Time To Stop Hiding Behind The Skirts of NICE—The UK Renal Cell Carcinoma Expert

Time to stop hiding behind the skirts of NICE—the UK Renal Cell Carcinoma Expert Group 

Barry Hancock, John Anderson , Tim Eisen, Martin Gore, Robert Hawkins, Paul Nathan, Poulam Patel, Alastair Ritchie, John Wagstaff

Introduction

In an era of evidence-based medicine, treatment choices should be clear cut. Our economy, however, precludes such an idealistic philosophy. Naive notions of provision of ‘best-available care’ are hence replaced, in the UK NHS at least, with complex mechanisms to ensure equality of care within the constraints of available funding.

The impact of NICE on new drug uptake

The National Institute for Health and Clinical Excellence (NICE) was established in 1999 to meet the need to standardise healthcare across England and Wales and, later, Northern Ireland. The institute’s remit is to provide national guidance on treatments and care, based on the best available clinical and cost-effectiveness evidence, in order to abolish discrepancies in prescribing nationwide. Its current level of success—moderate!

While prescribing of those drugs positively appraised by NICE has become more uniform,¹ the backlog of new treatments yet to be considered, or even considered for referral by the Department of Health, renders the UK a country slow to formally introduce potentially life-saving drugs compared with the rest of Europe and the USA; in cancer at least, this slow uptake may go part of the way to explaining our still relatively poor position in the international league table for cancer survival rates.³ Furthermore, while NICE’s ability to review and recommend new treatments and technologies is potentially limitless, the amount of money available to honour the promise to make these treatments available within a 3-month window to all who need them is finite. In the not too distant future, the model will need to be revised.

Use of drugs prior to NICE appraisal

In the meantime, what of those new drugs that are not yet NICE appraised? In the absence of guidance, every local funding authority is individually responsible for establishing the criteria that they will use to determine whether a drug not approved by NICE is available in their patch. It is of importance however, that clinicians are involved in the decisions made about drug availability pre-NICE. To that end, strategic health authorities and primary care organisations cannot withhold funding for treatments solely on the grounds that guidance from NICE is unavailable or yet to be published; an open dialogue must be maintained between those treating patients and those responsible for funding that treatment.

With primary care trusts (PCTs) bowing under the financial burden of meeting the costs of those drugs that have already received a positive opinion, many will not consider non-NICE approved treatments for routine funding. It then becomes extremely difficult to obtain funding for these drugs—some PCTs allocate a budget every year from which requests for funding can be met; others allocate money on a case-by-case/exceptional-case basis. Frustratingly, exact information about who does what is not centrally collected, and the onus is on the clinician who wants to use a non-NICE approved drug to take the time to make a case, on behalf of their patient, to present to the commissioners via their directorate, or to put together a business case for inclusion in the local development plan, depending on local protocol. Such varying approaches to a common problem inevitably result in the unpredictable and disparate prescribing patterns (and the associated inequity of spend on cancer drugs) that it was postulated NICE would obviate. A mechanism of communication, or if not that, transparency, and hence reduced discrepancy between trusts, would surely represent a step forward. Going further, is the possibility of a lead group of PCTs working together to establish strict guidelines for the national limited use of particular drugs prior to NICE appraisal so ridiculous? Importantly, as the number of new drugs flooding onto the market continues to rise year on year, PCTs will need to be increasingly creative in delivering solutions—be that through disinvestment where appropriate, increased focus on preventions or community-based care or otherwise—for their funding.

The problem of the ‘postcode lottery’ in healthcare, it appears, has not been solved by NICE. Worryingly, the presence of NICE also stands to accelerate the development of a two-tier healthcare system, where well-informed patients who can afford to pay gain access to new treatments prior to NICE approval, while those dependent on the NHS are forced to wait for effective treatments to jump the regulatory hurdles. As well as geographical discrepancies in prescribing, a degree of discrepancy in the process, according to disease, is also apparent—the stories of two drugs illustrate this point well (though they possibly represent extreme cases); the first for breast cancer—a ‘sexy’ disease backed by high-profile lobby groups—and the second for renal cell carcinoma.

