Working with NICE: the ingredients for success
pharmafile | February 29, 2008 | Feature | Research and Development, Sales and Marketing | NICE, healthcare, industry relations, pharma
NICE fascinates everyone in the industry, and NICE knows only too well that every move it makes is studied by an array of sharp pharma minds. But even NICE cannot be accustomed to the attention it has received this year.
Its decision-making on treatments for Alzheimer's disease have been dissected at length by the High Court, and the Commons' Health Select Committee recently issued a report recommending further changes to how it operates.
The stakes have been raised further by the suggestion that health technology assessments, possibly by NICE or a successor organisation, might be used to set the prices the NHS pays for drugs. And the organisation itself is consulting on a rethink of its appraisal methods.
Despite this turmoil, NICE rulings on medicines remain absolutely vital for pharmaceutical companies trying to increase the uptake of their products. So what are the keys to making a successful submission?
To find out, Pharmafocus spoke to four people with extensive experience of the process from different points of view: Carole Longson, director of NICE's Health Technology Evaluation Centre; Christie Niziol, consultant with Abacus, a health technology assessment and health economics specialist consultancy that has worked closely with NICE since its earliest days; Mike Baldwin, ex-Sanofi-Aventis head of health technology appraisals, now working with the specialist health technology data and research provider Cardiff Research Consortium; John Blenkinsopp, academic pharmacist at Keele University, POM to P switch expert and NICE submissions consultant.
Get to grips with the project
NICE submissions can fail for many reasons, but Longson, Niziol and Baldwin agree that the commonest problems lie in what's often called the scoping – the essential task of identifying the strengths of the drug, defining the case the manufacturer needs to make, and then planning to establish the data required to support it.
A common problem mentioned by all three is that company expectations may not match reality. For example, senior company managers based in the US have not always appreciated the significance of NICE's Health Technology Assessments (HTA) in the UK or what it demands. The result can be that the available study data has sometimes not been available to submit to NICE and to make a relevant case.
"Global pharma companies tend to look to their main market, which may be the USA, where they may be comparing drug A versus B," explains Baldwin. "But B might be the wrong comparator for the UK, which might be using drug C.
"What you then need is data comparing treatment A versus treatment C – but if there's no trial that compares them, you have to get the statisticians to do some clever extrapolating."
Niziol goes further. "With a board as stringent in its methods as NICE, that really doesn't go down well – you need to have chosen the most appropriate comparator."
Expectations that come from experience in a different market can cause other problems, Niziol adds. "You might get a case where a drug is promoted in the USA as first-line, but here in the UK we might find ourselves saying we think it will only get a recommendation in a particularly severely affected sub-group, or as a second-line drug. That can be very difficult message for a large company to swallow.
"In planning a submission," she says, "the first task is to conduct a horizon-scanning exercise looking at what is currently being appraised, what is coming up in the company's pipeline, and when they are going to be required to come under HTA scrutiny."
A systematic literature review may find instances where other people may have done work on survival or quality of life for your drug. "If you plan far enough ahead you can make plans to fill the gaps with secondary research. This might be an audit or a retrospective study looking at GP records, or perhaps a survey of patients or clinicians looking at quality of life," Niziol adds.
Other useful sources include the approaches that competitors have taken in submitting to HTA. "Looking at the documents produced by these boards allows a company to assess whether their products are competitive, and to identify the pitfalls and advantages of their approach."
Don't be frightened of involvement
Companies making NICE submissions need to get involved, says Niziol. "Make sure you are registered as a stakeholder through the NICE website, so you are able to comment. Sign up for the updates, and make sure you attend all the workshops and meetings available."
Also, don't be shy to ask questions when you need to. "NICE is happy to give advice when it's needed, but I think people are not always aware of this. The dedicated pages on the NICE website include a phone number and the name of an individual, and I have very frequently phoned these people and been given very up to date information on an appraisal.
"I think manufacturers may sometimes be reluctant to talk with the people at NICE for fear their information might be published, particularly if the drug concerned is at an early stage. It may be that sometimes the lack of communication is on the company side, not with NICE. Generally, I think NICE is much better and more helpful than many people think.
"Also, the documentation is good and very clear when you can find it. The website can sometimes be a little troublesome to navigate round – but once you have found the information, it's clear."
Get the team right early in the game
Niziol identifies staffing as another key issue, and always asks the company to appoint a small review team early. "It can be difficult if a large team produces large numbers of comments that may be conflicting. The argument can become much less tight because of an effect where too many cooks spoil the broth.
"Another problem arises when someone new comes in who disagrees with decisions made earlier in the project, which seems to be almost inevitable when teams change."
Make use of the outsider's view
NICE requires a lot of detailed information, and the amount it needs is increasing as health economics becomes more sophisticated; and of course it has to be correct.
Blenkinsopp uses a colourful but apt analogy, arguing that preparing an HTA submission is like cooking a seafood bouillabaisse. "Good ingredients are the key, he says, "but one rotten prawn will make the whole thing inedible."
A key task, therefore, is finding and eliminating the rotten prawn; perhaps spotting the assumption that's out of line or the safety issue that has been underestimated.
