Is early dialogue worth the effort?
The experience from the company's viewpoint was extremely positive, in that specific advice was obtained on major aspects of the design of key clinical trials in order to help inform the downstream decisions of pricing and reimbursement agencies. Potentially, this could save the company considerable time and resources by focussing effort on the main requirements for an evidence package to support the compound in the desired indication/target patient population. There was no evidence that payers had used the opportunity of providing advice to enter into negotiations about price or reimbursement status of the product. Rather, the advice was given and it was left up to the company as to how best to respond. Another way of obtaining scientific evidence would be to assemble a group of expert advisors in the area of pricing and market access. This approach had also been followed by the company for the compound concerned. Early dialogue with the agencies, however, was judged to provide additional value, mainly because direct advice from the payers themselves enhances the awareness of the project team to the evidence issues that will need to be addressed.
The assessment of value is more difficult from the perspective of the agencies. It could be argued that time spent on offering advice could divert the agencies from other important tasks. On the other hand, if companies are given advice on the appropriateness of different types of evidence, the process of making ‘correct’ (i.e., more informed) reimbursement decisions would be enhanced; submissions may be shorter and more focused, explicitly addressing evidence known to be relevant to payer decisions. Compounds discussed at this early stage, however, may not reach the market, for one reason or another.
From a societal viewpoint the value of early dialogue would depend on whether it leads to a fairer and more efficient (i.e., timely) reimbursement process. This can only be assessed once more experience is accumulated. One important point to assess is whether the advice is ‘wasted,’ either because it is ignored by the companies concerned or because some of the compounds discussed at this early stage may not reach the market. Advice, however, once developed, is likely to be partially transferable to other developers with products for treatment of the same disease in the future.
Another reason why early dialogue might not be useful is that, owing to changes in circumstances, advice could change over time. For example, another alternative therapy could become available after the time that the advice was given. However, there was recognition from all sides that advice can only be given based on existing knowledge and the potential for changes in the future should not undermine the process.
One societal concern is the possibility of ‘regulatory capture’ as a result of agencies having more dialogue with manufacturers (that is, agencies may become overly sensitive to the concerns of manufacturers, to the detriment of the interests of consumers). Again, this would need to be assessed in the longer term, but the possibility of this is unlikely, given the rigorous procedures for technology assessment that have been established by most of the agencies. In addition, stakeholder engagement is recognized as a desirable characteristic of the pricing and reimbursement process by most agencies [
- Neumann P.J.
- Drummond M.F.
- Jönsson B.
- et al.
Are key principles for improved health technology assessment supported and used by health technology assessment organizations?.
]. Indeed, it might be argued that the early dialogue initiative could lead to a paradigm shift; a change from an (at times) adversarial relationship between the developer of a new technology and the pricing and reimbursement agency, to that of a partnership in evidence development for market access. Certainly, the developer involved in this pilot study was keen to give feedback to the agencies concerned about the value and practical implications of the advice offered.
If, on balance, early dialogue is judged to be socially beneficial, it would make sense for the budgets of the agencies to be increased to enable them to engage in such activities. In particular, it would be important that those individuals offering advice on behalf of agencies are adequately trained and also have personal experience of the agencies' decision-making processes (e.g., through having been an expert committee member in the past). Since the time of this pilot study, one agency has initiated a consultancy service, whereby manufacturers can pay for scientific advice on clinical trial design (and other matters). National Institute for Health and Clinical Excellence (NICE) scientific advice consultancy service. Details available from www.nice.org.uk
. (Accessed October 1, 2010.)
One concern is that, given the large number of pricing and reimbursement agencies, having early dialogue with all of them could be very resource-intensive both for companies and the agencies themselves. To this end, the finding that the key elements of the advice did not differ greatly across agencies is encouraging, although more investigation is required before we could be confident to suggest that companies need only consult a subset of the agencies.
Where resource constraints prevent an otherwise willing agency to provide advice, it may be possible for pan-national consortia to evolve, in order to spread the load of offering early advice. However, the scope for this is likely to be limited to considerations of comparative clinical evidence due to the fact that views about economic value and decision-making criteria vary from jurisdiction to jurisdiction. Also, the differing remits and objectives of the various agencies might further limit the scope for joint advice.
How could the process be improved?
The company received feedback that some elements of the process worked well, such as the production of a briefing book. However, it was also observed that, in most cases, the time allocated for the meetings was too short. One minor disappointment from the company's viewpoint was that only one of the agencies was willing, or able, to provide written feedback. This was regarded as important by the company—it removed any doubt about precisely what advice was being given. In the future, it might be possible to produce a summary of the advice and send it to the agency for comment or even approval.
A related issue is whether the advice offered should be binding on either party. Although this would further reduce any uncertainty on the part of the company, it is probably premature to take such a step. Indeed, it is probably unrealistic to expect such advice to be binding because the assessment of a given product is comparative to any other relevant alternatives existing at the time. Therefore, it will depend not only on the evidence of the company's compound, but also on that of the current and future alternatives. In any case, as with the advice given by regulatory agencies, the advice offered relates only to desirable evidential standards and does not include a discussion of what the agency would be likely to recommend if presented with a given set of data about the compound.
Another question is whether the advice, and the discussions that lead to it, should remain confidential to the parties concerned, or be made public. This echoes a similar debate about whether company submissions to pricing and reimbursement agencies should be in the public domain [
Should commercial-in-confidence data be used by decision makers when making assessments of cost-effectiveness?.
]. The main argument against publication is that some of the material discussed is likely to be commercially sensitive (e.g., the company's aspirations for market positioning, or the results of the phase 2 trials).
In some instances, however, there may be arguments to make public some of the elements of the advice being given. For example, if several companies are developing compounds in the same clinical area there may be benefits from standardizing the design or data collection within clinical trials. This would assist payers in making comparisons among the compounds concerned and would be analogous to the process, followed by some regulatory agencies, of issuing disease-specific guidance notes [
Raising the standards of trial-based economic evaluation: the devil is in the detail.
Therefore, the need to preserve the confidentiality of advice is not an easy issue to resolve, although in situations where the developer is asked to pay for the advice, it must surely remain proprietary. Should the provision of early advice be considered beneficial from a societal perspective, there would need to be more discussion of the terms on which it is offered; it clearly has both ‘private good’ and ‘public good’ components.