Evaluation of four chemotherapy regimens for treatment of advanced AIDS-associated Kaposi sarcoma in Kenya: a cost-effectiveness analysis.

BACKGROUND: The most effective treatment for advanced AIDS-associated Kaposi sarcoma is paclitaxel or pegylated liposomal doxorubicin (PLD); neither is routinely used in sub-Saharan Africa due to limited availability and high cost. We examined the clinical impact, costs, and cost-effectiveness of paclitaxel or PLD in Kenya, compared with etoposide or bleomycin-vincristine. METHODS: In this study, we use the Cost-Effectiveness of Preventing AIDS Complications (CEPAC)-International Model to project clinical outcomes and costs among people living with HIV and advanced Kaposi sarcoma on antiretroviral therapy. We compared four different treatment strategies: etoposide, bleomycin-vincristine, paclitaxel, or PLD. We derived cohort characteristics and costs from the Kenyan Academic Model for Providing Access to Healthcare network, and adverse events, efficacy, and mortality from clinical trials. We projected model outcomes over a lifetime and included life expectancy, per-person lifetime costs, and incremental cost-effectiveness ratios (ICERs). We conducted budget impact analysis for 5-year total costs and did deterministic and probabilistic sensitivity analyses to evaluate the effect of uncertainty in input parameters. FINDINGS: We found that paclitaxel would be more effective than bleomycin-vincristine and would increase life expectancy by 4·2 years per person. PLD would further increase life expectancy by 0·6 years per person. Paclitaxel would be the most cost-effective strategy (ICER US$380 per year-of-life-saved compared with bleomycin-vincristine) and would remain cost-effective across a range of scenarios. PLD would be cost-effective compared with paclitaxel if its price were reduced to $100 per cycle (base case $180 per cycle). Implementing paclitaxel instead of bleomycin-vincristine would save approximately 6400 life-years and would increase the overall 5-year Kenyan health-care costs by $3·7 million; increased costs would be primarily related to ongoing HIV care given improved survival. INTERPRETATION: Paclitaxel would substantially increase life expectancy and be cost-effective compared with bleomycin-vincristine for advanced AIDS-associated Kaposi sarcoma in Kenya and should be the standard of care. PLD would further improve survival and be cost-effective with a 44% price reduction. FUNDING: US National Institutes of Health and Massachusetts General Hospital. TRANSLATION: For the Swahili translation of the abstract see Supplementary Materials section.

Cost-effectiveness of a Novel Lipoarabinomannan Test for Tuberculosis in Patients With Human Immunodeficiency Virus.

BACKGROUND: A novel urine lipoarabinomannan assay (FujiLAM) has higher sensitivity and higher cost than the first-generation AlereLAM assay. We evaluated the cost-effectiveness of FujiLAM for tuberculosis testing among hospitalized people with human immunodeficiency virus (HIV), irrespective of symptoms. METHODS: We used a microsimulation model to project clinical and economic outcomes of 3 testing strategies: (1) sputum Xpert MTB/RIF (Xpert), (2) sputum Xpert plus urine AlereLAM (Xpert+AlereLAM), (3) sputum Xpert plus urine FujiLAM (Xpert+FujiLAM). The modeled cohort matched that of a 2-country clinical trial. We applied diagnostic yields from a retrospective study (yields for Xpert/Xpert+AlereLAM/Xpert+FujiLAM among those with CD4 <200 cells/µL: 33%/62%/70%; among those with CD4 ≥200 cells/µL: 33%/35%/47%). Costs of Xpert/AlereLAM/FujiLAM were US$15/3/6 (South Africa) and $25/3/6 (Malawi). Xpert+FujiLAM was considered cost-effective if its incremental cost-effectiveness ratio (US$/year-of-life saved) was <$940 (South Africa) and <$750 (Malawi). We varied key parameters in sensitivity analysis and performed a budget impact analysis of implementing FujiLAM countrywide. RESULTS: Compared with Xpert+AlereLAM, Xpert+FujiLAM increased life expectancy by 0.2 years for those tested in South Africa and Malawi. Xpert+FujiLAM was cost-effective in both countries. Xpert+FujiLAM for all patients remained cost-effective compared with sequential testing and CD4-stratified testing strategies. FujiLAM use added 3.5% (South Africa) and 4.7% (Malawi) to 5-year healthcare costs of tested patients, primarily reflecting ongoing HIV treatment costs among survivors. CONCLUSIONS: FujiLAM with Xpert for tuberculosis testing in hospitalized people with HIV is likely to increase life expectancy and be cost-effective at the currently anticipated price in South Africa and Malawi. Additional studies should evaluate FujiLAM in clinical practice settings.

