This is a critical abstract of an economic evaluation that meets the criteria for inclusion on NHS EED. Each abstract contains a brief summary of the methods, the results and conclusions followed by a detailed critical assessment on the reliability of the study and the conclusions drawn.

Screening for anal squamous intraepithelial lesions (SIL) and anal squamous cell carcinoma (SCC) in HIV positive men using anal cytology.

Primary prevention.

Cost-utility analysis.

Hypothetical cohort of HIV positive homosexual and bisexual men.

Hospital and community. The economic analysis was conducted in Boston, USA.

Effectiveness data were collected from a review of literature published between 1986 and 1998. Resources used were estimated from studies and data sets published between 1993 and 1998. 1997 price years were used.

Effectiveness data were derived from a review of previously completed studies.

A state transition Markov model was used to extrapolate lifetime costs and life expectancy from data obtained in the literature review, for patients receiving screening every 3 years, 2 years or six months or not at all. For HIV patients the level of CD4 cell count was also taken into account in the model, and patients initially with CD4 counts greater 0.50 x 10 exp 9/L (500/mu L), between 0.20 and 0.50 x 10 exp 9 /L and less than 0.20 x 10 exp 9 /L were considered.

Outcomes assessed in the review included prevalence of ASIL and the rate of progression to anal SCC. Regression rates from ASIL to normal status, five year life expectancy rates for patients with invasive cancer, length of disease staging and overall mortality were also estimated. The sensitivity and specificity of screening tests were also determined from the literature review.

Studies used in the review included prospective controlled cohort studies examining screening and incidence/prevalence of ASIL in homosexual HIV positive and HIV negative men. No inclusion or exclusion criteria for studies appear to be stated.

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Thirty five studies in total were included in the review; 2 prospective controlled cohort studies were used to identify prevalence of ASIL in homosexual men. Incidence of cancer symptoms and survival rates were taken from two publications in the literature. Cancer incidence rates were taken from a 1987 study of sexually transmitted diseases and the incidence of anal cancer. The sensitivity/specificity of pap screening was taken from one study in the literature and the levels of efficacy and toxicity from cancer treatment were deemed to be equal for HIV positive and negative patients based on four publications in the literature.

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The prevalence of uncertain atypical squamous cells was estimated to be 15.1% in the >0.50 x 10^9/L group, 14.1% in patients with CD4 cell counts between 0.20 and 0.50 x 10^9 /L and 21.9% in patients with CD4 cell counts less than 0.20 x 10^9 /L. Similarly the prevalence of low grade ASIL in these three groups was estimated to be 20.9%, 33.1% and 36.0% and similarly for high grade ASIL these figures were 3.5%, 2.8% and 8.8%. The prevalence of invasive cancer was estimated to be 0.012% in all three groups. Progression rates from normal to low grade ASIL were 1.43% (range: 0.90 - 2.15)in the first group and 2.14% (range: 1.34 - 3.21) in the other groups respectively. Progression rates from normal to high grade ASIL similarly were 0.54% (range: 0 - 0.81) in the first group and 0.81% (range: 0 - 1.21) in the other groups respectively. Progression rates from low grade to high grade ASIL were 1.73% (range: 0.73 - 2.33) in the first group and 2.58% (range: 1.09 - 3.48) in the other groups. The progression rate from high grade ASIL to cancer was 0.43% in all three groups. The regression rates from low grade ASIL to normal were 2.12% (range: 1.06 - 3.18) in the first group and 0.23% (range: 0.12- 2.12) in both other groups. The regression rates from high grade ASIL to normal were 0% (range: 0 - 3.18) in all groups. The annual rate of invasive cancer symptoms in all three groups was estimated to be 30% (range: 20 - 40) and 56% (range: 37 - 84) of patients with invasive cancer were expected to live at least five years. The mean duration of the three HIV stages, represented by the CD4 cell counts was estimated to be 5.52 years, 3.63 years and 3.26 years respectively. Overall annual mortality rates for the three groups were estimated to be 0.0023%, 0.2787% and 2.2373% respectively.

