Economic models in type 2 diabetes.

OBJECTIVE: To identify and critically appraise cost-effectiveness models developed to evaluate type 2 diabetes (T2D) treatments and to assess which types of treatment effects they capture. RESEARCH DESIGN AND METHODS: A systematic search was performed in MEDLINE, EMBASE, Centre for Reviews and Dissemination databases at the University of York, and Health Economic Evaluation Database for the period to September 2008. The websites of Health Technology Assessment (HTA) bodies in different countries were also screened for relevant models. For each of the identified original models, details of the structure, data in- and outputs were extracted and the overall quality of the model in terms of the combination of structure, assumptions and data inputs were appraised using published criteria. RESULTS: Seventy-eight articles and 41 HTAs reporting relevant economic evaluations were identified. There were ten models with multiple publications, and a further ten models with one associated publication. The critical review demonstrated that most had the same fundamental structure, used similar micro-simulation techniques and were based on the same key data sources. However, the process for identification of relevant data and their synthesis, and the selection of outcomes lacked transparency. The models differed according to the extent and type of interventions they evaluated and which diabetes complications and treatment-related adverse events were captured. For example, just one model incorporated changes in patient weight, despite the fact that weight gain can be a side-effect of some treatments, and weight loss a potential benefit of others. CONCLUSIONS: Whilst many economic models exist in T2D, most share common features such as the model type. Identified shortcomings are lack of transparency in data identification and evidence synthesis as well as the selection of the modelled outcomes. Future models should aim to include all relevant treatment outcomes, whether these relate to effects on underlying diabetes and its complications or to short- or long-term side effects of treatment.

Management of low-grade cervical abnormalities detected at screening: which method do women prefer?

OBJECTIVE: To establish whether women with low-grade abnormalities detected during screening for cervical cancer prefer to be managed by cytological surveillance or by immediate colposcopy. METHODS: TOMBOLA (Trial of Management of Borderline and Other Low-grade Abnormal smears) is a randomized controlled trial comparing alternative management strategies following the screen-detection of low-grade cytological abnormalities. At exit, a sample of TOMBOLA women completed a questionnaire eliciting opinions on their management, contingent valuations (CV) of the management methods and preferences. Within-trial quality of life (EQ-5D) data collected for a sample of TOMBOLA women throughout their follow-up enabled the comparison of self-reported health at various time points, by management method. RESULTS: Once management had been initiated, self-reported health in the colposcopy arm rose relative to that in the surveillance arm, although the effect was short-term only. For the majority of women, the satisfaction ratings and the CV indicated approval of the management method to which they had been randomized. Of the minority manifesting a preference for the method which they had not experienced, relatively more would have preferred colposcopy than would have preferred surveillance. CONCLUSIONS: The findings must be interpreted in the light of sample bias with respect to preferences, whereby enthusiasm for colposcopy was probably over-represented amongst trial participants. The study suggests that neither of the management methods is preferred unequivocally; rather, individual women have individual preferences, although many would be indifferent between methods.

Prenatal screening and treatment strategies to prevent group B streptococcal and other bacterial infections in early infancy: cost-effectiveness and expected value of information analyses.

