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.

[1]  U. Siebert,et al.  When is enough evidence enough? - Using systematic decision analysis and value-of-information analysis to determine the need for further evidence. , 2013, Zeitschrift fur Evidenz, Fortbildung und Qualitat im Gesundheitswesen.

[2]  S. Sansom,et al.  Cost Effectiveness of the National HIV/AIDS Strategy Goal of Increasing Linkage to Care for HIV-Infected Persons , 2012, Journal of acquired immune deficiency syndromes.

[3]  M. Weinstein,et al.  Economic Savings Versus Health Losses: The Cost-Effectiveness of Generic Antiretroviral Therapy in the United States , 2013, Annals of Internal Medicine.

[4]  Sandeep Vijan,et al.  The value of medical spending in the United States, 1960-2000. , 2006, The New England journal of medicine.

[5]  D. Katzenstein,et al.  Atazanavir Plus Ritonavir or Efavirenz as Part of a 3-Drug Regimen for Initial Treatment of HIV-1 , 2011, Annals of Internal Medicine.

[6]  Lynne Peeples,et al.  Class-sparing regimens for initial treatment of HIV-1 infection. , 2008, The New England journal of medicine.

[7]  John B. Wong,et al.  Heterogeneity and uncertainty , 2014 .

[8]  Michael Rayment,et al.  Prevention of HIV-1 infection with early antiretroviral therapy , 2012, Journal of Family Planning and Reproductive Health Care.

[9]  W. Gerth,et al.  Use of cost-effectiveness analysis in health-care resource allocation decision-making: how are cost-effectiveness thresholds expected to emerge? , 2004, Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research.

[10]  Adriano Lazzarin,et al.  Safety and efficacy of raltegravir-based versus efavirenz-based combination therapy in treatment-naive patients with HIV-1 infection: a multicentre, double-blind randomised controlled trial , 2009, The Lancet.

[11]  Clare Brennan,et al.  Once-daily dolutegravir versus raltegravir in antiretroviral-naive adults with HIV-1 infection: 48 week results from the randomised, double-blind, non-inferiority SPRING-2 study , 2013, The Lancet.

[12]  J. Manson,et al.  Economic Return From the Women's Health Initiative Estrogen Plus Progestin Clinical Trial , 2014, Annals of Internal Medicine.

[13]  A. Lazzarin,et al.  Atazanavir plus ritonavir or saquinavir, and lopinavir/ritonavir in patients experiencing multiple virological failures. , 2005, AIDS.

[14]  Bas Groot Koerkamp,et al.  Identifying key parameters in cost-effectiveness analysis using value of information: a comparison of methods. , 2006, Health economics.

[15]  Milton C Weinstein,et al.  Cost-effectiveness of HIV treatment in resource-poor settings--the case of Côte d'Ivoire. , 2006, The New England journal of medicine.

[16]  J. J. Henning,et al.  Guidelines for the Use of Antiretroviral Agents in HIV-Infected Adults and Adolescents, January 28, 2000 , 1998, HIV clinical trials.

[17]  Michael E. Chernew,et al.  Willingness to Pay for a Quality-adjusted Life Year , 2000, Medical decision making : an international journal of the Society for Medical Decision Making.

[18]  A. Lazzarin,et al.  Rilpivirine versus efavirenz with tenofovir and emtricitabine in treatment-naive adults infected with HIV-1 (ECHO): a phase 3 randomised double-blind active-controlled trial , 2011, The Lancet.

[19]  S. Grosse.  Assessing cost-effectiveness in healthcare: history of the $50,000 per QALY threshold , 2008, Expert review of pharmacoeconomics & outcomes research.

[20]  M. Weinstein,et al.  Preevaluation of clinical trial data: the case of preemptive cytomegalovirus therapy in patients with human immunodeficiency virus. , 2001, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[21]  B. Clotet,et al.  Once-daily dolutegravir versus darunavir plus ritonavir in antiretroviral-naive adults with HIV-1 infection (FLAMINGO): 48 week results from the randomised open-label phase 3b study , 2014, The Lancet.

