Objectives: Shoulder complaints (SCs) constitute the second largest group of musculoskeletal disorders after low back pain. The economic burden in terms of costs of healthcare use and costs due to work absenteeism underlines the need for a cost-effectiveness analysis of the interventions involved. The education and activation program (EAP) is a newly developed early intervention to prevent the development of chronic SCs. A cost-effectiveness analysis should provide more information on the effect of an EAP on total costs related to SCs.

Methods: We conducted a cost-effectiveness analysis alongside a randomized clinical trial comparing the effectiveness of the EAP in addition to usual care (EAP group) with that of usual care alone (UC group) in terms of preventing chronicity in patients with acute SCs. The aim of the cost-effectiveness analysis was to compare the observed difference in costs with the clinical effectiveness (i.e., patient-perceived recovery after 26 weeks), using bootstraps.

Results: The comparison of total costs between treatment groups showed no significant (p = .077) difference after 26 weeks. The majority (82 percent) of the cost-effect pairs after bootstrap analysis were located in the northeast quadrant, suggesting more effect but at higher costs.

Conclusions: In view of the clinical relevance of the clinical outcomes and the considerable costs needed to achieve this, it can be concluded that the EAP is currently not cost-effective.

Objectives: To compare the cost-effectiveness of the treatment of ankylosing spondylitis (AS) with infliximab in the United Kingdom over lifetime estimated from two different clinical trials and adjusted for clinical practice guidelines.

Methods: A cost-effectiveness model was developed to incorporate clinical, epidemiological, and economic data and allow extrapolation of trial results and incorporation of long-term treatment. Assumptions regarding treatment beyond the trials were based on open extensions from the trials and treatment guidelines by the British Society for Rheumatology. Results are presented for both the societal perspective and the perspective of the National Health Service (UK £, discounted 3.5 percent).

Results: Under the assumption that disease activity would be controlled and functional capacity would remain stable while on drug, treatment with infliximab (5 mg/kg every 6 weeks) dominates standard treatment in the societal perspective. In the National Health Service perspective, the cost per quality-adjusted life-year (QALY) gained over lifetime was £28,300 and £26,800 for the two trials. If functional capacity were to deteriorate at half the rate of untreated patients, the cost per QALY gained would be £35,300 and £34,100, respectively. The results are sensitive to the dosing regimen adopted, the discontinuation rate, and assumptions concerning disease progression while on treatment.

Conclusions: The two clinical trials yield the same cost-effectiveness results and the cost per QALY gained with treatment was found to be in the acceptable range.

Objectives: This study was undertaken to understand how women view characteristics of tests for cervical dysplasia, because these characteristics can affect patient decision-making about screening and follow-up.

Methods: We recruited women who participated in a clinical trial of optical spectroscopy for the diagnosis of cervical dysplasia and used conjoint analysis to assess the women's preferences concerning test attributes. One group of women had a history of an abnormal Papanicolaou smear (diagnostic sample), while the other group did not (screening sample). Participants rated pairs of test scenarios that varied on characteristics such as test sensitivity and painfulness. Based on their responses, the relative importance of test sensitivity, specificity, timing of results feedback and treatment, and pain were calculated, and a cluster analysis was done to identify subgroups of participants with different preference patterns.

Results: In the overall sample, sensitivity was the most important attribute, followed by timing, specificity, and pain. Cluster analysis revealed four distinct groups who placed varying importance on each characteristic. The participants in the cluster for which pain was the most important attribute were more likely to be diagnostic patients, non-white, and have low education levels. They also reported more anxiety and pain during the examination than participants in other clusters.

Conclusions: To continue to reduce morbidity and mortality from cervical cancer, developers of new testing procedures should take into account test attributes such as these, which may affect adherence to screening and diagnostic follow-up to further minimize morbidity and mortality from cervical cancer.

Objectives: Major depression is common in elderly patients. Interpersonal psychotherapy (IPT) is a potentially effective treatment for depressed elderly patients. The objective of this study was to evaluate the cost-effectiveness of IPT delivered by mental health workers in primary care practices, for depressed patients 55 years of age and older identified by screening, in comparison with care as usual (CAU).

Methods: We conducted a full economic evaluation alongside a randomized controlled trial comparing IPT with CAU. Outcome measures were depressive symptoms, presence of major depression, and quality of life. Resource use was measured from a societal perspective over a 12-month period by cost diaries. Multiple imputation and bootstrapping were used to analyze the data.

