BEACON: A Summary Framework to Overcome Potential Reimbursement Hurdles

In total, five frameworks and ten HTA guidelines were reviewed. Although this list was not exhaustive, the frameworks considered in this paper represent a sample of those utilised by the pharmaceutical industry to align to payer requirements. Additionally, a number of decision-making approaches were identified, such as risk–benefit analyses and multicriteria decision analysis (MCDA); these approaches were captured, where possible, through the evaluation of representative tools, e.g. the Clinical Utility Index and the Evidence and Value: Impact on Decision Making (EVIDEM) framework, respectively [21, 22]. The following frameworks were included within this review:

These existing frameworks and guidance were reviewed and categorised on the basis of (1) their purpose or application; and (2) their perspective. Each framework was evaluated to identify any criteria that were of relevance from the payer perspective, to be incorporated into the new conceptual framework.

The frameworks were broadly classified as non-HTA or HTA frameworks:

However, it was acknowledged the majority of the frameworks feed into the HTA process, and a degree of overlap exists.

A summary of the criteria considered in the ‘non-HTA decision-making’ frameworks is provided in Table 1. As can be seen in the table, there is a wide variety of different approaches taken. Some frameworks utilise a more clinical approach (such as the Clinical Utility Index), whereas others take an approach that is closer to the payer perspective.

Risk–benefit frameworks, such as the approach taken by the Clinical Utility Index, are commonly used by pharmaceutical companies and regulatory agencies in drug development and pre-approval. The Clinical Utility Index combines multiple attributes of a product profile with appropriate weighting to generate a single utility value, and it has previously been implemented in early exploratory development programmes or at the ‘proof of concept’ stage, i.e. to assess whether the available evidence suggests that success is ‘reasonably likely’ on the basis of the presence of key success attributes and lack of failure attributes [21, 27]. However, these risk–benefit tools, such as the Clinical Utility Index, may inform the likelihood of clinical efficacy or safety but do not necessarily link to the commercial viability of the intervention: estimates suggest that in 2005/2006, approximately 50 % of pharmaceuticals that achieved proof of concept proceeded to development. Of these, the registration rate varied from approximately 20 % for cardiovascular drugs to 8–12 % for oncology drugs, despite oncology drugs having the highest rate of successful ‘proof of concept’ [27].

It has also been acknowledged that appropriate comparative clinical evidence, demonstrating an additional therapeutic value of a pharmaceutical, may be lacking at the time of the launch because of the use of inadequate comparators, control groups or outcomes. The EVITA tool was developed as a simple, transparent tool for early evaluation of the additional therapeutic value of a pharmaceutical. The tool assesses clinical benefit, e.g. improved efficacy and reduced adverse events, and follows an algorithm that captures the relevance of outcomes and the strength of evidence [23].

Furthermore, the volumes of data required to demonstrate the incremental benefit of a new pharmaceutical are increasing. A number of tools have been developed to aid in the critical appraisal of evidence, such as an assessment tool for prospective observational studies developed by an ISPOR task force [24]. This tool consists of 33 questions to assess the relevance and credibility of a study, and it was developed to allow an individual to critically appraise an individual study to assess whether it is of sufficient quality to be included within a body of evidence for a new technology appraisal.

Two further approaches—MCDA and a US-based payer assessment framework—were identified, which were considered to be more closely aligned with the purpose of the pilot conceptual framework (i.e. to take into account budgetary factors that can influence decision makers in an ever-increasingly resource-constrained environment), rather than focusing on clinical data. Moreover, MCDA takes into consideration multiple criteria and scores each criterion on the basis of importance or relevance to generate an overall estimate [28]. An MCDA-based decision-making approach has already been piloted by the Office of Health Economics (OHE) for the assessment of orphan indications in the UK [29], and in the USA, there is an MCDA-based decision-making framework for prioritisation of vaccines [28]. However, it is important to note that this type of approach to assessments is not widely used by major HTA bodies such as HAS, IQWIG or NICE. The EVIDEM framework has been developed to assess healthcare interventions using an MCDA core model and context-specific decision criteria with the aim of bridging HTA and MCDA approaches [22]. EVIDEM assigns 15 decision-making determinants to form an MCDA value matrix (Table 1). Each criterion is scored, and a weight is allocated to generate a final score. However, there are some components that are not quantifiable, such as ethical factors (opportunity costs, population priority, access and fairness) and context (system capacity and appropriate use of an intervention). Furthermore, some methodological issues have also been identified that can arise when applying this method to HTA—in particular, choosing the criteria to include in the decision process, choosing an appropriate scoring or weighting method, or modelling scores and weights [30, 31]. Although interest in the MCDA approach has been expressed, there is a lack of guidance on the appropriate approach to conducting such an analysis, and the complexity and length of the analysis may impact upon its wider utilisation.

