James Raftery: End of life drugs – what premium? Pt 2

Having recommended NHS use of sunitinib for renal cancer, the appraisal committee of the National Institute of Health and Clinical Excellence (NICE) issued separate draft guidance for consultation, recommending against the use of bevacizumab, sorafenib, and temsirolimus, which – along with sunitinib – had been rejected for renal cancer in 2008.

Bevacizumab (Avastin) was judged not to meet the end of life criteria because of the size of the patient group for which it is licensed. Besides renal cancer bevacizumab is licensed for cancers of the lung, colon, rectum, and breast.
<p>Although not licensed for macular degeneration (age related, wet) bevacizumab is widely used in place of the much more expensive ranibizumab (Lucentis).

The judgment that bevacizumab failed the small patient group test on the basis of being licensed for multiple indications makes it clear that indications cannot be “salami sliced”. Instead the cumulative population for all licensed indications will be considered, an important finding since many of these drugs, notably the monoclonal antibodies, have multiple indications.

Both temsirolimus and sorafenib were deemed to meet the end of life criteria with most plausible cost per QALY estimates of £102k and £66k, respectively. For each, “the additional weight that would need to be assigned to the original QALY benefits in this patient group for the cost effectiveness of the drug to fall within the current threshold range would be much too great”. The gain in quality of life with sorafenib in the company model was put at 0.189 (0.737 in progression free survival and 0.548 for progressed disease). These values were based on an unpublished survey of physicians. They are just over double the 0.08 gain attributed to sunitinib.

The decision in favour of sunitinib at around £50k per QALY but against sorafenib at £66k per QALY should not be interpreted as indicating a new threshold between these values. This is because the decision was based on the weight that would have to be given to the quality of life in each instance to reduce the cost effectiveness to usual threshold. Sunitinib qualified because the quality of life gain from treatment in the model was small (0.08) while the equivalent for sorafenib was relatively large (0.189) Even with a relatively large gain in quality of life, sorafenib still had a higher cost per QALY than sunitinib. The qualify of life gain is unlikely to differ between these two drugs. If the quality of life gain for sorafenib was used for sunitinib, it would reduce the cost per QALY for the latter by around half. The committee considered that an increased utility difference between the health states (“progression free” and “progressed”) was plausible for sunitinib but not for sorafenib.

I think these judgements indicate that the new end-of-life rules have been carefully constructed by NICE to enable its independent appraisal committee to recommend some but not all drugs that qualify. For renal cancer it recommended the most cost effective and rejected the rest.

What is the premium? My guess here is around 2, based on the effect this would have on the most plausible cost/QALY estimate for sunitinib and the clinician based value used for sorafenib.

I think the ruling that bevacizumab did not qualify under the end-of-life rules because of being licensed for other indications is important. NICE is already scheduled to appraise three of the drugs considered here (bevacizumab, sunitinib and sorafenib) for other indications. Following the precedent outlined here, these drugs seem unlikely to qualify for any premium under the end-of-life rules.

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.