Results: At 6 and 12 months, the differences in clinical outcomes between IPT and CAU were small and nonsignificant. Total costs at 12 months were €5,753 in the IPT group and €4,984 in the CAU group (mean difference, €769; 95 percent confidence interval, −2,459 – 3,433). Cost-effectiveness planes indicated that there was much uncertainty around the cost-effectiveness ratios.

Conclusions: Based on these results, provision of IPT in primary care to elderly depressed patients was not cost-effective in comparison to CAU. Future research should focus on improvement of patient selection and treatments that have more robust effects in the acute and maintenance phase of treatment.

Objectives: Surveillance programs are recommended to both families at high risk (Amsterdam-positive families with known- and unknown mutation) and moderate risk (families not fulfilling all Amsterdam criteria) of colorectal cancer (CRC). Cost-effectiveness has so far only been estimated for the group at high risk. The aim of the present study is to determine cost-effectiveness of surveillance programs where families at both high and moderate risk of HNPCC participate.

Methods: A decision analytic model (Markov model) is developed to assess surveillance programs where families at high and moderate risk of HNPCC are offered surveillance from age 25 and age 45, respectively. The model includes costs for all families referred to genetic counseling, including genetic risk assessment, mutation analysis, and surveillance in relevant families with or without known mutation, plus the costs related to any surgical treatment. The risk of metachronous CRC is also modeled.

Results: Incremental costs per life year gained are estimated to be €980 when families at both high and moderate risk of HNPCC undergo surveillance (€508 for high risk and €1600 for moderate risk) and €1947 when the moderate risk group is evaluated genetically but not offered surveillance. Sensitivity analysis showed these findings to be robust, although cost-effectiveness can be improved in cases of more conservative referrals to genetic counseling.

Conclusions: The result for high risk families confirms the findings in similar studies. Somewhat surprisingly, cost-effectiveness improves when surveillance of the moderate risk groups are included in the decision model.

Objectives: The impact of learning effects on the variability of costs of new health technologies in a prospective payment system (PPS) through the case of intensity modulated radiation therapy (IMRT) was studied.

Methods: A series of consecutive patients treated in nine medical centers was enrolled in a prospective study. Direct costs were assessed from the perspective of the healthcare providers. We used a two-level model to explain the variability of costs: patients nested within centers. Learning effects at the center level were considered through a fixed effect (the learning curve slope) and a random effect (the initial cost level). Covariates were introduced to explain the patterns of variation in terms of patient characteristics.

Results: The mean direct cost of IMRT was €5,962 (range, €2,414–€24,733). Manpower accounted for 53 percent of this cost. Learning effects explained 42 percent of the variance between centers (which was 88 percent of the total variance) and were associated with a substantial decrease in treatment costs. The mean initial treatment direct cost was €6,332 in centers with a previous experience of IMRT, whereas it was €14,192 in centers implementing IMRT for the first time. Including logistics costs and overhead, the full cost of IMRT was €10,916. Average reimbursement was €6,987.

Conclusions: Learning effects are a strong confounding factor in the analysis of costs of innovative health technologies involving learning effects. In a PPS, innovative health technology involving learning effects necessitates specific reimbursement mechanisms.

Objectives: To compare the cost-effectiveness of endoscopy and empirical proton pump inhibition (PPI) therapy for management of dyspepsia in primary care.

Methods: A randomized controlled trial, including prospective collection of economic resource data, was conducted in general practice from June 2000 to August 2002, Aarhus County, Denmark. We randomly assigned 368 dyspeptic patients from thirty-two general practices to treatment with omeprazol 40 mg for 2 weeks (n=184) or endoscopy (n=184). The study adopted a societal perspective, and the year of costing was 2006. Outcome measures: days free of dyspeptic symptoms and proportion of patients with dyspepsia after 1 year based on patients' and general practitioners' (GPs) assessment. Costs were estimated from patient and GP questionnaires and from medical records.

Results: The incremental cost-effectiveness (CE) ratio for 1 day free of dyspeptic symptoms using the endoscopy strategy was €/day 154 compared with the PPI strategy. The incremental CE ratio for one person free of dyspeptic symptoms after 1 year using the endoscopy strategy was €13,905 based on the patients' evaluation, and the incremental CE ratio for one person free of predominant symptoms after 1 year was €5,990 according to the GPs' evaluation. The PPI strategy was both cheaper and more effective than the endoscopy strategy when reflux was the predominant symptom.

Conclusions: A strategy using empirical antisecretory PPI therapy should be recommended if the alternative is an endoscopy strategy for managing dyspeptic patients in general practice, especially if reflux was the predominant symptom.

