up-to-date data available for the indication requested.
• A seminar was held which was attended by with consultant oncologists, pharmacists, commissioners and patient representatives, to validate the scores assigned to the applications received.
• The output from the seminar was ranked into a list, with those scoring more highly at the top and those with lower clinical benefit and evidence at the bottom. The list was colour coded to indicate whether the drugs would be recommended to be funded by the commissioners, once a full positive review had been completed by the LCNDG, see Table 1 for detail of colour coding and funding recommendations.
• The financial impact of those medicines recommended was then calculated and reported to the commissioners.

*Table 1 pending to upload.

Following successful implementation of the prioritization process in 2008–09, SELCN was asked to roll the process out across London, UK, for the following year. This would cover a patient population of GBP 7.6198 million (mid-2008 estimate, Office for National Statistics), 30 acute hospitals and 31 PCTs. At this time there was inequity of routine baseline commissioning funding for cancer medicines across the five cancer networks. Four drugs and indications which had been approved by the LCNDG and were routinely funded in SELCN were not universally routinely funded across all five cancer networks London, UK, in 2008–09, these are summarised in Table 2.

*Table 2 pending to upload.

Figure 2 shows an example of the colour coded ranked medicines and indications for London, UK. Green, blue and light green highlighted drugs and indications would be recommended to commissioners for funding. It was recognised that the scoring tool was a crude tool, which would essentially put drugs and indications into a ranked order. In circumstances where evidence for use of a particular drug or indication was intended to demonstrate non-inferiority or a preferred toxicity profile, for the new indication the tool was often unable to differentiate these circumstances effectively. Therefore, the ‘blue’ category was introduced in order to highlight such indications to recommend for funding. Equally, it was recognised that for rare drugs and indications that a lower level of evidence to support the use of the drug may be appropriate. In these circumstances they were highlighted in light green.

*Figure 2 pending to upload.

In August 2009, NICE issued supplementary advice to appraisal committees, where ‘end of life criteria’ would be used to inform their recommendations [13]. The appraisal committee would be able to consider whether treatment was indicated for patients with a short life expectancy, normally less than 24 months and whether there was sufficient evidence to indicate that the treatment offers an extension to life, normally of at least an additional three months, compared to current NHS treatment and the treatment was licensed or otherwise indicated, for small patient populations. Although amber drugs were not routinely recommended for funding, they were highlighted as being potentially likely to meet NICE ‘end of life criteria’, so it was possible to highlight the financial implications of this for commissioners.

The implementation of a definitive process for making recommendations to commissioners for funding of new cancer medicines has resulted in a dramatic reduction in the number of IFR applications made to PCTs in SELCN. As demonstrated in Figure 3, two years after introducing a prioritization process, the number of IFRs in SELCN fell by half; this is in a background of steeply rising numbers of applications..

*Figure 3 pending to upload.

Over subsequent years, similar processes for prioritization of cancer medicines have been adopted by many other cancer networks across England. The scoring tool has been reviewed each year the prioritization process has been run, incorporating comments from clinicians, to ensure the detail remains fit for purpose, for example, additional sections for toxicity and cost have been added.

Introduction of the cancer drugs fund

The white paper ‘Equity and excellence: liberating the NHS’ Department of Health, July 2010 introduced an interim Cancer Drugs Fund (ICDF) of GBP 50 million which would be available to fund cancer medicines and would help patients get the cancer drugs their doctors recommend [5]. The Cancer Drugs Fund (CDF) of GBP 200 million per year for three years was then made available for each year for three years from April 2011, this was planned to bridge the gap until the introduction of value-based pricing in 2014. National guidance for the implementation of the CDF was issued in March 2011 and revised guidance issued in April 2012 [11, 12]. Each of the 10 strategic health authorities in England was tasked with the implementation of this fund for their population.

