Sarah Wordsworth

Ranibizumab versus Bevacizumab to Treat Neovascular Age-related Macular Degeneration: One-Year Findings from the IVAN Randomized Trial.

PURPOSE To compare the efficacy and safety of ranibizumab and bevacizumab intravitreal injections to treat neovascular age-related macular degeneration (nAMD). DESIGN Multicenter, noninferiority factorial trial with equal allocation to groups. The noninferiority limit was 3.5 letters. This trial is registered (ISRCTN92166560). PARTICIPANTS People >50 years of age with untreated nAMD in the study eye who read ≥ 25 letters on the Early Treatment Diabetic Retinopathy Study chart. METHODS We randomized participants to 4 groups: ranibizumab or bevacizumab, given either every month (continuous) or as needed (discontinuous), with monthly review. MAIN OUTCOME MEASURES The primary outcome is at 2 years; this paper reports a prespecified interim analysis at 1 year. The primary efficacy and safety outcome measures are distance visual acuity and arteriothrombotic events or heart failure. Other outcome measures are health-related quality of life, contrast sensitivity, near visual acuity, reading index, lesion morphology, serum vascular endothelial growth factor (VEGF) levels, and costs. RESULTS Between March 27, 2008 and October 15, 2010, we randomized and treated 610 participants. One year after randomization, the comparison between bevacizumab and ranibizumab was inconclusive (bevacizumab minus ranibizumab -1.99 letters, 95% confidence interval [CI], -4.04 to 0.06). Discontinuous treatment was equivalent to continuous treatment (discontinuous minus continuous -0.35 letters; 95% CI, -2.40 to 1.70). Foveal total thickness did not differ by drug, but was 9% less with continuous treatment (geometric mean ratio [GMR], 0.91; 95% CI, 0.86 to 0.97; P = 0.005). Fewer participants receiving bevacizumab had an arteriothrombotic event or heart failure (odds ratio [OR], 0.23; 95% CI, 0.05 to 1.07; P = 0.03). There was no difference between drugs in the proportion experiencing a serious systemic adverse event (OR, 1.35; 95% CI, 0.80 to 2.27; P = 0.25). Serum VEGF was lower with bevacizumab (GMR, 0.47; 95% CI, 0.41 to 0.54; P<0.0001) and higher with discontinuous treatment (GMR, 1.23; 95% CI, 1.07 to 1.42; P = 0.004). Continuous and discontinuous treatment costs were £9656 and £6398 per patient per year for ranibizumab and £1654 and £1509 for bevacizumab; bevacizumab was less costly for both treatment regimens (P<0.0001). CONCLUSIONS The comparison of visual acuity at 1 year between bevacizumab and ranibizumab was inconclusive. Visual acuities with continuous and discontinuous treatment were equivalent. Other outcomes are consistent with the drugs and treatment regimens having similar efficacy and safety. FINANCIAL DISCLOSURE(S) Proprietary or commercial disclosures may be found after the references.

Liberal or Restrictive Transfusion after Cardiac Surgery

BACKGROUND Whether a restrictive threshold for hemoglobin level in red-cell transfusions, as compared with a liberal threshold, reduces postoperative morbidity and health care costs after cardiac surgery is uncertain. METHODS We conducted a multicenter, parallel-group trial in which patients older than 16 years of age who were undergoing nonemergency cardiac surgery were recruited from 17 centers in the United Kingdom. Patients with a postoperative hemoglobin level of less than 9 g per deciliter were randomly assigned to a restrictive transfusion threshold (hemoglobin level <7.5 g per deciliter) or a liberal transfusion threshold (hemoglobin level <9 g per deciliter). The primary outcome was a serious infection (sepsis or wound infection) or an ischemic event (permanent stroke [confirmation on brain imaging and deficit in motor, sensory, or coordination functions], myocardial infarction, infarction of the gut, or acute kidney injury) within 3 months after randomization. Health care costs, excluding the index surgery, were estimated from the day of surgery to 3 months after surgery. RESULTS A total of 2007 patients underwent randomization; 4 participants withdrew, leaving 1000 in the restrictive-threshold group and 1003 in the liberal-threshold group. Transfusion rates after randomization were 53.4% and 92.2% in the two groups, respectively. The primary outcome occurred in 35.1% of the patients in the restrictive-threshold group and 33.0% of the patients in the liberal-threshold group (odds ratio, 1.11; 95% confidence interval [CI], 0.91 to 1.34; P=0.30); there was no indication of heterogeneity according to subgroup. There were more deaths in the restrictive-threshold group than in the liberal-threshold group (4.2% vs. 2.6%; hazard ratio, 1.64; 95% CI, 1.00 to 2.67; P=0.045). Serious postoperative complications, excluding primary-outcome events, occurred in 35.7% of participants in the restrictive-threshold group and 34.2% of participants in the liberal-threshold group. Total costs did not differ significantly between the groups. CONCLUSIONS A restrictive transfusion threshold after cardiac surgery was not superior to a liberal threshold with respect to morbidity or health care costs. (Funded by the National Institute for Health Research Health Technology Assessment program; Current Controlled Trials number, ISRCTN70923932.).

