Quality-of-life effects of screening mammography in Norway.

Mammography screening may save women from dying of breast cancer, although it has not been shown to reduce all-cause mortality. Screening also leads to overdiagnosis and many false positive mammograms aggravating women's quality-of-life. Quality adjusted life years (QALY) analyses of mammography screening have so far, calculated life years gained assuming that all prevented breast cancer deaths translate into a reduction in all-cause mortality. We calculated net QALYs in two hypothesized cohorts of 100,000 Norwegian women; one screened biennially from age 50 to 69 years and one not screened. We followed both cohorts to age 85 years. We used EQ-5D and an alternative equity weighted QALY instrument to estimate utility losses. In the screening cohort, we assumed 20% false positive tests during screening, different levels of overdiagnosis (20-75%) and different levels of breast cancer mortality reduction (10-30%). We assumed that reductions in breast cancer mortality only to a limited extent (20, 50 or 80%), resulted in reductions in all-cause mortality. We calculated both undiscounted and discounted (4%) QALYs. Assuming that 50% of the reduction in breast cancer mortality translated to a reduction in all-cause mortality and using estimated levels of benefits and harms in modern screening programs (50-75% overdiagnosis and 10% reduction in breast cancer mortality), undiscounted equity weighted QALY loss varied from 437 to 875 per 100,000 women. Using the levels of benefit and harms as reported in 30-40 years old randomized trials (30% overdiagnosis and 15% reduction in breast cancer mortality), undiscounted equity weighted QALY gain was 535 per 100,000. Net QALY in modern mammography screening in Norway is negative. Results could also be representative for Sweden, Denmark, UK and the US.

Determining Value in Health Technology Assessment: Stay the Course or Tack Away?

The economic evaluation of new health technologies to assess whether the value of the expected health benefits warrants the proposed additional costs has become an essential step in making novel interventions available to patients. This assessment of value is problematic because there exists no natural means to measure it. One approach is to assume that society wishes to maximize aggregate health, measured in terms of quality-adjusted life-years (QALYs). Commonly, a single 'cost-effectiveness' threshold is used to gauge whether the intervention is sufficiently efficient in doing so. This approach has come under fire for failing to account for societal values that favor treating more severe illness and ensuring equal access to resources, regardless of pre-existing conditions or capacity to benefit. Alternatives involving expansion of the measure of benefit or adjusting the threshold have been proposed and some have advocated tacking away from the cost per QALY entirely to implement therapeutic area-specific efficiency frontiers, multicriteria decision analysis or other approaches that keep the dimensions of benefit distinct and value them separately. In this paper, each of these alternative courses is considered, based on the experiences of the authors, with a view to clarifying their implications.

Beyond QALYs: Multi-criteria based estimation of maximum willingness to pay for health technologies.

The QALY is a useful outcome measure in cost-effectiveness analysis. But in determining the overall value of and societal willingness to pay for health technologies, gains in quality of life and length of life are prima facie separate criteria that need not be put together in a single concept. A focus on costs per QALY can also be counterproductive. One reason is that the QALY does not capture well the value of interventions in patients with reduced potentials for health and thus different reference points. Another reason is a need to separate losses of length of life and losses of quality of life when it comes to judging the strength of moral claims on resources in patients of different ages. An alternative to the cost-per-QALY approach is outlined, consisting in the development of two bivariate value tables that may be used in combination to estimate maximum cost acceptance for given units of treatment-for instance a surgical procedure, or 1 year of medication-rather than for 'obtaining one QALY.' The approach is a follow-up of earlier work on 'cost value analysis.' It draws on work in the QALY field insofar as it uses health state values established in that field. But it does not use these values to weight life years and thus avoids devaluing gained life years in people with chronic illness or disability. Real tables of the kind proposed could be developed in deliberative processes among policy makers and serve as guidance for decision makers involved in health technology assessment and appraisal.

Determining the value of medical technologies to treat ultra-rare disorders: a consensus statement.