In London, UK, the CDF allocation was GBP 30.4 million and implementation of the fund built on the existing prioritization process and developed a policy whereby cohorts of drugs and indications were identified to produce a London Cancer Drugs Fund (LCDF) list. This required the LCNDG to review the NICE guidance over the previous five years to identify drugs which had been declined on ‘cost-effectiveness’ grounds, in addition to do this the ‘amber drugs’ from the 2011–12 prioritization round were incorporated into the LCDF list of medicines and indications which would be funded. The LCNDG agreed that a minimum two-month clinical benefit should be demonstrated for medicines to be included in the CDF list [14]. The prioritization process now informs the work plan of the LCNDG on an ongoing basis.

Consultants apply to the fund for individual patients for each indication using a specific ‘tick box’ form for that indication, where criteria for use have been developed using the summary of medical characteristics for the individual drug and the eligibility criteria of the primary study demonstrating clinical benefit for that drug. The forms have been hosted in cancer network websites [15].

The London CDF list has been implemented and maintained by the five London cancer network pharmacists with responses to applications being approved within 48 hours. The list is amended at the bimonthly LCNDG meetings and remains dynamic, as the content changes in line with new evidence and publication of reviews by LCNDG, where new medicines are added or removed—for instance as the move into standard commissioning processes when NICE approves them.

In 2011, the prioritization process for 2012–13, reviewed 45 drugs and indications, five were already on the LCDF list, seven drugs have been added to the LCDF list and a further seven remain on the LCNDG work plan. The ranked list also highlighted ten drugs and indications, where the data were not yet published. It was therefore possible to highlight that as data matures, the ranking of these medicines may change, if for instance the results of ongoing studies are published.

The pharmacist’s role

Implementation of the prioritization process has been coordinated and led by lead cancer network pharmacists in London, UK, by working closely with cancer clinicians and supported by the regional Medicines Information Department at Guy’s and St Thomas’ NHS Foundation Trust, who prepare the clinical reviews for discussion at LCNDG meetings.

Pharmacists contribute to clinical discussion at LCNDG meetings and are responsible for the ongoing management of CDF, development of LCDF lists, administration and communication of applications, approval of individual applications against criteria for use, ongoing audit of uptake from LCDF, defining and recording predicted uptake of CDF using ‘clinical trial data’ and collating actual uptake data in relation to the CDF. The pharmacist is able to ensure consistency of application of the prioritization tool, so that different drugs and indications are assessed in an equitable manner.

Summary

HTA is an important part of the managed entry of new cancer medicines and the cancer pharmacist has an integral role in this process, working closely with cancer clinicians and commissioners, using their skills of independent critical appraisal in addition to their clinical expertise in relation to cancer medicines and a complete working knowledge of patient treatment pathways across all tumour types.

The prioritization of cancer medicines to inform the commissioning of new cancer medicines and uptake of the CDF in London, UK, has been directly implemented by lead cancer network pharmacists working as a team with their medical colleagues.

The cancer pharmacist has an independent role to advise and implement the managed entry of new cancer medicines.

Acknowledgements

The author would like to note that the work presented here would not have been possible without the support of Mr Alastair Whitington, Network Director, Dr Jamie Ferguson, Consultant in Public Health, cancer network pharmacists in London, Mr Rajinder Nijjar, Mr Dermot Ball, Ms Pauline McCalla and Ms Susan Kilby, the membership of the London Cancer New Drugs Group chaired by Professor Adrian Newland, Mr David Erskine, the Director of the London and South East Medicines Information Centre based at Guy’s and St Thomas’ NHS Foundation Trust and his team.

Conflict of interest

Ms Jacky Turner has received sponsorship to attend conferences and/or attended advisory boards for the following companies for which payment has been received: Amgen Ltd, AstraZeneca UK Ltd, Bristol Myers Squibb Pharmaceuticals Ltd, Celgene Ltd, Eli Lilly & Co Ltd, Merck Serono Ltd, Merck Sharp & Dohme Ltd, Novartis Pharmaceuticals UK Ltd, Pierre-Fabre Ltd, Pfizer Ltd, Roche Products Ltd and sanofi-aventis Ltd.