Sunitinib and sorafenib uptake

Lapatinib (Tyverb, GlaxoSmithKline), an oral tyrosine kinase inhibitor for the treatment of breast cancer, was placed on the NICE assessment list before a licence was granted. Originally due to be reviewed in October 2007, the NICE assessment process then had to be postponed because the UK licence has taken longer to be granted than expected (UK approval now granted in June 2008). Contrast this scenario with that of the oral targeted agents sorafenib (Nexavar, Bayer) and sunitinib (Sutent, Pfizer). These oral drugs were licensed over the summer of 2006 by the European Medicines Evaluation Agency for use throughout the EU for the treatment of advanced or metastatic renal cell carcinoma. Their licensing represents excellent news, since their clinical effectiveness far outweighs that of alternative treatments (namely interferon alpha and interleukin 2),^3-9 which are more difficult to administer and make only a small impression on the course of the disease.¹⁰ Both have been adopted as standards of care in many countries worldwide. However, without NICE endorsement (not expected until 2009—after the review of lapatinib will have taken place), uptake in the UK of these two novel drugs has been poor for the reasons stated above. The pressure on clinicians to prescribe sorafenib and sunitinib will continue to grow, and, with no effective alternative treatment options available, arguments against their use will be increasingly difficult to muster or, indeed, defend. As such, those treating renal cell cancer are compelled to fight for access to sorafenib and sunitinib for their patients. With approximately 6,600 patients a year developing kidney cancer in the UK, and half of those either presenting with or going on to develop metastatic disease, this is quite an undertaking.¹¹

The UK Renal Cell Carcinoma Expert Group’s recommendations

The UK Renal Cell Carcinoma Expert Group recommends that sunitinib and sorafenib should be made available for the treatment of appropriate patients with metastatic renal cell carcinoma. Such endorsement, along with the evidence base for the drugs and active petitioning of the government by patient lobbying groups, will mean that those who can afford to pay will pay, while those who cannot will continue to receive drugs that are known to be relatively less effective—a way needs to be found to expedite availability of these treatment options, and others like them, in the NHS before the injustices of postcode prescribing and two-tier healthcare provision damage the confidence of the public. Their understanding is that funding for an important therapeutic option is being restricted because of bureaucracy.

Future prospects

There are no immediate solutions to the problems outlined above, and a step-wise approach is postulated to be the most appropriate. In terms of improving the timeliness of NICE assessment of drugs, the recommendation made in the Cancer Reform Strategy¹² at the end of 2007, and echoed by the House of Commons Select Committee earlier this year, is to be welcomed. They call for NICE to publish guidance for the use of all new drugs in time for their launch. Along with a drive by NICE to encourage disinvestment into technologies that are no longer cost effective and the institute’s perceived heightened interest in risk-sharing strategies, optimism about the system slowly begins to return.

The government, and those responsible for prioritising spend at a local level, should not hide behind the skirts of NICE. It needs to stand back and recognise that, while it is an effective framework for a solution to the problem of post-code prescribing and inequalities in healthcare provision, the institute and the way that it works must continually evolve, in line with the changing healthcare environment and the increase in cost and pace of introduction of new therapeutic options. Otherwise, NICE will find itself at the heart of the very problems that it was established to solve.

Acknowledgment

We have, in the past, received honoraria from Pfizer and Bayer.

References

1. Department of Health. Usage of cancer drugs approved by NICE: report of review undertaken by the National Cancer Director. Gateway number 7124. London: DoH, 2006.
2. Verdecchia A, Francisci S, Brenner H et al. Recent cancer survival in Europe: a 2000–02 period analysis of EUROCARE-4 data. Lancet Oncol 2007; 8: 784–796.
3. Motzer RJ, Michaelson MD, Redman BG et al. Activity of SU11248, a multitargeted inhibitor of vascular endothelial growth factor receptor and platelet-derived growth factor receptor, in patients with metastatic renal cell carcinoma. J Clin Oncol 2006; 24: 16–24.
4. Motzer R J, Rini B, Bukowski RM et al. Sunitinib in patients with metastatic renal cell carcinoma. JAMA 2006; 295: 2516–2524.
5. Motzer RJ, Hutson TE, Tomczak P et al. Phase III randomized trial of sunitinib malate (SU11248) versus interferon-alfa (IFNα) as first-line systemic therapy for patients with metastatic renal cell carcinoma (mRCC). J Clin Oncol  2006; 24: LBA3.
6. Motzer RJ, Hutson TE, Tomczak P et al. Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med 2007; 356: 115–124.
7. Ratain MJ, Eisen T, Stadler WM et al. Phase II placebo-controlled randomized discontinuation trial of sorafenib in patients with metastatic renal cell carcinoma. J Clin Oncol 2006; 24: 2505–2512.
8. Eisen T, Bukowski RM, Staehler M et al, for the TARGET Clinical Trial Group. Randomized phase III trial of sorafenib in advanced renal cell carcinoma (RCC): Impact of crossover on survival. J Clin Oncol 2006; 24: 4524.
9. Escudier B, Eisen T, Stadler WM et al, for the TARGET Clinical Trial Group. Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med 2007; 356: 125–134.
10. Shaheen PE, Bukowski RM. Targeted therapy for renal cell carcinoma: a new therapeutic paradigm. Cancer Invest 2006; 24: 640–656.
11. Lipworth L, Tarone RE, McLaughlin JK. The epidemiology of renal cell carcinoma. J Urol 2006; 176: 2353–2358.
12. Department of Health. Cancer reform strategy. London: DH, 2007.