Life years gained and quality-adjusted life years gained (QALYs). A Markov model was used to estimate long term outcomes and quality weights were taken from a previously published study examining AIDS. In this study weights were not determined using either standard gamble or time trade off but were stratified across CD4 cell counts and reported a weight for AIDS and cancer. In the sensitivity analysis utility weights identified in another study of patients with HIV were also used.

Costs associated with anal cancer screening, diagnosis and treatment were estimated using 1997 Medicare average allowed charges. Resources used for ASIL treatment were based on a clinical algorithm developed by the University of San Francisco Faculty of General Practice. The costs of initial treatment, continuing and terminal care for anal cancer were assumed to be similar to 1995 published costs for colorectal cancer. Monthly HIV care costs were taken from the AIDS Cost and Utilisation Survey. 1997 price years were used and costs were adjusted where necessary using the medical component of the US Bureau of Labour Consumer Price Index. Costs and benefits were discounted at a rate of 3% per annum. Direct costs were determined from the perspective of the health care payer.

Patient time costs were estimated including waiting, travel, screening and treatment time from published literature. Due to uncertainty about patient wage rates these costs were only included in sensitivity analysis and not in the base case scenario.

US dollars ($).

One way sensitivity analyses were conducted on a wide range of parameters including natural history probabilities and prevalence of ASIL and cancer, as well as on cost of treatment and screening, sensitivity and specificity and the annual discount rate. Areas of uncertainty investigated were variability in the data due to limited access to data and analytical methods to be used in the analysis.

With no screening the mean unadjusted life months gained (quality adjusted life months gained in parentheses) for patients in the early stage of HIV (with a CD4 cell count >0.50 x 10^9/L) were 109.49 months (102.25). The incremental additional months gained using pap screening every three years were 2.68 (2.42). Increasing screening to every two years would lead to incremental life months gained of 0.32 (0.30) compared with the three year strategy. Similarly screening every year would lead to further incremental life months gained of 0.27 (0.25) and every six months would increase life months gained by an additional 0.09 (0.08). With no screening the mean unadjusted life months gained (quality adjusted life months gained in parentheses) for patients in a more advanced stage of HIV (with a CD4 cell count between 0.20 - 0.50 x 10^9 /L) were 70.42 (63.97) months The incremental additional months gained using pap screening every three years were 0.96 (0.84). Increasing screening to every two years would lead to incremental life months gained of 0.18 (0.16) compared with the three year strategy. Similarly screening every year would lead to further incremental life months gained of 0.17 (0.15) and every six months would increase life months gained by an additional 0.06 (0.05). With no screening the mean unadjusted life months gained (quality adjusted life months gained in parentheses) for patients in a more advanced stage of HIV (with a CD4 cell count less than 0.20 x 10^9 /L) were 38.52 (33.13) months The incremental additional months gained using pap screening every three years were 0.22 (0.18). Increasing screening to every two years would lead to incremental life months gained of 0.06 (0.06) compared with the three year strategy. Similarly screening every year would lead to further incremental life months gained of 0.06 (0.05) and every six months would increase life months gained by an additional 0.03 (0.03). It is not clear whether side effects associated with treatment were included in the weighting of quality of life for patients.

The mean lifetime costs of treatment for HIV, screening and anal cancer with no screening for patients in the early stages of HIV (with a CD4 cell count greater than 0.50 x 10^9 /L) were $69,960. The incremental costs using pap screening every three years were $2,660. Increasing screening to every two years would lead to additional costs of $280 compared with the three year strategy. Similarly screening every year would lead to further costs of $340 and every six months would increase costs by an additional $360. The mean lifetime costs of treatment for HIV, screening and anal cancer with no screening for patients in the more advanced stages of HIV (with a CD4 cell count between 0.20 and 0.50 x 10^9 /L) were $71,640. The incremental costs using pap screening every three years were $1,720 Increasing screening to every two years would lead to additional costs of $270 compared with the three year strategy. Similarly screening every year would lead to further costs of $290 and every six months would increase costs by an additional $240. The mean lifetime costs of treatment for HIV, screening and anal cancer with no screening for patients in the late stages of HIV (with a CD4 cell count less than 0.20 x 10^9 /L) were $75,540. The incremental costs using pap screening every three years were $740. Increasing screening to every two years would lead to additional costs of $230 compared with the three year strategy. Similarly screening every year would lead to a further costs of $270 and every six months would increase costs by an additional $200.

