"No!" says NICE, to Sprycel, Tasigna

The UK cost-effectiveness watchdog NICE today delivered a resounding "no" to the use on the National Health Service of Bristol's dasatinib (Sprycel) and Novartis' nilotinib (Tasigna) in chronic myeloid leukemia patients intolerant to imatinib (Glivec).

"The evidence available to support [the clinical effectiveness] of dasatinib and nilotinib was very poor," declared Professor Peter Littlejohns, clinical and public health director at NICE. "The drugs' cost is also very high," he added, in a press release announcing the latest draft guidance.

Sprycel costs about £30,477 per year, and nilotinib about £31,711, according to appraisal documents on NICE's website. And the drugs are taken for several years, with no evidence-based 'cut-off' point currently in use.

It doesn't even look as if the drugs came close, in other words. And Bristol and Novartis can't even consider one of the loopholes now available to companies, the end-of-life guidance issued in late-2008, which permits a somewhat higher cost-per-QALY (quality-adjusted life year) than usual for drugs that extend life in niche yet terminal diseases. (This, you will recall, is what allowed Celgene's multiple myeloma drug Revlimid to slip past the agency.)

The available evidence on the drugs' extension of life--typically required to be of at least three months--"is too weak", declares the NICE PR in yet another blow to the products' manufacturers. That the drugs, both second-generation tyrosine kinase inhibitors, offer such an extension, documents declare, "is plausible, but definitely not proven."

But at the end of this rather damning announcement came an olive branch. "It would be heartening to hear that pharmaceutical company manufacturers are prepared to share some of the very high cost of these drugs with the NHS," suggested Littlejohns.

Now if that isn't a call for a cost-share (or should we say 'patient-access') scheme, then I don't know what is. Recall that such schemes have allowed NICE to green-light a good handful of expensive drugs that likely would not have otherwise made the cut--including most recently UCB's RA drug certolizumab (Cimzia). (Interestingly, although Celgene also put forward such a plan for Revlimid, this wasn't what tipped the decision in its favor.)

So we understand NICE's call for companies to make an effort on the cost-share front--indeed, the agency's CEO Andrew Dillon has told us clearly that he'd prefer if manufacturers simply submitted such schemes up front rather than waiting for a rejection in order to fish one out.

But is Littlejohns implying that a cost-share proposal would simply eliminate all the problems that the appraisal committee identified in the submission, around trial data and design? These seemed considerable: no studies submitted assessed either drug against relevant comparator; trials were 'heterogenous in terms of design, population, implementation and analysis'.

We put this question to NICE. Their reply:

Although there is some evidence to suggest that dasatinib and nilotinib could be considered clinically effective in cases of chronic myeloid leukaemia (CML), the quality of that evidence was extremely poor. This, coupled with the very high cost of the drugs, meant that the independent appraisal committee could not recommend them as an appropriate use of NHS resources.

During the public consultation on the draft recommendations manufacturers will have the opportunity to propose a patient access scheme, to make it easier for the NHS to afford expensive new treatments. We would be happy to look at such a scheme.

The answer is still not entirely clear (to me anyway; and I'm pushing for further clarification). But it sure looks as if patient access schemes will trump poor data.

If that's true, we're not sure that will do anyone any good--the NHS (paying, if a reduced price, for drugs that aren't effective), companies (forced to submit access schemes above all else), or patients (potentially receiving an ineffective drug and, as a group, perhaps not getting something else as a result).

We hope, then, that we're wrong.

image by flikrer greenchartreuse used under a creative commons license

"We're Not Like NICE," Barks Germany's IQWiG

It's not as if the UK's cost-effectiveness watchdog NICE isn't used to a bit of bashing. Patient groups, spurned companies, disease foundations, the good 'ole British public have all had a go over the decade or so since this fourth hurdle came into being.

But NICE has stood up relatively well, we feel. Sure, it has U-turned on a few decisions, and has bowed to pressure for increased transparency. No bad thing. But overall its role and influence are growing, not shrinking. And its measure for assessing cost-effectiveness, the controversial QALY (quality-adjusted-life-year), remains central.

So nice isn't going to flinch at a dig from its German counterpart, IQWiG, which in October declared what it clearly views--perhaps justifiably, we're not judging--as a far superior method for evaluating cost-benefit. (So we're a bit slow to react, but the English translation has only just been made available.) Note that IQWiG has only since 2007 been allowed to take cost into account at all--this is the outcome of a two-year study.

Basically, IQWiG's new method doesn't impose a uniform upper cost threshold across all diseases, akin to NICE's £30,000-per QALY guideline limit. "We compare the relation between cost and benefit for each individual disease," says the PR, using existing treatment prices in that area as benchmarks. Indeed, "such a [NICE-style, uniform upper] threshold "would not be in keeping with the German Social Code Book," the release continues. (But should cancer or heart disease sufferers have a right to more expensive treatment than, say, diabetes patients....?)

Then the socio-cultural philosophy kicks in: "Peter Sawicki [IQWiG's Director, unlikely to be appointed for another term next year] is convinced that the utilitarian mindset which underpins the British approach would not be accepted in Germany," pipes the release. Sawicki is then quoted as saying: "This benefit maximization ethic leads, for example, to cancer patients not receiving the expensive drug Avastin, because the costs are seen as too high in relation to extending life. On the other hand, despite doubts surrounding their additional benefit, diabetes patients are prescribed insulin analogs because the higher costs seem reasonable in the face of the supposed increase in the quality of life. In Germany, this would be seen as unfair."

Talk about mobilizing the anti-NICE troops. (Regarding insulin: in Germany rapid-acting analogs must be priced no higher than human insulins because of these 'doubts' over additional benefit; never mind speed-of-onset or convenience.)

IQWiG, it seems, is cosying up instead to the Australians. Its approach is to outline a maximum reimbursable price for products, taking into account additional benefit relative to other therapies within the same TA, and performing budget impact analyses not just on overall health care spend, but also taking into account other costs, such as social insurance and productivity losses resulting from sick leave. (Another subject that came under recent scrutiny at NICE.) "There are clear parallels with Australia, the country with the longest experience in matters concerning health economic evaluation," the PR goes on.

And another kick at the QALY: "While our British colleagues work more or less exclusively with QALYs.....after 15 years' experience, the Australian Pharmaceutical Benefits Advisory Committee (the Aussie version of nice) has warned that there is a high price to pay for carrying out general therapeutic comparisons using QALYs. The utility weightings required for this are often based on many ambiguous assumptions."

Most of the drug industry would agree with Sawicki on this one. Shame, then, that IQWiG's bark is so much louder than its bite. Unlike NICE, whose yes/no decision determines whether a drug will be commercially successful in the UK, IQWiG has no such power. It can only make recommendations--if requested to--as to the relative benefit of a drug and, from now on, as to a maximum reimbursable price. Health insurers can either follow those recommendations, or not.

And in contrast to most other countries, where health technology assessment agencies are gaining sharper teeth, IQWiG's likely going the other way: most expect the newly-elected government to appoint a more pharma-friendly chief, effectively putting the agency in industry's pocket. But that's a whole other blog post.

image by flikrer stereonaut used under a creative commons license