孕妇药物临床试验中的伦理问题及其解决方案综述
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摘要
由于孕妇及胎儿对药物较为敏感、孕妇用药具有普遍性以及孕妇药物临床试验的缺失,孕妇进行药物临床试验是必要的。然而,目前此类试验在开展过程中面临诸多伦理问题,主要包括孕妇受试者招募不足、风险与受益难以平衡以及孕妇受试者保护体系不够完善。因此,可通过有效地招募和保留孕妇受试者、防控风险和提高受益以及完善保护孕妇受试者的相关体系等科学对策解决。
It is necessary for pregnant women to conduct drug clinical trials because of the sensitivity of pregnant women and fetuses to drugs, the universality of medication used in pregnant women and the absence of drug clinical trials of pregnant women. However, such trials are facing with many ethical problems in the process of implementation at present. It mainly includes the insufficiency of pregnant women subjects, difficulty in balancing risks and benefits, and inadequate protection system for pregnant women subjects. Therefore, scientific countermeasures can be taken effectively, including: to recruit and retain pregnant women subjects, to prevent and control risks and increase benefits, to prefect the relevant system to protect pregnant women, and so on.
It is necessary for pregnant women to conduct drug clinical trials because of the sensitivity of pregnant women and fetuses to drugs, the universality of medication used in pregnant women and the absence of drug clinical trials of pregnant women. However, such trials are facing with many ethical problems in the process of implementation at present. It mainly includes the insufficiency of pregnant women subjects, difficulty in balancing risks and benefits, and inadequate protection system for pregnant women subjects. Therefore, scientific countermeasures can be taken effectively, including: to recruit and retain pregnant women subjects, to prevent and control risks and increase benefits, to prefect the relevant system to protect pregnant women, and so on.
引文
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[35] 王继年,潘荣华,杨芳.医院药物临床试验机构伦理委员会规范化管理中的问题与对策[J].辽宁医学院学报(社会科学版),2014,12(1):11-14.
[36] 郑小藇,张金钟.论生物医药研究伦理审查的合力效应[J].中国医学伦理学,2016,29(2):280-284.
[2] Abduljalil K,Furness P,Johnson T N,et al.Anatomical,Physiological and Metabolic Changes with Gestational Age during Normal Pregnancy[J].Clinical Pharmacokinetics,2012,51(6):365-396.
[3] Koren G ,Pariente G .Pregnancy-Associated Changes in Pharmacokinetics and their Clinical Implications[J].Pharmaceutical Research,2018,35(3):61.
[4] Baylis F.Pregnant women deserve better[J].Nature,2010,465(7299):689.
[5] Yang Z,Hebert M F,Venkataramanan R.Basic obstetric pharmacology[J].Seminars in Perinatology,2014,38(8):475-486.
[6] Martin J A,Hamilton B E,Osterman M J K,et al.Births:Final Data for 2013[J].National vital statistics reports,2015,64(1):1-68.
[7] Martin J A,Hamilton B E,Ventura S J,et al.Births:final data for 2010[J].Natl Vital Stat Rep,2012,61(1):1-116.
[8] Graaf R V D,Zande I S E V D,Ruijter H M D,et al.Fair inclusion of pregnant women in clinical trials:an integrated scientific and ethical approach[J].Trials,2018,19(1):78.
[9] Pariente G ,Leibson T ,Carls A ,et al.Pregnancy-Associated Changes in Pharmacokinetics:A Systematic Review[J].Plos Medicine,2016,13(11):e1002160.
[10] White A.Accelerating the paradigm shift toward inclusion of pregnant women in drug research:Ethical and regulatory considerations[J].Seminars in Perinatology,2015,39(7):537-540.
[11] Shields K E,Lyerly A D.Exclusion of pregnant women from industry-sponsored clinical trials[J].Obstetrics & Gynecology,2013,122(5):1077.
[12] Str?mmer S,Lawrence W,Rose T,et al.Improving recruitment to clinical trials during pregnancy:A mixed methods investigation[J].Social Science & Medicine,2018,200:73-82.
[13] Brumatti L V,Montico M,Russian S,et al.Analysis of motivations that lead women to participate (or not) in a newborn cohort study[J].Bmc Pediatrics,2013,13(1):1-7.