Objectives: Stereotactic radiosurgery (SRS) is used to treat intracranial lesions and vascular malformations as an addition or replacement to whole brain radiotherapy and microsurgery. SRS can be delivered by hardware and software appended to standard linear accelerators (Linacs) or by dedicated systems such as Gamma Knife, which has been proposed as a more accurate and user friendly technology. Internationally, dedicated systems have been funded, despite limitations in evidence. However, some countries including Australia have not recommended additional reimbursement for dedicated systems. This study compares the costs of Linac radiosurgery with Gamma Knife radiosurgery.

Methods: Due to limited evidence on comparative effects, the economic analysis was restricted to a cost evaluation. The base-case analysis assumed a modified Linac was used only to treat SRS patients. However, because a modified Linac could be used to treat other radiotherapy patients, a second analysis assumed spare time was used to meet other radiotherapy needs, and Linac capital costs were apportioned according to SRS use.

Results: The incremental cost of Gamma Knife versus a modified Linac was estimated as AU$209 per patient. This result is sensitive to variations in assumptions. A second analysis proportioning capital costs according to SRS use showed that Gamma Knife may cost up to AU$1673 more per patient.

Conclusions: Gamma Knife may be cost competitive only if demand for SRS services is high enough to fully use equipment working time. However, given low patient demand and competing radiotherapy needs, Gamma Knife appears more costly and further evidence of survival or quality of life advantages may be required to justify reimbursement.

Objectives: The aim of this study was to compare the generic health-related quality of life (HRQoL) instruments, the 15D and the Nottingham Health Profile (NHP), in terms of feasibility, cross-sectional construct validity, discriminatory power, and responsiveness to the change in patients with lower limb atherosclerosis disease (LLAD).

Methods: Patients who were treated conservatively (64 patients), scheduled for endovascular treatment (85 patients), or for elective surgery (31 patients) filled in the NHP and the 15D questionnaires before treatment and 12 months after. The methods of analysis included calculations of the completion rate, the multitrait–multimethod matrix, extreme group comparisons with the t-test, and calculations of “floor” and “ceiling” effects and effect sizes.

Results: Both the 15D and the NHP instruments were feasible because full data were obtained at baseline from 84.1 percent of patients and 82 percent at 12 months with the 15D and, respectively, 75.8 percent and 79 percent with the NHP. The multitrait–multimethod matrix and extreme group comparisons provided a clear convergent and discriminant evidence of the cross-sectional construct validity of the instruments. The convergent validity correlations were quite high, ranging between .40 and .682. The tendency for higher percentages at the “ceiling” and “floor” for the NHP suggests that it has less discriminatory power than the 15D on roughly comparable dimensions. The 15D and the NHP were almost equally responsive to change.

Conclusions: This study provided evidence that both the 15D and the NHP are appropriate for measuring HRQoL among patients with LLAD.

Objectives: The aim of this study was to assess whether a literature review of a technology can allow a learning curve to be quantified.

Methods: The literature for fiberoptic intubation was searched for studies reporting information relevant to the learning curve. The Cochrane Library, Medline, Embase, and Science Citation index were searched. Studies that reported a procedure time were included. Data were abstracted on the three features of learning: initial level, rate of learning, and asymptote level. Random effects meta-analysis was performed.

Results: Only twenty-one studies gave explicit information concerning the previous experience of the operator(s). There were thirty-two different definitions of procedure time. From four studies of fiberoptic nasotracheal intubation, the mean starting level and time for the 10th procedure was estimated to be 133 seconds (95 percent confidence interval, 113–153) and 71 seconds (95 percent confidence interval, 62–79), respectively.

Conclusions: The review approach allowed learning to be quantified for our example technology. Poor and insufficient reporting constrained formal statistical estimation. Standardized reporting of nondrug techniques with adequate learning curve details is needed to inform trial design and cost-effectiveness analysis.

Objectives: A recent study showed that estimates of cost-effectiveness submitted to National Institute for Health and Clinical Excellence (NICE) by manufacturers had significantly lower incremental cost-effectiveness ratios (ICERs) than those submitted by university-based Assessment Groups. This study extends that analysis.

Methods: Data were abstracted from relevant NICE documentation for thirty-two of eighty-two possible appraisals.

Results: The results from the analysis showed that sources of the difference in ICERs appear to be the effectiveness estimates relating to the comparator technology and the cost estimates relating to the technology under evaluation. That is, manufacturers estimated lower average benefits for the comparator technology and lower costs relating to the technology under evaluation compared with estimates submitted by the Assessment Groups.

