The Potential Economic Impact of the Updated COVID-19 mRNA Fall 2023 Vaccines in Japan.

This analysis estimates the economic and clinical impact of a Moderna updated COVID-19 mRNA Fall 2023 vaccine for adults ≥18 years in Japan. A previously developed Susceptible-Exposed-Infected-Recovered (SEIR) model with a one-year analytic time horizon (September 2023-August 2024) and consequences decision tree were used to estimate symptomatic infections, COVID-19 related hospitalizations, deaths, quality-adjusted life years (QALYs), costs, and incremental cost-effectiveness ratio (ICER) for a Moderna updated Fall 2023 vaccine versus no additional vaccination, and versus a Pfizer-BioNTech updated mRNA Fall 2023 vaccine. The Moderna vaccine is predicted to prevent 7.2 million symptomatic infections, 272,100 hospitalizations and 25,600 COVID-19 related deaths versus no vaccine. In the base case (healthcare perspective), the ICER was ¥1,300,000/QALY gained ($9400 USD/QALY gained). Sensitivity analyses suggest results are most affected by COVID-19 incidence, initial vaccine effectiveness (VE), and VE waning against infection. Assuming the relative VE between both bivalent vaccines apply to updated Fall 2023 vaccines, the base case suggests the Moderna version will prevent an additional 1,100,000 symptomatic infections, 27,100 hospitalizations, and 2600 deaths compared to the Pfizer-BioNTech vaccine. The updated Moderna vaccine is expected to be highly cost-effective at a ¥5 million willingness-to-pay threshold across a wide range of scenarios.

Projections of the incidence of COVID-19 in Japan and the potential impact of a Fall 2023 COVID-19 vaccine.

BACKGROUND: The study objective was to estimate the incidence of COVID-19 infection, hospitalization, and deaths in Japan from September 2023 to August 2024 and potential impact of a monovalent XBB.1.5 variant-adapted Fall 2023 COVID-19 vaccine (modified version: XBB monovalent) for adults aged ≥18 years on these outcomes. METHODS: A previously developed Susceptible-Exposed-Infected-Recovered model for the United States (US) was adapted to Japan. The numbers of symptomatic infections, COVID-19-related hospitalizations, and deaths were calculated. Given differences in vaccination coverage, masking practices and social mixing patterns between the US and Japan, all inputs were updated to reflect the Japanese context. Vaccine effectiveness (VE) values are hypothetical, but predicted based on existing VE values of bivalent BA.4/BA.5 boosters against BA.4/BA.5 in Japan, from the VERSUS test-negative case-control study. Sensitivity analyses were performed. RESULTS: The base case model predicts overall that there will be approximately 35.2 million symptomatic COVID-19 infections, 690,000 hospitalizations, and 62,000 deaths in Japan between September 2023 and August 2024. If an updated COVID-19 vaccine is offered to all adults aged 18 years and older in Fall 2023, the model predicts that 7.3 million infections, 275,000 hospitalizations and 26,000 deaths will be prevented. If vaccines are only given to those aged 65 years and older, only 2.9 million infections, 180,000 hospitalizations and 19,000 deaths will be prevented. Sensitivity analysis results suggest that hospitalizations and deaths prevented are most sensitive to initial VE against infection and hospitalizations, and the waning rate associated with VE against infection. Symptomatic infections prevented was most sensitive to initial VE against infection and VE waning. CONCLUSIONS: Results suggest that a Fall 2023 COVID-19 vaccine would reduce total numbers of COVID-19-related infections, hospitalizations, and deaths.

Clinical impact and cost-effectiveness of the updated COVID-19 mRNA Autumn 2023 vaccines in Germany.