BACKGROUND: In most jurisdictions, policies have been adopted to encourage the development of treatments for rare or orphan diseases. While successful as assessed against their primary objective, these policies have prompted concerns among payers about the economic burden that might be caused by an annual cost per patient in some cases exceeding 100,000 Euro. At the same time, many drugs for rare disorders do not meet conventional standards for cost-effectiveness or 'value for money'. Owing to the fixed (volume-independent) cost of research and development, this issue is becoming increasingly serious with decreasing prevalence of a given disorder. METHODS: In order to critically appraise the problems posed by the systematic valuation of interventions for ultra-rare disorders (URDs), an international group of clinical and health economic experts was convened in conjunction with the Annual European ISPOR Congress in Berlin, Germany, in November 2012. Following this meeting and during subsequent deliberations, the group achieved a consensus on the specific challenges and potential ways forward. RESULTS: The group concluded that the complexities of research and development for new treatments for URDs may require conditional approval and reimbursement policies, such as managed entry schemes and coverage with evidence development agreements, but should not use as justification surrogate end point improvement only. As a prerequisite for value assessment, the demonstration of a minimum significant clinical benefit should be expected within a reasonable time frame. As to the health economic evaluation of interventions for URDs, the currently prevailing logic of cost-effectiveness (using benchmarks for the maximum allowable incremental cost per quality-adjusted life year gained) was considered deficient as it does not capture well-established social preferences regarding health care resource allocation. CONCLUSION: Modified approaches or alternative paradigms to establish the 'value for money' conferred by interventions for URDs should be developed with high priority.

Cost-value analysis of health interventions: introduction and update on methods and preference data.

According to the consensus statement from the International Society for Pharmacoeconomics and Outcomes Research Quality-Adjusted Life-Year (QALY) workshop in Philadelphia in 2007 "concerns for fairness may cause social resource allocation preferences to deviate considerably from the ranking that consideration of costs per QALY would suggest." Salient concerns for fairness include the view that priority should be given to the severely ill over the less severely ill, that people have a right to realize their potential for health even if their capacity to benefit from treatment is moderate, and that everybody has the same right to treatment that averts premature death, even if their health and functional level is less than perfect. Cost-value analysis incorporates these concerns in formal economic evaluation of health interventions and programs and thus has a potential for ranking interventions and programs in a way that is more consistent with societal values. Data on the strength of public concerns for fairness are now sufficient to be useful in formal economic evaluation. The data may, within a context of fair and open deliberations, help societal decision makers to roughly indicate the societal value of a QALY in different circumstances and thus determine a tentative grading of willingness to pay for a QALY.

Transforming EQ-5D utilities for use in cost­value analysis of health programs.

In a number of jurisdictions there is increasing interest in incorporating concerns for fairness in models for economic evaluation of health interventions. Cost­value analysis is a name for evaluations with such a broader aim. The most widely held concern for fairness is a concern for the worse off, i.e. the idea that severity of illness should count in determining priorities. In economic evaluations of improvements in health-related quality of life this concern may be taken into account by replacing conventional health state utilities with societal values for health states that are characterised by strong upper end compression and decreasing marginal value of utility gains. We review evidence on the strength of concerns for the worse off--measured at the cardinal level--in 15 articles published in peer-reviewed journals in the time period 1978­2010, with reports from altogether 20 individual studies in nine different countries. We report 116 individual observations of paired comparisons of utility improvements with different start levels. Concerns for severity show up quite strongly across countries, sample types and question framings. By means of regression analyses we fit a societal value function to the data that has the property of decreasing marginal value of utility gains. Using the central tendency in the data we present two plausible transformations of EQ-5D utilities into societal values that reflect concerns for the worse off.

Incremental cost per quality-adjusted life year gained? The need for alternative methods to evaluate medical interventions for ultra-rare disorders.