Clomifene citrate or unstimulated intrauterine insemination compared with expectant management for unexplained infertility: pragmatic randomised controlled trial

Objective To compare the effectiveness of clomifene citrate and unstimulated intrauterine insemination with expectant management for the treatment of unexplained infertility. Design Three arm parallel group, pragmatic randomised controlled trial. Setting Four teaching hospitals and a district general hospital in Scotland. Participants Couples with infertility for over two years, confirmed ovulation, patent fallopian tubes, and motile sperm. Intervention Expectant management, oral clomifene citrate, and unstimulated intrauterine insemination. Main outcome measures The primary outcome was live birth. Secondary outcome measures included clinical pregnancy, multiple pregnancy, miscarriage, and acceptability. Results 580 women were randomised to expectant management (n=193), oral clomifene citrate (n=194), or unstimulated intrauterine insemination (n=193) for six months. The three randomised groups were comparable in terms of age, body mass index, duration of infertility, sperm concentration, and motility. Live birth rates were 32/193 (17%), 26/192 (14%), and 43/191 (23%), respectively. Compared with expectant management, the odds ratio for a live birth was 0.79 (95% confidence interval 0.45 to 1.38) after clomifene citrate and 1.46 (0.88 to 2.43) after unstimulated intrauterine insemination. More women randomised to clomifene citrate (159/170, 94%) and unstimulated intrauterine insemination (155/162, 96%) found the process of treatment acceptable than those randomised to expectant management (123/153, 80%) (P=0.001 and P<0.001, respectively). Conclusion In couples with unexplained infertility existing treatments such as empirical clomifene and unstimulated intrauterine insemination are unlikely to offer superior live birth rates compared with expectant management. Trial registration ISRCT No: 71762042

DNA testing for hypertrophic cardiomyopathy: a cost-effectiveness model

Aims To explore the cost-effectiveness of alternative methods of screening family members for hypertrophic cardiomyopathy (HCM), the most common monogenic cardiac disorder and the most frequent cause of sudden cardiac death (SCD) in young people. Methods and results Economic decision model comparing cascade screening by genetic, as opposed to clinical methods. The incremental cost per life year saved was 14,397 euro for the cascade genetic compared with the cascade clinical approach. Genetic diagnostic strategies are more likely to be cost-effective than clinical tests alone. The costs for cascade molecular genetic testing were slightly higher than clinical testing in the short run, but this was largely because the genetic approach is more effective and identifies more individuals at risk. Conclusion The use of molecular genetic information in the diagnosis and management of HCM is a cost-effective approach to the primary prevention of SCD in these patients.

Economic methods for valuing the outcomes of genetic testing: beyond cost-effectiveness analysis.

Genetic testing in health care can provide information to help with disease prediction, diagnosis, prognosis, and treatment. Assessing the clinical utility of genetic testing requires a process to value and weight different outcomes. This article discusses the relative merits of different economic measures and methods to inform recommendations relative to genetic testing for risk of disease, including cost-effectiveness analysis and cost-benefit analysis. Cost-effectiveness analyses refer to analyses that calculate the incremental cost per unit of health outcomes, such as deaths prevented or life-years saved because of some intervention. Cost-effectiveness analyses that use preference-based measures of health state utility such as quality-adjusted life-years to define outcomes are referred to as cost-utility analyses. Cost-effectiveness analyses presume that health policy decision makers seek to maximize health subject to resource constraints. Cost-benefit analyses can incorporate monetary estimates of willingness-to-pay for genetic testing, including the perceived value of information independent of health outcomes. These estimates can be derived from contingent valuation or discrete choice experiments. Because important outcomes of genetic testing do not fit easily within traditional measures of health, cost-effectiveness analyses do not necessarily capture the full range of outcomes of genetic testing that are important to decision makers and consumers. We recommend that health policy decision makers consider the value to consumers of information and other nonhealth attributes of genetic testing strategies.

Collecting unit cost data in multicentre studies

International comparisons of health care systems and services have created increased interest in the comparability of cost results. This study compared top-down and bottom-up approaches to collecting unit cost data across centres in the context of examining the cost-effectiveness of dialysis therapy across Europe. The study tested whether health care technologies in different countries can be costed using consistent and transparent methods to increase the comparability of results. There was more agreement across the approaches for peritoneal dialysis than for than haemodialysis, with differences, respectively of €91–1,687 vs. 333–7,314 per patient per year. Haemodialysis results showed greatest differences where dialysis units were integrated as part of larger hospitals. Deciding which approach to adopt depends largely on the technology. However, bottom-up costing should be considered for technologies with a large component of staff input or overheads, significant sharing of staff or facilities between technologies or patient groups and health care costing systems which do not routinely allocate costs to the intervention level. In these circumstances this costing approach could increase consistency and transparency and hence comparability of cost results.

