HEDS is part of the School of Health and Related Research (ScHARR) at the University of Sheffield. We undertake research, teaching, training and consultancy on all aspects of health related decision science, with a particular emphasis on health economics, HTA and evidence synthesis.

Monday, 25 June 2012

PAS, end-of-life, ‘novel action’, ‘elaborate extrapolation’ and still too expensive to mention

In an ACD, NICE have decided not to recommend Vemurafenib (Zelboraf, Roche Products) for the treatment of unresectable locally advanced or metastatic BRAF V600 mutation-positive melanoma.  The manufactuer’s basecase is £56,000 per QALY (including PAS) which increases to £130,000 when the ERG introduced what it considered to be more plausible methods.  The ERG wasn’t HEDS this time, but the work is worth noting all the same for several reasons.

In terms of extrapolation of survival, things have changed dramatically.  The simple single curve models of a few years ago have gone, however, Roche are criticized for over-elaboration:

“The method of extrapolation used by the manufacturer to project OS from the observed BRIM 39 data (up to 10-12 months) out to 30 years is extremely elaborate, involving three different sources, six time phases and multiple assumptions each of which is vulnerable to challenge. The ERG notes the industry involved in its development but is concerned that resultant extrapolation appears to lack a coherent underlying and compelling logic connecting the natural history of the disease, the mode of action of the interventions, and the accumulated experience of clinicians and patients. In summary, it focuses on accurate description of the available information at the risk of compromising the credibility of any projections produced.”

HEDS and CHE are in the process of completing a review of extrapolation methods for the Medical Research Council and will be making recommendations shortly.  Vemurafenib looks like an interesting case study for inclusion and further work.

Other points about this decision are of note.  The ACD gives special attention to innovation, even quoting Sir Ian Kennedy’s view of when innovation should be given additional weight in a decision.  There is even a tacit appreciation of the oral formulation improving QoL – “the Committee considered that the oral formulation and symptomatic improvement attributable to vemurafenib had been captured in the higher utility value assigned to the progression-free survival health state for those receiving vemurafenib”.  However, having used every opportunity to capture all possible benefits the ICER is so high and uncertain, the Committee do not report the most plausible figure.