OBJECTIVES: To determine the cost-effectiveness of prenatal strategies for preventing group B streptococci (GBS) and other serious bacterial infections in early infancy and to establish the expected value of further information. DATA SOURCES: Electronic databases were searched up to March 2006. Expert opinion was also sought. REVIEW METHODS: Twelve mutually exclusive maternal risk groups were defined at presentation in labour and the consequences considered of early-onset GBS and non-GBS bacterial infections and late onset GBS infection, measured in terms of lifetime NHS costs and quality-adjusted life-years (QALYs). These were for preterm delivery (<37 weeks): (1) planned Caesarean section, (2) previous baby with GBS disease, (3) positive urine or vaginal swab for GBS in current pregnancy, (4) fever >or=38 degrees C during labour, (5) membrane rupture >or=2 hours before labour onset, (6) membrane rupture <2 hours before labour onset. For term delivery (>or=37 weeks): (7) planned Caesarean section, (8) previous baby with GBS disease, (9) positive urine or vaginal swab for GBS in current pregnancy, (10) fever >or=38 degrees C during labour, (11) membrane rupture >or=18 hours, and (12) none of the above risk factors. Fourteen intervention strategies were applied to each maternal risk group. Data inputs were obtained from systematic reviews, primary data and expert opinion. The model parameters were simultaneously estimated from the data inputs using Bayesian evidence synthesis. The expected net benefit was calculated relative to no intervention for each intervention within each risk group for two scenarios, with and without vaccination. Interventions with more than a 1% probability of being cost-effective (i.e. maximising net benefit at a threshold of 25,000 pounds per QALY gained) in a specific risk group were combined to form strategies. To limit antibiotic exposure, women who were low risk at presentation could not be treated without a positive culture or polymerase chain reaction result. RESULTS: Current best practice, comprising intravenous treatment for pyrexia, previous GBS baby and previous GBS swab or urine culture, and oral treatment for preterm pre-labour membrane rupture (groups 2-5 and 8-10) was not cost-effective. All cost-effective options involved treatment of all preterm groups and high-risk term groups (groups 8-10). Testing high-risk women for maternal GBS colonisation would not be cost-effective, as even those with negative results would be better off treated to reduce the risk of early-onset non-GBS infection. In the absence of vaccination, culture-based testing of women in groups 11 and 12, combined with treatment for the rest, would be the most cost-effective strategy. If vaccination was available, vaccination for all and treatment for groups 1-10 would be marginally more cost-effective than treatment for groups 1-10 and culture for groups 11 and 12, but this is uncertain and is based on expert opinion on vaccine efficacy. The expected value of perfect information results suggest that moderate investment in research would be worthwhile. CONCLUSIONS: Based on our findings, immediate extension of current practice to treat all preterm and high-risk term groups would be beneficial. Further research aimed at the realisation of a GBS vaccine should be prioritized.

Psychological effects of a low-grade abnormal cervical smear test result: anxiety and associated factors.

Receipt of an abnormal cervical smear result often generates fear and confusion and can have a negative impact on a woman's well-being. Most previous studies have focussed on high-grade abnormal smears. This study describes the psychological and psychosocial effects, on women, of having received a low-grade abnormal smear result. Over 3500 women recruited to TOMBOLA (Trial Of Management of Borderline and Other Low-grade Abnormal smears) participated in this study. Anxiety was assessed using the Hospital Anxiety and Depression Scale (HADS) at recruitment. Socio-demographic and lifestyle factors, locus of control and factors associated with the psychosocial impact of the abnormal smear result were also assessed. Women reported anxiety levels consistent with those found in previous studies of women with high-grade smear results. Women at highest risk of anxiety were younger, had children, were current smokers, or had the highest levels of physical activity. Interventions that focus particularly on women's understanding of smear results and pre-cancer, and/or directly address their fears about cancer, treatment and fertility might provide the greatest opportunity to reduce the adverse psychosocial impact of receiving a low-grade abnormal cervical smear result.

Developing a questionnaire to measure the psychosocial impact of an abnormal cervical smear result and its subsequent management: the TOMBOLA (Trial of Management of Borderline and Other Low-grade Abnormal Smears) trial.

This paper describes the process of developing and testing a new questionnaire, Process Outcome Specific Measure (POSM), including an assessment of its content validity and reliability. The questionnaire was developed within the context of Trial Of Management of Borderline and Other Low-grade Abnormal smears (TOMBOLA) to assess the psychosocial impact of a low-grade abnormal cervical smear result and the subsequent management. A literature search, focus groups and thorough pre-testing involving experts and patients resulted in a short (15-item), easily completed and understood questionnaire. Questions address issues including cancer, health, fertility and sexual concerns. Repeatability was assessed in 110 TOMBOLA recruits using weighted k; all but one of the questions showed levels of reliability near to, or above, 0.5. Cronbach's standardised alpha was 0.73, indicating acceptable internal consistency. Each POSM item was correlated with the anxiety and depression sub-scales of the Hospital Anxiety Depression Scale (HADS). All except one of the questions correlated more highly with the total POSM score than with the HADS sub-scales thus indicating discriminant validity. The POSM will enable comparison of the alternative management policies for low-grade cervical smears in terms of the benefits (or otherwise) perceived by the women managed by these policies.

Cost-effectiveness of alternative strategies for the initial medical management of non-ST elevation acute coronary syndrome: systematic review and decision-analytical modelling.

