Karissa Johnston

Expanded Access to Highly Active Antiretroviral Therapy: A Potentially Powerful Strategy to Curb the Growth of the HIV Epidemic

We developed a mathematical model using a multiple source of infection framework to assess the potential effect of the expansion of highly active antiretroviral therapy (HAART) coverage among those in medical need on the number of individuals testing newly positive for human immunodeficiency virus (HIV) and on related costs in British Columbia, Canada, over the next 25 years. The model was calibrated using retrospective data describing antiretroviral therapy utilization and individuals testing newly positive for HIV in the province. Different scenarios were investigated on the basis of varying assumptions regarding drug resistance, adherence to HAART, therapeutic guidelines, degree of HAART coverage, and the timing of HAART uptake. Expansion of HAART lead to substantial reductions in the growth of the HIV epidemic and related costs. These results provide powerful additional motivation to accelerate the roll out of HAART programs aggressively targeting those in medical need, both for their own benefit and as a means of decreasing new HIV infections.

The direct costs of HIV / AIDS care.

We reviewed published studies reporting the direct medical costs of treating HIV-infected people in countries using highly active antiretroviral therapy (HAART). Of 543 potentially relevant studies, only nine provided adequate data to make a meaningful statement about costs. Within studies, people with more advanced disease incurred higher total costs. Valid comparisons of total direct medical costs between studies were not possible because of differences in the specific components included, the heterogeneous nature of study populations in terms of disease stage, the sources and methods used to estimate unit costs, and the level of aggregation at which results were reported. The advent of HAART has major implications for the cost of treating HIV-infected individuals. Although this information is important for planning purposes, only a small number of published studies provide useful estimates of the direct cost. A useful method of estimating resource use and costs is computer simulation.

Expanding access to HAART: a cost-effective approach for treating and preventing HIV.

Objective:HIV continues to present a substantial global health burden. Given the high direct medical costs associated with the disease, prevention of new transmission is an important element in limiting economic burden. In addition to providing therapeutic benefit, treatment with HAART has potential to prevent transmission of HIV. The objective in this study was to perform an economic evaluation of the incremental net benefit associated with an intervention to expand treatment with HAART in British Columbia, Canada. Design:A mathematical model describing transmission of HIV, integrated with a microsimulation model describing the clinical and economic course of HIV. Methods:The primary outcome was the incremental net benefit of expanding treatment with HAART from 50 to 75% of clinically eligible individuals in British Columbia, assuming a willingness-to-pay threshold of US

Associations of Renal Function at 1-Year After Kidney Transplantation With Subsequent Return to Dialysis, Mortality, and Healthcare Costs

50 000 per quality-adjusted life year. Direct medical costs included were antiretroviral and nonantiretroviral medications, hospitalizations, physician visits, and laboratory tests. The mathematical and microsimulation models were based on patient characteristics observed in British Columbia. Longitudinal data described health services utilization, clinical progression, and survival for all individuals receiving treatment for HIV in British Columbia. Results:Over 30 years, the HAART expansion scenario was associated with a net benefit of US

International comparison of comparative effectiveness research in five jurisdictions: insights for the US.

900 million (95% confidence interval US

Indirect comparison of the efficacy of cetuximab and cisplatin in squamous cell carcinoma of the head and neck

493 million to 1.45 billion). Conclusion:Increasing the HAART treatment rate from 50 to 75% of clinically eligible individuals in British Columbia appears to be a cost-effective strategy based on this model. These cost-effectiveness results are consistent with public health objectives: all individuals who are eligible for an established life-saving treatment should receive it.

The Impact of Disease Stage on Direct Medical Costs of HIV Management: A Review of the International Literature

