The Use of Child-Specific Utility Instruments in Decision Making in Australia

Cate Bailey, PhD, MAppSci, University of Melbourne, Victoria, Australia; and Rosalie Viney, PhD, University of Technology Sydney, New South Wales, Australia; on behalf of the QUOKKA Research Project Team

Background and Rationale
Estimating quality-adjusted life years (QALYs) is an important part of economic evaluation in healthcare. This requires robust approaches to measuring and valuing health-related quality of life (HRQoL) so that different outcomes, populations, and conditions can be compared.^2,3 These methods have typically been developed for adults and are often based on the use of specific instruments that have a standardized approach to measuring and describing quality of life and a preference-based scoring algorithm to provide values that can be used to estimate QALYs. Measures that are used in adults, however, were not designed with children (persons aged under 18 years) in mind and therefore, may be unsuitable for children’s development stages and inappropriate if children are asked to self-report their own health.⁴

"Estimating quality-adjusted life years is an important part of economic evaluation in healthcare."

The methods for eliciting preferences to provide the values may also be inappropriate for children, especially when considering children’s abilities at different ages. For instance, commonly used methods such as time trade-off and standard gamble ask respondents to make choices that involve trading off between length of life and quality of life and involve explicit consideration of death. Child-specific utility measures with relevant dimensions and suitable valuation methods are needed to value health improvements in health conditions in children,⁵ leading to a funding call from the Australian government to address this need, which has established the QUality OF Life in Kids: Key evidence to strengthen decisions in Australia (QUOKKA) program of research (https://www.quokkaresearchprogram.org/).

At the start of our research program, we wanted to know how often child-specific utility measures were used in decision making in Australia. Specifically, how many decisions on children’s medicines had been made, how many of these involved explicit considerations of quality of life, and how many were informed by child-specific, adult, or through other measures and utilities. We also asked how much the measurement and valuation of HRQoL contributed to uncertainty in decision making for children’s medicines.

Our approach
Recommendations to include medicines on the Australian Pharmaceutical Benefits Scheme (PBS), which provides subsidized access, are made by the Pharmaceutical Benefits Advisory Committee (PBAC) based on evaluation of submissions received from sponsors. The PBAC publishes public summary documents, which are summary versions of each submission and the committee’s deliberations, thus providing an excellent resource for our research question. The PBAC provides guidance to sponsors preparing submissions and has a preference for cost-utility analysis, but does not mandate the type of economic evaluation or the choice of HRQoL measures to be used in a cost-utility analysis.⁶

To determine which medicines were relevant for children, we sought information from 4 sources: (1) the World Health Organization (WHO) Model Lists of Essential Medicines for Children, (2) medicines used by children who are part of the Longitudinal Study of Australian Children (LSAC), (3) searches on the PBAC website, and (4) vaccines listed for children on the Australian National Immunisation Program. These sources were then used to develop a list of medicines for children that had been considered by PBAC since the publication of public summary documents commenced. We then determined whether submissions used cost-utility analysis using utility values or QALYs. Next, we categorized the public summary documents into whether the utilities were from child-specific measures, adult measures, or had been directly elicited.

What we found
There were 1889 submission documents available on the PBAC website from 2005 (when the documents were first available) to when we extracted the data in mid-February 2021). We had sourced 174 medicines used by children from our 4 sources, after duplicates were removed. This resulted in 62 public summary documents from PBAC submissions covering 29 medicines/vaccines (each medicine may have multiple documents). As shown in Figure 1, only 6% of the documents included child-specific HRQoL instruments, 26% used adult, and 18% used direct elicitation. In half the documents, we could not determine the sources of the utility values. The 4 documents for 2 medicines with child-specific measures both used the Health Utility Index Mark 2 (HUI2).⁷ Adult instruments used included the EQ-5D,⁸ the Assessment of Quality-of-life Questionnaire (AQoL),⁹ and 2 used the Asthma Quality of Life Questionnaire 5 Dimensions (AQL-5D).¹⁰ Direct elicitation methods included time trade-off, standard gamble, discrete choice experiment (DCE), willingness to pay, and a vertical rating scale.


Figure 1. Number of documents and medicines in 4 groups and percentage of
documents per group.

Of the 34 medicines that did not include child-specific utilities, we determined that in 85.3% of cases using child-specific utility measures would have reduced or potentially reduced uncertainty in decision making about subsidization of medicines for children (Table 1). This determination was made based on: (a) if cost-utility analysis was used in the submission, (b) whether utility values were thought to be sensitive and/or important in the economic model, and (c) whether children were a significant part of the population being considered.