A US-based payer assessment framework is also being developed by the Institute for Clinical and Economic Review [26]. This value framework is a categorical, part quantitative, part qualitative approach to assessing the value of a pharmaceutical. The tool aims to improve the reliability and consistency of decisions by payers and to provide the basis for transparent discussions between the pharmaceutical company and decision makers when value is being considered [26].

Established HTA agencies (e.g. CADTH, HAS, IQWiG, PBAC, KCE, TLV and NICE) inform decisions on coverage and reimbursement for a new pharmaceutical. Both comparative effectiveness and cost effectiveness are considered within these assessment procedures, which are detailed in Table 2.

Some frameworks place a greater emphasis on certain criteria—for example, NICE in the UK, PBAC in Australia, KCE in Belgium and TLV in Sweden focus on the economic element of the review in cost–utility or cost-effectiveness analyses presented by pharmaceutical companies, alongside assessments of the comparative clinical benefit [6, 9, 18‐20, 28]. All of the frameworks consider life-years gained or quality-adjusted life-years (QALYs) as appropriate measures of effect in economic analyses; however, it is worth pointing out that only NICE uses a specific threshold for each QALY gained (i.e. £20,000–£30,000) [6], and TLV uses an individual’s willingness to pay per QALY gained threshold rather than a set budgetary threshold, while PBAC and KCE do not use an explicit cost-effectiveness threshold when assessing new pharmaceuticals [9, 18, 32]. Despite that, it is important to note that within single countries, there may be different payer bodies, depending on the geography or the nature of the pharmaceutical. For example, the NICE assessment procedure is not applied to all new pharmaceuticals launched in the UK and, in addition, the CDF was established in 2010 to provide access to cancer therapies that are not approved or not reviewed by NICE [33]. The assessment criteria used by the CDF, in its current form, are slightly different from those used by NICE, mainly prioritising the magnitude of survival and toxicity, as well as unmet need and strength of evidence over costs and cost effectiveness (Table 2) [33, 34]. However, it is worth noting that a new assessment process led by NICE for the appraisal of cancer drugs is expected in 2016 [35].

In other established HTA countries in Europe, there is a different approach by payers to the assessment of new technologies. In Germany, there is a clear separation of the assessment of added clinical benefit from the assessment of cost effectiveness [8]. In particular, IQWiG is usually commissioned by the Gemeinsamer Bundesausschuss (G-BA) to conduct an early benefit assessment of a health technology to determine whether there is proof of added or comparable patient-relevant clinical benefit. Price negotiations are completed only following a decision on the added patient-relevant clinical benefit of a pharmaceutical. In exceptional cases, i.e. when pricing negotiations fail to reach an agreement between a pharmaceutical company and the national statutory health insurance association, a health economic analysis may be conducted [8]. On the other hand, in France, clinical assessments are carried out first during the HTA of a new pharmaceutical, followed by economic evaluations if an appropriate level of clinical benefit is achieved and if the new pharmaceutical is anticipated to have a significant budget impact on the healthcare system. However, their outputs are used to inform different decisions. For example, the added clinical benefit of a medical intervention is used as a criterion for reimbursement decisions, while cost-effectiveness results are used during pricing negotiations [36].

Because of the recognised differences in approaches across Europe, the European body EUnetHTA has also developed a core framework for the assessment of pharmaceuticals, which embodies all of the core criteria typically used across Europe (Table 2).

Furthermore, in addition to national HTA processes, extra guidance has been developed to complement the national HTA process. For example, in Canada, in addition to a national body review by the CADTH [16], there are regional drug assessments, such as those conducted by the Ontario Health Technology Advisory Committee (OHTAC). OHTAC has developed its own framework for assessment (the Ontario DD framework), which also encompasses many of the national-level assessment criteria but explicitly includes an assessment of the feasibility of implementation in the current healthcare system, which is important for regional or local-level decision making [37].