OBJECTIVES: To identify and prioritise key areas of clinical uncertainty regarding the medical management of non-ST elevation acute coronary syndrome (ACS) in current UK practice. DATA SOURCES: Electronic databases. Consultations with clinical advisors. Postal survey of cardiologists. REVIEW METHODS: Potential areas of important uncertainty were identified and 'decision problems' prioritised. A systematic literature review was carried out using standard methods. The constructed decision model consisted of a short-term phase that applied the results of the systematic review and a long-term phase that included relevant information from a UK observational study to extrapolate estimated costs and effects. Sensitivity analyses were undertaken to examine the dependence of the results on baseline parameters, using alternative data sources. Expected value of information analysis was undertaken to estimate the expected value of perfect information associated with the decision problem. This provided an upper bound on the monetary value associated with additional research in the area. RESULTS: Seven current areas of clinical uncertainty (decision problems) in the drug treatment of unstable angina patients were identified. The agents concerned were clopidogrel, low molecular weight heparin, hirudin and intravenous glycoprotein antagonists (GPAs). Twelve published clinical guidelines for unstable angina or non-ST elevation ACS were identified, but few contained recommendations about the specified decision problems. The postal survey of clinicians showed that the greatest disagreement existed for the use of small molecule GPAs, and the greatest uncertainty existed for decisions relating to the use of abciximab (a large molecule GPA). Overall, decision problems concerning the GPA class of drugs were considered to be the highest priority for further study. Selected papers describing the clinical efficacy of treatment were divided into three groups, each representing an alternative strategy. The strategy involving the use of GPAs as part of the initial medical management of all non-ST elevation ACS was the optimal choice, with an incremental cost-effectiveness ratio (ICER) of 5738 pounds per quality-adjusted life-year (QALY) compared with no use of GPAs. Stochastic analysis showed that if the health service is willing to pay 10,000 pounds per additional QALY, the probability of this strategy being cost-effective was around 82%, increasing to 95% at a threshold of 50,000 pounds per QALY. A sensitivity analysis including an additional strategy of using GPAs as part of initial medical management only in patients at particular high risk (as defined by age, ST depression or diabetes) showed that this additional strategy was yet more cost-effective, with an ICER of 3996 pounds per QALY compared with no treatment with GPA. Value of information analysis suggested that there was considerable merit in additional research to reduce the level of uncertainty in the optimal decision. At a threshold of 10,000 pounds per QALY, the maximum potential value of such research in the base case was calculated as 12.7 million pounds per annum for the UK as a whole. Taking account of the greater uncertainty in the sensitivity analyses including clopidogrel, this figure was increased to approximately 50 million pounds. CONCLUSIONS: This study suggests the use of GPAs in all non-ST elevation ACS patients as part of their initial medical management. Sensitivity analysis showed that virtually all of the benefit could be realised by treating only high-risk patients. Further clarification of the optimum role of GPAs in the UK NHS depends on the availability of further high-quality observational and trial data. Value of information analysis derived from the model suggests that a relatively large investment in such research may be worthwhile. Further research should focus on the identification of the characteristics of patients who benefit most from GPAs as part of medical management, the comparison of GPAs with clopidogrel as an adjunct to standard care, follow-up cohort studies of the costs and outcomes of high-risk non-ST elevation ACS over several years, and exploring how clinicians' decisions combine a normative evidence-based decision model with their own personal behavioural perspective.

Knowledge of cervical cancer and screening among women in east-central England.

This study assesses the extent and accuracy of women's knowledge of cervical cancer, risk factors, and the efficacy of the national screening program. Data were obtained from a questionnaire survey of randomly selected women eligible for screening, drawn from a population in east-central England. The majority of women in the sample overestimated the current incidence of cervical cancer, both absolutely and relative to other cancers. Perceiving incidence to be high was associated with reporting worries about the disease. With respect to the screening process, 78.3% believe that the smear abnormality rate is higher than it actually is, and only 7.6% correctly appreciate that the abnormality rate is highest at younger ages. With respect to performance, 16.3% believed the smear test to be completely accurate, and more than half overestimated the likely number of cancer cases prevented by screening. While certain cervical cancer risk factors were correctly assigned by the majority of women, undue emphasis was placed on genetic influence, while the risks posed by human papillomavirus infection were unfamiliar to almost half of the sample. We conclude that women typically possess only a partial picture of risk factors and overestimate both the incidence of cervical cancer and the efficacy of screening.