Background. Improved early kidney transplant outcomes limit the contemporary utility of standard clinical endpoints. Quantifying the relationship of renal function at 1 year after transplant with subsequent clinical outcomes and healthcare costs may facilitate cost-benefit evaluations among transplant recipients. Methods. Data for Medicare-insured kidney-only transplant recipients (1995–2003) were drawn from the United States Renal Data System. Associations of estimated glomerular filtration rate (eGFR) level at the first transplant anniversary with subsequent death-censored graft failure and patient death in posttransplant years 1 to 3 and 4 to 7 were examined by parametric survival analysis. Associations of eGFR with total health care costs defined by Medicare payments were assessed with multivariate linear regression. Results. Among 38,015 participants, first anniversary eGFR level demonstrated graded associations with subsequent outcomes. Compared with patients with 12-month eGFR more than or equal to 60 mL/min/1.73 m2, the adjusted relative risk of death-censored graft failure in years 1 to 3 was 31% greater for eGFR 45 to 59 mL/min/1.73 m2 (P<0.0001) and 622% greater for eGFR 15 to 30 mL/min/1.73 m2 (P<0.0001). Associations of first anniversary eGFR level with graft failure and mortality remained significant in years 4 to 7. The proportions of recipients expected to return to dialysis or die attributable to eGFR less than 60 mL/min/1.73 m2 over 10 years were 23.1% and 9.4%, respectively, and were significantly higher than proportions attributable to delayed graft function or acute rejection. Reduced eGFR was associated with graded and significant increases in health care spending during years 2 and 3 after transplant (P<0.0001). Conclusion. eGFR is strongly associated with clinical and economic outcomes after kidney transplantation.

Cost-Effectiveness of the Addition of Rituximab to CHOP Chemotherapy in First-Line Treatment for Diffuse Large B-Cell Lymphoma in a Population-Based Observational Cohort in British Columbia, Canada

Spurred by a desire to improve quality of care and to understand the relative value of medical treatments, there has been a recent surge of interest in publicly funded comparative effectiveness research (CER) in the US. As health technology assessment (HTA) shares some of the same goals as CER, and publicly funded HTA has been a feature within other industrialized countries for many years, a review of HTA activities in some of these countries can be a helpful source of information for the US debate.Informed by a literature review, and in two cases augmented by informant interviews, we reviewed the organization of HTA activities in five jurisdictions: Canada, Sweden, Scotland, the Netherlands and Australia. We provide a summary description of the healthcare system in each country as well as a description of the key features of their HTA bodies, with a particular focus on the processes of HTA for listing medications on public formularies.Four of the committees evaluating medications for formulary inclusion are funded by, but remain at arm’s length from, the government (Canada, Australia, Sweden and Scotland), while the process is fully embedded within the government in the Netherlands. Each of these jurisdictions has a stated preference for comparative outcomes evidence from randomized controlled trials, but will, under certain circumstances, accept randomized evidence using surrogate markers, other comparators that are not directly relevant or non-randomized evidence. Health technology evaluation committees largely comprise health professionals, with public representatives included in the Canadian, Australian and Scottish committees. Scotland is the only one of the five jurisdictions reviewed to have industry representation on the evaluation committee.We identified seven characteristics that are shared across the jurisdictions reviewed and that potentially serve as insights for development of CER in the US: (i) the process must be responsive to stakeholders’ interests, in that the turn-around time for assessments must be minimized, transparency must be maximized, the process must be considered fair using universally agreed standards and the process must be modifiable based on stakeholders’ requirements; (ii) the assessment of medical technologies other than drugs may present different challenges and is managed separately in other HTA organizations; (iii) because of the link between HTA and reimbursement decisions, completion of the HTA process following regulatory approval can delay market access to new technologies, thus closer integration between regulatory approval and HTA processes is being explored internationally; (iv) there is a direct or indirect link to reimbursement in the jurisdictions explored–without this link the role of CER in the US will remain advisory; (v) each jurisdiction reviewed benefits from a single payer that is informed by the process–given the diverse multipayer environment in the US, CER in the US may usefully focus on generating comparative effectiveness evidence; (vi) a common metric for assessing intended and unintended effects of treatment allows comparison across different technologies; and (vii) one stated focus of CER is on therapeutic benefit among ‘high-priority populations’, including specific demographic groups (the elderly and children, racial and ethnic minorities) and individuals with disabilities, multiple chronic conditions and specific genomic factors. This will be difficult to achieve because epidemiological evidence of differences in therapeutic benefit among subgroups is detected through effect modification, or more specifically, statistical evidence of effect measure modification, typically on relative measures of effect. Few randomized trials have enough power to detect effect modification and these have been uncommon in the scientific literature. As consideration is given to the development of a publicly funded CER body in the US, much can be learned from the international experience. Nevertheless, there are some distinctive features of the US healthcare system that must be taken into account when assessing the transferability of these insights.

