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Research Article

Comparing the cost-per-QALYs gained and cost-per-DALYs averted literatures

[version 1; peer review: 3 approved]
PUBLISHED 18 Jan 2018
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Abstract

Background: We examined the similarities and differences between studies using two common metrics used in cost-effectiveness analyses (CEAs): cost per quality-adjusted life years (QALYs) gained and cost per disability-adjusted life year (DALY) averted.
Methods: We used the Tufts Medical Center CEA Registry, which contains English-language cost-per-QALY gained studies, and  Global Cost-Effectiveness Analysis (GHCEA) Registry, which contains cost-per-DALY averted studies. We examined study characteristics including intervention type, sponsor, country, and primary disease, and also analysed the number of CEAs versus disease burden estimates for major diseases and conditions across three geographic regions.
Results: We identified 6,438 cost-per-QALY and 543 cost-per-DALY studies published through 2016 and observed rapid growth in publication rates for both literatures. Cost-per-QALY studies were most likely to examine pharmaceuticals and interventions in high-income countries. Cost-per-DALY studies predominantly focused on infectious disease interventions and interventions in low and lower-middle income countries. We found discrepancies in the number of published CEAs for certain diseases and conditions in certain regions, suggesting “under-studied” areas (e.g., cardiovascular disease in Southeast Asia, East Asia, and Oceania and “overstudied” areas (e.g., HIV in Sub Saharan Africa) relative to disease burden in those regions.
Conclusions: The number of cost-per QALY and cost-per-DALY analyses has grown rapidly with applications to diverse interventions and diseases.  Discrepancies between the number of published studies and disease burden suggest funding opportunities for future cost-effectiveness research.

Keywords

Quality-adjusted life years, Disability-adjusted life years, Cost-effectiveness

Introduction

Researchers conducting cost-effectiveness analyses (CEAs) commonly use quality-adjusted life years (QALYs) or disability-adjusted life years (DALYs) as health outcome measures to account for both longevity and quality of life (or life with disability)1. These broadly applicable metrics facilitate comparisons across conditions and diseases.

Analysts have used these measures in different contexts and settings26. CEAs using the cost-per-QALY metric, which first appeared in the late 1970s, have typically focused on interventions in higher incomes settings78. In the 1990s, the World Bank and the World Health Organization (WHO) developed the DALY to quantify disease burden (reflecting both years of life lost (YLL) and years of life with disability (YLD))910. CEAs using DALYs have tended to focus on lower- and middle-income countries11.

QALYs and DALYs, which both quantify health related quality of life by assigning a value ranging from zero to one to each year with a health condition, have somewhat different methodological underpinnings12. QALY preference weights range from 0 (corresponding to “dead”) to 1 (corresponding to a hypothetical state of “perfect health”) and reflect a set of health state “attributes”, “dimensions”, or “domains” – e.g., discomfort, mobility, depression, etc. – associated with an individual’s health condition or conditions. DALY weights have a similar intuitive interpretation, although in the case of DALYs, 1 corresponds to “dead” and 0 corresponds to “perfect health. For DALYs, however, each weight corresponds not to a set of health state attributes but to a specific disease13.

DALY calculations have in the past depended on the age of the affected populations. “Age-weighting” reflected the contention that an additional life year accrued during childhood or old age is worth less than a year accrued during young and middle adulthood, when productivity contributions to societal well-being are typically greatest14,15. Because the unequal treatment of different age groups raised substantial ethical concerns, the most recent DALY calculation methods have no age-weighting16.

We analysed the cost-per-QALY gained and cost-per-DALY averted literatures to examine their growth and regional variation, and to analyze the extent to which the focus of each literature corresponded to those diseases and conditions imposing the largest burden on the population.

