A cost-utility analysis of cervical cancer vaccination in preadolescent Canadian females.

BACKGROUND: Despite the fact that approximately 70% of Canadian women undergo cervical cancer screening at least once every 3 years, approximately 1,300 women were diagnosed with cervical cancer and approximately 380 died from it in 2008. This study estimates the effectiveness and cost-effectiveness of vaccinating 12-year old Canadian females with an AS04-adjuvanted cervical cancer vaccine. The indirect effect of vaccination, via herd immunity, is also estimated. METHODS: A 12-health-state 1-year-cycle Markov model was developed to estimate lifetime HPV related events for a cohort of 12-year old females. Annual transition probabilities between health-states were derived from published literature and Canadian population statistics. The model was calibrated using Canadian cancer statistics. From a healthcare perspective, the cost-effectiveness of introducing a vaccine with efficacy against HPV-16/18 and evidence of cross-protection against other oncogenic HPV types was evaluated in a population undergoing current screening practices. The base-case analysis included 70% screening coverage, 75% vaccination coverage, $135/dose for vaccine, and 3% discount rate on future costs and health effects. Conservative herd immunity effects were taken into account by estimated HPV incidence using a mathematical model parameterized by reported age-stratified sexual mixing data. Sensitivity analyses were performed to address parameter uncertainties. RESULTS: Vaccinating 12-year old females (n = 100,000) was estimated to prevent between 390-633 undiscounted cervical cancer cases (reduction of 47%-77%) and 168-275 undiscounted deaths (48%-78%) over their lifetime, depending on whether or not herd immunity and cross-protection against other oncogenic HPV types were included. Vaccination was estimated to cost $18,672-$31,687 per QALY-gained, the lower range representing inclusion of cross-protective efficacy and herd immunity. The cost per QALY-gained was most sensitive to duration of vaccine protection, discount rate, and the correlation between probability of screening and probability of vaccination. CONCLUSION: In the context of current screening patterns, vaccination of 12-year old Canadian females with an ASO4-ajuvanted cervical cancer vaccine is estimated to significantly reduce cervical cancer and mortality, and is a cost-effective option. However, the economic attractiveness of vaccination is impacted by the vaccine's duration of protection and the discount rate used in the analysis.

Sexual risk behaviour of Canadian participants in the first efficacy trial of a preventive HIV-1 vaccine.

BACKGROUND: Phase I and phase II HIV-1 vaccine trials have revealed increases in risky sexual activity among study subjects during the trials, perhaps because the subjects believe that the vaccine being tested is efficacious; subjects may thus suffer harm from their participation. We evaluated the sexual behaviour of Canadian men who have sex with men (MSM) who participated in the phase III Vax004 trial of an HIV-1 vaccine. METHODS: Using self-reports of sexual behaviours during the 6 months before trial entry as a baseline, we determined changes in reported sexual behaviour after 6, 12 and 18 months of participation in the trial. RESULTS: Of 291 HIV-seronegative MSM enrolled from July to October 1999, 260 (89%) completed 18 months of follow-up, 19 (7%) experienced seroconversion, and 12 (4%) did not complete follow-up. Unprotected receptive anal intercourse during the previous 6 months with partners whose HIV-1 serostatus was positive or unknown was reported by 21% of men at enrollment and by 27% at any point during 18 months of follow-up. No increase in this behaviour from baseline was reported by participants, including among men who were motivated to enroll because of expected protection from HIV-1 infection, men who believed they had received the vaccine, men who believed that the vaccine had greater than 50% efficacy, or men who believed that they had received the vaccine and that vaccine efficacy was greater than 50%. INTERPRETATION: MSM can be successfully enrolled in HIV-1 vaccine efficacy trials without evident increases in those sexual behaviours most associated with HIV-1 risk.

The inhibition of tryptophan hydroxylase, not protein synthesis, reduces the brain trapping of alpha-methyl-L-tryptophan: an autoradiographic study.

