Can Modeling of Health Outcomes Facilitate Regulatory Decision Making?: The Benefit-Risk Tradeoff for Rosiglitazone in 1999 vs. 2007
Can Modeling of Health Outcomes Facilitate Regulatory Decision Making?: The Benefit-Risk Tradeoff for Rosiglitazone in 1999 vs. 2007
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DOI：
10.1038/clpt.2010.350
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发表时间：
2011-03-01
影响因子：
6.7
通讯作者：
Garrison, L. P., Jr.
中科院分区：
文献类型：
--
作者：
Cross, J. T.;Veenstra, D. L.;Garrison, L. P., Jr.
罗格列酮最初被批准用于2型糖尿病的单一治疗。我们通过量化罗格列酮（相对于比较物）的增量净收益（IN B）值，在首次批准（1999年）和FDA咨询委员会审查（2007年）时，测试了健康结果模型作为监管决策的辅助。使用1999年的数据，预计罗格列酮相对于安慰剂提供额外的0.639年（0.373质量调整生命年（QALY）），但相对于格列本脲损失0.312年（0.173质量调整生命年），血红蛋白A1c （HbA(1c)）水平降低的不确定性对获益-风险概况影响最大。到2007年，罗格列酮预计比格列本脲多提供0.222年（0.091 QALY），比二甲双胍多提供0.026年（0.009 QALY）。模型显示，考虑到益处的不确定性，罗格列酮作为单药治疗最初是不合理的。尽管上市后数据显示，罗格列酮的净获益（NB）与二甲双胍相似，但残留的心血管（CV）担忧并不支持罗格列酮作为一线治疗。我们采用数学糖尿病模型来估计糖尿病单药治疗的NB和不确定性。
Rosiglitazone was initially approved for type 2 diabetes monotherapy. We tested health-outcomes modeling as an aid to regulatory decision making by quantifying the incremental net benefit (IN B) value of rosiglitazone (relative to a comparator), both at the time of first approval (1999) and at the FDA advisory committee review (2007). Using 1999 data, rosiglitazone was projected to provide an additional 0.639 years of life (0.373 quality- adjusted life years (QALY s)) relative to placebo but a loss of 0.312 years (0.173 QALY s) relative to glyburide, with uncertainty in reduction of hemoglobin A1c (HbA(1c)) level having the greatest impact on the benefit- risk profile. By 2007, rosiglitazone was projected to provide an additional 0.222 years (0.091 QALY s) vs. glyburide and 0.026 years vs. metformin (0.009 QALY s). Modeling suggested that the use of rosiglitazone as monotherapy was not initially warranted, given the uncertainty with regard to benefit. Despite similar net benefit (NB) as metformin shown in postmarketing data, residual cardiovascular (CV) concerns did not support the use of rosiglitazone as first- line therapy. We adapted a mathematical diabetes model to estimate NB and uncertainty of diabetes monotherapy.