The identified frameworks assess a broad range of criteria, each of which has differing subcriteria or associated key questions, which vary depending on the perspective taken and the purpose of the tool or framework. The criteria assessed by each framework were categorised into 11 broader criteria: efficacy outcomes, safety outcomes, QoL outcomes, unmet need, environment, evidence quality, cost, comparator, ethics, indication and pharmaceuticals. All of the frameworks consider the clinical safety and efficacy outcomes (n = 15) as a key criterion, whereas fewer consider the dosing or formulation of a new pharmaceutical (n = 9) or ethics (n = 8); this is summarised in Fig. 3, which provides an overview of the criteria that are currently covered by the existing tools discussed in the preceding sections.

The frameworks outlined in Tables 1 and 2 were reviewed, and all criteria that were relevant from the payer perspective were considered for inclusion within the new framework (Fig. 3). The selection of the criteria deemed relevant to payers was based on a consensus from all authors of the manuscript.

As the overall objective was to develop a simple communication tool, the overall number of discrete criteria included were limited by grouping similar criteria into broader single criterion. For instance, the most frequently identified criteria were efficacy (n = 15), safety (n = 15) and QoL (n = 13), all of which represent outcomes; therefore, these were combined as a single criterion. Other criteria such as comparator (n = 13), unmet need (n = 12), cost (n = 12) and evidence quality (n = 11) were also frequently assessed by the frameworks reviewed and thus were considered by the authors to be important and distinct enough to warrant separate categories. Indication (n = 10), environment (n = 10), pharmaceutics (n = 9) and ethics (n = 8) were the least frequently identified criteria. Indication, pharmaceutics and ethics were not regarded as unique drivers of decision making from the payer perspective. Consequently, these three criteria were grouped with other categories defined above. Key aspects for ‘indication’, which are required for regulatory licensing, were incorporated under the headings of common categories that were also likely to be of interest to the payer: ‘unmet need’ and ‘outcomes’. Pharmaceutics, which included dosing formulation and pharmacokinetics, were considered potential influencers on the appropriateness of comparators and outcomes, and thus were included under the ‘comparator’ and ‘outcomes’ categories. Ethical considerations were taken into account under the ‘environment’ heading. Environment—which takes into account aspects such as clinical guidelines, drug reimbursement and healthcare systems—which are of importance to payers in their decision making, was also included as a single criterion.

Therefore, overall, six broad categories to be included in the final communication framework were identified from the existing frameworks in descending order of frequency: outcomes, comparator, unmet need (or burden/target population), affordability/value and cost (to encompass the broad range of considerations relating to costs, cost effectiveness and budgetary implications, which are of importance to the payer), number of studies/evidence quality, and environment.

The proposed list of key criteria for inclusion in the framework and the key questions and sub-questions to be answered are detailed in Table 3.

For ease of communication of this framework, we propose the following mnemonic, based on the identified broad categories: BEACON (Burden/target population, Environment, Affordability/value, Comparator, Outcomes, Number of studies/quality of evidence). The BEACON mnemonic was perceived to be simple to remember and reflective of the purpose of the summary framework, as the term has connotations of ‘guiding’ stakeholders through complex payer requirements.

It is recognised that the proposed BEACON framework provides a broad set of criteria and that in practice, the sub-questions are likely to be adapted to the respective situation, e.g. the stage of the pharmaceutical life cycle, the country and local payer priorities.

As a payer’s perception of the value of a pharmaceutical may be influenced by a number of factors, we propose that all criteria are assessed within the context of an overarching value statement and target product profile, i.e. to differentiate between decisions on expensive pharmaceuticals that are associated with a significant clinical benefit and decisions on pharmaceuticals whose clinical efficacy and safety are equivalent to those of the standard of care but that are associated with a cost saving.

Figure 4 demonstrates how the BEACON framework could be applied when payer-focused decisions are being made regarding a biosimilar, orphan drug product or high-cost oncology product (all of which are hypothetical products). A colour-coding system is proposed to highlight key areas where focus is required in the development of the new pharmaceutical, in a simple manner. It is recognised that there will be differences between regions—therefore, this assessment would need to be undertaken from different perspectives—and also that, depending on the decision problem, greater complexity may be required than the example applications presented in Fig. 4.

On the basis of this description of the benefits of the new pharmaceuticals, pharmaceutical companies can then effectively communicate the potential value of a new in-development pharmaceutical to a range of stakeholders (both internally and externally) in order to shape the future development of the pharmaceutical.