OBJECTIVES: To assess the potential clinical impact and cost-effectiveness of coronavirus disease 2019 (COVID-19) mRNA vaccines updated for Autumn 2023 in adults aged ≥60 years and high-risk persons aged 30-59 years in Germany over a 1-year analytic time horizon (September 2023-August 2024). METHODS: A compartmental Susceptible-Exposed-Infected-Recovered model was updated and adapted to the German market. Numbers of symptomatic infections, a number of COVID-19 related hospitalizations and deaths, costs, and quality-adjusted life-years (QALYs) gained were calculated using a decision tree model. The incremental cost-effectiveness ratio of an Autumn 2023 Moderna updated COVID-19 (mRNA-1273.815) vaccine was compared to no additional vaccination. Potential differences between the mRNA-1273.815 and the Autumn Pfizer-BioNTech updated COVID-19 (XBB.1.5 BNT162b2) vaccines, as well as societal return on investment for the mRNA-1273.815 vaccine relative to no vaccination, were also examined. RESULTS: Compared to no autumn vaccination, the mRNA-1273.815 campaign is predicted to prevent approximately 1,697,900 symptomatic infections, 85,400 hospitalizations, and 4,100 deaths. Compared to an XBB.1.5 BNT162b2 campaign, the mRNA-1273.815 campaign is also predicted to prevent approximately 90,100 symptomatic infections, 3,500 hospitalizations, and 160 deaths. Across both analyses we found the mRNA-1273.815 campaign to be dominant. CONCLUSIONS: The mRNA-1273.815 vaccine can be considered cost-effective relative to the XBB.1.5 BNT162b2 vaccine and highly likely to provide more benefits and save costs compared to no vaccine in Germany, and to offer high societal return on investment.

The potential clinical impact and cost-effectiveness of the updated COVID-19 mRNA fall 2023 vaccines in the United States.

AIMS: To assess the potential clinical impact and cost-effectiveness of COVID-19 mRNA vaccines updated for fall 2023 in adults aged ≥18 years over a 1-year analytic time horizon (September 2023-August 2024). MATERIALS AND METHODS: A compartmental Susceptible-Exposed-Infected-Recovered model was updated to reflect COVID-19 cases in summer 2023. The numbers of symptomatic infections, COVID-19-related hospitalizations and deaths, and costs and quality-adjusted life-years (QALYs) gained were calculated using a decision tree model. The incremental cost-effectiveness ratio (ICER) of a Moderna updated mRNA fall 2023 vaccine (Moderna Fall Campaign) was compared to no additional vaccination. Potential differences between the Moderna and the Pfizer-BioNTech fall 2023 vaccines were also examined. RESULTS: Base case results suggest that the Moderna Fall Campaign would decrease the expected 64.2 million symptomatic infections by 7.2 million (11%) to 57.0 million. COVID-19-related hospitalizations and deaths are expected to decline by 343,000 (-29%) and 50,500 (-33%), respectively. The Moderna Fall Campaign would increase QALYs by 740,880 and healthcare costs by $5.7 billion relative to no vaccine, yielding an ICER of $7700 per QALY gained. Using a societal cost perspective, the ICER is $2100. Sensitivity analyses suggest that vaccine effectiveness, COVID-19 incidence, hospitalization rates, and costs drive cost-effectiveness. With a relative vaccine effectiveness of 5.1% for infection and 9.8% for hospitalization for the Moderna vaccine versus the Pfizer-BioNTech vaccine, use of the Moderna vaccine is expected to prevent 24,000 more hospitalizations and 3300 more deaths than the Pfizer-BioNTech vaccine. LIMITATIONS AND CONCLUSIONS: As COVID-19 becomes endemic, future incidence, including patterns of infection, are highly uncertain. The effectiveness of fall 2023 vaccines is unknown, and it is unclear when a new variant that evades natural or vaccine immunity will emerge. Despite these limitations, our model predicts the Moderna Fall Campaign vaccine is highly cost-effective across all sensitivity analyses.

The potential clinical impact of implementing different COVID-19 boosters in fall 2022 in the United States.