Verification of imatinib cost-effectiveness in advanced gastrointestinal stromal tumor in British Columbia (VINCE-BC study).

Abstract Background: Cetuximab (Erbitux *Erbitux is a registered trade name of Bristol–Myers Squibb, Princeton, NJ, USA.) is the only new medical therapy for locally and regionally advanced SCCHN to be licensed in industrialized countries in the past 15 years and presents an alternative to cisplatin which is the current therapeutic standard. In the absence of a published head-to-head trial, we estimated the relative benefit of cetuximab and cisplatin using an indirect comparison methodology. Methods: We performed a systematic review of the Medline and Embase databases between 1998 and 2008 to find published trials of cisplatin plus radiotherapy vs. radiotherapy alone and synthesized the information with meta-analysis. Those results were combined with trial-based results of cetuximab plus radiotherapy vs. radiotherapy alone. Inclusion criteria stipulated that cisplatin be administered concurrently with radiation, the radiation protocol be comparable to the registration trial for cisplatin (once-daily, twice-daily, or concomitant boost) and cisplatin dosing be comparable to that in common use (i.e. day 1, 22 and 43 of treatment). Endpoints were locoregional control and overall survival. Two reviewers examined 269 abstracts which yielded four trials meeting the inclusion criteria. Results: There was little evidence of superiority of either platinum-based radiotherapy or cetuximab-based radiotherapy. All estimated hazard ratios were near 1.0 (equivalence), all confidence intervals spanned the null value (1.0), and no consistent pattern was observed regarding the direction of the effect. The results remained robust in sensitivity analysis. Conclusion: This is the first quantitative analysis allowing formal comparison between cetuximab and radiotherapy versus cisplatin and radiotherapy. Based on state-of-the-art methodology for indirect comparisons, it was not possible to identify either treatment regimen as superior in prolonging either locoregional control or overall survival. Until the publication of more studies, and particularly a head-to-head comparison, the two treatments may be considered equally efficacious when given alongside radiotherapy. The choice of treatment may focus on the toxicity profile of the medications.

Cost-effectiveness of pharmacist care for managing hypertension in Canada:

The global prevalence of HIV infection continues to grow, as a result of increasing incidence in some countries and improved survival where highly active antiretroviral therapy (HAART) is available. Growing healthcare expenditure and shifts in the types of medical resources used have created a greater need for accurate information on the costs of treatment. The objectives of this review were to compare published estimates of direct medical costs for treating HIV and to determine the impact of disease stage on such costs, based on CD4 cell count and plasma viral load.A literature review was conducted to identify studies meeting prespecified criteria for information content, including an original estimate of the direct medical costs of treating an HIV-infected individual, stratified based on markers of disease progression. Three unpublished cost-of-care studies were also included, which were applied in the economic analyses published in this supplement. A two-step procedure was used to convert costs into a common price year (2004) using country-specific health expenditure inflators and, to account for differences in currency, using health-specific purchasing power parities to express all cost estimates in US dollars.In all nine studies meeting the eligibility criteria, infected individuals were followed longitudinally and a ‘bottom-up’ approach was used to estimate costs. The same patterns were observed in all studies: the lowest CD4 categories had the highest cost; there was a sharp decrease in costs as CD4 cell counts rose towards 100 cells/mm3; and there was a more gradual decline in costs as CD4 cell counts rose above 100 cells/mm3. In the single study reporting cost according to viral load, it was shown that higher plasma viral load level (>100 000 HIV-RNA copies/mL) was associated with higher costs of care. The results demonstrate that the cost of treating HIV disease increases with disease progression, particularly at CD4 cell counts below 100 cells/mm3. The suggestion that costs increase as the plasma viral load rises needs independent verification. This review of the literature further suggests that publicly available information on the cost of HAART by disease stage is inadequate. To address the information gap, multiple stakeholders (governments, pharmaceutical industry, private insurers and non-governmental organizations) have begun to establish and support an independent, high quality and standardized multicountry data collection for evaluating the cost of HIV management. An accurate, representative and relevant cost-estimate data resource would provide a valuable asset to healthcare planners that may lead to improved policy and decision-making in managing the HIV epidemic.