Drugs for ultra-rare disorders (URDs) rank prominently among the most expensive medicines on a cost-per-patient basis. Many of them do not meet conventional standards for cost-effectiveness. In light of the high fixed cost of R&D, this challenge is inversely related to the prevalence of URDs. The present paper sets out to explain the rationale underlying a recent expert consensus on these issues, recommending a more rigorous assessment of the clinical effectiveness of URDs, applying established standards of evidence-based medicine. This may include conditional approval and reimbursement policies, which should be combined with a firm expectation of proof of a minimum significant clinical benefit within a reasonable time. In contrast, current health economic evaluation paradigms fail to adequately reflect normative and empirical concerns (i.e., morally defensible 'social preferences') regarding healthcare resource allocation. Hence there is a strong need for alternative economic evaluation models for URDs.

Guidance on priority setting in health care (GPS-Health): the inclusion of equity criteria not captured by cost-effectiveness analysis.

This Guidance for Priority Setting in Health Care (GPS-Health), initiated by the World Health Organization, offers a comprehensive map of equity criteria that are relevant to health care priority setting and should be considered in addition to cost-effectiveness analysis. The guidance, in the form of a checklist, is especially targeted at decision makers who set priorities at national and sub-national levels, and those who interpret findings from cost-effectiveness analysis. It is also targeted at researchers conducting cost-effectiveness analysis to improve reporting of their results in the light of these other criteria. THE GUIDANCE WAS DEVELOP THROUGH A SERIES OF EXPERT CONSULTATION MEETINGS AND INVOLVED THREE STEPS: i) methods and normative concepts were identified through a systematic review; ii) the review findings were critically assessed in the expert consultation meetings which resulted in a draft checklist of normative criteria; iii) the checklist was validated though an extensive hearing process with input from a range of relevant stakeholders. The GPS-Health incorporates criteria related to the disease an intervention targets (severity of disease, capacity to benefit, and past health loss); characteristics of social groups an intervention targets (socioeconomic status, area of living, gender; race, ethnicity, religion and sexual orientation); and non-health consequences of an intervention (financial protection, economic productivity, and care for others).

Concerns for severity in priority setting in health care: a review of trade-off data in preference studies and implications for societal willingness to pay for a QALY.

OBJECTIVE: In a wide range of health care jurisdictions, to give priority to the severely ill over the less severely ill is important in decisions about resource allocation across patient groups. We summarise data on concerns for severity measured at a cardinal level in preference studies in various countries and show how the data may provide guidance for determining severity graded willingness to pay for a QALY. METHODS: We review evidence in 15 articles published in peer reviewed journals in the time period 1978-2010, with reports from altogether 20 individual studies in 9 different countries. The studies all focus on the quality of life dimension of severity, i.e. utility losses on the 0-1 scale used in QALY-calculations. We report 116 individual observations of paired comparisons of utility improvements with different start levels. We argue that the strength of concerns observed on the quality of life dimension may be assumed to apply also to losses in length of life and thus to severity in terms of proportional shortfall of QALYs. By means of regression analyses we estimate a severity gradient in each study that suggests the span in societal willingness to pay for a QALY to people at high and low levels of severity respectively. RESULTS: Concerns for severity show up quite strongly across countries, sample types and question framings, although the size of the severity gradient varies very much. Interested policy makers may hopefully find the central tendency in the results to be useful as an input to determining severity dependent willingness to pay for a QALY.

Disability weights in the Global Burden of Disease 2010: unclear meaning and overstatement of international agreement.

The Global Burden of Disease Project (GBD) is a huge international enterprise that provides vast amounts of valuable data on (a) the prevalence of different diseases in the world as a whole, in regions and in individual countries, (b) their causes (risk factors), and (c) their burden on populations in terms of Disability Adjusted Life Years (DALYs). However, the methods used for disability weighting of life years are problematic. After a long history of changing concepts and methods the GBD in its 2010 version has landed on 'health' as a unidimensional construct to be used for weighing multi-dimensional non-fatal health problems against each other and against death. The unidimensional health construct does not have a clear meaning. It likely also leads to biases in assessments of conditions that in everyday language are associated with 'being ill' as opposed to conditions which are not associated with 'being ill' (states of physical disability and the state dead). Furthermore, the transformation of ordinal data from paired comparisons into disability weights with purported ratio scale properties is not validated nor explained in a way that allows judgements of face validity. There are also issues related to the way in which different health problems were described to respondents. Lastly, international agreement on disability weights is clearly overstated. Policy makers at national and international levels should understand the GBD 2010 methods properly and carefully consider their validity before deciding to implement the methods, or the disability weights estimated so far by means of them, in further projects and studies. Considerable local adjustments of the weights offered presently are a likely outcome of such methodological scrutiny.

