藥品仿單(package insert)係附隨於藥品包裝內的使用說明書，其內容經過衛生主管機關的評估及確認後，刊載了有關藥品之療效及安全性資料。藥品仿單標示外使用(off-label use)係指醫師開立處方未遵照藥品仿單之指示說明內容，如使用藥品未依仿單所載之適應症、劑量、患者群、給藥途徑或劑型等。藥品off-label use在臨床治療是一個常見的處方類型，其存在之原因主要在於藥品仿單刊載之內容過於限縮、藥商怠於申請仿單之變更或為滿足臨床治療之需求。雖然off-label use於臨床治療具有其重要性且不可或缺，然其中存有疑慮之處，則在於off-label use是否為藥事法所指之新藥？其與作為人體試驗用途之藥品差異為何？藥品off-label use之安全性及有效性脫逸衛生主管機關之確保，該如何控管其風險？文中針對上述爭議作逐一之釐清。
藥品off-label use所衍生患者身體傷害或死亡之民事責任，藉由實務判決案例可得知法院對於醫師開立off-label use處方之法律評價，爭點在於醫師是否違反off-label use之用藥注意義務及說明義務之履行。藥品off-label use用藥適當性之判斷標準，本文以醫師處方決策作成所參考臨床研究證據之可信賴度，依其證明力之不同，將off-label use處方區分為三種類型，包括「標準治療」、「已被研究的治療」及「創新治療」，並配合不同臨床治療個案情境作調整。若醫師開立處方係依據充分之研究證據，並以病患之治療利益為出發，則難認有違用藥注意義務。有關off-label use說明義務之履行，本文將說明義務依其所保護權利客體之不同，區分為保護生命、身體權有關藥物安全使用之「安全說明」及保護病患用藥自主權之「病患自主權說明(告知後同意)」，並由侵權及契約責任探討說明義務違反之法律效果。「病患自主權說明(告知後同意)」之部分，醫師有義務告知off-label use相關資訊以利病患決定是否接受該治療，惟資訊揭露的範圍則須進一步依據off-label use處方類型，界定病患自主權應受保護之強度。若醫師開立off-label use處方之資訊來源是證據品質愈低者，所須說明的內容要愈完整。
基於藥品本身就是一個既存的風險，當醫師開立off-label use處方符合醫療照護水準並履行說明，亦不能確保病患得避免藥物不良反應的發生。由於藥害救濟法第十三條第八款規定之存在，使得病患在適應症外用藥發生藥害時，無法透過藥害救濟法予以填補損害。而off-label use所致藥害應藉由何種方式予以填補，文中將進行討論並提出藥害救濟法之修法建議。
面對off-label use於臨床治療之高度盛行率，本文建議衛生主管機關應將藥政管理之觸角延伸至藥品上市後研究，主動介入確認被臨床治療廣為採用之off-label use其療效及安全性，要求藥商針對當中之治療利弊更新藥品仿單之標示，提供即時精確之官方指引供醫師參考，以解決off-label use相關之用藥風險問題。

The package inserts (label) accompany prescription drug packages and outline a drug’s efficacy and safety informations which have been reviewed and confirmed by the Department of Health. Off-label use refers to prescribing a registered drug for a use that is not included or is disclaimed in the package insert. Examples include use in a different indication, dose, patient population, route, or dosage form to that which is approved by regulatory authorities. Prescribing drugs off-label is widespread in the medical community and some reasons can be speculated about the popularity of off-label uses. One is that package inserts usually do not show complete information of drug uses; the second is drug manufacturers will not often seek to obtain approval for off-label uses; and the last is off-label uses are essential for optimal patient care. It is admitted that off-label uses are necessary for clinical treatments, but several doubts also arise from that. Whether an off-label use of a drug should be regarded as a “new drug” that falls under Pharmaceutical Affairs Acts regulation? What’s the difference between an off-label drug use and an investigational drug? Off-label drug uses create special risks which do not arise when drugs are used in manners that are approved by Department of Health. Which measures should be taken to control the risks？ The issues mentioned above will be elucidated in this article.
Physicians may incur civil liability for prescribing off-label use of drugs. Two civil cases have been found that patients brought a malpractice claim against a physician who prescribed a drug for an allegedly improper off-label use, and the causes of action were in two ways: the first, for failing to meet the standard of care in choosing off-label therapy, and the second, for breaching the physicians’ duty of disclosure. Determining the appropriateness of off-label use in individual patients, the best available patients-based research evidence which supports the drug used off-label is a crucial factor to be evaluated. According to the different levels of the quality of research evidence, this article proposed a framework of dividing off-label use into three separate categories that include “standard therapies”, “studied therapies”, and “innovative therapies”. A physician may avoid professional liability, when prescribing off-label uses if he or she puts the patient’s interest first and can point to sound scientific and clinical data that support the off-label use in feasible. Doctors’ duty of disclosure can be divided into two types, one is “information disclosure for safe drug use” and the other is “informed consent”. The civil liability of doctors’ duty of disclosure will be discussed in the field of tort and contract law separately. In applying the doctrine of informed consent to off-label drug prescriptions, off-label use of a drug is a material risk inherently involved in a proposed therapy which physicians should disclose to patients prior to the therapy. The scope of disclosure that physicians give patients for making therapeutic decisions is based on the category of off-label uses. The lower the evidence level of research supports the off-label use, the more information about off-label uses should be disclosed to protect the autonomy of patients.
Based on drug use itself is a risk, even though doctors prescribe orders of off-label uses to conform an accepted professional standard that doesn’t guarantee therapeutic results without occurrence of adverse drug reactions. Subparagraph 8 of Article 13 of Drug Hazard Relief Act constitutes a restriction against the remedy for adverse drug reactions of drug using outside the labeled indications. In order to establish a relief mechanism for adverse drug reactions in off-label use of drugs, amendment of Drug Hazard Relief Act is suggested.
In the presence of high prevalence of off-label uses among drug prescriptions, the competent authority should consider undertaking a range of activities in regulating off-label uses to resolve the problem of drug use uncertainties and risks with off-label uses, including systematically collecting post-marketing data to quantify the harms and benefits of common off-label uses; synthesizing evidence regarding off-label uses and requesting drug manufacturers to renew the label; and providing current and precise official drug information to physicians.

