Sometimes, at the earlier stages of drug development, getting a drug approval, reimbursement, and access to markets can feel as daunting as standing beneath the Eiffel Tower and looking up through all the intricate metal fretwork to the narrow and distant top. It’s a long way and, as with climbing the Eiffel Tower, is best accomplished in stages (and, if you are like me, with some fear and trepidation). Once you begin the journey, you find many other people doing the same things you are (for better or worse). But once you do get to the top, there is the exhilarating feeling that the world is now at your feet, and the possibilities are tremendous.
At the 12th Annual Conference of the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) held in Paris last week, the main theme was healthcare decision-making in Europe – in essence, the pinnacle of the drug and device development process. Many of the sessions were concerned with how to attain the best decisions possible – how the decision-making process differs from country to country and the types of evidence and agreements that are welcomed by the national reimbursement agencies.
As most of us who are intimately involved in creating the evidence base and presentation materials for such decision-making know, each Health Technology Assessment (HTA) national agency has its own way of viewing and prioritising the data. So much so, that while some basic elements are the same, essentially if you have seen one HTA submission, you have seen just one HTA submission – the need to consider the next submission with fresh eyes is essential to a successful process.
This point was illustrated in a plenary session that compared three of the most influential HTA agencies in Europe: from France, England, and Germany.
Dr Laurent Degos, the Chairman of the Haute Autorité de Santé (HAS) of France, outlined the four principles for the French approach to HTA :
- Use of an independent body to carry out HTA, separate from the decision-makers
- An immediate assessment for each new product
- Separate medical and economic assessment
- Delayed multiple full HTA
By these principles, the HAS ensures that innovative products are rapidly assessed by an objective authority; that the cost of the product does not affect the medical decision, and that eventually, when there is more evidence about the comparative position of the product relative to alternative treatments, that this is reassessed in context. Essentially, the questions the French are asking of the product are:
- Is it good enough to be reimbursed?
- Is it better than any other treatment?
In Germany, on the other hand, the Institut fϋr Qualität und Wirtschaftlichkeit im Gesundheitswesen (IQWiG) thinks of HTA assessment as answering two slightly different questions, with some underlying sub-questions:
- Do we need it?
- Does it have patient-oriented benefit?
- Is it better than what we already have?
- Is it necessary?
- Is the price right?
- Do we have alternatives?
- What are the costs of other treatments in this field?
- What is the relation between the additional benefit and the additional costs?
Dr Peter Sawicki, IQWiG’s Director, confirmed that the most desired level of evidence is head-to-head trials with comparative treatments; placebo-controlled trials are acceptable only if there is no comparator. Interestingly, if there is no adequate alternative, then cost-benefit analysis is not allowed – in this way the German system gives incentive for truly innovative products. And only if the answer to the first question (do we need it?) is yes, will the assessment continue to the second question. In IQWiG pricing is negotiated using an efficiency frontier – a graphical comparison of benefits and costs for all treatments in a therapeutic area to help determine an appropriate price (‘ceiling price’) for a new drug. This system is different from that of the National Institute for Health and Clinical Excellence (NICE) in England, which tends to use the quality-adjusted life-year (QALY).
NICE, as the most venerable (and possibly venerated) of the three national agencies, has 5 principles to its guidance — that its assessment must be:
Using these principles NICE tends to “muddle through elegantly,” as Sir Michael Rawlins (Chairman of NICE) put it. NICE analysis uses a Citizen’s Council to make social value judgements, performs scientific assessments on the reliability of the evidence, and makes case-by-case decisions, especially if the cost per QALY is greater than £30,000. For NICE, the QALY is ‘a tool not a rule’; and NICE, unlike IQWiG, doesn’t apply a hierarchy to the evidence. WIth more than 624 types of published guidance that spans appraisals, clinical guidelines, interventional procedures and public health, NICE’s history is impressive, and many other countries look to NICE as a benchmark for their own appraisal system.
So, is an international appraisal system likely in the near future? A resounding No! seemed to be the answer – even when considering only the scientific evidence. For those of us who enjoyed the magnificent views from the Eiffel Tower during our sojourn in Paris, the realisation that a different tower in a different country will give us an entirely new perspective seems only fitting.