NICE Scientific Advice Program May Seek Broader Application Through Boosting Regulator Link-Up

NICE’s scientific advice program, now in its third year, may need refocusing and increased co-operation with regulators to appeal to small and medium-sized companies.

Three years after its inception, the scientific advice program of the National Institute for Health and Clinical Excellence of England has gained a committed following among top pharmaceutical companies. However, while cost considerations are clearly keeping smaller manufacturers at bay, an integrated approach together with regulators may help to resolve this problem.

The obvious problem with NICE’s scientific advice program is that it is geared towards the big guns – the top 20 pharma companies. Because the fees are structured in such a way as to enable NICE to recuperate its costs – and its efforts involve hiring external expertise – small- to medium-sized manufacturers simply don’t have the cash. On the other hand, larger companies already tend to have in-house health economists who have factored the health technology assessment (HTA) process into overall development plans.

And clearly, big pharma likes what it sees. “We have used NICE's scientific advice service before and have found it to be a worthwhile exercise,” a spokesperson for Sanofi said. Similarly, a spokesperson for AstraZeneca PLC said that the company “believes the quality of the advice received from the NICE represents value for money.”

Seren Philips, Associate Director Scientific Advice Programme at NICE, concedes that a lack of resources leaves small and medium-sized firms unprepared to fully address HTA issues at the development stage. “NICE is not there to simply fill in the blank sheets of paper,” she said, noting that the advice program can only comment on what companies are able to present. NICE is, however, looking into the affordability issue, although there is no timetable for reducing prices and Philips adds that the institute is not in a position to offer discounts as a result of the funding structure.

However, another means of opening up a channel to small and medium-sized firms could be through developing an existing joint advice program that NICE offers together with the European Medicines Agency (EMA). “This is verbal advice and I expect we are going to be giving a lot more of this type in the future,” Philips said.

Small and medium-sized firms do not tend to have the overall planning ability of the larger companies and so often adopt a step-by-step approach to reaching the market. This means that they will initially be more aware of the role of the regulator, at which point a joint advice program with NICE could have more of an impact.

Joint Advice Is The Way Forward

Philips believes that joint advice from both the regulator and the HTA body has significant advantages over individual offerings. But it involves all parties trying to understand each others needs. “What you gain from a joint meeting is that the sides are aware that there may be differing issues, but you may be able to think about a compromise way of looking at things,” Philips says. Moreover, companies need to attend only a single meeting, thereby reducing costs.

The problem, of course, is getting it right. A pilot between the Swedish national medicines authority, MPA, and the reimbursement body, TLV, which ran between 2009 and 2010 was judged by companies to have been a step in the right direction, but one that ultimately flew wide of the mark. Industry felt that the advice from both authorities was not co-ordinated and so in effect was not “joint,” but “parallel” advice (Also see "Sweden Leads In Linking Regulatory And Reimbursement Scientific Advice" - Pink Sheet, 22 Nov, 2010.).

Financing Advice And Measuring Success

NICE scientific advice became a fully-fledged reality in 2009, after manufacturers asked for same early advantage in the HTA process that was given to them by national competent authorities in the regulatory process. NICE was the first HTA body in Europe to set up this type of program, says Philips, so it was not a case of cherry-picking from other scientific advice offering across the EU.

Other programs have now emerged across Europe, include in in Sweden and Germany, but the low number on offer may be a result of funding issues, Philips suggested. “If you are not permitted to accept payment from the company, there is not an easy way of affording to do this,” she added. “In terms of resources it needs to be a sustainable business. Needless to say, the NICE program is funded directly through fees. “I have to do that, because we are part of the NHS and this is not part of core business,” Philips explained.

NICE says that its program is a success, although there has been no comprehensive assessment of the uptake. “I think the measure of success is that pretty much everybody comes back for repeat business,” Philips noted. Manufacturers are particularly keen on face-to-face meetings and it is a telling sign that many of them book in early, planning the HTA discussion as part of their overall development process.

But even if a company opts for scientific advice, there is no guarantee that this will end in a NICE recommendation – and it may simply be too early to tell; NICE scientific advice has only been available since early 2009.

“Since registration Phase III trials can take a number of years to complete, and then with the regulatory filing process adding further time, we would not yet expect NICE to have made recommendations to the NHS on any of the technologies that have sought scientific advice to date,” the Sanofi spokesperson said.

AstraZeneca said it was using NICE scientific advice to inform the development plans for some of its early stage investigational compounds, but added: “None of the compounds we have received advice for so far have been appraised by NICE yet.”

“There might be lots of reasons why a company might not be able to do what is perfect for NICE,” Philips said. For example, FDA will often prefer placebo controlled trials, but – as a “sweeping generalization” – it is going to be an active comparator study that is more appropriate for NICE. There is also the simple matter that a company can receive regulatory approval without carrying out an active comparator study. There could also be post-advice changes and developments in scientific knowledge or appraisal requirements, over which the institute has no power.

Seeking NICE scientific advice at too early a stage is probably a mistake, because it is not likely to be product-specific. This could mean that companies will be unable to amend the clinical trial design at a later stage, as they might then risk diverging from the advice and ultimately failing to gain a recommendation. The best approach is to request advice during Phase II studies, before the planning of Phase III studies, Philips said.

But while some companies, including AstraZeneca suggest that scientific advice is “of most value to help planning Phase III study programs,” others may yet be looking for more. “We do see a value for this kind of independent advice at other stages in the drug development pathway, and indeed post-marketing,” the Sanofi spokesperson confirmed.