OBJECTIVE: Emerging SARS-COV-2 variants are spurring the development of adapted vaccines as public health authorities plan for fall vaccinations. This study estimated the number of infections and hospitalizations prevented by three potential booster strategies for adults (≥18 years) in the United States: boosting with either Moderna's (1) licensed first generation monovalent vaccine mRNA-1273 (ancestral strain) or (2) candidate bivalent vaccine mRNA-1273.214 (ancestral + BA.1 variant of concern [VOC]) starting in September 2022, or (3) Moderna's updated candidate bivalent vaccine mRNA-1273.222 (ancestral + BA.4/5 VOC) starting November 2022 due to longer development time. METHODS: An age-stratified, transmission dynamic, Susceptible-Exposed-Infection-Recovered (SEIR) model, adapted from previous literature, was used to estimate infections over time; the model contains compartments defined by SEIR and vaccination status. A decision tree was used to estimate clinical consequences of infections. Calibration was performed so the model tracks the actual course of the pandemic to present time. RESULTS: Vaccinating with mRNA-1273(Sept), mRNA-1273.214(Sept), and mRNA-1273.222(Nov) is predicted to reduce infections by 34%, 40%, and 18%, respectively, and hospitalizations by 42%, 48%, and 25%, respectively, over 6 months compared to no booster. Sensitivity analyses around transmissibility, vaccine coverage, masking, and waning illustrate that boosting with mRNA-1273.214 in September prevented more cases of infection and hospitalization than the other vaccines. LIMITATIONS AND CONCLUSIONS: With the emergence of new variants, key characteristics of the virus that affect estimates of spread and clinical impact also evolve, making parameter estimation difficult. Our analysis demonstrated that boosting with mRNA-1273.214 was more effective over 6 months in preventing infections and hospitalizations with a BA.4/5 subvariant than the tailored vaccine, simply because it could be deployed 2 months earlier. We conclude that there is no advantage to delay boosting until a more effective BA.4/5 vaccine is available; earlier boosting with mRNA-1273.214 will prevent the most infections and hospitalizations.

The Cost-Effectiveness of Vaccination of Older Adults with an MF59-Adjuvanted Quadrivalent Influenza Vaccine Compared to Other Available Quadrivalent Vaccines in Germany.

Enhanced quadrivalent influenza vaccines that include an adjuvant (aQIV) or a high dose of antigen (QIV-HD), which stimulate a stronger immune response in older adults than the standard vaccine (QIVe), are now approved. The objective of this research is to compare available vaccines and determine the cost-effectiveness of immunizing persons aged 65 years and above with aQIV compared to QIVe and QIV-HD in Germany. A compartmental transmission model calibrated to outpatient visits for influenza in Germany was used to predict the number of medically attended infections using the three vaccines. The rates of hospitalizations, deaths, and other economic consequences were estimated with a decision tree using German data where available. Based on meta-analysis, the rVE of -2.5% to 8.9% for aQIV versus QIV-HD, the vaccines are similar clinically, but aQIV is cost saving compared to QIV-HD (unit cost of EUR 40.55). All results were most sensitive to changes in vaccine effectiveness. aQIV may be cost-effective compared to QIVe depending on the willingness to pay for additional benefits in Germany. As aQIV and QIV-HD are similar in terms of effectiveness, aQIV is cost saving compared to QIV-HD at current unit prices.

An Economic Comparison of Influenza Vaccines Recommended for Use in Eligible Adults under 65 Years in the United Kingdom.

Background: In the United Kingdom (UK), a cell-based quadrivalent influenza vaccine (QIVc) and a recombinant vaccine (QIVr) are recommended for eligible adults under 65 years. The objective of this analysis was to determine the potential cost-effectiveness of QIVc compared to QIVr for this age group using a range of assumptions about relative vaccine effectiveness (rVE). Methods: A dynamic transmission model, calibrated to match infection data from the UK, was used to estimate the clinical and economic impact of vaccination across 10 influenza seasons. The list price was £12.50 for QIVc and £22.00 for QIVr. The base case effectiveness of QIVc was 63.9%. As there are no data comparing the vaccines in the 18 to 64-year-old age group, rVE was varied. Results: For the base case, the rVE of QIVr compared with QIVc must be at least 25% in order for the cost per quality-adjusted life-year gained to be £20,000 or lower. Sensitivity analysis demonstrated that the rVE required for QIVr to be cost-effective was most dependent on the absolute effectiveness of QIVc. Conclusion: At list prices, our analysis predicts that the rVE for QIVr must be at least 25% compared to QIVc in order to be considered cost-effective.

The cost-effectiveness of an adjuvanted quadrivalent influenza vaccine in the United Kingdom.

