Investigation of willingness on individualized medication of high-dose methotrexate in patients with osteosarcoma or hematological malignancy_Chinese Journal of Evidence-Based Medicine

Authors：

SONG Zaiwei ^1,2,3 , HUANG Zhencheng ^1,2,3 ,  ZHAO Rongsheng ^1,3

1. Department of Pharmacy, Peking University Third Hospital, Beijing, 100191, P.R.China;
2. Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, P.R.China;
3. Institute for Drug Evaluation, Peking University Health Science Center, Beijing, 100191, P.R.China;

Corresponding author：

ZHAO Rongsheng, Email: zhao_rongsheng@163.com

Keywords：

High-dose methotrexate; Personalized medication; Guideline; Investigation of willingness

DOI：

10.7507/1672-2531.201901094

Video：

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Objectives To analyze patients’ values and preferences on individualized medication of high-dose methotrexate so as to support the development of the practice guideline for clinical medication of high-dose methotrexate.Methods A multicenter cross-sectional study involving patients with osteosarcoma or hematological malignancy in 7 hospitals was conducted by questionnaires to evaluate the perception and willingness on detection of gene polymorphisms (MTHFR C677T, MTHFR A1298C, ABCB1 C3435T and RFC1 G80A) related to methotrexate (MTX) and therapeutic drug monitoring (TDM) of MTX. SPSS24.0 software was used to analyze the data.Results A total of 124 patients were involved, including 40 (32.26%) with osteosarcoma and 84 (67.74%) with hematological malignancy. 106 (85.48%) and 117 (94.35%) patients agreed on detection of gene polymorphisms and TDM, respectively. There was a significant difference on preference towards TDM between patients with risk factors for MTX and patients in which risk factors for MTX were not discovered (76.19% vs. 95.08%, P=0.003). The ranking of factors that contributed to the two decision-making was consistent (P<0.01), and specific orders of factors were identical. The clinical efficacy was the primary factor (mean rank 3.45 for detection of genetic polymorphisms and 3.52 for TDM), followed by safety (mean rank 3.01 and 3.16, respectively) and comfort (mean rank 1.73 and 1.79, respectively). Cost (mean rank 1.39 and 1.31, respectively) was the least important factor.Conclusions The preferences of patients toward detection of gene polymorphisms and TDM were generally similar, with well acceptance. No significant differences were found on the preferences toward detection of gene polymorphisms. However, patients with or without risk factors for MTX may differ significantly when making decisions on TDM, which may impact on clinical decision-making of clinicians and clinical pharmacists. The perception and willingness of patients should be considered adequately during the development of clinical practice guidelines and clinical practice.

Citation： SONG Zaiwei, HUANG Zhencheng, ZHAO Rongsheng. Investigation of willingness on individualized medication of high-dose methotrexate in patients with osteosarcoma or hematological malignancy. Chinese Journal of Evidence-Based Medicine, 2019, 19(6): 639-644. doi: 10.7507/1672-2531.201901094 Copy

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3.	Richardson PE. David Sackett and the birth of evidence based medicine: how to practice and teach EBM. BMJ, 2015, 350: h3089.
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10.	魏来临, 张岩, 邢冰. 疾病诊疗决策中如何具体融合患者的价值观. 医学与哲学(临床决策论坛版), 2008, (8): 1-2, 12.
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12.	丁泓帆, 杨楠, 邓围, 等. WHO指南制定的基本原则和方法. 中国循证医学杂志, 2016, 16(4): 471-477.
13.	Preference Collaborative Review Group. Patients' preferences within randomised trials: systematic review and patient level meta-analysis. BMJ, 2008, 337: a1864.
14.	王明辉, 张菁, 曾宪涛, 等. 临床实践指南制订方法-患者的价值观和意愿. 中国循证心血管医学杂志, 2018, 10(10): 1153-1156, 1161.
15.	解染, 徐晓涵, 陈恳, 等. 感染患者关于万古霉素治疗药物监测的价值观与意愿调查(英文). 药物流行病学杂志, 2016, (6): 390-395.
16.	徐晓涵, 陈恳, 孙浩, 等. 真菌感染患者对伏立康唑个体化用药的意愿调查. 中国临床药理学杂志, 2017, 33(5): 456-458, 466.
17.	Yang L, Hu X, Xu L. Impact of methylenetetrahydrofolate reductase (MTHFR) polymorphisms on methotrexate-induced toxicities in acute lymphoblastic leukemia: a meta-analysis. Tumour Biol, 2012, 33(5): 1445-1454.
18.	Lopez-Lopez E, Martin-Guerrero I, Ballesteros J, et al. A systematic review and meta-analysis of MTHFR polymorphisms in methotrexate toxicity prediction in pediatric acute lymphoblastic leukemia. Pharmacogenomics J, 2013, 13(6): 498-506.
19.	何霞. 还原叶酸载体基因多态性与大剂量甲氨蝶呤药物不良反应关系的Meta分析. 中国临床药理学杂志, 2016, 32(15): 1432-1434.
20.	解染, 陈耀龙, 陈昊, 等. 循证指南制定中患者价值观和偏好的研究方法. 中国循证医学杂志, 2015, 15(5): 586-591.

