Adjusting for treatment switching in randomised controlled trials - A simulation study and a simplified two-stage method.

Estimates of the overall survival benefit of new cancer treatments are often confounded by treatment switching in randomised controlled trials (RCTs) - whereby patients randomised to the control group are permitted to switch onto the experimental treatment upon disease progression. In health technology assessment, estimates of the unconfounded overall survival benefit associated with the new treatment are needed. Several switching adjustment methods have been advocated in the literature, some of which have been used in health technology assessment. However, it is unclear which methods are likely to produce least bias in realistic RCT-based scenarios. We simulated RCTs in which switching, associated with patient prognosis, was permitted. Treatment effect size and time dependency, switching proportions and disease severity were varied across scenarios. We assessed the performance of alternative adjustment methods based upon bias, coverage and mean squared error, related to the estimation of true restricted mean survival in the absence of switching in the control group. We found that when the treatment effect was not time-dependent, rank preserving structural failure time models (RPSFTM) and iterative parameter estimation methods produced low levels of bias. However, in the presence of a time-dependent treatment effect, these methods produced higher levels of bias, similar to those produced by an inverse probability of censoring weights method. The inverse probability of censoring weights and structural nested models produced high levels of bias when switching proportions exceeded 85%. A simplified two-stage Weibull method produced low bias across all scenarios and provided the treatment switching mechanism is suitable, represents an appropriate adjustment method.

Evaluation of surgical procedures for sex reassignment: a systematic review.

OBJECTIVES: To evaluate earlier reviews and literature concerning five individual surgical procedures for male-to-female (MTF) transsexism: clitoroplasty, labiaplasty, orchidectomy, penectomy and vaginoplasty. Further evaluations were made of eight surgical procedures for female-to-male (FTM) transsexism: hysterectomy, mastectomy, metoidoplasty, phalloplasty, salpingo-oophorectomy, scrotoplasty/placement of testicular prostheses, urethroplasty and vaginectomy. BACKGROUND: Increased prevalence and advances in surgical options available to patients requesting gender reassignment surgery have made this an important consideration for research. There remains a lack of systematic reviewing of the evidence, in particular, of the individual surgical options available. METHODS: Searches were undertaken in six electronic databases (Applied Social Sciences Index and Abstracts [ASSIA], Cochrane Library [Wiley Online], Embase [Ovid Online], Medline [Ovid Online], Medline in Process [Ovid Online], Psycinfo) providing coverage of the biomedical, grey literature and current research. RESULTS: Eighty-two published papers (38 MTF; 44 FTM) met the inclusion criteria identified across the 13 surgical procedures. For MTF transsexism there was no evidence satisfying the inclusion criteria concerning labiaplasty, penectomy or orchidectomy procedures. A large amount of evidence was available concerning vaginoplasty and clitoroplasty procedures. For FTM transsexism satisfactory outcomes were reported. Outcomes related to the ability to perform sexual intercourse, achieve orgasm and void whilst standing. Some complications were reported for both MTF and FTM procedures. CONCLUSIONS: The evidence concerning gender reassignment surgery in both MTF and FTM transsexism has several limitations in terms of: (a) lack of controlled studies, (b) evidence has not collected data prospectively, (c) high loss to follow up and (d) lack of validated assessment measures. Some satisfactory outcomes were reported, but the magnitude of benefit and harm for individual surgical procedures cannot be estimated accurately using the current available evidence.

Effectiveness and cost-effectiveness of prognostic markers in prostate cancer.

This paper demonstrates how economic modelling can be used to derive estimates of the cost-effectiveness of prognostic markers in the management of clinically localised and moderately graded prostate cancer. The model uses a Markov process and is populated using published evidence and local data. The robustness of the results has been tested using sensitivity analysis. Three treatment policies of 'monitoring' (observation), radical prostatectomy, or a selection-based management policy using DNA-ploidy as an experimental marker, have been evaluated. Modelling indicates that a policy of managing these tumours utilising experimental markers has an estimated cost per quality-adjusted life year (QALY) of pound 12 068. Sensitivity analysis shows the results to be relatively sensitive to quality-of-life variables. If novel and experimental markers can achieve specificity in excess of 80%, then a policy of radical surgery for those identified as being at high risk and conservative treatment for the remainder would be both better for patients and cost-effective. The analysis suggests that a radical prostatectomy treatment policy for the moderately graded tumours (Gleason grades -7) modelled in this paper may be inferior to a conservative approach in the absence of reliable prognostic markers, being both more costly and yielding fewer QALYs.

[Modeling long-term results of basiliximab (SIMULECT) use in patients after kidney transplantation in Great Britain]. / Modelowanie dlugotrwalych skutków stosowania basiliximabu (SIMULECTU) u chorych po przeszczepieniu nerki w Wielkiej Brytanii.

Kidney graft survival prognosis could be performed in relation to the number of acute rejection episodes and their severity. The episodes of rejection could be modelled and based and the results obtained on this way could serve for prediction of a length of graft survival as well as for basiliximab treatment planning.