Conclusions: These findings may be particularly important, given the introduction of the “Single Technology Appraisal.” Considerable difficulties were encountered when undertaking this study, highlighting, above all else, the complexity of explaining why results from economic evaluations purporting to answer the same question diverge.

Objectives: The aim of this study was to identify research and development on genetic testing to find out if research addresses important disease areas, how far it is from potential clinical use, and what consequences might arise for the prioritization of health technology assessment (HTA) activities. Also a horizon scanning methodology developed in Germany is demonstrated.

Methods: A systematic search on genetic testing was conducted in an innovation database (ZIM database). Based on a daily monitoring of literature and Internet sources, reports from 2003 up to 2005 were classified related to the type of innovation, the addressed disease categories, and the developmental phase of the technology. More detailed analyses for the most frequently addressed groups of diseases were conducted.

Results: From 239 relevant reports, 41 percent referred to neoplasms; 10 percent to diseases of the cardiovascular system; 9 percent to diseases of the nervous system; 7 percent to mental and behavioral disorders; and 5 percent to endocrine, nutritional, and metabolic diseases. A total of 69 percent of research is situated in basic preclinical research, 22 percent in clinical/experimental research, and 6 percent are genetic tests being used. Diagnostic applications were most frequently reported (28 percent), followed by therapeutic prediction (22 percent), preventive prediction (18 percent), pharmacogenetics (16 percent), and screening (16 percent).

Conclusions: Widespread diseases are frequently addressed in research. HTA on genetic testing might focus on innovations addressing neoplastic diseases (in particular breast, colon, and prostate cancers) and pharmacogenetic applications for therapeutic prediction. The horizon scanning approach seems useful in the early steps of HTA processes to identify emerging new technologies that might have significant impact on future health care.

Objectives: The clinical and cost-effectiveness of left ventricular assist devices as destination therapy for people with end-stage heart failure is assessed through a systematic review and economic evaluation.

Methods: Systematic review was performed of randomized controlled trials, quasiexperimental studies, case series, and case studies identified through searching eighteen electronic databases, bibliographies, and consultation with experts and manufacturers. Studies assessed survival, functional capacity, and quality of life. Cost-effectiveness was assessed through a 5-year decision analytic model to estimate the incremental cost-effectiveness ratio for using left ventricular assist devices compared with usual care.

Results: Six studies met the inclusion criteria, showing that left ventricular assist devices appear beneficial, improving survival and quality of life. Adverse events are a serious concern. The economic evaluation showed that left ventricular assist devices had a cost per quality adjusted life year of £170,616. Sensitivity analysis showed that the cost-effectiveness was not sensitive to changes in costs or utility.

Conclusions: Although left ventricular assist devices appear clinically effective as destination therapy, it is unlikely they will be cost-effective unless costs decrease or the benefits of their use increase.

All of the panelists who participated in this conference and contributed to the writing of this statement were identified as having no financial or scientific conflict of interest, and all signed forms attesting to this fact. Unlike the expert speakers who present scientific data at the conference, the individuals invited to participate on the consensus panel are reviewed prior to selection to ensure they are not proponents of an advocacy position with regard to the topic.

Objectives: Conducting economic evaluation in the context of clinical studies is common but has been the subject of extensive discussion due to its limitations. Various standard approaches and guidelines how such studies should be conducted have been proposed, but there is very limited information available about how common these studies are, what type of data that is collected, and how the quality of the protocols compares to the suggested standards. This study examines the prevalence and study design of health economic evaluations conducted alongside clinical trials in Sweden between 1995 and 2005.

Methods: A systematic assessment of clinical trial protocols that had arrived as applications to the Medical Products Agency between 1995 and 2005 was performed. Only protocols arriving during the first half of odd years within the time period were included.

Results: A total number of 680 protocols from 1995 to 2005 were examined, and among them, 14.4 percent included a health economic part. With the exception of year 2001, a trend toward an increased prevalence of economic evaluations next to clinical trials can be seen.

Conclusions: This study shows that economic evaluations alongside clinical trials are becoming more common, although most trials still lack a health economic part of the protocol. The information about the economic evaluation provided in the protocols is in many cases scarce, possibly due to the fact that there currently are no generally accepted and applied guidelines for economic evaluations in clinical trial protocols. Introducing requirements for detailed study plans also for the economic evaluation should improve the quality of economic evaluations alongside clinical trials.

