Global cross-sectional survey of women with vasomotor symptoms associated with menopause: prevalence and quality of life burden.

OBJECTIVE: To determine prevalence and health-related quality of life (HRQOL) of moderate-to-severe vasomotor symptoms (VMS) in postmenopausal women in Europe, the US, and Japan, and among subgroups of women not taking hormone therapy (HT). METHODS: Screening surveys were sent to a random sample of women aged 40 to 65 years; full questionnaires followed to those who completed them and met inclusion criteria. Women with successfully treated VMS, breast cancer, or on HT for medical conditions were excluded. The Menopause-Specific QOL (MENQOL) and Work Productivity and Activity Impairment (WPAI) questionnaires were included in the questionnaire. RESULTS: Of 25,161 women completing the screening survey, 11,771 were postmenopausal and 3,460 met inclusion criteria and completed the full questionnaire. Prevalence of moderate-to-severe VMS was 40%, 34%, and 16% in Europe, the US, and Japan, respectively. A large proportion were HT averse, albeit eligible (Europe 56%, US 54%, Japan 79%). In total, 12%, 9%, and 8% in Europe, the US, and Japan, respectively, were HT-contraindicated. A high proportion were HT-cautious (Europe 70%, US 69%, Japan 52%). Most common menopausal symptoms reported in the MENQOL were feeling tired or worn out (Europe/US 74%, Japan 75%), aching in muscles and joints (Europe 69%, US 68%, Japan 61%), difficulty sleeping (Europe 69%, US 66%, Japan 60%), and hot flashes (Europe 67%, US 68%, Japan 62%). Overall, the most bothersome symptom was weight gain. As measured by the WPAI, hot flashes and night sweats had a greater impact on daily activities than on working activities. CONCLUSIONS: A high proportion of women experienced moderate-to-severe VMS, with associated symptoms impacting QOL.

Qualitative study: burden of menopause-associated vasomotor symptoms (VMS) and validation of PROMIS Sleep Disturbance and Sleep-Related Impairment measures for assessment of VMS impact on sleep.

PURPOSE: We evaluated the impact of menopause-associated vasomotor symptoms (VMS) on sleep. We also sought to establish the content validity of Patient-Reported Outcomes Measurement Information System (PROMIS) short form Sleep-Related Impairment and Sleep Disturbance measures in postmenopausal women with moderate to severe VMS. METHODS: Cross-sectional, in-person, qualitative interviews were conducted in the United States (Texas, Illinois) and European Union (UK, France) with women aged 40-64 years experiencing moderate to severe VMS (≥35/wk). Main outcomes were impact of VMS on sleep based on concept elicitation and content validity of PROMIS Sleep-Related Impairment and Sleep Disturbance short forms via cognitive debriefing. RESULTS: Thirty-two women (US: n = 16; EU: n = 16) participated. A majority (US: 93.8%; EU: 93.8%) said VMS affected sleep; specifically, they had sleep interrupted by sweating or overheating and had difficulty returning to sleep. Sleep disturbance was the most bothersome aspect of VMS (US: 75%; EU: 50%). VMS-associated sleep disturbance affected next-day work productivity, mood, relationships, daily activities, concentration, social activities, and physical health. Participants found both PROMIS sleep measures relevant and easy to answer; the Sleep Disturbance measure was considered the most relevant. Participants had no difficulty remembering their experiences over the 7-day recall period and found the response options to be distinct. CONCLUSION: VMS associated with menopause significantly interferes with sleep and next-day functioning (e.g., work productivity), supporting assessment of sleep outcomes in studies evaluating treatment of VMS. Women with moderate to severe VMS found that the PROMIS Sleep-Related Impairment and Sleep Disturbance short forms assessed constructs important to understanding sleep in the context of menopause-associated VMS.

HPV testing in combination with liquid-based cytology in primary cervical screening (ARTISTIC): a randomised controlled trial.