Author

Jacky Turner, BSc, MMedSci, MRPharmS
Macmillan Principal Pharmacist Oncology & Haematology
Guy’s and St Thomas’s NHS Foundation Trust
Lead for South East London Cancer Network
4/F, Management Offices, Bermondsey Wing
Guy’s Hospital
Great Maze Pond
London SE1 9RT, UK

References

1. Laing & Buisson. BUPA. Cancer diagnosis and treatment: A 2021 projection. c2011 [cited 2013 Mar 13]. Available from: www.bupa.com/media/355766/cancer_diagnosis_and_treatment_-_a_2021_projection_-_final.pdf
2. Grogan K. Nearly 1,000 cancer drugs in development in USA. Pharma Times [homepage on the Internet]. 2012 June 1 [cited 2013 Mar 13]. Available from: www.pharmatimes.com/article/12-06-01/Nearly_1_000_cancer_drugs_in_development_in_USA.aspx
3. Drum K. Do other countries control health costs better? The Economist. 2011 June 9 [cited 2013 Mar 13]. Available from: www.economist.com/blogs/democracyinamerica/2011/06/health-reform-0.
4. Sant M, Allemani C, Santaquilani M, Knijn A, Marchesi F, Capocaccia R, EUROCARE Working Group. EUROCARE-4. Survival of cancer patients diagnosed in 1995–1999. Results and commentary. Eur J Cancer. 2009 Apr;45(6):931-91.
5. Department of Health. Equity and excellence: liberating the NHS [homepage on the Internet]. 2010 July [cited 2013 Mar 13]. Available from: www.dh.gov.uk/en/Publicationsandstatistics/Publications/PublicationsPolicyAndGuidance/DH_117353.
6. International Network of Agencies for Health Technology Assessment. HTA Resources [homepage on the Internet]. 2009 May 15 [cited 2013 Mar 13]. Available from: http://inahta.episerverhotell.net/HTA/.
7. Littlejohns P, Garner S, Doyle N, Macbeth F, Barnett D, Longson C. 10 years of NICE: still growing and still controversial. Lancet Oncol. 2009 Apr;10(4):417-24.
8 Haycox A. Does ‘NICE blight’ exist, and if so, why? Pharmacoeconomics. 2008;26(12):987-9.
9. Gray H. Terms of Reference London Cancer New Drugs Group. 2010 March [cited 2013 Mar 13]. Available from: www.nelm.nhs.uk/en/Communities/NeLM/LCNDG/.
10. Stout D. NHS Confederation 2008. Priority setting: managing independent funding requests. 2008 [cited 2013 Mar 13]. Available from: www.nhsconfed.org/Publications/Documents/Priority%20setting%20managing%20individual%20funding%20requests.pdf.
11. Department of Health. The cancer drugs fund: guidance to support operation of the cancer drugs fund in 2011–12 [homepage on the Internet]. 2011 March 24 [cited 2013 Mar 13]. Available from: www.dh.gov.uk/en/Publicationsandstatistics/Publications/PublicationsPolicyAndGuidance/DH_125445.
12. Department of Health. The cancer drugs fund Guidance to support operation of the cancer drugs fund in 2012–13 [homepage on the Internet]. 2012 Apr 23 [cited 2013 Mar 13]. Available from: www.dh.gov.uk/en/Publicationsandstatistics/Publications/PublicationsPolicyAndGuidance/DH_133682.
13. National Institute for Health and Clinical Excellence. Appraising life-extending end of life treatments [homepage on the Internet]. 2009 Jul [cited 2013 Mar 13]. Available from: www.nice.org.uk/media/E4A/79/SupplementaryAdviceTACEoL.pdf.
14. National Health Service. Cancer drugs fund [homepage on the Internet]. c2012 [cited 2013 Mar 13]. Available from: www.london.nhs.uk/what-we-do/our-current-projects/cancer-drugs-fund.
15. South East London Cancer Network. Chemotherapy, cancer drugs fund documents. c2012 [cited 2013 Mar 13]. Available from: www.selcn.nhs.uk/content/dynamic.asp?id=869&dynamic_id=88&sn=Cancer%20Drugs%20Fund%20documents.