In the United Kingdom (UK), both the MF59-adjuvanted quadrivalent influenza vaccine (aQIV) and the high-dose QIV (QIV-HD) are preferred for persons aged 65 years and older but only aQIV is reimbursed by the National Health Service (NHS). The objective was to determine the potential cost-effectiveness of vaccinating adults aged 65 years and above with aQIV compared with QIV-HD in the UK. A dynamic transmission model, calibrated to match infection data from the UK, was used to estimate the impact of vaccination in 10 influenza seasons. Vaccine effectiveness was based on a meta-analysis that concluded the vaccines were not significantly different. Vaccine coverage, physician visits, hospitalizations, deaths, utility losses and NHS costs were estimated using published UK sources. The list price of aQIV was £11.88 while a range of prices were tested for QIV-HD. The price of the trivalent high-dose vaccine (TIV-HD) is £20.00 but a list price for QIV-HD is not yet available. The projected differences between the vaccines in terms of clinical cases and influenza treatment costs are minimal. Our analysis demonstrates that in order to be cost-effective, the price of QIV-HD must be similar to that of aQIV and may range from £7.57 to £12.94 depending on the relative effectiveness of the vaccines. The results of the analysis were most sensitive to variation in vaccine effectiveness and the rate of hospitalization due to influenza. Given the evidence, aQIV is cost-saving unless QIV-HD is priced lower than the existing list price of TIV-HD.

The Cost-Effectiveness of Expanding Vaccination with a Cell-Based Influenza Vaccine to Low Risk Adults Aged 50 to 64 Years in the United Kingdom.

BACKGROUND: In response to COVID-19, the UK National Health Service (NHS) extended influenza vaccination in 50- to 64-year-olds from at-risk only to all in this age group for the 2020/21 season. The objective of this research is to determine the cost-effectiveness of continuing to vaccinate all with a quadrivalent cell-based vaccine (QIVc) compared to returning to an at-risk only policy after the pandemic resolves. METHODS: A dynamic transmission model, calibrated to match infection data from the UK, was used to estimate the clinical and economic impact of vaccination across 10 influenza seasons. The base case effectiveness of QIVc was 63.9% and the list price was GBP 9.94. RESULTS: Vaccinating 50% of all 50- to 64-year-olds with QIVc reduced the average annual number of clinical infections (-682,000), hospitalizations (-5800) and deaths (-740) in the UK. The base case incremental cost per quality-adjusted life-year gained (ICER) of all compared to at-risk only was GBP6000 (NHS perspective). When the cost of lost productivity was considered, vaccinating all 50- to 64-year-olds with QIVc became cost-saving. CONCLUSION: Vaccinating all 50- to 64-year-olds with QIVc is likely to be cost-effective. The NHS should consider continuing this policy in future seasons.

The potential public health and economic value of a hypothetical COVID-19 vaccine in the United States: Use of cost-effectiveness modeling to inform vaccination prioritization.

BACKGROUND: Researchers are working at unprecedented speed to develop a SARS-CoV-2 vaccine. We aimed to assess the value of a hypothetical vaccine and its potential public health impact when prioritization is required due to supply constraints. METHODS: A Markov cohort model was used to estimate COVID-19 related direct medical costs and deaths in the United States (US), with and without implementation of a 60% efficacious vaccine. To prioritize the vaccine under constrained supply, the population was divided into tiers based on age; risk and age; and occupation and age; and outcomes were compared across one year under various supply assumptions. The incremental cost per quality-adjusted life-year (QALY) gained versus no vaccine was calculated for the entire adult population and for each tier in the three prioritization schemes. RESULTS: The incremental cost per QALY gained for the US adult population was $8,200 versus no vaccination. For the tiers at highest risk of complications from COVID-19, such as those ages 65 years and older, vaccination was cost-saving compared to no vaccination. The cost per QALY gained increased to over $94,000 for those with a low risk of hospitalization and death following infection. Results were most sensitive to infection incidence, vaccine price, the cost of treating COVID-19, and vaccine efficacy. Under the most optimistic supply scenario, the hypothetical vaccine may prevent 31% of expected deaths. As supply becomes more constrained, only 23% of deaths may be prevented. In lower supply scenarios, prioritization becomes more important to maximize the number of deaths prevented. CONCLUSIONS: A COVID-19 vaccine is predicted to be good value for money (cost per QALY gained <$50,000). The speed at which an effective vaccine can be made available will determine how much morbidity and mortality may be prevented in the US.