To help you do that, he says, it's useful to have someone critical scrutinise what you produce, including data and assumptions. "Don't choose a yes-man for the job – it's far better to know the worst than to find out later."
"NICE itself is pretty clear in warning that companies should not put in an undercooked submission," says Baldwin, "and there are a number of organisations around to help companies to make submissions."
Niziol would also agree that an outsider's view can be very useful, and uses them herself. "When considering HTA, we're usually looking at secondary research: it's systematic reviewing and the health economic model. So you might call an advisory board and say: these are the results of a systematic review, do you agree with our numbers?
"It can be wise to recruit an external health economics professor with experience to review the model – to read it through NICE's eyes if you like – and tell you how they think NICE will see it. That expert may also be willing to become a co-author on articles and papers relevant to the submission."
Another approach might be to assemble a model appraisal committee to scrutinise a submission.
Finally, some consultancies can help also in the area of implementation – working with budget holders to promote the advantages of complying with NICE decisions. This can be achieved through conducting workshops, publishing and distributing the health economic argument. Another option is to use computer software to demonstrate to the budget holder or clinician the benefits of implementing NICE guidance, for example by using local population data.
Supplementary strategies and preparing the ground
Beyond the hard data of the submission itself, Niziol believes the traditional approach of working with key opinion leaders can help.
"I would involve a clinical expert at an early stage. This will make sure that when they are called upon by NICE to act as expert commentator they already know and may potentially promote the argument the pharma company is advocating.
"A second advantage of getting clinical experts involved early is that they will ensure the argument stands up in a real-life setting. They're very critical, and instead of relying simply on clinical trials they can tell you how a drug performs in real life, how they would usually treat a particular condition or an adverse event, and their estimates for use of resources.
"Key opinion leaders can also help in getting a particular drug on the agenda for assessment. If the company invites KOLs to advisory boards at an early time, it can help if they can make a noise about the need to appraise a drug if an assessment hasn't come about by the normal route."
And finally they can help by writing about the product, says Niziol. "KOLs may also become key authors promoting the health economic message developed from the systematic review. They can also help in getting the essential material written up and published – NICE would find it difficult to consider data that had not been published."
NICE continues to evolve
It's striking that the professionals who work most closely with NICE are very quick to defend it, both in terms of its aims and the way it pursues them. In fact, the organisation has clearly built up a store of goodwill among professionals in the health technology assessment submission industry that belies the picture that's often painted by campaigners on specific issues.
More than many goverment bodies, NICE has been under great pressure to become more transparent. One new initiative in this process has been teams from NICE visiting companies engaged in making submissions and giving presentations on the principles of the Single Technology Assessment procedure, and how to make an effective STA submission.
But from talking with NICE Health Technology Evaluation Centre director Carole Longson it seems the most important developments of the year might yet turn out be two initiatives first revealed at the recent NICE 2007 conference, and which NICE hopes will significantly help pharmaceutical companies in planning and making their submissions.
The first will bring a new degree of flexibility in the analytical approaches that can be used to compare drug treatments, says Longson. "Our new methods guide now in consultation goes into quite a bit of detail about what to do when the comparator used in the clinical trial isn't the one used in clinical practice in the UK.
"Head-to-head RCTs are still preferred, but we're trying to be pragmatic in recognising that these tensions do exist, and we're keen to provide a toolkit of methods that we hope is useful. The new options include using indirect or mixed-treatment comparison – that is, using pair-wise comparisons of head-to-head RCTs that have a common comparator."
Longson also points to a recent pilot in which NICE has trialled becoming involved much earlier involvement in the development of a new treatment. It seems that NICE has noticed that pharmaceutical companies have to take important business decisions very early in the development cycle.
"This is something we recognise as extremely important, and hope that it will help enable companies to know what they need to be thinking about early in the process."
No doubt the industry would second that sentiment. As reported by Pharmafocus a short time ago, the first phase of a pilot with Novartis has been completed, and the indications are that NICE is likely to offer the service in return for a fee.
Box: NICE's Single Technology Assessment
The Single Technology Assessment is NICE's answer to the pressure to issue guidance on treatments closer to the time of their launch.
HTA consultant Niziol says that in many ways it's similar to the SMC appraisal. "There's no academic group submission to provide a parallel NICE-developed model, so the only evidence is what the pharma company provides to Nice. In a way it's more challenging and weighty than a Multiple Technology Assessment submission.
"What's more, while with the traditional Multiple Technology Assessment there's a sense that you're innocent until proven guilty, with an STA you're guilty until proven innocent – you really have got to win your case."
This is important, because the STA involves more work, and more cost for the company.
What isn't yet clear to Niziol are the criteria by which drugs are chosen for the STA process. "This matters because there is a perception that while one drug might be in the slower MTA process, another drug might get the opportunity to go through the quicker STA process.
"I've asked about this and they have acknowledged that it's not that transparent. However, I am sure it will become clearer in time. NICE has a huge job to do and a big workload, but they're very good at identifying flaws and fixing them. The actual logistics can take a little time to tease out."
Gavin Atkin is a freelance writer specialising in medical and pharmaceutical topics. He can be contacted at gmatkin@gmail.com
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