Mike Paulden

Methods to identify postnatal depression in primary care: an integrated evidence synthesis and value of information analysis.

OBJECTIVES To provide an overview of methods to identify postnatal depression (PND) in primary care and to assess their validity, acceptability, clinical effectiveness and cost-effectiveness, to model estimates of cost, to assess whether any method meets UK National Screening Committee (NSC) criteria and to identify areas for future research. DATA SOURCES Searches of 20 electronic databases (including MEDLINE, CINAHL, PsycINFO, EMBASE, CENTRAL, DARE and CDSR), forward citation searching, personal communication with authors and searching of reference lists. REVIEW METHODS A generalised linear mixed model approach to the bivariate meta-analysis was undertaken for the validation review with quality assessment using QUADAS. Within the acceptability review, a textual narrative approach was employed to synthesise qualitative and quantitative research evidence. For the clinical and cost-effectiveness reviews methods outlined by the Centre for Reviews and Dissemination and the Cochrane Collaboration were followed. Probabilistic models were developed to estimate the costs associated with different identification strategies. RESULTS The Edinburgh Postnatal Depression Scale (EPDS) was the most frequently explored instrument across all of the reviews. In terms of test performance, postnatally the EPDS performed reasonably well: sensitivity ranged from 0.60 (specificity 0.97) to 0.96 (specificity 0.45) for major depression only; from 0.31 (specificity 0.99) to 0.91 (specificity 0.67) for major or minor depression; and from 0.38 (specificity 0.99) to 0.86 (specificity 0.87) for any psychiatric disorder. Evidence from the acceptability review indicated that, in the majority of studies, the EPDS was acceptable to women and health-care professionals when women were forewarned of the process, when the EPDS was administered in the home, with due attention to training, with empathetic skills of the health visitor and due consideration to positive responses to question 10 about self-harm. Suggestive evidence from the clinical effectiveness review indicated that use of the EPDS, compared with usual care, may lead to reductions in the number of women with depression scores above a threshold. In the absence of existing cost-effectiveness studies of PND identification strategies, a decision-analytic model was developed. The results of the base-case analysis suggested that use of formal identification strategies did not appear to represent value for money, based on conventional thresholds of cost-effectiveness used in the NHS. However, the scenarios considered demonstrated that this conclusion was primarily driven by the costs of false positives assumed in the base-case model. CONCLUSIONS In light of the results of our evidence synthesis and decision modelling we revisited the examination of PND screening against five of the NSC criteria. We found that the accepted criteria for a PND screening programme were not currently met. The evidence suggested that there is a simple, safe, precise and validated screening test, in principle a suitable cut-off level could be defined and that the test is acceptable to the population. Evidence surrounding clinical and cost-effectiveness of methods to identify PND is lacking. Further research should aim to identify the optimal identification strategy, in terms of key psychometric properties for postnatal populations. In particular, research comparing the performance of the Whooley and help questions, the EPDS and a generic depression measure would be informative. It would also be informative to identify the natural history of PND over time and to identify the clinical effectiveness of the most valid and acceptable method to identify postnatal depression. Further research within a randomised controlled trial would provide robust estimates of the clinical effectiveness.

Discounting and decision making in the economic evaluation of health-care technologies

Discounting costs and health benefits in cost-effectiveness analysis has been the subject of recent debate - some authors suggesting a common rate for both and others suggesting a lower rate for health. We show how these views turn on key judgments of fact and value: on whether the social objective is to maximise discounted health outcomes or the present consumption value of health; on whether the budget for health care is fixed; on the expected growth in the cost-effectiveness threshold; and on the expected growth in the consumption value of health. We demonstrate that if the budget for health care is fixed and decisions are based on incremental cost effectiveness ratios (ICERs), discounting costs and health gains at the same rate is correct only if the threshold remains constant. Expecting growth in the consumption value of health does not itself justify differential rates but implies a lower rate for both. However, whether one believes that the objective should be the maximisation of the present value of health or the present consumption value of health, adopting the social time preference rate for consumption as the discount rate for costs and health gains is valid only under strong and implausible assumptions about values and facts.

Screening for postnatal depression in primary care: cost effectiveness analysis

Objective To evaluate the cost effectiveness of routine screening for postnatal depression in primary care. Design Cost effectiveness analysis with a decision model of alternative methods of screening for depression, including standardised postnatal depression and generic depression instruments. The performance of screening instruments was derived from a systematic review and bivariate meta-analysis at a range of instrument cut points; estimates of other relevant parameters were derived from literature sources and relevant databases. A decision tree considered the full treatment pathway from the possible onset of postnatal depression through identification, treatment, and possible relapse. Setting Primary care. Participants A hypothetical population of women assessed for postnatal depression either via routine care only or supplemented by use of formal identification methods six weeks postnatally, as recommended in recent guidelines. Main outcome measures Costs expressed in 2006-7 prices and impact on health outcomes expressed in terms of quality adjusted life years (QALYs). The time horizon of the analysis was one year. Results The routine application of either postnatal or general depression questionnaires did not seem to be cost effective compared with routine care only. The Edinburgh postnatal depression scale (at a cut point of 16) had an incremental cost effectiveness ratio (ICER) of £41 103 (€45 398,