A Budget Impact Model of the Addition of Telotristat Ethyl Treatment to the Standard of Care in Patients with Uncontrolled Carcinoid Syndrome.

BACKGROUND: Carcinoid syndrome, a rare condition in patients with neuroendocrine tumours, characterised by flushing and diarrhoea, severely affects patients' quality of life. The current carcinoid syndrome standard of care includes somatostatin analogues, but some patients experience uncontrolled symptoms despite somatostatin analogue therapy. Telotristat ethyl is a novel treatment approved by the European Medicines Agency (EMA) and US FDA that significantly reduces bowel movement frequency in patients with uncontrolled carcinoid syndrome. OBJECTIVE: We developed a model to evaluate the 5-year budget impact of introducing telotristat ethyl to standard care in Swedish patients with uncontrolled carcinoid syndrome. METHODS: Treatment response in the 12-week phase III TELESTAR trial (NCT01677910) informed telotristat ethyl efficacy; subsequently, health states were captured by a Markov model using 4-week cycles. TELESTAR open-label extension data informed telotristat ethyl discontinuation. The number of treatment-eligible patients was estimated from literature reviews reporting the prevalence, incidence and mortality of carcinoid syndrome. A Swedish database study informed real-world costs related to carcinoid syndrome and carcinoid heart disease costs. Telotristat ethyl market share was assumed to increase annually from 24% (year 1) to 70% (year 5). RESULTS: Over the 5-year model horizon, 44 patients were expected to initiate telotristat ethyl treatment. The cumulative net budget impact of adding telotristat ethyl to current standard of care was €172,346; per-year costs decreased from €66,495 (year 1) to €29,818 (year 5). Increased drug costs from adding telotristat ethyl were offset by reduced costs elsewhere. CONCLUSIONS: The expected budget impact of adding telotristat ethyl to the standard of care in Sweden was relatively low, largely because of the rarity of carcinoid syndrome.

Review of seasonal influenza in Canada: Burden of disease and the cost-effectiveness of quadrivalent inactivated influenza vaccines.

In the 2015/16 influenza season, the Canadian National Advisory Committee on Immunization (NACI) recommended vaccination with quadrivalent inactivated influenza vaccine (QIV) for infants aged 6-23 months and trivalent inactivated influenza vaccines (TIVs) or QIVs in adults. The objective of this review (GSK study identifier: HO-13-14054) is to examine the epidemiology and disease burden of influenza in Canada and the economic benefits of vaccination. To inform this review, we performed a systematic literature search of relevant Canadian literature and National surveillance data. Influenza B viruses from phylogenetically-distinct lineages (B/Yamagata and B/Victoria) co-circulate in Canada, and are an important cause of influenza complications. Modeling studies, including those postdating the search suggest that switching from TIV to QIV in Canada reduces the burden of influenza and would likely be cost-effective. However, more robust real-world outcomes data is required to inform health policy decision makers on appropriate influenza vaccination strategies for Canada.

Despite High Cost, Improved Pneumococcal Vaccine Expected To Return 10-Year Net Savings Of $12 Billion.

In 2010 the US Advisory Committee on Immunization Practices recommended that the seven-valent pneumococcal conjugate vaccine (PCV7) be replaced by the thirteen-valent version (PCV13), which provides protection against six additional serotypes of the bacterium Streptococcus pneumoniae. The higher price of PCV13, compared to PCV7, may be a concern for funding agencies and payers, as has been the case with other new vaccines. This study estimated the budgetary impact on both public and private US insurance payers of the routine use of PCV13 instead of PCV7 from 2010 to 2019. Implementing the PCV13 vaccine is projected to cost public and private payers $3.5 billion and $2.6 billion, respectively, more than PCV7. However, PCV13 is expected to provide net cost savings of $6.1 billion and $4.2 billion, respectively, to those payers during the ten-year period by preventing pneumococcal disease and its associated costs. An additional $1.7 billion in cost savings would be realized for uninsured patients, whose costs ultimately fall on those payers. Despite its higher price, compared to PCV7, this new vaccine is expected to provide payers with substantial net budgetary savings.