A randomized controlled trial of a senior centre group programme for increasing social support and preventing depression in elderly people living at home in Norway.

BACKGROUND: Late-life depression is a common condition and a challenging public health problem. A lack of social support is strongly associated with psychological distress. Senior centres seem to be suitable arenas for community-based health promotion interventions, although few studies have addressed this subject. The objectives were to examine the effect of a preventive senior centre group programme consisting of weekly meetings, on social support, depression and quality of life. METHODS: A questionnaire was sent to a random sample of 4,000 persons over 65 in Oslo, and a total of 2,387 completed questionnaires were obtained. These subjects served as a basis for recruitment of participants for a trial, with scores on HSCL-10 being used as a main inclusion criterion. A total of 138 persons were randomized into an intervention group (N = 77) and control group (N = 61). Final analyses included 92 persons. Social support (OSS-3), depression (BDI), life satisfaction and health were measured in interviews at baseline and after 12 months (at the end of the intervention programme). Perceptions of benefits from the intervention were also measured. Mean scores, SD, SE and CI were used to describe the changes in outcomes. Effect sizes were calculated based on the original scales and as Cohen's d. Paired sample tests and ANOVA were used to test group differences. RESULTS: There was an increase in social support in both groups, but greatest in the intervention group. The level of depression increased for both groups, but more so in the control than the intervention group. There was a decrease in life satisfaction, although the decrease was largest among controls. There were almost no differences in reported health between groups. However, effect sizes were small and differences were not statistically significant. In contrast, most of the participants said the intervention meant much to them and led to increased use of the centre. CONCLUSIONS: In all probability, the intervention failed to meet optimistic targets, but possibly met quite modest ones. Since intention-to-treat analysis was not possible, we do not know the effect on the intervention group as a whole. A further evaluation of these programmes is necessary to expand the group programme. For the depressed, more specialized programmes to cope with depression may be a more appropriate intervention. TRIAL REGISTRATION: DRKS00003120 on DRKS.

Measuring concerns for severity: re-examination of a health scale with purported equal interval properties.

Severity of illness is an important official criterion for priority setting in health care in a number of jurisdictions. An 8-point scale of severity and functional status has been used in a number of studies in Norway in order to estimate the strength of concerns for severity in population samples. The scale has attracted international attention and may be of interest to researchers in other countries. For confidence in interpretations of results, the scale should have equal interval properties with respect to individual utility. Close examination suggest that some deviations from equal intervals occur. These deviations do not impact significantly on earlier findings and do not prevent the scale from being a potentially useful tool in future studies of the strength of societal concerns for fairness in health care. However, further research with larger and more representative samples is encouraged.

Discounting future health benefits: the poverty of consistency arguments.

In economic evaluation of health care, main stream practice is to discount benefits at the same rate as costs. But main papers in which this practice is advocated have missed a distinction between two quite different evaluation problems: (1) How much does the time of program occurrence matter for value and (2) how much do delays in health benefits from programs implemented at a given time matter? The papers have furthermore focused on logical and arithmetic arguments rather than on real value considerations. These 'consistency arguments' are at best trivial, at worst logically flawed. At the end of the day, there is a sensible argument for equal discounting of costs and benefits rooted in microeconomic theory of rational, utility maximising consumers' saving behaviour. But even this argument is problematic, first because the model is not clearly supported by empirical observations of individuals' time preferences for health, second because it relates only to evaluation in terms of overall individual utility. It does not provide grounds for claiming that decision makers with a wider societal perspective, which may include concerns for fair distribution, need to discount Copyright © 2010 John Wiley & Sons, Ltd.