[22]  Joel E Gallant,et al.  Efficacy and safety of tenofovir DF vs stavudine in combination therapy in antiretroviral-naive patients: a 3-year randomized trial. , 2004, JAMA.

[23]  S. Walmsley,et al.  Dolutegravir plus abacavir-lamivudine for the treatment of HIV-1 infection. , 2013, The New England journal of medicine.

[24]  M. Johnson,et al.  96-week comparison of once-daily atazanavir/ritonavir and twice-daily lopinavir/ritonavir in patients with multiple virologic failures , 2006, AIDS.

[25]  R. Kuchenbecker,et al.  Atazanavir plus ritonavir or efavirenz as part of a 3-drug regimen for initial treatment of HIV-1. , 2011, Annals of internal medicine.

[26]  D. Aschenbrenner.  New Drug to Treat HIV Infection , 2011 .

[27]  M G Myriam Hunink,et al.  Uncertainty and Patient Heterogeneity in Medical Decision Models , 2010, Medical decision making : an international journal of the Society for Medical Decision Making.

[28]  M. Roberts,et al.  What Does the Value of Modern Medicine Say About the $50,000 per Quality-Adjusted Life-Year Decision Rule? , 2008, Medical care.

[29]  A. Willan,et al.  Value of Information and Pricing New Healthcare Interventions , 2012, PharmacoEconomics.

[30]  Milton C Weinstein,et al.  Expanded screening for HIV in the United States--an analysis of cost-effectiveness. , 2005, The New England journal of medicine.

[31]  Richard D Moore,et al.  Late presentation for human immunodeficiency virus care in the United States and Canada. , 2010, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[32]  J. Lave,et al.  Willingness to Pay for a Quality-Adjusted Life Year: Implications for Societal Health Care Resource Allocation , 2005, Medical decision making : an international journal of the Society for Medical Decision Making.

[33]  S. Hammer,et al.  HIV Vaccine Research: The Way Forward , 2008, Science.

[34]  D. Whynes,et al.  Eliciting Willingness to Pay: Comparing Closed-Ended with Open-Ended and Payment Scale Formats , 2003, Medical decision making : an international journal of the Society for Medical Decision Making.

[35]  J. Nachega,et al.  Lower Pill Burden and Once-Daily Antiretroviral Treatment Regimens for HIV Infection: A Meta-Analysis of Randomized Controlled Trials , 2014, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[36]  Joshua T. Cohen,et al.  Updating cost-effectiveness--the curious resilience of the $50,000-per-QALY threshold. , 2014, The New England journal of medicine.

[37]  M. Johnson,et al.  Atazanavir plus ritonavir or saquinavir, and lopinavir/ritonavir in patients experiencing multiple virological failures , 2005, AIDS.

[38]  K. White,et al.  Co-formulated elvitegravir, cobicistat, emtricitabine, and tenofovir versus co-formulated efavirenz, emtricitabine, and tenofovir for initial treatment of HIV-1 infection: a randomised, double-blind, phase 3 trial, analysis of results after 48 weeks , 2012, The Lancet.

[39]  Lynne Peeples,et al.  Abacavir-lamivudine versus tenofovir-emtricitabine for initial HIV-1 therapy. , 2009, The New England journal of medicine.

[40]  Kenneth A. Freedberg,et al.  Genotype assays and third-line ART in resource-limited settings: a simulation and cost-effectiveness analysis of a planned clinical trial , 2012, AIDS.

[41]  M. Sculpher,et al.  Decision Modelling for Health Economic Evaluation , 2006 .

[42]  Mardge H. Cohen,et al.  HIV and Aging: State of Knowledge and Areas of Critical Need for Research. A Report to the NIH Office of AIDS Research by the HIV and Aging Working Group , 2012, Journal of acquired immune deficiency syndromes.

[43]  V. Retèl,et al.  A Systematic and Critical Review of the Evolving Methods and Applications of Value of Information in Academia and Practice , 2012, PharmacoEconomics.