Modeling the impact of the difference in cross-protection data between a human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine and a human papillomavirus (HPV)-6/11/16/18 vaccine in Canada.

BACKGROUND: In Canada, two vaccines that have demonstrated high efficacy against infection with human papillomavirus (HPV) types -16 and -18 are available. The HPV-6/11/16/18 vaccine provides protection against genital warts (GW) while the HPV-16/18 vaccine may provide better protection against other oncogenic HPV types. In this analysis, the estimated clinical and economic benefit of each of these vaccines was compared in the Canadian setting. METHODS: A Markov model of the natural history of HPV infection among women, cervical cancer (CC) and GW was used to estimate the impact of vaccinating a cohort of 100,000 12-year-old females on lifetime outcomes and healthcare system costs (no indirect benefit in males included). A budget impact model was used to estimate the impact of each vaccine by province. RESULTS: In the base case, vaccination with the HPV-16/18 vaccine was predicted to prevent 48 additional CC cases, and 16 additional CC deaths, while vaccination with the HPV-6/11/16/18 vaccine was predicted to prevent 6,933 additional GW cases. Vaccination with the HPV-16/18 vaccine was estimated to save 1 additional discounted quality adjusted life year (QALY) at an overall lower lifetime cost to the healthcare system compared to the HPV-6/11/16/18 vaccine (assuming vaccine price parity). In sensitivity analyses, the HPV-6/11/16/18 vaccine was associated with greater QALYs saved when the cross-protection efficacy of the HPV-16/18 vaccine was reduced, or the burden of GW due to HPV-6/11 was increased. In most scenarios with price parity, the lifetime healthcare cost of the strategy with the HPV-16/18 vaccine was predicted to be lower than the HPV-6/11/16/18 vaccine. In the probabilistic sensitivity analyses, the HPV-16/18 vaccine provided more QALY benefit than the HPV-6/11/16/18 vaccine in 49.2% of scenarios, with lower relative lifetime costs in 83.5% of scenarios. CONCLUSIONS: Overall, the predicted lifetime healthcare costs and QALYs saved by implementing each of the vaccines are similar. Vaccination with the HPV-16/18 vaccine is expected to be associated with reduced CC disease morbidity and mortality compared to vaccination with the HPV-6/11/16/18 vaccine. Differences in these outcomes depend on the extent of cervical disease prevented by cross-protection and the burden of GW caused by HPV-6/11.

Cost effectiveness of adding ezetimibe to atorvastatin therapy in patients not at cholesterol treatment goal in Canada.

INTRODUCTION: This analysis compared the cost effectiveness of adding ezetimibe to atorvastatin therapy versus atorvastatin titration or adding cholestyramine (a resin) for patients at high risk of a coronary artery disease (CAD) event who did not reach target cholesterol levels on their current atorvastatin dosage. The primary analysis focused on 65-year-old patients with low-density lipoprotein cholesterol (LDL-C) levels of 3.1 or 3.6 mmol/L with a treatment goal of <2.5 mmol/L, classified as very high risk according to the 2000 Canadian Guidelines for Management and Treatment of Hyperlipidaemia. METHODS: A previously developed Markov model was utilised to capture the cost and clinical consequences of lipid-lowering therapy in primary and secondary prevention of CAD. Comparisons between treatment strategies were made using ICERs (cost per QALY) from a Canadian Ministry of Health perspective. The effects of lipid-lowering therapies were based on clinical trial data. The risks of CAD events were estimated using Framingham Heart Study risk equations. Treatment costs and the costs of acute and long-term care for CAD events were included in the analysis. Costs (Canadian dollar, 2002 values) and outcomes were discounted at 5% per annum. RESULTS: Ezetimibe added to atorvastatin therapy compared with treatment with the most common fixed atorvastatin daily dosage (10 mg) or with common atorvastatin titration strategies (up to 20 mg daily; up to 40 mg daily) resulted in cost per QALY estimates ranging from 25,344 to 44,332 Canadian dollars. The addition of ezetimibe to atorvastatin therapy was less costly and more effective than the addition of cholestyramine (dominant). CONCLUSION: Our analysis suggests that adding ezetimibe to atorvastatin for patients not achieving treatment goals with their current atorvastatin dose produces greater clinical benefits than treatment with a fixed-dose atorvastatin or atorvastatin titration at an increased overall cost. The cost-effectiveness ratios provide strong evidence for the adoption of ezetimibe within the Canadian healthcare system.

