Which multi-attribute utility instruments are recommended for use in cost-utility analysis? A review of national health technology assessment (HTA) guidelines

Several methods of economic evaluation are utilized in health technology assessment (HTA), including cost-utility analysis (CUA), a form of cost-effectiveness analysis that assesses the value of interventions, typically according to the incremental cost per quality-adjusted life-year (QALY). A patient’s health state preferences may be measured directly to derive utilities, using methods such as standard gamble (SG) or time trade-off (TTO). Utilities may also be determined indirectly by means of generic or disease-specific preference-based questionnaires, with responses mapped onto a utility scale using an algorithm that attaches weights—generally derived from societal preferences for health states. Generic multi-attribute utility instruments (MAUIs) are commonly used for the indirect measurement of utilities. Several MAUIs are available for indirect measurement of utilities in CUA, including the EQ-5D (two versions: EQ-5D-3L and EQ-5D-5L) [1], the Short-Form 6-Dimension (SF-6D) [2], the Health Utilities Index (two versions: HUI2 and HUI3) [3], Assessment of Quality of Life (several versions, e.g. AQoL 6D and 8D) [4], 15D [5], VR-6D [6] and the Quality of Well-Being (QWB) instrument [7]. Each MAUI has its own descriptive health classification system and preference-based algorithm used to derive utility scores [8].

Official pharmacoeconomic (PE) guidelines inform manufacturers and others on which methods to follow with respect to CUA to support applications for access, reimbursement, or pricing. Understanding these recommended methods is important to facilitate planning for studies and gain a better appreciation of the needs of decision-makers. There is no international consensus about the content of PE guidelines, so recommendations differ among countries around the world [9].

As such, the objective of this review was to identify recommendations from official national PE guidelines about the use of MAUIs within CUA; in addition, the review sought to understand in which countries national preference weights (value sets) were required for the determination of utilities using a MAUI.

The objective of this review was to provide an overview of recommendations from HTA agencies on the use of MAUIs in CUA. As far as we are aware, this is the first published review to comprehensively summarize the contents of HTA guidelines relating to the use of MAUIs in CUA around the world. Previous reviews, such as the 2017 study by Rowen and colleagues [9], have also explored this topic but restricted themselves to specific countries/regions (Australia, Canada, Catalonia, England and Wales, France, Germany, The Netherlands, Scotland, Sweden). In a 2016 review of the use of EQ-5D in Central and Eastern Europe, Rencz and colleagues [12] noted the countries where EQ-5D is recommended in HTA guidelines. Others have taken a much broader approach in their summaries of HTA guidelines and only briefly consider recommendations on MAUIs [13].

Six MAUIs were recommended or cited in guidelines; EQ-5D, HUI, and SF-6D were the most frequently mentioned, with EQ-5D found to be the most dominant measure. Of the 34 sets of guidelines from around the world that were identified in the review, EQ-5D was mentioned in 85% (n = 29) as a preferred instrument for the determination of health utilities or as an example of a suitable instrument. Whenever a guideline-recommended specific MAUIs (n = 15 guidelines), EQ-5D was found to be the only preferred instrument in 13 guidelines and one of two preferred instruments, along with another MAUI or the DALY, in the remaining two guidelines. No other MAUI came close to this level of prominence. Reasons provided in some of the PE guidelines for preferring a particular MAUI include that EQ-5D is a commonly used instrument enabling consistency and comparability between data sets, and that a national value set is available (Table 2).

The dominance of EQ-5D as a MAUI used in clinical studies mirrors the preferences provided in the PE guidelines. A review of articles listed on the Web of Science between 2005 and 2010 identified 1663 studies that had included a MAUI [14]. Of these, 63% used EQ-5D; 15% the HUI2 or HUI3; 9% the SF-6D; and the remaining 15% used the 15D, QWB, or AQoL.

Most of the guidelines referred to EQ-5D in general or to the EQ-5D-3L version. Some of these PE guidelines are several years old, and therefore the number citing the EQ-5D-5L—developed to increase sensitivity (discriminatory power) while maintaining ease of use [15]—remains relatively low.

Of the 19 PE guidelines that recommend CUA, but provide no preference for a specific MAUI, 12 included a preference for MAUIs utilizing national value sets. The use of some MAUIs could, therefore, be limited in PE analysis in these countries, since preference weights in the national general population may not be available.

It is interesting to note that official PE guidelines were available from only 34 countries that specified the use of QALYs for use in CUA within economic evaluations. Although this may in part reflect policy decisions by a few governments to use different methods to assess the value of medications (e.g. in Germany), in other countries the lack of detailed published guidelines is more likely to reflect the current more nascent state of their HTA systems. However, as resources available for public healthcare continue to be stretched around the globe, it will be increasingly important for policymakers to be supported with the best available evidence on new and existing medications to make informed choices with respect to resource allocation [16]. Consequently, the HTA environment will continue to develop, most notably as countries that did not previously have systems in place (e.g. in parts of Eastern Europe, Latin America, and Asia) begin to develop and implement them [17‐20]. As these HTA systems evolve, more official PE guidelines will be developed and the number recommending the use of indirect methods for deriving utilities within CUA can be expected to grow accordingly.

Guidelines relating specifically to medical devices or technology were considered outside the scope of this review. However, as in the present study, a recently published review of European HTA guidelines for medical devices also found that EQ-5D was the most frequently mentioned MAUI and it was the preferred measure in most national HTA guidelines [21].

While the current review provides some interesting insights into recommendations on MAUI use in official PE guidelines, the findings must be interpreted within the limitations of the study. Although a wide range of sources was reviewed, and references cross-checked, some guidelines may have been overlooked. Likewise, some of the guidelines were not available in English, Dutch, or German, necessitating online translation. Although such translations were validated by local experts, there is always a risk that some ambiguity remains. In some cases, it was also unclear which guideline from a particular country should be used and included in the review; and it may be that even in countries where official PE guidelines do exist, these are not published or publicly available and would not have been identified by the current searches. A further limitation of the review is that supplemental informal guidance may be provided by HTA authorities in addition to that published in official guidelines.

Finally, it is important to recognize that the HTA environment is continually evolving and an overview of the sort provided here can quickly become outdated. For example, several countries (e.g. Argentina) are considering developing new HTA structures, and existing PE guidelines will also be refined as the science of economic evaluation evolves. Regular updating of the review is, therefore, required.

Published official PE guidelines from around the world were identified in the current review. There appears to be substantial consensus among them in terms of choice of MAUI instruments, and three instruments (EQ-5D, HUI, SF-6D) are each cited in at least 10 country guidelines. By far the most common was the EQ-5D, which was cited in 85% of PE guidelines either as the preferred MAUI or as an example of a suitable MAUI for use in CUA in HTA economic evaluations. The preference for EQ-5D in guidelines was variously described as being due to its widespread use in studies, enabling consistency and comparability, and the availability of national value sets. Where PE guidelines provided examples of MAUIs but did not give a preference, a majority explicitly recommended the use of national value sets for the determination of utilities.

This review provides an overview of the global picture on preferences for the use of the MAUIs in official PE guidelines. It also provides insight for stakeholders seeking to understand what instruments are used in HTA across different countries, and for those developing HTA systems and PE guidelines in countries that have not previously been part of the landscape.