ARTISTIC: a randomised trial of human papillomavirus (HPV) testing in primary cervical screening.

OBJECTIVES: Primary cervical screening uses cytology to detect cancer precursor lesions [cervical intraepithelial neoplasia stage 3 or beyond (CIN3+)]. Human papillomavirus (HPV) testing could add sensitivity as an adjunct to cytology or as a first test, reserving cytology for HPV-positive women. This study addresses the questions: Does the combination of cytology and HPV testing achieve a reduction in incident CIN3+?; Is HPV testing cost-effective in primary cervical screening?; Is its use associated with adverse psychosocial or psychosexual effects?; and How would it perform as an initial screening test followed by cytology for HPV positivity? DESIGN: ARTISTIC was a randomised trial of cervical cytology versus cervical cytology plus HPV testing, evaluated over two screening rounds, 3 years apart. Round 1 would detect prevalent disease and round 2 a combination of incident and undetected disease from round 1. SETTING: Women undergoing routine cervical screening in the NHS programme in Greater Manchester. PARTICIPANTS: In total 24,510 women aged 20-64 years were enrolled between July 2001 and September 2003. INTERVENTIONS: HPV testing was performed on the liquid-based cytology (LBC) sample obtained at screening. Women were randomised in a ratio of 3:1 to have the HPV test result revealed and acted upon if persistently positive in cytology-negative cases or concealed. A detailed health economic evaluation and a psychosocial and psychosexual assessment were also performed. MAIN OUTCOME MEASURES: The primary outcome was CIN3+ in round 2. Secondary outcomes included an economic assessment and psychosocial effects. A large HPV genotyping study was also conducted. RESULTS: In round 1 there were 313 CIN3+ lesions, representing a prevalence in the revealed and concealed arms of 1.27% and 1.31% respectively (p = 0.81). Round 2 (30-48 months) involved 14,230 (58.1%) of the women screened in round 1 and only 31 CIN3+ were detected; the CIN3 rate was not significantly different between the revealed and concealed arms. A less restrictive definition of round 2 (26-54 months) increased CIN3+ to 45 and CIN3+ incidence in the arms was significantly different (p = 0.05). There was no difference in CIN3+ between the arms when rounds 1 and 2 were combined. Prevalence of high-risk HPV types was age-dependent. Overall prevalence of HPV16/18 increased with severity of dyskaryosis. Mean costs per woman in round 1 were 72 pounds and 56 pounds for the revealed and concealed arms (p < 0.001); an age-adjustment reduced these mean costs to 65 pounds and 52 pounds. Incremental cost-effectiveness ratio for detecting additional CIN3+ by adding HPV testing to LBC screening in round 1 was 38,771 pounds. Age-adjusted mean cost for LBC primary screening with HPV triage was 39 pounds compared with 48 pounds for HPV primary screening with LBC triage. HPV testing did not appear to cause significant psychosocial distress. CONCLUSIONS: Routine HPV testing did not add significantly to the effectiveness of LBC in this study. No significant adverse psychosocial effects were detected. It would not be cost-effective to screen with cytology and HPV combined but HPV testing, as either triage or initial test triaged by cytology, would be cheaper than cytology without HPV testing. LBC would not benefit from combination with HPV; it is highly effective as primary screening but HPV testing has twin advantages of high negative predictive value and automated platforms enabling high throughput. HPV primary screening would require major contraction and reconfiguration of laboratory services. Follow-up continues in ARTISTIC while maintaining concealment for a further 3-year round of screening, which will help in screening protocol development for the post-vaccination era.

Assessing the wellbeing of cytoscreeners: experience in two NHS cytology laboratories.

OBJECTIVE: Cervical screening programmes in England are in transition as the liquid-based cytology (LBC) method replaces conventional Papanicolaou screening and staff in NHS laboratories are trained to analyse LBC smears. Cytoscreeners and biomedical scientists undertake routine microscopy of slides, but the scientists usually have a wider professional role. Attitudinal surveys were carried out in laboratories where LBC was partially introduced. METHODS: Staff in two cytology laboratories in Greater Manchester were surveyed twice over 6 months. The questionnaire assessed work pressures using scales from the Measures of Work Characteristics instrument, work-related stress using the General Survey version of the Maslach Burnout Inventory, job intentions and job satisfaction. RESULTS: Cytoscreeners, many aged over 50 years, formed over 60% of respondents in both surveys (27/42 in the first survey), and biomedical scientists and doctors, 30%. Both groups were under moderate pressure from work demands in each survey, but cytoscreeners had significantly less autonomy over their working methods (P < 0.001). Although both groups experienced similar levels of exhaustion, cytoscreeners were much more cynical or indifferent towards work in the second survey (P = 0.008) and had lower expectations of being effective (P < 0.001). For the cytoscreeners, there were strong negative correlations in both surveys between cynicism and the work characteristics of influencing decisions and autonomy/control. CONCLUSIONS: The strength of the relationship between work performance and wellbeing serves to emphasize the importance of the new LBC technology in ameliorating low morale where it exists. Further attitudinal research involving larger samples of laboratories is warranted to assess the full impact of this innovation.

Liquid-based cytology can improve efficiency of cervical smear readers: evidence from timing surveys in two NHS cytology laboratories.