Projected clinical benefits and cost-effectiveness of a human papillomavirus 16/18 vaccine.

BACKGROUND: Human papillomavirus (HPV) vaccine may be commercially available in a few years. We explored the clinical benefits and cost-effectiveness of introducing an HPV16/18 vaccine in a population with an organized cervical cancer screening program. METHODS: A computer-based model of the natural history of HPV and cervical cancer was used to project cancer incidence and mortality, life expectancy (adjusted and unadjusted for quality of life), lifetime costs, and incremental cost-effectiveness ratios (i.e., the additional cost of a strategy divided by its additional clinical benefit compared with the next most expensive strategy) associated with different cancer prevention policies, including vaccination (initiated at age 12 years), cytologic screening (initiated at 18, 21, 25, 30, or 35 years), and combined vaccination and screening strategies. We assumed that vaccination was 90% effective in reducing the risk of persistent HPV16/18 infections and evaluated alternative assumptions about vaccine efficacy, waning immunity, and risk of replacement with non-16/18 HPV types. RESULTS: Our model showed that the most effective strategy with an incremental cost-effectiveness ratio of less than 60 dollars-000 per quality-adjusted life year is one combining vaccination at age 12 years with triennial conventional cytologic screening beginning at age 25 years, compared with the next best strategy of vaccination and cytologic screening every 5 years beginning at age 21 years. This triennial strategy would reduce the absolute lifetime risk of cervical cancer by 94% compared with no intervention. These results were sensitive to alternative assumptions about the underlying patterns of cervical cancer screening, duration of vaccine efficacy, and natural history of HPV infection in older women. CONCLUSIONS: Our model predicts that a vaccine that prevents persistent HPV16/18 infection will reduce the incidence of HPV16/18-associated cervical cancer, even in a setting of cytologic screening. A program of vaccination that permits a later age of screening initiation and a less frequent screening interval is likely to be a cost-effective use of health care resources.

The cost-effectiveness of screening blood donors for malaria by PCR.

BACKGROUND: The cost-effectiveness of four blood donor screening strategies for malaria was estimated to determine whether transmission by transfusion can be reduced. STUDY DESIGN AND METHODS: A decision analysis model was developed to compare 1) not screening allogeneic blood donors for malaria (Strategy 1); 2) using the standard questionnaire (Strategy 2); 3) using the standard questionnaire followed by testing blood donors with risk factors for malaria with PCR (Strategy 3); and 4) screening all blood donors using PCR (Strategy 4). The expected costs and the number of cases of malaria for each strategy were compared and incremental cost-effectiveness ratios were calculated as the cost per case of malaria averted. All costs are in Canadian dollars. RESULTS: Strategies 2 and 3 had the same effectiveness but different costs, with Strategy 3 being less costly. Compared to Strategy 1, the incremental cost effectiveness ratio was 6463 dollars per case of malaria averted for Strategy 3. Strategy 4 resulted in less transmission of malaria (0.4/million donors), but the cost compared to Strategy 3 was 3,972,624 dollars per case of malaria averted. CONCLUSION: The addition of PCR to the standard screening questionnaire is economically attractive compared to the current standard screening questionnaire.

A comprehensive natural history model of HPV infection and cervical cancer to estimate the clinical impact of a prophylactic HPV-16/18 vaccine.