Review of guidelines for good practice in decision-analytic modelling in health technology assessment.

OBJECTIVES: To identify existing guidelines and develop a synthesised guideline plus accompanying checklist. In addition to provide guidance on key theoretical, methodological and practical issues and consider the implications of this research for what might be expected of future decision-analytic models. DATA SOURCES: Electronic databases. REVIEW METHODS: A systematic review of existing good practice guidelines was undertaken to identify and summarise guidelines currently available for assessing the quality of decision-analytic models that have been undertaken for health technology assessment. A synthesised good practice guidance and accompanying checklist was developed. Two specific methods areas in decision modelling were considered. The first method's topic is the identification of parameter estimates from published literature. Parameter searches were developed and piloted using a case-study model. The second topic relates to bias in parameter estimates; that is, how to adjust estimates of treatment effect from observational studies where there are risks of selection bias. A systematic literature review was conducted to identify those studies looking at quantification of bias in parameter estimates and the implication of this bias. RESULTS: Fifteen studies met the inclusion criteria and were reviewed and consolidated into a single set of brief statements of good practice. From this, a checklist was developed and applied to three independent decision-analytic models. Although the checklist provided excellent guidance on some key issues for model evaluation, it was too general to pick up on the specific nuances of each model. The searches that were developed helped to identify important data for inclusion in the model. However, the quality of life searches proved to be problematic: the published search filters did not focus on those measures specific to cost-effectiveness analysis and although the strategies developed as part of this project were more successful few data were found. Of the 11 studies meeting the criteria on the effect of selection bias, five concluded that a non-randomised trial design is associated with bias and six studies found 'similar' estimates of treatment effects from observational studies or non-randomised clinical trials and randomised controlled trials (RCTs). One purpose of developing the synthesised guideline and checklist was to provide a framework for critical appraisal by the various parties involved in the health technology assessment process. First, the guideline and checklist can be used by groups that are reviewing other analysts' models and, secondly, the guideline and checklist could be used by the various analysts as they develop their models (to use it as a check on how they are developing and reporting their analyses). The Expert Advisory Group (EAG) that was convened to discuss the potential role of the guidance and checklist felt that, in general, the guidance and checklist would be a useful tool, although the checklist is not meant to be used exclusively to determine a model's quality, and so should not be used as a substitute for critical appraisal. CONCLUSIONS: The review of current guidelines showed that although authors may provide a consistent message regarding some aspects of modelling, in other areas conflicting attributes are presented in different guidelines. In general, the checklist appears to perform well, in terms of identifying those aspects of the model that should be of particular concern to the reader. The checklist cannot, however, provide answers to the appropriateness of the model structure and structural assumptions, as these may be seen as a general problem with generic checklists and do not reflect any shortcoming with the synthesised guidance and checklist developed here. The assessment of the checklist, as well as feedback from the EAG, indicated the importance of its use in conjunction with a more general checklist or guidelines on economic evaluation. Further methods research into the following areas would be valuable: the quantification of selection bias in non-controlled studies and in controlled observational studies; the level of bias in the different non-RCT study designs; a comparison of results from RCTs with those from other non-randomised studies; assessment of the strengths and weaknesses of alternative ways to adjust for bias in a decision model; and how to prioritise searching for parameter estimates.

A pilot study on the use of decision theory and value of information analysis as part of the NHS Health Technology Assessment programme.

