In order to guarantee patient access and commercial success, pharmaceutical companies must ensure that they can achieve both regulatory approval and payer acceptance for reimbursement. Historically, manufacturers have been very proactive in seeking advice from regulators but have struggled to determine the payer evidence requirements. Today, manufacturers have a choice of options related to engaging in early dialogue with regulators and payers/HTA agencies to facilitate evidence generation that can address both regulator and payer needs.
As pricing and reimbursement decisions are undertaken at the national level, it is not surprising that the concept of early scientific payer advice was initially adapted by national HTA agencies (such as NICE in the UK). More recently, there are now European platforms for seeking early scientific advice with multiple payer organisations as well as regulators. These include Multi-HTA scientific advice provided through EUnetHTA and SEED (Shaping European Early Dialogues for health technologies), as well as the parallel scientific advice by the EMA. Considering the number of potential options to seek payer and regulator advice, the question is now: whom to ask for advice on what and when.
National payer guidance
At the moment NICE in the UK, G-BA in Germany and TLV in Sweden have a formal structure in place to offer early payer scientific advice to manufactures. Additionally, HAS in France, AIFA in Italy, as well as regional HTA agencies in Spain can offer informal HTA advice. This approach offers the opportunity of gaining in-depth local guidance based on national treatment pathways, but is time and resource intensive and does not allow for a consensual payer approach as to what evidence should be collated within the clinical development program. In most countries there is a fee for seeking the advice and it can that can take up to 20 weeks (in the case of NICE) before receiving the payer guidance. However, manufacturers will gain a better understanding of country specific HTA requirements which are often vital when it comes to seeking reimbursement.
Combined EU payer guidance
EUnetHTA and the SEEDs consortium have piloted a Multi-HTA early dialogue approach. The aim of this approach is to provide a cooperative/consensus advice across several EU national HTA bodies (14 at the time of writing). As Multi-HTA advice was in a pilot phase, there were no fees as it was funded by the European Commission, with manufacturers invited to participate in the process. To date, 24 early dialogues were conducted during which manufacturers gained a better understanding of payer evidence requirements across the EU. The ultimate aim of Multi-HTA dialogue is to reach a consensus advice for the manufacturer. The initial pilots have highlighted the challenges in obtaining consensus advice from payer across the EU but it is hoped that with a refinement of the evaluation process that these challenges can be addressed. This process also allows, under certain circumstances, for the EMA to participate with the benefit that the manufacturer will also profit from EMA as well as payer/HTA insights. At the current time it is not clear how the Multi-HTA process will work in the future as the learning from the pilots need to be adopted into a robust multi-HTA approach and there needs to be a shift from an EU funded service to a fee based service.
Parallel payer guidance with the EMA
Parallel scientific advice is coordinated by the EMA in association with national HTA bodies to bring all stakeholders together to provide the manufacturer with early scientific advice. Tomas Salmonson, chair of the EMA’s Committee for Medicinal products for Human Use (CHMP), said “This simultaneous feedback will ultimately lead to better advice for companies, to help them meet the requirements of all stakeholders and consequently increase predictability”. Within this advice a joint EMA/Payer meeting is held whereby they can respond to manufacturer’s questions, which have been provided in a briefing book. Whilst several HTA agencies can be invited by the manufacturer to participate in the parallel process, the manufacturer cannot expect to receive uniform advice as each HTA agency will give advice specific to their country in line with local treatment pathways. This often leads to manufacturers receiving multiple, sometimes contradictory, guidance from the HTA agencies, which can make it challenging to determine the appropriate guidance to incorporate into the clinical development program. Whilst the parallel scientific advice process is still in its early stages, there is a robust process in place to provide the scientific advice and it looks to continue for the foreseeable future.
With the above options in mind manufacturers need to decide on the right source of payer as they each come with their own advantages and disadvantages. One might think that the parallel dialogue is the best option as regulatory and payer advice can be sourced at the same time. However, manufacturers need to keep in mind that this is a time and resource intense process and that the provided payer advice is not always aligned. Manufacturers should seek parallel EMA/HTA scientific advice when there is a significant need to clarify and potentially align clinical evidence expectations of EMA and HTA agencies. On the other hand, manufacturers should continue to engage with national HTA agencies in order to understand how to best address the vast majority of other context-specific aspects of HTA e.g. health economic modelling questions. One critical point to remember, regardless of the approach adopted, is that payers do expect that the outcomes of the scientific advice will be utilised in the clinical development program. If this is not to be the case, manufacturers should be prepared to justify this when it comes to seeking reimbursement.