Methods

Data

The cost-effectiveness analysis literature. We analyzed two databases maintained by the Center for the Evaluation of Value and Risk in Health at Tufts Medical Center in Boston, Massachusetts: the Cost-Effectiveness Analysis (CEA) Registry (www.cearegistry.org), which contains information on cost-per-QALY studies, and the Global Health CEA Registry (www.ghcearegistry.org), which houses information on cost-per-DALY studies. Both registries contain information on PubMed-indexed, English-language CEAs published through 2016. Previous publications further detail the search strategies, data collection processes, and review methods, which are similar for both registries5,6. We received ethics exemption for this study because it did not involve human subjects. Data from these registries used in this analysis appear in Dataset 1 and Dataset 2; Supplemental file 1 and Supplemental file 2 contain documentation for the variables in these datasets.

Disease burden. Dataset 3 contains population disease burden estimates (total DALYs incurred) reported by the Institute for Health Metrics and Evaluation (IHME) stratified by Global Burden of Disease (GBD) Super Region17. Within each Super Region, we substratified population burden by GBD level two disease category. Dataset 3 also lists the number of articles from the cost-per-QALY literature and from the cost-per-DALY literature for each of these strata and substrata. Articles focusing on multiple countries could be counted in more than one of the Table 3 strata – e.g., if two countries of focus for a particular study belong to two distinct GBD Super Regions.

Analysis of data

Study characteristics. Using data from Dataset 1 and Dataset 2 and definitions from the World Bank and the GBD initiative, we stratified studies by: GBD Super Region, World Bank Income Level, Intervention type, Study Funder category, Prevention stage, and GBD Category. As detailed in Table 1, some of these categories are mutually exclusive, while others are not. We computed the proportion of studies in each stratum using total article counts for the cost-per-QALY and cost-per-DALY literature from Dataset 1 and Dataset 2, respectively.

Table 1. Characteristics of published CEAs using cost-per-QALY and cost-per-DALY through 2016.

Countries are classified on 2016 USD into the following categories: low-income (GNI/Capita < $1,005), lower-middle income (GNI $1,006 – $3,955), upper-middle income (GNI $3,956 – $12,235), and high-income (GNI > $12,235)18. GBD Super regions are as reported in the GBD study, 2010.

Cost-per-QALY
studies
Cost-per-DALY
studies
Overall
Number of studies64385436981
GBD Super Region
             High income89%20%84%
             Southeast Asia, East Asia, and Oceania4%11%5%
             Sub-Saharan Africa1%30%4%
             Multiple Regions#1%16%1%
             Latin America and Caribbean1%8%2%
             Central Europe, Eastern Europe, and Central Asia1%2%1%
             South Asia0%8%1%
             North Africa and Middle East1%2%1%
             NA2%3%2%
World Bank Income Category
             Low-Income and Lower-Middle-Income1%43%4%
             Upper Middle-Income and High-Income97%37%92%
             Both0%17%2%
             None2%3%2%
Intervention*
             Pharmaceutical44%32%43%
             Surgical13%8%13%
             Screening12%14%12%
             Care delivery11%17%11%
             Medical procedure12%4%12%
             Health education or behavior9%21%10%
             Immunization6%27%8%
             Other5%46%22%
Study funder*
             Government33%47%34%
             Pharmaceutical or device company29%4%27%
             Foundation10%33%11%
             Healthcare organization^4%9%5%
             None/Not determined24%24%24%
             Other8%21%9%
Prevention stage*
             Primary15%59%18%
             Secondary16%20%16%
             Tertiary62%38%60%
GBD Category
             Neoplasms18%3%17%
             Cardiovascular and circulatory diseases17%5%16%
             Diabetes, urogenital, blood, and endocrine
             diseases
12%5%11%
             Other communicable, maternal, neonatal, and
             nutritional disorders
10%7%9%
             Musculoskeletal disorders10%1%9%
             Mental and behavioral disorders6%7%6%
             HIV/AIDS and tuberculosis4%20%6%
             Digestive diseases4%1%4%
             Diarrhea, LRI, and other common infectious
             diseases
2%20%3%
             Other18%31%19%

Key: # “Multiple regions” refers to studies that reported cost-effectiveness estimates for countries in different regions.

^ Health care organizations include insurance companies, hospitals, HMOs, WHO.