Objectives: The association between type and amount of clinical evidence and type of National Institute for Health and Clinical Excellence recommendations for interventional procedures was examined.

Methods: The evidence about 736 studies (including 183,729 patients) relating to 130 different interventional procedures and about relevant recommendations was analyzed. Associations were examined between type of recommendation (“normal arrangements” or “cautionary guidance”) and evidence type, total number of treated patients, and mean follow-up length. Evidence type was categorized as (a) randomized, (b) nonrandomized controlled, and (c) case series/reports. The main outcome measures were frequency of evidence type, total number of patients treated, and mean follow-up length, by type of recommendation.

Results: “Normal arrangements” recommendations were made for 70 (54 percent) procedures and “cautionary guidance” was issued for 60 (46 percent) procedures. Procedures supported by at least one randomized study (34 percent, n = 44) were more likely to receive a “normal arrangements” recommendation (relative risk 1.38, p = .063). Overall, there were 85 (12 percent), 135 (18 percent), and 516 (70 percent) studies in categories a–c, respectively. The number of treated patients was significantly larger among procedures with “normal arrangements” (median, 605; range, 26–6,842) than among those with “cautionary guidance” (median, 240; range, 1–3,261; p < .001) recommendation. Mean follow-up length was longer in studies relating to procedures with “normal arrangements” recommendation (median, 16.7; range, 0–84 months) compared with those with “cautionary guidance” (median, 14.6; range, 0–67 months; p = .160).

Conclusions: Procedures supported by randomized studies, and with larger numbers of patients and longer follow-up length, were more likely to receive positive guidance. Future research and development on interventional procedures should aim to produce better and more relevant evidence to optimize the possibility of such procedures being accepted by policy makers.

Objectives: Ongoing developments in design have improved the outlook for left-ventricular assist device (LVAD) implantation as a therapy in end-stage heart failure. Nevertheless, early cost-effectiveness assessments, based on first-generation devices, have not been encouraging. Against this background, we set out (i) to examine the survival benefit that LVADs would need to generate before they could be deemed cost-effective; (ii) to provide insight into the likelihood that this benefit will be achieved; and (iii) from the perspective of a healthcare provider, to assess the value of discovering the actual size of this benefit by means of a Bayesian value of information analysis.

Methods: Cost-effectiveness assessments are made from the perspective of the healthcare provider, using current UK norms for the value of a quality-adjusted life-year (QALY). The treatment model is grounded in published analyses of the Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure (REMATCH) trial of first-generation LVADs, translated into a UK cost setting. The prospects for patient survival with second-generation devices is assessed using Bayesian prior distributions, elicited from a group of leading clinicians in the field.

Results: Using established thresholds, cost-effectiveness probabilities under these priors are found to be low (∼.2 percent) for devices costing as much as £60,000. Sensitivity of the conclusions to both device cost and QALY valuation is examined.

Conclusions: In the event that the price of the device in use would reduce to £40,000, the value of the survival information can readily justify investment in further trials.

To the Editor:

In a recent study in this Journal, Drummond and colleagues (5) attempt to address the question “Whether the standard methods of HTA are adequate for assisting decisions on patient access to and funding of orphan drugs” before proposing “a research agenda to help understand the societal value of orphan drugs and issues surrounding their development, funding, and use.”

Objectives: The aim of this study was to examine the influence of participants' characteristics on the results produced by formal consensus methods.

Methods: The approach was an experimental study of 346 participants in 20 groups rating the appropriateness of four mental health interventions for the treatment of chronic fatigue syndrome, irritable bowel syndrome, and chronic back pain. There were four factors in the design: systematic literature review provided or not, decisions made under realistic or “ideal” resource assumptions, clinically mixed (general practitioners and mental health professionals) or homogenous group (general practitioners only), convened or mail-only group. A group's rating was defined as the median of participants' ratings. The influence of participants' characteristics (age, sex, and specialty) was examined using multilevel models.

Results: The largest differences were between the GPs and mental health professionals, both in their initial ratings of the different interventions, and in how much they altered their ratings between rounds. There were smaller but statistically significant (p<.05) differences between specialty and age groups in initial ratings for the treatment (by whatever means) of different conditions, and for certain conditions women increased their ratings more than men. Women rated intervention more favorably when assuming “ideal” rather than realistic levels of resources, but men did not.

Conclusions: Our findings support the practice of treating professional specialty as an important determinant of the results in consensus panels.

The email address provided for Hussein Z. Noorani in the “Contact Information” section of the above article is incorrect. The correct email address is [email protected].