1. Evidence-Based Medicine Working Group. Evidence-based medicine. A new approach to teaching the practice of medicine. JAMA, 1992, 268(17): 2420-2425.
2. Sackett DL, Rosenberg WM, Gray JA, et al. Evidence based medicine: what it is and what it isn't. BMJ, 1996, 312(7023): 71-72.
3. Richardson PE. David Sackett and the birth of evidence based medicine: how to practice and teach EBM. BMJ, 2015, 350: h3089.
4. Institute of Medicine (US) Committee on standards for developing trustworthy clinical practice guidelines; Graham R, Mancher M, Miller Wolman D, Greenfield S, Steinberg E, editors. Clinical Practice Guidelines We Can Trust. Washington (DC): National Academies Press (US); 2011.
5. 张亮. 重症医学-十年循证带给我们的启示. 中华医学信息导报, 2012, 27(11): 12.
6. 倪伟建, 方焱, 张善堂, 等. 基于药物基因组学与血药浓度监测指导的个体化用药研究. 中国医院药学杂志, 2018, 38(17): 1863-1868.
7. Moran S, Martinez-Cardús A, Boussios S, et al. Precision medicine based on epigenomics: the paradigm of carcinoma of unknown primary. Nat Rev Clin Oncol, 2017, 14(11): 682-694.
8. Howard SC, McCormick J, Pui CH, et al. Preventing and managing toxicities of high-dose methotrexate. Oncologist, 2016, 21(12): 1471-1482.
9. Mikkelsen TS, Thorn CF, Yang JJ, et al. Pharm GKB summary: methotrexate pathway. Pharmacogenet Genomics, 2011, 21(10): 679-686.
10. 魏来临, 张岩, 邢冰. 疾病诊疗决策中如何具体融合患者的价值观. 医学与哲学(临床决策论坛版), 2008, (8): 1-2, 12.
11. 李幼平, 李静, 孙鑫, 等. 循证医学在中国的起源与发展: 献给中国循证医学20周年. 中国循证医学杂志, 2016, 16(1): 2-6.
12. 丁泓帆, 杨楠, 邓围, 等. WHO指南制定的基本原则和方法. 中国循证医学杂志, 2016, 16(4): 471-477.
13. Preference Collaborative Review Group. Patients' preferences within randomised trials: systematic review and patient level meta-analysis. BMJ, 2008, 337: a1864.
14. 王明辉, 张菁, 曾宪涛, 等. 临床实践指南制订方法-患者的价值观和意愿. 中国循证心血管医学杂志, 2018, 10(10): 1153-1156, 1161.
15. 解染, 徐晓涵, 陈恳, 等. 感染患者关于万古霉素治疗药物监测的价值观与意愿调查(英文). 药物流行病学杂志, 2016, (6): 390-395.
16. 徐晓涵, 陈恳, 孙浩, 等. 真菌感染患者对伏立康唑个体化用药的意愿调查. 中国临床药理学杂志, 2017, 33(5): 456-458, 466.
17. Yang L, Hu X, Xu L. Impact of methylenetetrahydrofolate reductase (MTHFR) polymorphisms on methotrexate-induced toxicities in acute lymphoblastic leukemia: a meta-analysis. Tumour Biol, 2012, 33(5): 1445-1454.
18. Lopez-Lopez E, Martin-Guerrero I, Ballesteros J, et al. A systematic review and meta-analysis of MTHFR polymorphisms in methotrexate toxicity prediction in pediatric acute lymphoblastic leukemia. Pharmacogenomics J, 2013, 13(6): 498-506.
19. 何霞. 还原叶酸载体基因多态性与大剂量甲氨蝶呤药物不良反应关系的Meta分析. 中国临床药理学杂志, 2016, 32(15): 1432-1434.
20. 解染, 陈耀龙, 陈昊, 等. 循证指南制定中患者价值观和偏好的研究方法. 中国循证医学杂志, 2015, 15(5): 586-591.

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Investigation of willingness on individualized medication of high-dose methotrexate in patients with osteosarcoma or hematological malignancy

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