BACKGROUND: Testing for human papillomavirus (HPV) DNA is reportedly more sensitive than cytology for the detection of high-grade cervical intraepithelial neoplasia (CIN). The effectiveness of HPV testing in primary cervical screening was assessed in the ARTISTIC trial, which was done over two screening rounds approximately 3 years apart (2001-03 and 2004-07) by comparing liquid-based cytology (LBC) combined with HPV testing against LBC alone. METHODS: Women aged 20-64 years who were undergoing routine screening as part of the English National Health Service Cervical Screening Programme in Greater Manchester were randomly assigned (between July, 2001, and September, 2003) in a ratio of 3:1 to either combined LBC and HPV testing in which the results were revealed and acted on, or to combined LBC and HPV testing where the HPV result was concealed from the patient and investigator. The primary outcome was the detection rate of cervical intraepithelial neoplasia grade 3 or worse (CIN3+) in the second screening round, analysed by intention to treat. This trial is registered with the International Standard Randomised Controlled Trial Number ISRCTN25417821. FINDINGS: There were 24 510 eligible women at entry (18 386 in the revealed group, 6124 in the concealed group). In the first round of screening 233 women (1.27%) in the revealed group had CIN3+, compared with 80 (1.31%) women in the concealed group (odds ratio [OR] 0.97, 95% CI 0.75-1.25; p>0.2). There was an unexpectedly large drop in the proportion of women with CIN3+ between the first and second rounds of screening in both groups, at 0.25% (29 of 11 676) in the revealed group and 0.47% (18 of 3866 women) in the concealed group (OR 0.53, 95% CI 0.30-0.96; p=0.042). For both rounds combined, the proportion of women with CIN3+ were 1.51% (revealed) and 1.77% (concealed) (OR 0.85, 95% CI 0.67-1.08; p>0.2). INTERPRETATION: LBC combined with HPV testing resulted in a significantly lower detection rate of CIN3+ in the second round of screening compared with LBC screening alone, but the effect was small. Over the two screening rounds combined, co-testing did not detect a higher rate of CIN3+ or CIN2+ than LBC alone. Potential changes in screening methodology should be assessed over at least two screening rounds. FUNDING: National Institute of Health Research Health Technology Assessment Programme.

Putting National Institute for Health and Clinical Excellence guidance into practice: a cost minimization model of a national roll-out of liquid based cytology in England.

OBJECTIVES: In 2003, the National Institute for Health and Clinical Excellence (NICE) advised that liquid based cytology (LBC) should be adopted for cervical screening in England. The aim of this study was to explore the cost implications of implementing the NICE guidance in cytology laboratories. The ThinPrep technology was used as the case study. METHODS: An optimization model was developed to analyze options for leasing alternative LBC processing machines with different capacities. Variables entered in the model included: the cost of the contract with the supplier, the laboratory labor cost, and inter-laboratory transport costs. All costs referred to the 2005-06 financial year. A simulation program calculated mileages within laboratory networks. Alternative strategies for contracting by laboratories acting independently and by Quality Assessment Regional Centres (QARC) were analyzed. RESULTS: Centralizing the processing of specimens in "hub and spoke" laboratory networks was the least costly strategy. Total annual costs for England using existing transport links were 14,807,000 UK pounds for 5-year contracts. If all laboratories installed processors, the annual cost for 5-year contracts placed by QARCs was 14,941,000 UK pounds compared with 16,359,000 pounds if the laboratories placed their own contracts. Three-year contracts averaged an additional 1 million UK pounds: 15,912,000 pounds for networks and 17,304,000 pounds for independent laboratory contracts. CONCLUSIONS: Deciding on the mode of implementation of a NICE guidance can be challenging for decision makers. These cost minimization appraisal techniques are equally applicable to national screening programs in general and to other health technologies for which there are significant cost implications associated with innovative policy directives.

A randomized trial of exercise treadmill ECG versus stress SPECT myocardial perfusion imaging as an initial diagnostic strategy in stable patients with chest pain and suspected CAD: cost analysis.

BACKGROUND: Exercise electrocardiography (ETT) is frequently used in patients with suspected coronary artery disease (CAD). Single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) improves diagnostic stratification. There are no randomized trials comparing ETT and MPI. We hypothesized that first-line MPI would be effective and cost-saving versus ETT. METHODS AND RESULTS: We randomized 457 outpatients with stable chest pain and suspected CAD to either treadmill electrocardiography or MPI. The post-test likelihood incorporated the pretest likelihood and the test result, with clinically driven testing. The primary endpoint was cost to diagnosis based on institutional and National Institute for Clinical Excellence costs. MPI significantly reduced the intermediate post-test likelihood of CAD (30% for ETT vs 3% for MPI, P < .0001) and further investigations (71% for ETT vs 16% for MPI, P < .0001). Despite the reduction in downstream resource utilization after MPI, mean costs were not different between the 2 initial strategies: 490.44 pounds sterling (95% confidence interval, 453.80-527.08) for ETT versus 512.41 pounds sterling (95% confidence interval, 481.41-543.41) for MPI. MPI cost was no different from ETT cost in patients with an intermediate or high pretest likelihood (P = not significant). ETT was less expensive in low-risk patients. CONCLUSIONS: In this study there was no difference in cost to diagnosis between initial ETT and MPI. In low-likelihood patients ETT was less costly, whereas there was no cost difference in intermediate- or high-likelihood patients.

Clinical and economic impact of stress echocardiography compared with exercise electrocardiography in patients with suspected acute coronary syndrome but negative troponin: a prospective randomized controlled study.

