Zeldis J B, Williams B A, Thomas S D, Elsayed M E
Department of Medical Affairs, Celgene Corporation, Warren, New Jersey 07059, USA.
Clin Ther. 1999 Feb;21(2):319-30. doi: 10.1016/s0149-2918(00)88289-2.
In July 1998, the US Food and Drug Administration approved the marketing of thalidomide for the treatment of cutaneous manifestations of erythema nodosum leprosum. To ensure that fetal exposure to this teratogenic agent does not occur, the manufacturer has instituted a comprehensive program to control prescribing, dispensing, and use of the drug. This program, known as the System for Thalidomide Education and Prescribing Safety (S.T.E.P.S. [Celgene Corporation, Warren, New Jersey]), is based in part on experience gained with other drugs--specifically isotretinoin and clozapine--that offer important clinical benefits but carry the potential for serious harm. To achieve its goal of the lowest possible incidence of drug-associated teratogenicity, the S.T.E.P.S. program uses a three-pronged approach: (1) controlling access to the drug; (2) educating prescribers, pharmacists, and patients; and (3) monitoring compliance. Clinicians who wish to prescribe thalidomide must be registered in the S.T.E.P.S. Prescriber Registry and agree to prescribe the drug in accordance with S.T.E.P.S. patient eligibility criteria and monitoring procedures. Pharmacies must also register and agree to comply with patient identification and monitoring criteria. Finally, patients receive visual aids, including a videotape, written material, and verbal counseling about the benefits and risks of thalidomide therapy, the importance of not becoming pregnant during therapy, and the types of contraception required (including emergency contraception) and their availability. Women of childbearing potential must agree to undergo pregnancy testing before starting therapy and on a regular schedule during therapy. All patients must agree to complete a confidential survey about their compliance with contraception, testing, and drug therapy. The manufacturer is monitoring survey results and outcome data and is prepared to make whatever modifications to the S.T.E.P.S. program are necessary to ensure its effectiveness. In addition to minimizing the potential risk for fetal harm associated with thalidomide therapy, the S.T.E.P.S. program may provide a model for future cases in which a drug offers compelling benefits but poses profound risks unless its distribution is carefully controlled.
1998年7月，美国食品药品监督管理局批准沙利度胺上市，用于治疗麻风结节性红斑的皮肤表现。为确保不会发生胎儿接触这种致畸药物的情况，制造商制定了一项全面计划，以控制该药物的处方、配药和使用。该计划名为沙利度胺教育与处方安全系统（S.T.E.P.S. [新泽西州沃伦市的赛尔基因公司]），部分基于从其他药物（特别是异维甲酸和氯氮平）中获得的经验，这些药物虽提供重要的临床益处，但有造成严重伤害的可能性。为实现药物相关致畸发生率尽可能低的目标，S.T.E.P.S. 计划采用三管齐下的方法：（1）控制药物获取；（2）对开处方者、药剂师和患者进行教育；（3）监测依从性。希望开具沙利度胺处方的临床医生必须在S.T.E.P.S. 开处方者登记处注册，并同意按照S.T.E.P.S. 患者资格标准和监测程序开具该药物。药房也必须注册，并同意遵守患者识别和监测标准。最后，患者会收到视觉辅助材料，包括录像带、书面材料，并接受关于沙利度胺治疗的益处和风险、治疗期间不怀孕的重要性、所需避孕措施的类型（包括紧急避孕）及其可获得性的口头咨询。有生育潜力的女性必须同意在开始治疗前以及治疗期间定期进行妊娠检测。所有患者必须同意完成一项关于其避孕、检测和药物治疗依从性的保密调查。制造商正在监测调查结果和结果数据，并准备对S.T.E.P.S.计划进行任何必要的修改，以确保其有效性。除了将沙利度胺治疗对胎儿造成伤害的潜在风险降至最低外，S.T.E.P.S. 计划可能为未来的案例提供一个模式，即一种药物虽有显著益处，但除非其分发得到严格控制，否则会带来巨大风险。