OBJECTIVES: To demonstrate the benefits of using appropriate decision-analytic methods and value of information analysis (DA-VOI). Also to establish the feasibility and implications of applying these methods to inform the prioritisation process of the NHS Health Technology Assessment (HTA) programme, and possibly extending their use therein. DATA SOURCES: Three research topics that were considered by the HTA panels in the September 2002 and February 2003 prioritisation rounds. REVIEW METHODS: A brief and non-technical overview of DA-VOI methods was circulated to the panels and Prioritisation Strategy Group (PSG). For each case study the results were presented to the panels and the PSG in the form of brief case-study reports. Feedback on the DA-VOI analysis and its presentation was obtained in the form of completed questionnaires from panel members, and reports from panel senior lecturers and PSG members. RESULTS: Although none of the research topics identified met all of the original selection criteria for inclusion as case studies in the pilot, it was possible to construct appropriate decision-analytic models and conduct probabilistic analysis for each topic. In each case, the tasks were completed within the time-frame required by the existing HTA research prioritisation process. The brief case-study reports provided a description of the decision problem, a summary of the current evidence base and a characterisation of decision uncertainty in the form of cost-effectiveness acceptability curves. Estimates of value of information for the decision problem were presented for relevant patient groups and clinical settings, as well as the value of information associated with particular model inputs. The implications for the value of research in each of the areas were presented in general terms. Details were also provided on what the analysis suggested regarding the design of any future research in terms of features such as the relevant patient groups and comparators, and whether experimental design was likely to be required. CONCLUSIONS: The pilot study showed that, even with very short timelines, it is possible to undertake DA-VOI that can feed into the priority-setting process that has been developed for the HTA programme. There are however a number of areas that need to be established at the beginning of the process, such as clarification of the nature of the decision problem for which additional research is being considered, explicitness about which existing data should be used and how data that exhibit particular weaknesses should be down-weighted in the analysis. Other areas, including optimum application of researcher time, integrating the vignette (a summary of the clinical problem and existing evidence) and the use of DA-VOI, training, use of sensitivity analyses, and deployment of clinical expertise, are also considered in terms of the potential implementation of DA-VOI within the HTA programme. Recommendations for further research include how literature searching should focus on those variables to which the model's results are most sensitive and with the highest expected value of perfect information; methods of evidence synthesis (multiple parameter synthesis) to consider the evidence surrounding multiple comparators and networks of evidence; and ways in which the value of sample information can be used by the NHS HTA programme and other research funders to decide on the most efficient design of new evaluative research. There is also a need for an analytical framework to be developed that can jointly address the question of whether additional resources would better be devoted to additional research or interventions to change clinical practice.

Pharmaceutical care for elderly patients shared between community pharmacists and general practitioners: a randomised evaluation. RESPECT (Randomised Evaluation of Shared Prescribing for Elderly people in the Community over Time) [ISRCTN16932128].

BACKGROUND: This trial aims to investigate the effectiveness and cost implications of 'pharmaceutical care' provided by community pharmacists to elderly patients in the community. As the UK government has proposed that by 2004 pharmaceutical care services should extend nationwide, this provides an opportunity to evaluate the effect of pharmaceutical care for the elderly. DESIGN: The trial design is a randomised multiple interrupted time series. We aim to recruit 700 patients from about 20 general practices, each associated with about three community pharmacies, from each of the five Primary Care Trusts in North and East Yorkshire. We shall randomise the five resulting groups of practices, pharmacies and patients to begin pharmaceutical care in five successive phases. All five will act as controls until they receive the intervention in a random sequence. Until they receive training community pharmacists will provide their usual dispensing services and so act as controls. The community pharmacists and general practitioners will receive training in pharmaceutical care for the elderly. Once trained, community pharmacists will meet recruited patients, either in their pharmacies (in a consultation room or dispensary to preserve confidentiality) or at home. They will identify drug-related issues/problems, and design a pharmaceutical care plan in conjunction with both the GP and the patient. They will implement, monitor, and update this plan monthly. The primary outcome measure is the 'Medication Appropriateness Index'. Secondary measures include adverse events, quality of life, and patient knowledge and compliance. We shall also investigate the cost of pharmaceutical care to the NHS, to patients and to society as a whole.

An evaluation of liquid-based cytology and human papillomavirus testing within the UK cervical cancer screening programme.