 
Table 1. Numbers of medicines where the use of child-specific utility measures
may have reduced uncertainty

Child-specific utility measures
Preference-based measures have been developed for child and adolescent populations, such as the AHUM, AQoL-6D, CHU9D, EQ-5D-Y, HUI2/3, QWB, 16D, and 17D⁴; however, the HUI2 was the only measure reported in the PBAC submissions and only for 2 medicines. This may reflect the availability of appropriate preference-based measures being used in the clinical trials, as these form the basis of these submissions.

Utilities are a key input to the economic models that inform value for money, and uncertainty around utility values directly impacts the incremental cost-effectiveness ratio. Child-specific HRQoL instruments have been designed around the domains and descriptors of quality of life that are relevant to children. When used, these instruments should provide greater clarity to decision makers about how the interventions improve patient well-being in the treated population, compared to adult measures.

Non–child-specific utility measures
The use of adult measures to inform cost utility analysis of interventions for children was considered by the PBAC as not appropriate for children. For instance, in 1 case, the committee commented that “…the EQ-5D instrument was not developed for use in children, and the utilities derived describe the health of the parents of the children in several instances, rather than the health state of the children.”¹¹

The use of direct elicitation methods also raised methodological concerns; for example, adults trading off children’s lives (Atomoxetine, July 2006), and adults trading off their own lives (pneumococcal polysaccharide conjugate vaccine, November 2010). Direct elicitation techniques may also be focused directly on the specific aspects that the medicine improved without a broader consideration of quality of life; for instance, methods that were aimed at the mode of administration in the case of tobramycin (treatment of cystic fibrosis, March 2013). The committee also observed that vignette wording in these methods may introduce bias; for instance, vignettes for leuprorelin (treatment of central precocious puberty, November 2014) used the term “stunted growth.”

Uncertainty in decision making
Our finding that the lack of child-specific HRQoL measures increased uncertainty in decision making for medicines used by children highlights an important evidence gap for decision makers. In this review, we found that in almost every instance where patient HRQoL was relied on for a pediatric population, the PBAC did not have child-specific quality of life information or utility values to inform the recommendation.

Because recommendations by PBAC rely on available information, missing information on appropriate utility values is a key source of uncertainty. The consequences of inadequate or missing information about utilities are that the decisions could be based on an inappropriate incremental cost-effectiveness ratio, meaning the government could pay too much for a medicine, or not recommend a medicine, thus potentially delaying access for children and adolescents. Please see our full paper for a more complete outline of how we assessed uncertainty in this context.¹

"The lack of child-specific HRQoL measures increased uncertainty in decision making for medicines used by children highlights an important evidence gap for decision makers."

Future research
Future research directions include improving the evidence on the validity of existing child utility measures, investigation of methods for valuation of child-specific utility measures, and development of value sets for a range of countries. Another critical area is determining measures and valuation methods that are relevant at different ages, especially for younger children. It is also essential to establish the age that an adult instrument may be suitable for adolescents. Other aspects include the inclusion of child-specific instruments in clinical trials, and to develop guidelines and health technology assessment evaluation processes.

Limitations
The study relied on the information in the public summary documents, but in half of the documents reviewed, we were unable to determine the source of the utilities. These documents are summaries of the submission and evaluation, and commercial in confidence material (such as drug costs, and incremental cost-effectiveness ratios) is redacted. Further, not all aspects of the submission, including information that may not be commercial in confidence or sensitive, are reported in the documents.

Conclusions
There is increasing interest internationally
on improving the evidence base for reimbursement decision making for healthcare. We now require better evidence about children’s health-related quality of life. The use of child-specific instruments was minimal in decision making in Australia, and increased use of such instruments would reduce uncertainty in this process. Our judgment that many of the PBAC’s decisions on medicines could have been informed (providing greater certainty) through the use of child-specific instruments of HRQoL suggests that there are significant knowledge gaps about quality-of-life impacts on children.

QUality OF Life in Kids: Key evidence for decision makers in Australia (QUOKKA) research program aims to strengthen measurement and valuation of pediatric HRQoL. For information and news about our research, follow us on Twitter: @QUOKKA_Research and check our website: https://www.quokkaresearchprogram.org

References

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