Take Home Messages from HTAi 2018

Last month, my colleague Katie Noon and I headed off to Vancouver to attend the HTAi 2018 Annual Meeting where we gave two oral presentations on Costello Medical’s research on the NICE Diagnostics Assessment Programme (DAP) and the timing of nationally available discounts. The conference took a pragmatic and forward-looking approach to HTA, considering the impact of new technologies, a move towards collaborative working and the need for living evidence-generation tools.

Maximising Efficiency in HTA

Efficiency was a key topic throughout the conference, which was raised in the initial plenary session by Jon Brassey (Trip Database Ltd, UK) who opened his presentation with the Voltaire quote “perfect is the enemy of good”. Jon argued for the use of rapid reviews as opposed to systematic reviews, the latter of which can suffer from being neither quick nor robust enough. Although rapid reviews do miss more of the available literature than systematic approaches, when considering the huge amount of unpublished literature that wouldn’t be captured by either the difference is minimal and more than outweighed by the efficiency savings.

Later on the Sunday, a sponsored symposium by Decision Resources Group (DRG) discussed whether HTA should be conducted at the local, national or global level. From the UK perspective, Ed Wilson (University of Cambridge, UK) noted that clearly an average decision made at a national level will not be right for everyone at a local level. Ed suggested that perhaps all decisions should be advisory only and therefore more adaptable to the needs of a particular region and Clinical Commissioning Group (CCG), an idea which runs the risk of taking us back to the problems of a ‘postcode lottery’. Prashanth Kandaswamy (Grünenthal GmBH, Germany) discussed the practicalities of managing a global HTA programme within industry considering how unresponsive such programmes can be and the need to work efficiently alongside local affiliates. This challenge is often faced by our clients, and our experience completely supports what was mentioned by DRG in their closing presentation – the key is clearly defined roles and responsibilities. We have also found that an external consultancy such as Costello Medical can play a really crucial role as a ‘data champion’ updating local affiliates and ensuring messages are aligned across all parties, saving global teams time and therefore money.

The ongoing debate surrounding the use of open-access models, was continued during a really engaging panel discussion moderated by Tammy Clifford (CADTH, Canada). Stirling Bryan (University of British Columbia, Canada) highlighted that importance of developing high quality models that minimise waste, with the entire panel agreeing that shareable models could offer a solution to this. Chris Sampson (Office of Health Economics, UK) described key issues such as a lack of vested interest by manufacturers’ in sharing models, publication pressures within the academic community and a need for really flexible models that are able to adapt to local contexts. Rick Chapman (ICER, USA) described the ICER transparency pilot, in which ICER developed a model in collaboration with an academic team and the manufacturer themselves. Although successful in many ways, the pilot did highlight the additional time needed to generate shareable files suitable for use by all stakeholders and the issue of confidential data, which can stop the model being shared widely. With notable exceptions, such as project HERCULES in Duchenne muscular dystrophy and OncoSim, we continue to be a long way off collaborative development of open-access models being the norm. However, the small steps towards increasing transparency taken by all stakeholders suggest that it may be a matter of time rather than just a pipe dream.

Moving Towards Joint European HTA

As joint European HTA has taken the step forward to become a reality over the next few years through joint clinical assessments, many talks at the conference focused on examples of joint HTA collaboration so far, highlighting their strengths and weaknesses. Overall, the concept of Joint European HTA was met tentatively at the conference, with many people expressing scepticism over the benefits of this initiative.

The potential efficiency savings that could be made by using joint clinical reviews produced by EUnetHTA was made clear during the DRG sponsored symposium, however, the fact they had not been widely adopted as yet raises questions as to why. In addition, it is unclear how much can realistically be overcome by further dialogue with the participating nations. Practically the panellists asked whether joint clinical assessment will in fact increase speed of access considering they are aiming to be made available as close to marketing authorisation as possible, or is this just too late for the purposes of HTA.

The example of joint early dialogue with the EMA and EUnetHTA was given by Jesmine Cai (Centre for Innovation in Regulatory Science [CIRS], UK). Here, if a new technology meets the eligibility criteria then a meeting is arranged. Since July 2017, there has been 33 requests for a meeting with only half considered for early dialogue; most were oncology indications. How to better involve patients in early dialogue is currently being considered, including interviewing individual patients with the condition (minimum two from each country); patient representatives from a minimum of two countries or an overall EU patient representative for the whole early dialogue process. The results from 10 joint early dialogues were also presented by Jesmine, with five early dialogues including discussion on health economics. Overall, there was approximately 70–90% agreement between European HTA agencies, with highest agreement on protocols and lower agreement on outcomes (differences in differentiating between primary and secondary outcomes) and the use of a single overall dataset for costs was low as countries prefer national datasets.

