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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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.
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9.	Mikkelsen TS, Thorn CF, Yang JJ, et al. Pharm GKB summary: methotrexate pathway. Pharmacogenet Genomics, 2011, 21(10): 679-686.
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11.	李幼平, 李靜, 孫鑫, 等. 循證醫學在中國的起源與發展: 獻給中國循證醫學20周年. 中國循證醫學雜志, 2016, 16(1): 2-6.
12.	丁泓帆, 楊楠, 鄧圍, 等. WHO指南制定的基本原則和方法. 中國循證醫學雜志, 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.	王明輝, 張菁, 曾憲濤, 等. 臨床實踐指南制訂方法-患者的價值觀和意愿. 中國循證心血管醫學雜志, 2018, 10(10): 1153-1156, 1161.
15.	解染, 徐曉涵, 陳懇, 等. 感染患者關于萬古霉素治療藥物監測的價值觀與意愿調查(英文). 藥物流行病學雜志, 2016, (6): 390-395.
16.	徐曉涵, 陳懇, 孫浩, 等. 真菌感染患者對伏立康唑個體化用藥的意愿調查. 中國臨床藥理學雜志, 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. 還原葉酸載體基因多態性與大劑量甲氨蝶呤藥物不良反應關系的Meta分析. 中國臨床藥理學雜志, 2016, 32(15): 1432-1434.
20.	解染, 陳耀龍, 陳昊, 等. 循證指南制定中患者價值觀和偏好的研究方法. 中國循證醫學雜志, 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. 張亮. 重癥醫學-十年循證帶給我們的啟示. 中華醫學信息導報, 2012, 27(11): 12.
6. 倪偉建, 方焱, 張善堂, 等. 基于藥物基因組學與血藥濃度監測指導的個體化用藥研究. 中國醫院藥學雜志, 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. 魏來臨, 張巖, 邢冰. 疾病診療決策中如何具體融合患者的價值觀. 醫學與哲學(臨床決策論壇版), 2008, (8): 1-2, 12.
11. 李幼平, 李靜, 孫鑫, 等. 循證醫學在中國的起源與發展: 獻給中國循證醫學20周年. 中國循證醫學雜志, 2016, 16(1): 2-6.
12. 丁泓帆, 楊楠, 鄧圍, 等. WHO指南制定的基本原則和方法. 中國循證醫學雜志, 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. 王明輝, 張菁, 曾憲濤, 等. 臨床實踐指南制訂方法-患者的價值觀和意愿. 中國循證心血管醫學雜志, 2018, 10(10): 1153-1156, 1161.
15. 解染, 徐曉涵, 陳懇, 等. 感染患者關于萬古霉素治療藥物監測的價值觀與意愿調查(英文). 藥物流行病學雜志, 2016, (6): 390-395.
16. 徐曉涵, 陳懇, 孫浩, 等. 真菌感染患者對伏立康唑個體化用藥的意愿調查. 中國臨床藥理學雜志, 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. 還原葉酸載體基因多態性與大劑量甲氨蝶呤藥物不良反應關系的Meta分析. 中國臨床藥理學雜志, 2016, 32(15): 1432-1434.
20. 解染, 陳耀龍, 陳昊, 等. 循證指南制定中患者價值觀和偏好的研究方法. 中國循證醫學雜志, 2015, 15(5): 586-591.

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