Alitretinoin for severe chronic hand eczema: a NICE single technology appraisal

67 130) per QALY compared with routine care only. The ICER for all other strategies ranged from £49 928 to £272 463 per QALY versus routine care only, while the probability that no formal identification strategy was cost effective was 88% (59%) at a cost effectiveness threshold of £20 000 (£30 000) per QALY. While sensitivity analysis indicated that the cost of managing incorrectly identified depression (false positive result) was an important driver of the model, formal identification approaches did not seem to be cost effective at any feasible estimate of this cost. Conclusions Formal identification methods for postnatal depression do not seem to represent value for money for the NHS. The major determinant of cost effectiveness seems to be the potential additional costs of managing women incorrectly diagnosed as depressed. Formal identification methods for postnatal depression do not currently satisfy the National Screening Committee’s criteria for the adoption of a screening strategy as part of national health policy.

How valuable are multiple treatment comparison methods in evidence-based health-care evaluation?

The National Institute for Health and Clinical Excellence (NICE) invited the manufacturer of alitretinoin (Basilea Pharmaceuticals Ltd, Basel, Switzerland) to submit evidence for the clinical and cost effectiveness of this drug for the treatment of patients with severe chronic hand eczema (CHE), as part of the Institute’s single technology appraisal (STA) process. The Centre for Reviews and Dissemination and the Centre for Health Economics at the University of York were commissioned to act as the Evidence Review Group (ERG). This article provides a description of the company submission, the ERG review and NICE’s subsequent decisions.The ERG produced a critical review of the evidence for the clinical and cost effectiveness of the technology based upon the manufacturer’s submission to NICE. The ERG also independently searched for relevant evidence and modified the manufacturer’s decision analytic model to examine the impact of altering some of the key assumptions.The main clinical effectiveness data were derived from a single-placebo randomized controlled trial (RCT) of daily treatment with alitretinoin for 12–24 weeks, with follow-up for a further 24 weeks, in patients with severe CHE unresponsive to topical corticosteroids. A significantly greater proportion of patients achieved ‘clear’ or ‘almost clear’ hands by week 24 with alitretinoin than those using placebo: 48% with alitretinoin 30mg (p < 0.001); 28% with alitretinoin 10 mg (p < 0.005); 17% with placebo. Most patients who responded remained in remission during the 24-week follow-up period. The most commonly reported adverse event was dose-dependent headache, with rates of 20% in the alitretinoin 30 mg group and 11% in the alitretinoin 10mg group, respectively. Serious adverse events were rare, although alitretinoin was associated with increases in both total cholesterol and triglycerides. No direct or indirect comparisons of alitretinoin with any of the relevant treatment comparators (psoralen +UVA [PUVA], ciclosporin or azathioprine) were available.In the manufacturer’s original submission to NICE, the base-case incremental cost-effectiveness ratios (ICERs) reported for alitretinoin were £8614 per QALY versus ciclosporin, −£469 per QALY versus PUVA (with alitretinoin dominant) and £10 612 per QALY versus azathioprine (year 2007–8 values). In response to a request from the ERG, the manufacturers provided a revised model that compared alitretinoin only with placebo, for which the ICER was reported to be £12 931. However, the omission of adverse events entirely from this revised model, in combination with a number of other factors, led the ERG to conclude that the model underestimated the costs of treatment associated with alitretinoin. Estimates of health-related quality of life (HR-QOL) were the primary source of uncertainty, with the use of values from an alternative source producing ICERs of around £30 000 per QALY gained.The ERG concluded that, although the evidence presented indicates that alitretinoin is efficacious in the treatment of severe CHE, it gives little indication of alitretinoin’s efficacy relative to likely alternative treatment options or its efficacy and safety in the longer term. Although the ICERs estimated by the manufacturer suggested that alitretinoin may be cost effective for use in the UK NHS, utilizing the alternative HR-QOL estimates resulted in a 2-fold increase in the ICER. Thus, there was considerable uncertainty as to the true ICER of alitretinoin versus the relevant treatment comparators. The Appraisal Committee recommended that alitretinoin be provided to those patients with severe CHE and a Dermatology Life Quality Index (DLQI) score of at least 15. They recommended that treatment be stopped as soon as an adequate response was observed, or if CHE remained severe at 12 weeks, or if response was inadequate at 24 weeks.