How effective are prevention strategies in reducing the prevalence of pressure ulcers?

The prevalence of pressure ulcers has remained constant at about 7% over the past 20 years, even though considerable time and money has been invested in various prevention strategies. This literature review explores whether pressure-prevention programmes can reduce the prevalence rate still lower or whether they are working but are limited by an increasingly aged population and rising patient acuity.

Doctor-nurse substitution: the workforce equation.

AIM: This paper examines the historical background and context to the doctor-nurse substitution debate, and then addresses the sufficiency assumptions inherent in the new nursing roles. BACKGROUND: The NHS Executive considers 'new nursing roles' as a means of substituting part of the doctors' skills. Whilst the literature abounds with professional debate related to the desirability of nurses extending their roles, the underlying assumption of a sufficiency of skilled nurses is not considered. METHODS: The NHS hospital workforce data for the year 1994/95 were analysed and the changes in the overall numbers of doctors and nurses available for work were calculated as the doctors' hours were progressively reduced. FINDINGS: The changes in skill mix were compared; firstly, as a result of the estimated potential reductions in nurses available to undertake the nursing function as movements up the nursing skills spectrum occurs, and secondly, as a result of the alteration in the balance of available skilled staff. CONCLUSION: The policy assumption that suggests that a sufficiency of nurses is available for doctor substitution, whilst still allowing the nursing element to function may be false.

Choice of NSAID and management strategy in rheumatoid arthritis and osteoarthritis. The impact on costs and outcomes in the UK.

OBJECTIVE: Although nonsteroidal anti-inflammatory drugs (NSAIDs) are an effective therapy for rheumatoid arthritis, they are associated with significant adverse effects, the management of which imposes additional costs on the healthcare system. Prescribing NSAIDs which have a lower risk of major adverse effects as the first-line NSAID for patients with rheumatoid arthritis and osteoarthritis may be expected to lead to an improvement in clinical outcomes and reduce overall treatment costs. This analysis examines data from a published randomised controlled trial of 5 NSAIDs to explore these hypotheses. DESIGN AND SETTING: Data from a clinical trial comparing 5 NSAIDs were combined with published cost data to construct 2 clinical decision models, reflecting alternative approaches to the management of major and minor adverse effects in the UK. INTERVENTIONS: The 5 NSAIDs evaluated in the analysis were nabumetone, diclofenac, ibuprofen, piroxicam and naproxen, although only the results for ibuprofen and nabumetone are reported. MAIN OUTCOME MEASURES AND RESULTS: The total cost of care per patient receiving nabumetone was estimated to be between 25 pounds sterling (Pound) and 41 Pounds more expensive than ibuprofen. In a hypothetical cohort of 100,000 patients, there were between 690 and 821 more major adverse effects using ibuprofen than nabumetone. The cost per life-year gained (LYG) from using nabumetone rather than ibuprofen ranged between 1880 Pounds and 2517 Pounds (1995 values), depending upon the management of adverse effects. CONCLUSIONS: These results indicate that: (i) prescribing the newer, currently more expensive, NSAIDs will not necessarily lead to cost savings; (ii) the management of adverse effects can have a significant impact on costs; and (iii) the additional cost may be justifiable in terms of the mortality and morbidity gains associated with the new lower-risk NSAIDs.

Health economics in rheumatology.

Economic evaluations of health-care technologies are playing an increasingly central role in determining which therapies are available to clinicians in the treatment of a whole range of conditions. In rheumatology, a large body of work has already been done on the cost effectiveness of alternative non-steroidal anti-inflammatory drugs (NSAIDs), and much of the current work on disease modifying therapies incorporates economic evaluations. This chapter describes the main techniques of economic evaluation and reviews the strengths and weaknesses of each. Two published economic evaluations are discussed in order to highlight what economic evaluations can offer to the care of people with rheumatoid arthritis, as well as the current limitations of economic evaluation. The objective of this chapter is to equip readers with a critical understanding of economic evaluation that can be used in considering the increasing volume of health economic data that they encounter in their clinical work.

Application of cost-benefit analysis to programmes for the prevention of mental handicap.

The paper is a discussion of the role of cost-benefit analysis in evaluating programmes for preventing mental handicap. It is divided into three broad sections. In the first section the technique of cost-benefit analysis is defined and the possible variants considered. It is concluded that policies for the prevention of mental handicap are most appropriately analysed using a mixture of monetary and non-monetary measures of outcome. The second section lays down some guidelines for undertaking a study: the importance of specifying alternatives to the policy being analysed; specifying input-output relationships; counting only the appropriate costs and benefits; and discounting costs and benefits which occur in the future. The third section looks at the current state of the art in the UK. It concludes that little cost-benefit analysis has been done in the field of mental handicap, indicates where work could usefully be directed, and highlights information that would have to be available before a cost-benefit study could give useful results.