The National Institute for Health and Clinical Excellence (NICE), the UK drugs watchdog, is currently appraising the use of four drugs—bevacizumab, sorafenib, sunitinib, and temsirolimus—for the treatment of advanced or metastatic renal cell cancer. NICE has decided to split this appraisal in two, in order to get guidance out to the NHS as quickly as possible. Its advice for the appraisal of “end of life” drugs installed a “greater weight” for quality adjusted life years (QALYs) in the later stages of terminal diseases, subject to four conditions:

• Life expectancy less than 24 months,
• Gain from treatment of at least 3 months,
• Small patient population, and
• No alternative treatment with comparable benefit available through the NHS.

These new rules, a curious mix of rule of rescue, orphan disease, and first in class, did not increase the cost/QALY threshold but instead specified a premium based on the quality of life of patients whose survival was extended. This was limited to “the full quality of life anticipated by a healthy individual of the same age”. The advice did not specify how great this premium might be, but its first application provides an indication.

NICE’s appraisal committee recommended NHS use of sunitinib for renal cancer explicitly due to the new rules and not due to any change in price since price changes had been included in its earlier negative appraisal of the same drug. In the first appraisal, the drug’s manufacturer, pharma giant Pfizer, had estimated the cost per QALY at £72k, and NICE’s independent experts at £105k. Updating the company model for more recent trial results reduced the estimate to around £50k. Since all these estimates were well above NICE’s higher threshold of £30k, sunitinib would be rejected unless it qualified for the end of life rules. According to the committee, it qualified because the number of patients was estimated at 4000, life expectancy was less than 2 years, and the gain in survival greater than 3 months. It considered sunitinib a “step change” improvement compared with interferon alpha and noted that 20% of patients and public had supported this in consultation.

The issue then was the most plausible cost effectiveness estimate, assuming the extended survival period is experienced at the full quality of life anticipated for a healthy person of the same age. The quality of life values used in the manufacturer’s model were 0.70 before treatment and 0.78 after treatment implying a small gain of 0.08 (or 8%), based on the pivotal trial. The QALY scale for quality of life runs from 0 (dead) to 1 (full health). Given the maximum quality of life score of 1, and the value pre treatment of 0.70, the maximum gain from treatment would be 0.3, or almost 4 times the difference of 0.08 in the manufacturer’s model. If all else can be assumed equal, using this maximum gain could reduce the cost per QALY by almost four. Regardless of which cost effectiveness estimate was used, this would be well within below the £30k threshold. The committee “considered what additional weight that would need to applied to the original QALY benefits for the drug to fall within the current threshold range”. It “concluded that while it might be at the upper end of any plausible range in this case there was a significant step change in treating a disease for which there is currently so little to offer patients”. On this basis it “concluded that sunitinib as a first line treatment for advanced and/or metastatic renal cell carcinoma could be recommended as a cost effective use of NHS resources”.The committee went on to recommend research on the quality of life in the extended survival period for patient treated with sunitinib.

Several points are notable.

First, the new rules apply to the quality of life of additional months and not directly to the cost/QALY threshold, which officially remains unchanged. I am not sure how tenable the distinction between the threshold and the quality of life value will prove in practice. So far journalists have do not seem to have accepted the distinction.

Second, I think some indication was provided as to the premium. The premium would have to be around two to reduce the most plausible cost per QALY of £50k by half to £25k (to be compared with sorafenib in next blog).

Third, by focusing on quality of life in those extra months from sunitinib, the appraisal committee was able to recommend research on this which may enable it revisit the issue when the results of any such research become available.

Fourth, the guidance on sunitinib clarified the interpretation of the criterion no alternative treatment available through the NHS. For sunitinib in renal cancer the alternative was interferon alpha-2a, not best supportive care. The criterion no alternative treatment has been made less restrictive. How much less requires consideration of the draft guidance the Committee issued on the other three renal cancer drugs (see next blog).

James Raftery is a health economist with several decades experience of the NHS. He is professor of health technology assessment at Southampton University. A keen “NICE watcher,” he has provided economic input to technical assessment reports for NICE but has never been a member of any of its committees. The opinions expressed here are his personal views. He welcomes comments to his blog.