Several examples of adapting EUnetHTA reports for specific countries were given (Karen Macpherson, Healthcare Improvement Scotland [HIS]; Katrina Fonsdal, Norwegian Institute of Public Health [NIPH]), with countries stating that the reports were useful as a ‘starting block’ and there must be an element of trust that the original document is accurate and of high quality. However, many noted that additional time and resource was also required, for example if including economics into the reports (e.g. time to build a de novo economic model).

There were also examples of countries adapting the EUnetHTA core model on a national level in countries that had limited prior experience of HTA. Overall the impression given was that the core model was useful in providing the building blocks for starting HTA. In particular, reducing the set questions to optimise it for different countries was seen as a good approach, particularly as resource is often limited. It was encouraging to see that countries outside of the EU (Kamilla Gaitova, Kazakhstan and Jani Mueller, South Africa) were utilising the EUnetHTA core model, demonstrating that joint European HTA could stretch further than just Europe in streamlining HTA.

Adapting to New Challenges

Brian O’Rourke (CADTH, Canada) mentioned during a discussion session that he felt the three greatest key challenges facing HTA at the moment are gene therapies, prices of orphan and ultra-orphan drugs and combination therapies. All of which can be associated with a high degree of uncertainty regarding long-term outcomes and therefore risk on the part of the payer. As noted by Peter Hall (University of Edinburgh, UK) perhaps we will see a shift towards access only in research recommendations.

Methods of tackling uncertainty were discussed at a number of sessions, with Chris McCabe (Institute of Health Economics, Canada) encouraging increasing emphasis on value of information analysis during the first plenary. Chris discussed the striking example that the decision by most countries to continue recommending 12 months of Herceptin (a treatment for HER2+ breast cancer), ultimately cost the UK NHS approximately ￡1.2 billion considering that data from the PERSEPHONE trial presented at the American Society of Clinical Oncology (ASCO) meeting earlier this year showed a 6-month regimen to be non-inferior.

Within oncology, the challenges of valuing combination therapies and precision medicine were touched on in a number of sessions. The oral presentation winner Deirdre Weymann (Canadian Centre for Applied Research in Cancer Control [ARCC], Canada) presented results of a review of economic evaluations of next generation sequencing in precision oncology, finding that 24% were conducted alongside clinical trials and only 11% had value of information analysis. While a Roche sponsored symposium focussed on how to divide value across multiple treatments when used in combination, sharing experiences from the Canadian, US and Swiss perspectives. The consensus was that HTA bodies are looking at manufacturers to come-up with simple solutions, which if based on utilisation or outcomes can be practically monitored by the collection of appropriate real world evidence.

It became apparent that the need for quality real world data will be even more important as we shift towards these new technologies that offer even greater uncertainty. Interestingly, Rachel Sachs (Associate Professor of Law, USA) flagged that the concept of ‘adaptive regulation’ could be a useful tool in HTA, allowing regulations, or perhaps reimbursement decisions, to adapt automatically when circumstances (or evidence) change – essentially an extension of payment by results.

The closing plenary looked at the broader HTA ecosystem, emphasising that it is critical to involve the right stakeholders at the right time and to the right degree, in order to balance the need to meet all collective objectives with maintaining efficiency in decision making. The final question posed by the moderator, Stirling Bryan, asked about how we can de-adopt and disinvest – with all panellists acknowledging that HTA is not yet equipped to address this. The conference left us considering how things may or could move towards a broader living healthcare ecosystem that can balance investment and disinvestment decisions across all healthcare services and treatments and update as new evidence becomes available – a move that will hopefully ensure that HTA approaches do not become outdated.

Annabel and Katie are employees at Costello Medical, who provides scientific support to the healthcare industry in the analysis, interpretation and communication of clinical and health economic data. Due to growing demand across an increasing range of service offerings and geographies, Costello Medical has grown organically since its foundation in 2008 to a team of over 100 based in Cambridge, London and Singapore. Alongside our evolving technical and creative capabilities, we remain committed to our core values of high quality scientific work coupled with exceptional customer service at competitive and transparent prices. Our talented team has experience with a variety of leading pharmaceutical and device companies across an extensive range of therapy areas and geographies, including Europe, Asia Pacific and North America. For more information on our services, please visit our website. If you would like any further information on the themes presented above, please do not hesitate to contact Annabel Griffiths or Katie Noon.