The aim of this study is to evaluate different options for introducing liquid-based cytology (LBC) and human papillomavirus (HPV) testing into the UK cervical cancer screening programme. These include options that incorporate HPV testing either as a triage for mild and borderline smear abnormalities or as a primary screening test. Outcomes include the predicted impact on resource use, total cost, life years and cost-effectiveness. Extensive sensitivity analysis has been carried out to explore the importance of the uncertainty associated with disease natural history and the impact of screening. Under baseline assumptions, the cost-effectiveness of different options for introducing LBC appears favourable, and these results are consistent under a range of assumptions for its impact on the diagnostic effectiveness of cytology. However, if we assume a higher marginal cost of LBC in comparison to conventional methods, primary smear testing options are predicted to be more cost-effective without LBC. Combined LBC primary smear and HPV testing with a 5-year interval is similar in both cost and effectiveness to the other 3-yearly options of primary smear testing or primary HPV testing alone. However, both primary HPV testing and combined options would give rise to a far greater risk of inappropriate colposcopy throughout a woman's lifetime. British Journal of Cancer (2004) 91, 84-91. doi:10.1038/sj.bjc.6601884 www.bjcancer.com Published online 25 May 2004

Women's interpretation of cervical smear test results.

Screening for cervical cancer using the Papanicolaou smear test has been available in England since the 1960s, yet very little is known about how women interpret their test results. This questionnaire study required women to explain, in their own words, the meaning of normal and abnormal test results. It was discovered that the use of the word cell as a description of findings was extremely common, and that a proportion of subjects equated abnormal results with technical inadequacy. The frequency of circularity in the interpretations, i.e. interpreting 'normal' as 'not abnormal' and vice versa, was striking. Contrary to previous research, we find that, whilst many women interpret normal results as indicating the current absence of cancer, few appear to believe that future cancer is thereby definitively ruled out. By the same token, only a very small minority interpret abnormal results as definitive of cancer.

Communicating mild and borderline abnormal cervical smear results: how and what are women told?

The way in which women are informed about borderline or mild smear results can have a significant psychological impact. By means of a questionnaire survey of general practices in Nottingham, England, this study audited the means by which abnormal smear results were normally communicated to subjects and analysed the content of these communications. Transmitting abnormal smear results, either by letter or by telephone call, was typically the responsibility of the practice nurse, and communications varied widely in informational content. We conclude that the method and content of communications imparting mild or borderline smear results differs between general practices, even within a small geographical area.

Early withdrawal from cervical cancer screening: the question of cost-effectiveness.

In countries such as the UK, mass population screening for cervical cancer has been undertaken since the 1960s. Although of established effectiveness, no formal evaluation of the screening protocol was carried out prior to its implementation. On the basis of a published mathematical modelling exercise, it has been speculated that withdrawing women from the screening programme at an earlier age than at present, whilst leading to a higher rate of invasive cervical cancer (ICC), could reduce resource use. Using estimates of screening and treatment costs, and of expected life-years lost following earlier withdrawal, we simulated cost-effectiveness ratios for various scenarios described by the model. Median cost savings resulting from a life-year lost never exceeded pound10000 for any scenario, although the estimates were particularly sensitive to the assumed age at cancer presentation and the rate of cancer progression. Our findings seem to offer little economic support for the early withdrawal of subjects from the cervical screening programme.

The role of community pharmacists in prescribing medication for the treatment of head lice.

BACKGROUND: The aim of the study was to discover whether the use of community pharmacy, rather than general practice, as the first port of call for suspected head lice infestation would represent an acceptable, effective and cost-reducing means of management in the community. METHODS: A before-and-after study was carried out of a new system of care delivery. Between September and November 1997, pharmacists in Nottingham City West recorded details of all patients attending with prescriptions for head lice treatment or those purchasing over-the-counter medication. The new system of care delivery began in January 1998, during which, pharmacists were providing advice and treatment for head lice, in the absence of a referral from general practice. Changes in prescribing behaviour were assessed from Prescribing Analysis and Cost (PACT) data. Acceptability and subjective assessment of the scheme (patients and professionals) was gauged from questionnaires. RESULTS: Referral patterns were altered drastically (away from general practice and towards self-referral) by the project, and the changes were apparent within the first month. This trend continued throughout and beyond the formal evaluation period. Cost analysis suggests that the community pharmacy scheme generates resource savings, largely driven by the lower cost of a pharmacy consultation, as opposed to a GP consultation. Questionnaire evidence suggests that both patients and health care professionals viewed the new arrangement as at least as acceptable as the old. CONCLUSION: With respect to the original objective, the new delivery system appears to provide no evidence of ineffectiveness; evidence of acceptability on the part of the majority of patients and professionals; and evidence of improved cost-effectiveness.

Deriving a compound quality of life measure from the EORTC-QLQ-C30/LC13 instrument for use in economic evaluations of lung cancer clinical trials.