Value-Based Reimbursement Decisions for Orphan Drugs: A Scoping Review and Decision Framework

OBJECTIVES To compare the use of pair-wise meta-analysis methods to multiple treatment comparison (MTC) methods for evidence-based health-care evaluation to estimate the effectiveness and cost-effectiveness of alternative health-care interventions based on the available evidence. METHODS Pair-wise meta-analysis and more complex evidence syntheses, incorporating an MTC component, are applied to three examples: 1) clinical effectiveness of interventions for preventing strokes in people with atrial fibrillation; 2) clinical and cost-effectiveness of using drug-eluting stents in percutaneous coronary intervention in patients with coronary artery disease; and 3) clinical and cost-effectiveness of using neuraminidase inhibitors in the treatment of influenza. We compare the two synthesis approaches with respect to the assumptions made, empirical estimates produced, and conclusions drawn. RESULTS The difference between point estimates of effectiveness produced by the pair-wise and MTC approaches was generally unpredictable-sometimes agreeing closely whereas in other instances differing considerably. In all three examples, the MTC approach allowed the inclusion of randomized controlled trial evidence ignored in the pair-wise meta-analysis approach. This generally increased the precision of the effectiveness estimates from the MTC model. CONCLUSIONS The MTC approach to synthesis allows the evidence base on clinical effectiveness to be treated as a coherent whole, include more data, and sometimes relax the assumptions made in the pair-wise approaches. However, MTC models are necessarily more complex than those developed for pair-wise meta-analysis and thus could be seen as less transparent. Therefore, it is important that model details and the assumptions made are carefully reported alongside the results.

Budget allocation and the revealed social rate of time preference for health

BackgroundThe rate of development of new orphan drugs continues to grow. As a result, reimbursing orphan drugs on an exceptional basis is increasingly difficult to sustain from a health system perspective. An understanding of the value that societies attach to providing orphan drugs at the expense of other health technologies is now recognised as an important input to policy debates.ObjectivesThe aim of this work was to scope the social value arguments that have been advanced relating to the reimbursement of orphan drugs, and to locate these within a coherent decision-making framework to aid reimbursement decisions in the presence of limited healthcare resources.MethodsA scoping review of the peer reviewed and grey literature was undertaken, consisting of seven phases: (1) identifying the research question; (2) searching for relevant studies; (3) selecting studies; (4) charting, extracting and tabulating data; (5) analyzing data; (6) consulting relevant experts; and (7) presenting results. The points within decision processes where the identified value arguments would be incorporated were then located. This mapping was used to construct a framework characterising the distinct role of each value in informing decision making.ResultsThe scoping review identified 19 candidate decision factors, most of which can be characterised as either value-bearing or ‘opportunity cost’-determining, and also a number of value propositions and pertinent sources of preference information. We were able to synthesize these into a coherent decision-making framework.ConclusionOur framework may be used to structure policy discussions and to aid transparency about the values underlying reimbursement decisions for orphan drugs. These values ought to be consistently applied to all technologies and populations affected by the decision.

Cost-Effectiveness of the 21-Gene Assay for Guiding Adjuvant Chemotherapy Decisions in Early Breast Cancer

Appropriate decisions based on cost-effectiveness evaluations of health-care technologies depend upon the cost-effectiveness threshold and its rate of growth as well as some social rate of time preference for health. A more traditional approach to this problem is outlined before a social decision-making approach is developed, which demonstrates that social time preference for health is revealed through the budget allocations made by a socially legitimate higher authority. The relationship between the social time preference rate for health, the growth rate of the cost-effectiveness threshold and the rate at which the higher authority can borrow or invest is then examined. We establish that the social time preference rate for health is implied by the budget allocation and the health production functions in each period. As such, the social time preference rate for health depends not on the social time preference rate for consumption or growth in the consumption value of health but on growth in the cost-effectiveness threshold and the rate at which the higher authority can save or borrow between periods. The implications for discounting and the policies of bodies such as NICE are then discussed.

Some Inconsistencies in NICE's Consideration of Social Values

OBJECTIVES Adjuvant chemotherapy decisions in early breast cancer are complex. The 21-gene assay can potentially aid such decisions, but costs US

Early Prevention of Pressure Ulcers Among Elderly Patients Admitted Through Emergency Departments: A Cost-effectiveness Analysis

4175 per patient. Adjuvant! Online is a freely available decision aid. We evaluate the cost-effectiveness of using the 21-gene assay in conjunction with Adjuvant! Online, and of providing adjuvant chemotherapy conditional upon risk classification. METHODS A probabilistic Markov decision model simulated risk classification, treatment, and the natural history of breast cancer in a hypothetical cohort of 50-year-old women with lymph node-negative, estrogen receptor- and/or progesterone receptor-positive, human epidermal growth factor receptor 2/neu-negative early breast cancer. Cost-effectiveness was considered from an Ontario public-payer perspective by deriving the lifetime incremental cost (2012 Canadian dollars) per quality-adjusted life-year (QALY) for each strategy, and the probability each strategy is cost-effective, assuming a willingness-to-pay of