AIMS: Patients attending hospital with suspected acute coronary syndrome (ACS), non-diagnostic electrocardiogram (ECG), and negative troponin present a diagnostic dilemma for admitting physicians. We sought to determine the clinical and economic impact of stress echocardiography (SEcho) when compared with exercise ECG (ExECG) in the assessment of these patients. METHODS AND RESULTS: Following pre-test assessment by (Thrombolysis in Myocardial Infarction) TIMI score, patients were randomized to ExECG (n=218) or SEcho (n=215). Subsequently, low-risk patients were discharged; those considered high risk were referred for coronary angiography. Patients were followed-up for cardiac events and a cost-analysis performed. SEcho was superior to ExECG in stratifying patients as low risk (77 vs. 33%, respectively, P<0.0001) with no difference in cardiac event rate (5 vs. 3%, respectively). SEcho classified fewer patients as intermediate risk (3 vs. 39%, respectively, P<0.0001) and fewer patients required further tests when compared with ExECG (3 vs. 47%, respectively, P<0.0001). Costs for detection of coronary artery disease were significantly less in patients undergoing SEcho (pound366.63 vs. pound515.48, P=0.004). CONCLUSION: SEcho is superior to ExECG in the risk stratification of patients with suspected ACS but negative troponin. SEcho resulted in less diagnostic uncertainty, fewer referrals for further investigation, and hence, a significant cost benefit over ExECG.

The lag between effectiveness and cost-effectiveness evidence of new drugs. Implications for decision-making in health care.

A new drug is approved for use if its efficacy and safety have been demonstrated. However, healthcare decision makers may also require data on the cost-effectiveness of new drugs if they are to make informed decisions about their place in therapy. Cost-effectiveness evidence may lag behind the effectiveness data in terms of its availability. We explored the timeliness of delivering cost-effectiveness information about new drugs with established effectiveness and significant financial impact. Drugs were identified, based on guidance documents and reports published by the UK National Institute for Clinical Excellence (NICE), and the following data were collected: dates of publication of first effectiveness and cost-effectiveness evidence, methodology of the cost-effectiveness analysis, quality scores of the clinical studies. Eighteen guidance documents on the use of new drugs/drug groups published by NICE by October 2001 covered 30 health technologies, which were included in the analysis. The analysis of the evidence showed that their effectiveness had been demonstrated in the last 12 years, with only two exceptions. However, cost-effectiveness evidence had been published for 21 (70%) of the technologies. The cost-effectiveness was estimated in 52.4% of cases using models. The good quality effectiveness evidence lagged behind the first effectiveness evidence by 1.40 years (95% CI 0.57-2.23), while the mean lag between the first effectiveness evidence and the first cost-effectiveness publications was estimated as 3.20 years (95% CI 1.76-4.65). Cost-effectiveness evidence thus often lags behind the effectiveness evidence. As a result healthcare decision makers are sometimes in a position of having to take decisions without having adequate cost-effectiveness data at their disposal.

Do health-care decision makers find economic evaluations useful? The findings of focus group research in UK health authorities.

OBJECTIVES: The impact of economic evaluation studies on health-care decision makers has been shown to be rather limited. However, there is an increasing requirement for the cost-effectiveness of health-care interventions to be considered in formulating and implementing guidelines for clinical practice. This paper reports the findings of recent focus group research among UK health authorities, which examined the usefulness of published economic evaluations within the decision-making processes. The findings are presented and discussed in light of other studies that have addressed this issue. METHODS: Focus group research was conducted with decision makers from a sample of two UK health authorities using the National Health Service Economic Evaluation Database (NHS EED) as a research vehicle to locate and report the findings of relevant economic studies. The study sample was initially invited to respond to questionnaires exploring the usefulness of published economic evaluations in the decision-making process and to outline particular topics that it felt would benefit from similar economic evidence. Following this, a detailed search was undertaken to retrieve structured NHS EED abstracts on these topics such that the usefulness and limitations of economic evaluations to decision making could be determined. RESULTS: Decision makers generally recognized the usefulness and necessity of published economic evaluations in informing their decision-making processes. However, the value of studies was often limited because of the poor generalizability of results, the narrowness of research questions, and the lack of methodological rigor common to many published studies. A total of 237 NHS EED full abstracts were retrieved in the specified areas of interest, which, within specified caveats, were generally found to be useful as decision-making tools. There was a general consensus among decision makers in favor of developing a quality-scoring system for studies, thereby going beyond the critical summaries given in NHS EED. CONCLUSIONS: Decision makers value information on cost-effectiveness as well as effectiveness alone, but methodological improvements are necessary to increase the reliability of economic studies. A quality-scoring system for published studies would be a useful development as a filtering mechanism for decision makers but would raise a number of challenges for health economists.