The effects of the tryptophan hydroxylase (TPH) inhibitor p-chlorophenylalanine (PCPA; 200mg/kg; 3 days), and of the protein synthesis inhibitor cycloheximide (CXM, 2mg/kg), on regional serotonin (5-HT) synthesis were studied using the alpha-[14C]methyl-L-tryptophan (alpha-[14C]MTrp) autoradiographic method. The objectives of these investigations were to evaluate the changes, if any, on 5-HT synthesis, as measured with alpha-MTrp method, following the inhibition of TPH by PCPA, or the inhibition of proteins synthesis by CXM. The rats were used in the tracer experiment approximately 24h after the last dose of PCPA was administered, and in the CXM experiments, they were used 30 min following a single injection of CXM. In both experiments, the control rats were injected with the same volume of saline (0.5 ml/kg; s.c.) and at the same times as the drug injections. The results demonstrate that trapping of alpha-MTrp, which is taken to be related to brain 5-HT synthesis, is drastically reduced (40-80%) following PCPA treatment. The inhibition of protein synthesis with CXM did not have a significant effect on the global brain trapping of alpha-MTrp and 5-HT synthesis. These findings suggest that the brain trapping of alpha-[14C]MTrp relates to brain 5-HT synthesis, but not to brain protein synthesis.

High uptake of HIV testing in pregnant women in Ontario, Canada.

In 1999, Ontario implemented a policy to offer HIV counseling and testing to all pregnant women and undertook measures to increase HIV testing. We evaluated the effectiveness of the new policy by examining HIV test uptake, the number of HIV-infected women identified and, in 2002, the HIV rate in women not tested during prenatal care. We analyzed test uptake among women receiving prenatal care from 1999 to 2010. We examined HIV test uptake and HIV rate by year, age and health region. In an anonymous, unlinked study, we determined the HIV rate in pregnant women not tested. Prenatal HIV test uptake in Ontario increased dramatically, from 33% in the first quarter of 1999 to 96% in 2010. Test uptake was highest in younger women but increased in all age groups. All health regions improved and experienced similar test uptake in recent years. The HIV rate among pregnant women tested in 2010 was 0.13/1,000; in Toronto, the rate was 0.28 per 1,000. In the 2002 unlinked study, the HIV rate was 0.62/1,000 among women not tested in pregnancy compared to 0.31/1,000 among tested women. HIV incidence among women who tested more than once was 0.05/1,000 person-years. In response to the new policy in Ontario, prenatal HIV testing uptake improved dramatically among women in all age groups and health regions. A reminder to physicians who had not ordered a prenatal HIV test appeared to be very effective. In 2002, the HIV rate in women who were not tested was twice that of tested women: though 77% of pregnant women had been tested, only 63% of HIV-infected women were tested. HIV testing uptake was estimated at 98% in 2010.

Incorporating herd immunity effects into cohort models of vaccine cost-effectiveness.

BACKGROUND: Cohort models are often used in cost-effectiveness analysis (CEA) of vaccination. However, because they cannot capture herd immunity effects, cohort models underestimate the reduction in incidence caused by vaccination. Dynamic models capture herd immunity effects but are often not adopted in vaccine CEA. OBJECTIVE: The objective was to develop a pseudo-dynamic approximation that can be incorporated into an existing cohort model to capture herd immunity effects. METHODS: The authors approximated changing force of infection due to universal vaccination for a pediatric infectious disease. The projected lifetime cases in a cohort were compared under 1) a cohort model, 2) a cohort model with pseudo-dynamic approximation, and 3) an age-structured susceptible-exposed-infectious-recovered compartmental (dynamic) model. The authors extended the methodology to sexually transmitted infections. RESULTS: For average to high values of vaccine coverage (P > 60%) and small to average values of the basic reproduction number (R(0) < 10), which describes school-based vaccination programs for many common infections, the pseudo-dynamic approximation significantly improved projected lifetime cases and was close to projections of the full dynamic model. For large values of R(0) (R(0) > 15), projected lifetime cases were similar under the dynamic model and the cohort model, both with and without pseudo-dynamic approximation. The approximation captures changes in the mean age at infection in the 1st vaccinated cohort. CONCLUSIONS: This methodology allows for preliminary assessment of herd immunity effects on CEA of universal vaccination for pediatric infectious diseases. The method requires simple adjustments to an existing cohort model and less data than a full dynamic model.