The object of our study is to project the impact of a prophylactic vaccine against persistent human papillomavirus (HPV)-16/18 infection on age-specific incidence of invasive cervical cancer. We developed a computer-based mathematical model of the natural history of cervical carcinogenesis to incorporate the underlying type-specific HPV distribution within precancerous lesions and invasive cancer. After defining plausible ranges for each parameter based on a comprehensive literature review, the model was calibrated to the best available population-based data. We projected the age-specific reduction in cervical cancer that would occur with a vaccine that reduced the probability of acquiring persistent infection with HPV 16/18, and explored the impact of alternative assumptions about vaccine efficacy and coverage, waning immunity and competing risks associated with non-16/18 HPV types in vaccinated women. The model predicted a peak age-specific cancer incidence of 90 per 100,000 in the 6th decade, a lifetime cancer risk of 3.7% and a reproducible representation of type-specific HPV within low and high-grade cervical precancerous lesions and cervical cancer. A vaccine that prevented 98% of persistent HPV 16/18 was associated with an approximate equivalent reduction in 16/18-associated cancer and a 51% reduction in total cervical cancer; the effect on total cancer was attenuated due to the competing risks associated with other oncogenic non-16/18 types. A vaccine that prevented 75% of persistent HPV 16/18 was associated with a 70% to 83% reduction in HPV-16/18 cancer cases. Similar effects were observed with high-grade squamous intraepithelial lesions (HSIL) although the impact of vaccination on the overall prevalence of HPV and low-grade squamous intraepithelial lesions (LSIL) was minimal. In conclusion, a prophylactic vaccine that prevents persistent HPV-16/18 infection can be expected to significantly reduce HPV-16/18-associated LSIL, HSIL and cervical cancer. The impact on overall prevalence of HPV or LSIL, however, may be minimal. Based on the relative importance of different parameters in the model, several priorities for future research were identified. These include a better understanding of the heterogeneity of vaccine response, the effect of type-specific vaccination on other HPV types and the degree to which vaccination effect persists over time.

A risk index for sternal surgical wound infection after cardiovascular surgery.

OBJECTIVES: To identify factors that increase the risk of sternal surgical wound infection after cardiovascular surgery and to develop a bedside clinical risk index using these factors. DESIGN: A risk index was developed using clinical data collected from a cohort of 11,508 cardiac surgery patients and validated using three independent subsets of the data. With two of these subsets, we derived a logistic regression equation and then modified the scoring algorithm to simplify the calculation of patient risk scores by clinicians. The final subset was used to validate the index. The area under the receiver operating characteristic (aROC) curve was the primary measure of goodness of fit. SETTING: Toronto General Hospital, a teaching hospital and the largest center for cardiac surgery in Ontario, Canada. PATIENTS: Cardiac surgery patients receiving cardiopulmonary bypass between April 1, 1990, and December 31, 1995, who survived at least 6 days after surgery. RESULTS: Variables that were used to construct the risk index included reoperation due to complication (odds ratio, 4.3; range, 1.9 to 8.5), diabetes (odds ratio, 2.4; range, 1.5 to 3.7), more than 3 days in the intensive care unit (odds ratio, 5.4; range, 3.2 to 8.7), and use of the internal mammary artery for revascularization (odds ratio, 3.2; range, 1.7 to 5.8). Validation showed that the index had an aROC curve of 0.64. CONCLUSIONS: The risk index described in this article allows clinicians to quickly stratify patients into four risk groups associated with an increasing risk of sternal surgical wound infection. It may be used perioperatively or as part of a wound infection surveillance system.

The burden of illness of severe nausea and vomiting of pregnancy in the United States.

OBJECTIVE: Our purpose was to determine the extent to which nausea and vomiting of pregnancy affects a woman's quality of life (QOL), ability to function, and health care resource use. STUDY DESIGN: We conducted an observational, multicenter, prospective cohort study by gathering data on the symptoms, QOL, and health care resource use from women who have nausea and vomiting of pregnancy. RESULTS: All 8 domains of health measured by the Short Form-36 QOL survey were limited by patient symptoms. This limitation manifested itself as patient-time loss from work and other normal activities, unpaid caregiver-time loss from work, and use of health care resources (eg, hospitalization). All types of time loss were correlated to severity of symptoms. CONCLUSIONS: Nausea and vomiting of pregnancy can severely reduce a woman's QOL and ability to function. The degree of limitation is associated with the severity of symptoms.