Indirect comparisons of treatments based on systematic reviews of randomised controlled trials.

Background:  Randomised controlled trials are the most effective way to differentiate between the effects of competing interventions. However, head‐to‐head studies are unlikely to have been conducted for all competing interventions.

Issues surrounding the health economic evaluation of genomic technologies

AIM Genomic interventions could enable improved disease stratification and individually tailored therapies. However, they have had a limited impact on clinical practice to date due to a lack of evidence, particularly economic evidence. This is partly because health economists are yet to reach consensus on whether existing methods are sufficient to evaluate genomic technologies. As different approaches may produce conflicting adoption decisions, clarification is urgently required. This article summarizes the methodological issues associated with conducting economic evaluations of genomic interventions. MATERIALS & METHODS A structured literature review was conducted to identify references that considered the methodological challenges faced when conducting economic evaluations of genomic interventions. RESULTS Methodological challenges related to the analytical approach included the choice of comparator, perspective and timeframe. Challenges in costing centered around the need to collect a broad range of costs, frequently, in a data-limited environment. Measuring outcomes is problematic as standard measures have limited applicability, however, alternative metrics (e.g., personal utility) are underdeveloped and alternative approaches (e.g., cost-benefit analysis) underused. Effectiveness data quality is weak and challenging to incorporate into standard economic analyses, while little is known about patient and clinician behavior in this context. Comprehensive value of information analyses are likely to be helpful. CONCLUSION Economic evaluations of genomic technologies present a particular challenge for health economists. New methods may be required to resolve these issues, but the evidence to justify alternative approaches is yet to be produced. This should be the focus of future work in this field.

Resource-Use Measurement Based on Patient Recall: Issues and Challenges for Economic Evaluation

Accurate resource-use measurement is challenging within an economic evaluation, but is a fundamental requirement for estimating efficiency. Considerable research effort has been concentrated on the appropriate measurement of outcomes and the policy implications of economic evaluation, while methods for resource-use measurement have been relatively neglected. Recently, the Database of Instruments for Resource Use Measurement (DIRUM) was set up at http://www.dirum.org to provide a repository where researchers can share resource-use measures and methods. A workshop to discuss the issues was held at the University of Birmingham in October 2011. Based on material presented at the workshop, this article highlights the state of the art of UK instruments for resource-use data collection based on patient recall. We consider methodological issues in the design and analysis of resource-use instruments, and the challenges associated with designing new questionnaires. We suggest a method of developing a good practice guideline, and identify some areas for future research. Consensus amongst health economists has yet to be reached on many aspects of resource-use measurement. We argue that researchers should now afford costing methodologies the same attention as outcome measurement, and we hope that this Current Opinion article will stimulate a debate on methods of resource-use data collection and establish a research agenda to improve the precision and accuracy of resource-use estimates.

Hemodialysis for end-stage renal disease: A cost-effectiveness analysis of treatment options

BACKGROUND During 2001, over 32,000 patients in the United Kingdom received renal replacement therapy (RRT). Approximately half had a functioning transplant, with the remainder receiving dialysis therapy. The main form of dialysis is hemodialysis (HD), which is provided to 37.1 percent of the RRT population. HD is provided in three main settings: hospital (24.5 percent), satellite (10.9 percent), or home (1.7 percent). The objective of this study is to explore the cost-effectiveness of these different modalities. METHODS By using clinical and cost data from a systematic review, a Markov model was developed to assess the costs and benefits of the three different modalities. The model included direct health service costs and quality-adjusted life years (QALYs). Sensitivity analyses were performed to assess the robustness of the results. RESULTS Satellite HD has lower costs 46,000 pounds sterling and 62,050 pounds sterling at 5 and 10 years than home HD 47,660 pounds sterling and 63,540 pounds sterling. The total effectiveness of home HD was slightly greater than for satellite HD, so the incremental cost per QALY of home versus satellite HD was modest at 6,665 pounds sterling at 5 years and 3,943 pounds sterling at 10 years. Both modalities dominated hospital HD. CONCLUSIONS Results from the study reveal that satellite HD was less costly than home HD, and home HD was less costly than hospital HD. The lack of robust data on the effectiveness and new dialysis equipment, which were not included in this review, throws some caution on these results. Nonetheless, the results are supportive of a shift from hospital HD to satellite and home HD.