Implementing Generalized Additive Models to Estimate the Expected Value of Sample Information in a Microsimulation Model: Results of Three Case Studies.

BACKGROUND: The expected value of sample information (EVSI) can help prioritize research but its application is hampered by computational infeasibility, especially for complex models. We investigated an approach by Strong and colleagues to estimate EVSI by applying generalized additive models (GAM) to results generated from a probabilistic sensitivity analysis (PSA). METHODS: For 3 potential HIV prevention and treatment strategies, we estimated life expectancy and lifetime costs using the Cost-effectiveness of Preventing AIDS Complications (CEPAC) model, a complex patient-level microsimulation model of HIV progression. We fitted a GAM-a flexible regression model that estimates the functional form as part of the model fitting process-to the incremental net monetary benefits obtained from the CEPAC PSA. For each case study, we calculated the expected value of partial perfect information (EVPPI) using both the conventional nested Monte Carlo approach and the GAM approach. EVSI was calculated using the GAM approach. RESULTS: For all 3 case studies, the GAM approach consistently gave similar estimates of EVPPI compared with the conventional approach. The EVSI behaved as expected: it increased and converged to EVPPI for larger sample sizes. For each case study, generating the PSA results for the GAM approach required 3 to 4 days on a shared cluster, after which EVPPI and EVSI across a range of sample sizes were evaluated in minutes. The conventional approach required approximately 5 weeks for the EVPPI calculation alone. CONCLUSION: Estimating EVSI using the GAM approach with results from a PSA dramatically reduced the time required to conduct a computationally intense project, which would otherwise have been impractical. Using the GAM approach, we can efficiently provide policy makers with EVSI estimates, even for complex patient-level microsimulation models.

Prioritizing HIV comparative effectiveness trials based on value of information: generic versus brand-name ART in the US.

BACKGROUND: Value of Information (VOI) analysis examines whether to acquire information before making a decision. We introduced VOI to the HIV audience, using the example of generic antiretroviral therapy (ART) in the US. METHODS AND FINDINGS: We used a mathematical model and probabilistic sensitivity analysis (PSA) to generate probability distributions of survival (in quality-adjusted life years, QALYs) and cost for three potential first-line ART regimens: three-pill generic, two-pill generic, and single-pill branded. These served as input for a comparison of two hypothetical two-arm trials: three-pill generic versus single-pill branded; and two-pill generic versus single-pill branded. We modeled pre-trial uncertainty by defining probability distributions around key inputs, including 24-week HIV-RNA suppression and subsequent ART failure. We assumed that, without a trial, patients received the single-pill branded strategy. Post-trial, we assumed that patients received the most cost-effective strategy. For both trials, we quantified the probability of changing to a generic-based regimen upon trial completion and the expected VOI in terms of improved health outcomes and costs. Assuming a willingness to pay (WTP) threshold of $100 000/QALY, the three-pill trial led to more treatment changes (84%) than the two-pill trial (78%). Estimated VOI was $48 000 (three-pill trial) and $35 700 (two-pill trial) per future patient initiating ART. CONCLUSIONS: A three-pill trial of generic ART is more likely to lead to post-trial treatment changes and to provide more value than a two-pill trial if policy decisions are based on cost-effectiveness. Value of Information analysis can identify trials likely to confer the greatest impact and value for HIV care.