* Not mutually exclusive

GBD: Global burden of disease

GNI: Gross National Income

HMO: Health maintenance organization

LRI: Lower respiratory infection

WHO: World Health Organization

Based on these counts and proportions, we report the proportion of studies in each stratum (Table 1), number of cost-per-QALY and cost-per-DALY studies published by year (Figure 1), proportion of published CEAs stratified by World Bank country income category and by study type (cost-per-QALY or cost-per-DALY) (Figure 2), and number of cost-per-QALY and cost-per-DALY studies focusing on each country (Figures 3A and 3B).

7935a36e-c859-45fc-8420-b5808cce9f79_figure1.gif

Figure 1. Published cost-per-DALY and cost-per-QALY studies by year.

Journals published 360 cost-per-QALY studies during the years 1976 through 2000. Journals published 13 cost-per-DALY studies during the years 1995 through 2000.

7935a36e-c859-45fc-8420-b5808cce9f79_figure2.gif

Figure 2. Cost-per-QALY vs. cost-per-DALY studies by world bank income level.

The area of each pie chart is proportional to the number of studies catalogued in each registry.

7935a36e-c859-45fc-8420-b5808cce9f79_figure3.gif

Figure 3.

Number of published cost-per-QALY (3A) and cost-per-DALY (3B) studies by country. The maps present the number of cost-per-QALY and cost-per-DALY studies for each country. Gray countries did not have any studies associated with them. If a study reported a cost-effectiveness estimate for two or more countries, we counted a CEA for each country (e.g. if a study reviewed an intervention in both Canada and the United States, both countries were counted for that study). If a study reported a “global” cost-effectiveness ratio, we excluded it from the counts used to produce this map. We also excluded from these counts studies that did not clearly specify an applicable country or region. (3A) We excluded one study classified as “international”. We excluded 144 studies because the country of study was unclear. (3B) We excluded 13 studies classified as “international”. We excluded 16 studies because the country of study was unclear.

Literature coverage vs. disease burden. We characterized the relationship between the number of CEA studies (cost-per-QALY plus cost-per-DALY) focusing on each disease and corresponding normalized burden for each of three GBD Super Regions: Southeast Asia, East Asia, and Oceania; high-income countries; and Sub-Saharan Africa. We limited attention to the top 10 diseases by total population DALY burden for each of these regions. We computed normalized disease burden as total DALYs attributed to each disease in a Super Region divided by that Super Region’s population. Finally, we identified “under-studied” diseases in each Super Region – i.e., diseases with a normalized burden in excess of the average for other diseases with the same coverage in the literature.

Each figure panel includes a diagonal line that represents the average disease burden as a function of the number of CEA studies (Figures 4A–C). Diseases plotted to the “northwest” of this line are “understudied” within that region because the disease-burden is higher, on average, for that disease than it is for other diseases receiving the same level of attention in the literature.

7935a36e-c859-45fc-8420-b5808cce9f79_figure4.gif

Figure 4. Number of CEAs vs. normalized disease burden for selected diseases and GBD Super Regions.

The figures show the relationship between literature coverge (number of cost-per-QALY plus cost-per-DALY studies) focusing on each disease (horizontal axis) and corresponding normalized disease burden (vertical axis) for each of three GBD Super Regions: (4A) Southeast Asia, East Asia, and Oceana; (4B) high-income countries; and (4C) Sub-Saharan Africa. Each panel displays results for the top 10 diseases by total population DALY burden in that region. Normalized disease burden on the vertical axis is the total number of DALYs attributed to each disease in that panel’s Super Region divided by the Super Region’s population. Each figure panel includes a diagonal line representing average disease burden as a function of literature coverage (total published CEAs). Each disease plotted above this line is “understudied” because its burden is higher, on average, than the corresponding burden for other diseases receiving the same level literature coverage.

Results

We identified 6,438 cost-per-QALY (Dataset 1) and 543 cost-per-DALY (Dataset 2) studies published up to 2016. The number of published studies in the cost-per-QALY and cost-per-DALY literatures has increased steadily since 2000 (Figure 1).