Many clinical trials involve parallel collection of quality of life (QoL) and economic data, requiring patients to complete similar questionnaires at regular intervals. This additional burden often leads to disappointing response rates and inconclusive results. Data obtained in the LU-16 trial with the European Organization for Research and Treatment of Cancer Quality of Life (EORTC-QLQ-C30)/LC-13 QoL instrument for lung cancer were re-analysed, using multivariate techniques. The analysis demonstrated the inherent non-linearity of QoL data, with resulting interpretational problems. A new integrated linear QoL measure was developed which maximises the use of the information collected and can serve as a proxy utility measure for economic evaluation. It was successfully validated with data from another lung cancer trial with encouraging results. For individual patients, trends in QoL are revealed more clearly with narrower confidence intervals. This approach yields relative weightings and rankings for the main issues affecting QoL ratings in lung cancer patients, most importantly fatigue, breathlessness, poor concentration and disruption to family and social life.

Cumulative conception and live birth rates in natural (unstimulated) IVF cycles.

IVF treatment, which involves ovarian stimulation, poses significant health problems such as ovarian hyperstimulation and is associated with a high incidence of multiple pregnancy and premature birth. In this paper, we demonstrate how natural cycle IVF is an effective and potentially cost-effective alternative treatment option for certain groups of infertile couples. The study was conducted in the Assisted Conception Unit at King's College School of Medicine, London. Fifty-two women with regular menstrual cycles whose partners had normal semen parameters were offered a total of 181 cycles of treatment (average 3.49 per couple). Life table analysis was used to calculate cumulative success rates after successive cycles of treatment. After four cycles, the cumulative probability of pregnancy was 46% with an associated live birth rate of 32%. To achieve maximal effectiveness, natural cycle IVF should be offered as a series of treatment cycles, for it is safer, less stressful and can be offered over consecutive cycles. Moreover, the avoidance of expensive drugs and reduced intensity of monitoring make natural cycle IVF less expensive than conventional treatment involving stimulation. We calculate that this treatment can be offered at approximately 23% of the cost of a stimulated cycle, suggesting that it may be a cost-effective alternative to conventional assisted conception techniques.

Evaluation of the relative cost-effectiveness of treatments for infertility in the UK.

This paper aims to complement existing clinical guidelines by providing evidence of the relative cost-effectiveness of treatments for infertility in the UK. A series of decision-analytical models have been developed to reflect current diagnostic and treatment pathways for the five main causes of infertility. Data to populate the models are derived from a systematic review and routine National Health Service activity data, and are augmented with expert opinion. Costs are derived from an analysis of extra-contractual referral tariffs and private sector data. Sensitivity analysis has been carried out to take account of the uncertainty of model parameters and to allow results to be interpreted in the light of local circumstances. Results of the modelling exercise suggest in-vitro fertilization is the most cost-effective treatment option for severe tubal factors and endometriosis, with surgery the most cost-effective in the case of mild or moderate disease. Ovulatory factors should be treated medically with the addition of laparoscopic ovarian diathermy in the presence of polycystic ovarian syndrome. For other causes, stimulated intrauterine insemination (unexplained and moderate male factor) and stimulated donor intrauterine insemination (severe male) are cost-effective.

Comparative cost-effectiveness of four-layer bandaging in the treatment of venous leg ulceration.

This paper reports the results of an analysis designed to estimate the expected annual cost per patient of treating venous leg ulcers, and to evaluate the relative cost-effectiveness of a systematic treatment regimen using a four-layer compression bandaging system (Profore) compared with usual care. A Markov model has been developed which simulates the transition of patients between health states (healed and unhealed) over a 52-week period. Healing rates used in the model are derived from those reported in the literature. By running the model for a cohort of 100 patients over 52 weeks it is possible to estimate expected outcomes and annual budgetary costs for alternative treatment regimens. Results suggest that, when compared with usual care, a systematic treatment regimen using Profore is unambiguously more cost-effective. Patient outcomes are improved and annual treatment costs reduced. An important implication is that failure to co-ordinate treatment policies and to use the most cost-effective treatments may result in substantial inefficiency in the use of NHS resources. This inefficiency could represent the equivalent of between 350,000 Pounds and 1.08 million Pounds annually for a typical health authority.