[14] Ise V D Z,Van d G R,Hooft L,et al.Facilitators and barriers to pregnant women’s participation in research:A systematic review[J].Women & Birth Journal of the Australian College of Midwives,2018,31(5):350-361.
[15]Baylis F,Macquarrie R.Why Physicians and Women Should Want Pregnant Women Included in Clinical Trials[M]// Clinical Research Involving Pregnant Women.Springer International Publishing,2016.
[16] Palmer S,Pudwell J,Smith G N,et al.Optimizing Participation of Pregnant Women in Clinical Trials:Factors Influencing Decisions About Participation in Medication and Vaccine Trials[J].Journal of Obstetrics & Gynaecology Canada,2016,38(10):945-954.
[17] Aktas S ,Calik K Y .Factors Affecting Depression During Pregnancy and the Correlation Between Social Support and Pregnancy Depression[J].Iranian Red Crescent Medical Journal,2015,17(9):e16640.
[18] Frew P M,Saint-Victor D S,Isaacs M B,et al.Recruitment and retention of pregnant women into clinical research trials:an overview of challenges,facilitators,and best practices[J].Clinical Infectious Diseases,2014,59(suppl_7):S400-S407.
[19] Franceschini R T.Clinical Research with Pregnant Women:Investigator Insights on Success[D].Seattle:University of Washington,2017.
[20] Rid A .Risk and risk-benefit evaluations in biomedical research[M].Netherlands:Springer,2012.
[21] Cragan J D.Medication use during pregnancy[J].Bmj,2014,349(349):g5252.
[22] Briggs G G,Polifka J E,Wisner K L,et al.Should Pregnant Women be Included in Phase IV Clinical Drug Trials?[J].American Journal of Obstetrics & Gynecology,2015,213(6):810-815.
[23] 张妞,张涛,徐菊华.中国医院伦理委员会发展的回顾与思考[J].医学与哲学,2017,38(11A):14-17.
[24] 王海臣,王彩霞,李实.药物临床试验伦理审查存在的问题及对策研究[J].中国医院管理,2015,35(12):75-76.
[25] 江一峰,耿雯倩,祝延红,等.临床试验中的弱势群体及其伦理保护[J].医学与哲学,2017,38(6A):25-27.
[26] 田剑波.医学临床试验中受试者法律保护的现状与完善[J].医学与法学,2017,9(4):36-40.
[27] Frew P M,Saintvictor D S,Owens L E,et al.Socioecological and message framing factors influencing maternal influenza immunization among minority women[J].Vaccine,2014,32(15):1736-1744.
[28] Van D K,Schwertnertiepelmann N,Thakar R,et al.Recruitment of pregnant women in research[J].Journal of Obstetrics & Gynaecology,2013,33(5):442-446.
[29] Gillies K,Sc C,Jc B,et al.Decision aids for people considering taking part in clinical trials (Review)[J].Cochrane Database of Systematic Reviews,2015,11(11):CD009736.
[30] Fogel D B.Factors associated with clinical trials that fail and opportunities for improving the likelihood of success:A review[J].Contemporary clinical trials communications,2018,11:156-164.
[31] Coleman-Phox K,Laraia B A,Adler N,et al.Peer reviewed:recruitment and retention of pregnant women for a behavioral intervention:lessons from the Maternal Adiposity,Metabolism,and Stress (MAMAS) study[J].Preventing chronic disease,2013,10:120096.
[32] 汤虹,张金钟.药物临床试验孕妇受试者风险防控[J].中国医学伦理学,2017,30(3):267-272.
[33] Forczek W,Ivanenko Y P,Bielatowicz J,et al.Gait assessment of the expectant mothers-Systematic review[J].Gait & Posture,2018,62:7.
[34] Saenz C,Cheah P Y,Van R D G,et al.Ethics,regulation,and beyond:the landscape of research with pregnant women:[J].Reproductive Health,2017,14(S3):173.
[35] 王继年,潘荣华,杨芳.医院药物临床试验机构伦理委员会规范化管理中的问题与对策[J].辽宁医学院学报(社会科学版),2014,12(1):11-14.
[36] 郑小藇,张金钟.论生物医药研究伦理审查的合力效应[J].中国医学伦理学,2016,29(2):280-284.