Study characteristics

Cost-per-QALY studies have tended to focus on upper-middle income and high-income countries (97%); e.g. United States has 2,321 and United Kingdom 1,149. Cost-per-DALY studies have focused to a much greater extent on low and lower-middle income countries (43%); e.g. India has 95, China has 51, and Uganda has 90 (Table 1, Figure 2, Figure 3A and 3B).

Tertiary prevention (treatment) dominated the cost-per-QALY registry (e.g. pharmaceuticals, 44%; surgery, 13%), whereas the cost-per-DALY registry focused far more on primary prevention (e.g. immunizations, 27%). Conditions most frequently addressed by studies in the cost-per-QALY literature included non-communicable diseases, such as cancer (18%) and cardiovascular diseases (17%), whereas most cost-per-DALY registry studies targeted infectious diseases.

Non-governmental cost-per-DALY study funding came most often from foundations (33%), while cost-per-QALY study funding derived most often from pharmaceutical or device companies (29%).

Literature coverage vs. disease burden

Neoplasms were the most studied diseases in Southeast Asia, East Asia, and Oceania (Figure 4A), while mental and behavioral disorders were less studied relative to their burden. High-income countries (Figure 4B) had relatively few studies addressing mental and behavioral disorders, and injuries. Relative to burden, HIV/AIDS and tuberculosis were the most studied diseases in Sub-Saharan Africa, while this region reported fewer studies on nutritional deficiencies (Figure 4C).

Discussion

Our review reveals a notable increase in the publication of cost-per-QALY and cost-per-DALY studies since 2000, thus making ever more cost-effectiveness information available to aid decision makers in their efforts to prioritize resources. The literature spans a wide range of interventions, diseases, and geographic regions.

The data demonstrate key differences between the cost-per-QALY and cost-per-DALY literatures (Table 1). The cost-per-QALY literature focuses on high-income countries, while cost-per-DALY studies focus more on lower- and middle-income income nations. This contrast seems to reflect the historic proclivities of health economist researchers, rather than any inherent advantages for one metric’s use for a particular category of countries. The differences extend to the types of interventions and diseases represented: cost-per-QALY studies tend to address diseases of wealthier countries (e.g., cardiovascular disease and cancer), while cost-per-DALY studies address diseases more prevalent in low-income countries (e.g., infectious diseases, such as tuberculosis and HIV). The two literatures also differ in terms of the interventions on which they focus. More cost-per-QALY studies evaluate pharmaceuticals, while cost-per-DALY studies focus more often on immunizations.

The most commonly studied diseases, regions, and interventions may reflect the financial interests of the CEA funders. For instance, pharmaceutical companies invest in pharmaceutical CEAs in high-income countries.

Our data also indicate discrepancies between literature coverage and burden of disease. These analyses suggest that some diseases and conditions (e.g., cardiovascular disease and mental health in Southeast Asia, South Asia and Oceania) are “understudied,” while other diseases and conditions (e.g., HIV in Sub-Saharan Africa) are “overstudied”. These discrepencies may represent opportunities for the re-direction of CEA research funding in the future.

Data availability

We have made the data used in this analysis available through the Open Science Foundation (OSF): http://doi.org/10.17605/OSF.IO/3BEK519.

License: CC0 1.0 Universal.

Dataset 1. Cost-per-QALY dataset.

Includes the cost-per-QALY data used in this paper.

Dataset 2. Cost-per-DALY dataset.

Includes the cost-per-QALY data used in this paper.

Dataset 3. Regional and disease level stratification dataset.

Includes disease burden and literature coverage data used in this paper.

Supplementary Material

Supplementary File 1. Cost-per-QALY manual. Documents the variables collected in the cost-per-QALY database.

Click here to access the data.

Supplementary File 2. Cost-per-DALY manual. Documents the variables collected in the cost-per-DALY database.

Click here to access the data.

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Neumann PJ, Anderson JE, Panzer AD et al. Comparing the cost-per-QALYs gained and cost-per-DALYs averted literatures [version 1; peer review: 3 approved]. Gates Open Res 2018, 2:5 (https://doi.org/10.12688/gatesopenres.12786.1)
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Version 2
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