The incremental cost per life year gained (quality adjusted life year in parentheses) gained using screening every 2 years for patients in the early stage of HIV was $11,800 ($13,000) compared with no screening. This strategy also had extended dominance over the 3 year strategy. The incremental cost per life year gained using the one year strategy was $15,200 ($16,600) compared with the two year strategy. Compared with one year strategy the incremental costs per life year gained using the six month screening strategy were $45,600 ($49,600). The incremental costs per life year (quality adjusted life year in parentheses) gained using screening every 2 years for patients in the middle stage of HIV were $21,000 compared with no screening. Using quality-adjusted life years both this strategy and the three year strategy were subject to extended dominance by the one year strategy. The incremental costs per life year gained using the one year strategy were $21,100 ($23,800) compared with the two year strategy (compared with the no screening strategy). Compared with one year strategy the incremental costs per life year gained using the six month screening strategy were $48,500 ($54,300). The incremental costs per life year (quality adjusted life year in parentheses) gained using screening every 3 years for patients in the late stage of HIV were $42,400 ($49,300) compared with no screening. The incremental costs using screening every two years were $44,200 ($51,400) compared with the three year screening strategy. The incremental cost per life year gained using the one year strategy were $49,100 ($57,100) compared with the two year strategy. Compared with one year strategy the incremental costs per life year gained using the six month screening strategy were $78,300 ($91,100). The results of the model were relatively robust in sensitivity analysis although varying the rate of progression from high grade ASIL to cancer and the efficacy of treatment for high grade ASIL had the greatest variability.

The authors concluded that screening led to increases in quality-adjusted life expectancy for all patients. For patients in all stages of HIV, screening every two or one year(s) has a cost effectiveness well within the currently acceptable range for interventions. The authors concluded that further research is required to identify barriers to the introduction of such a screening policy, such as shortage of trained professionals to conduct screenings. Furthermore, more research is required to determine the rate of progression from ASIL to anal cancer and also to determine the long term effectiveness of anti-retroviral treatments for HIV which may have an impact on life expectancy.

the intervention was screening followed by treatment, the comparator, no screening followed by treatment if symptoms of cancer occur, was justified.

efits were extrapolated using a Markov state transition model, based on data obtained from published literature. The authors do not appear to state what sources, criteria and methods were used in preparing the literature review, which could leave the study open to suggestions of bias. As the authors noted, quality of life measures used in the study are the subject of some uncertainty, although these did not greatly influence the results of sensitivity analysis.

ficient details of the source of cost data were provided by the authors. Costs were determined from published sources in the literature, but as the authors themselves note, these are still the subject of uncertainty, being based on estimates for colorectal cancer, as costs for anal cancer were not found in the literature. Costs (including indirect costs for patients) were varied in the sensitivity analysis, and were not found to influence the model greatly.

results of this study may not be generalisable to settings outside the United States.

Dr Goldie was supported by a post-doctoral fellowship award from the Agency for Health Care Policy and Research. The article was also supported by the General Clinical Research Center, University of California, San Francisco. Funds were provided by the US Public Health Service, Division of Research Resources 5 MO1-RR-00079 and by grants RO1-CA-54053 from the National Cancer Institute, U64/CCU114927-01 from the Centers for Disease Control and Prevention, and RO1-A142006-02 from the National Institute of Allergy and Infectious Disease.