OBJECTIVE: Cervical screening programmes in England and Wales were advised by the National Institute for Clinical Excellence in 2003 to adopt liquid-based cytology (LBC) in place of conventional Papanicolaou (Pap) cytology to facilitate laboratory efficiency. Pilot evaluations in England and Scotland monitored daily or weekly workloads of smear readers and concluded that LBC could increase hourly throughput rates. This study, instead, used timing surveys to determine screening rates. METHODS: Two National Health Service cytology laboratories in Manchester and Stockport were partially converted to the LBC ThinPrep process for a cervical screening trial. Three 1-week timing surveys were conducted over 7 months. The surveys covered all LBC-trained staff. The first survey in Manchester also covered staff undertaking conventional Pap screening. The smear readers used timers to record time taken for examining and reporting each slide. RESULTS: In Manchester, in the first survey, nearly 1 minute per slide was saved by the LBC method during primary microscopy. In both laboratories, the mean microscopy time for primary screening of LBC slides was reduced by almost 1 minute between the first and second surveys. There was no difference between the second and third surveys. Microscopy by cytopathologists was also 1 minute per slide quicker with LBC than conventional Pap. The LBC inadequate rates for both laboratories were <2.0%. Organizational factors impacted on the hourly LBC primary screening rates in the laboratories, the rate for Stockport being higher than the rates in the pilot evaluations. CONCLUSIONS: The timing surveys confirm that the LBC ThinPrep technology can improve laboratory efficiency. However, decision-makers should also consider the overall costs and benefits of introducing the technology in screening programmes, including the capital investment and workforce implications.

Assessing economics of treatments for gynecological cancer where clinical effectiveness meets value for money.

During the last 10 years, the management of gynecological cancer has been undergoing a great deal of change. This is due to a drive to reduce ineffective treatment and associated morbidity while at the same time maximizing the benefits of currently available treatment. The foundation for this approach has been high-quality clinical trials which have been performed in increasing numbers. These trials can provide strong evidence that treatments are equivalent or that a new drug adds superiority to previous treatment. The access that women have to the most effective forms of treatment often depends on the availability of healthcare resources and their affordability within the healthcare system. Healthcare decision makers increasingly require not just clinical effectiveness of treatments but also cost-effectiveness to be demonstrated. While health economic methods have been applied to many forms of cancer treatment and screening, there have been very few rigorous economic studies performed in gynecological cancer. This article discusses how economic analysis can be incorporated into clinical trials and how it can provide the sort of value for money determination that payers of healthcare are now requiring. Economic analysis may add a little to the cost of trials, but in the end, it may increase access to treatment by convincing decision makers of cost-effectiveness.

Ambulance emergency services for patients with coronary heart disease in Lancashire: achieving standards and improving performance.

OBJECTIVES: To examine the performance of a rural ambulance trust during two time periods, 1996/97 and 2001, with respect to achieving standards for ambulance journey times and delivery of clinical care for patients with suspected acute myocardial infarction (AMI). METHODS: Audit datasets on two cohorts of patients with chest pain and suspected AMI were assembled by the Lancashire Ambulance Service NHS Trust in north west England: 3706 patients during 1996/97 and 3423 in 2001. They were transported to four hospitals. The analyses covered journey timings, role of rapid response vehicles (RRV), and clinical procedures and the results were compared with prevailing national standards. RESULTS: Hourly and daily usage patterns were similar in the two periods. During 1996/97 the national rural target of 95% of response times being within 19 minutes was achieved (96% of calls), unlike the target of 50% within eight minutes (45.3% of calls). During 2001, 2684 (78.4%) calls had response times within eight minutes thus exceeding the revised national target of 75%. RRVs were despatched for 1214 (35.5%) of calls in 2001, and the mean response time (SD) for these vehicles was significantly shorter than for front line ambulances (0:05:53 (0:02:49) versus 0:07:04 (0:04:19), p<0.001), likewise the mean call to hospital time (0:32:38 (0:09:28) v 0:35:01 (0:12:09), p<0.001). Patients in 2001 were more likely to be given aspirin by the ambulance crews (74% of cases), while the rate of cannulation was lower. CONCLUSION: A significant improvement has been achieved in the performance of ambulance services in Lancashire since 1996, because of recently introduced strategies, notably RRVs, and in the presence of more demanding national standards and targets.

The U.K. NHS economic evaluation database. Economic issues in evaluations of health technology.

OBJECTIVE: The U.K. NHS Economic Evaluation Database (EED) project is commissioned to identify papers on economic evaluations of health technologies and to disseminate their findings to NHS decision makers by means of structured abstracts that are available through a public database and the Cochrane Library. This paper discusses current issues relating to the economic aspects of producing NHS EED abstracts. METHODS: A review of NHS EED was undertaken between 1994 and 1999 to determine the methodologies adopted and issues that influence the usefulness of economic evaluations. Methods adopted to improve the quality of NHS EED abstracts are also reported. RESULTS: Eighty-five percent of NHS EED abstracts are cost-effectiveness analyses (CEAs), 9.3% are cost-utility analyses (CUAs), and only 1.4% are cost-benefit analyses (CBAs). Of the total abstracts, 65.9% are based on single studies, 19.5% on reviews, 3.9% on estimates of effectiveness, and 10.7% on combinations of these sources. Models are utilized in 16.7% of CEAs, 60.2% of CUAs, and 20% of CBAs. Analyses of CBA studies reveal a degree of misuse of well-established definitions. NHS EED internal control mechanisms are reported that provide a means of ensuring that abstracts are based on sound academic principles. CONCLUSIONS: Most economic evaluations are conducted by means of CEA, followed by CUA, while CBA accounts for an extreme minority of cases. Single studies form the principal source of effectiveness data, although models are widely used, principally in CUA. The structure of NHS EED abstracts provides decision makers with the principal results and an interpretation of the relative strengths and weaknesses of economic evaluations.