(一) 書籍
Marcia A.著、曾育慧譯，藥廠黑幕-製藥公司如何掏空你的錢包和健康，商周出版，2006年5月。
McConnell T.C.著、王國裕譯，醫療照護上的道德問題，臺灣省公共衛生研究所 出版，1988年2月。
王澤鑑，侵權行為法第1冊，自版，2005年1月。
王澤鑑，債法原理第1冊，自版，2005年9月。
王澤鑑，法律思維與民法實例，自版，2005年9月。
朱柏松、詹森林、張新寶、陳忠五、陳聰富合著，醫療過失舉證責任之比較，元照出版公司，2008年5月。
朱懷祖，藥物責任與消費者保護，五南圖書出版公司，1997年11月。
朱懷祖、梁啟銘、孔繁璐，藥物科技發展與智財權保護，中華景康藥學基金會，2006年。
李震山，人性尊嚴與人權保障，元照出版公司，2001年11月。
胡幼慧，新醫療社會學-批判與另類的視角，心理出版社，2001年11月。
姚志明，債務不履行-不完全給付之研究，元照出版公司，2000年12月。
姚志明，誠信原則與附隨義務之研究，元照出版公司，2003年2月。
姚志明，侵權行為法研究(一)，元照出版公司，2003年10月。
侯英泠，論院內感染之民事契約責任，正典出版文化有限公司，2004年6月。
孫森焱，民法債編總論 下冊，自版，2007年9月。
張嘉麟，＜藥害救濟機制析論＞消費者保護研究第十一輯，行政院消費者保護委員會編印，2005年11月。
翁岳生，行政法(上)，元照出版公司，2006年10月。
黃丁全，醫事法，元照出版公司，2000年7月。
戴正德、李明濱，醫學倫理導論(Introduction to Medical Ethics)，教育部發行，2006年1月。
蔡維音，社會國之法理基礎，正典出版文化有限公司，2001年7月。
蘇永欽、黃立、王千維等合著，民法七十年之回顧與展望紀念論文集(一)總則．債編，元照出版公司，2000年10月。

(二) 期刊文章
王皇玉，醫師未盡說明義務之法律效果-簡評九四年台上字第二六七六號判決，台灣本土法學雜誌第75期，頁224-226，2005年10月。
王富仙，從醫療行為適用消費者保護法之爭議試論醫療爭議未來走向，法令月刊第56卷第9期，頁30-50，2005年9月。
王澤鑑，特殊侵權行為-無過失侵權責任(下)-危險責任的理論、體系及發展，台灣本土法學雜誌第77期，頁55-76，2005年12月。
汪紹銘，藥品仿單外之使用(off-label use)之法律問題，全國律師雜誌，頁73-81，2007年12月。
李明濱，病人自主與知情同意，醫學教育第一卷第四期，頁377-388，1997年。
姜世明，舉證責任分配法則之體系建構，法官協會雜誌第六期，頁83-99，2004年6月。
侯英泠，論消保法上醫師之安全說明義務-台灣高等法院八七年上字第一五一號評釋，台灣本土法學雜誌第37期，頁63-77，2002年8月。
侯英泠，從德國法論醫師之契約上說明義務，月旦法學雜誌第112期，頁9-23，2004年9月。
侯英泠、醫療機構、外科醫師與麻醉科醫師之說明義務-最高法院九六年台上字第二四七六號判決簡評，台灣本土法學雜誌第107期，頁291-297，2008年6月。
姚志明等，誠信原則與附隨義務--民法研究會第二十三次學術研討會記錄，法學叢刊第184期，頁135-161，2001年10月。
陳自強，民法侵權行為法體系之再構成(下)-民法一九一條之三之體系地位，台灣本土法學雜誌第17期，頁20-43，2000年12月。
陳自強等，「我國醫療事故損害賠償問題的現況與展望」研討會(一)，台灣本土法學雜誌第39期，頁93-113，2002年10月。
陳聰富，論違反保護他人法律之侵權行為，台灣本土法學雜誌第30期，頁1-28，2002年1月。
黃立，消保法第七條與民法第一九一條之三對醫療行為適用之研析，政大法學評論第75期，頁1-77，2003年9月。
黃俊杰，特別公課之憲法基礎研究，國立中正大學法學期刊第5期，頁3-95，2001年9月。
黃俊杰，特別公課類型化及其課徵正義之研究，臺北大學法學論叢第50期，頁103-143，2002年6月。
楊秀儀，誰來同意？誰來作決定？從「告知後同意法則」談病人自主權的理論與實際：美國經驗之考察，台灣法學會學報第20期，頁367-406，1999年11月。
楊秀儀，美國「告知後同意」法則之考察分析，月旦法學雜誌第121期，頁138-152，2005年6月。
楊秀儀，論病人自主權-我國法上「告知後同意」之請求權基礎探討，臺大法學論叢第36卷第2期，頁229-269，2007年。
楊秀儀，告知後同意之倫理法律再思考：縮小理論與實務，月旦法學雜誌第162期，頁5-16，2008年11月。
蔡佩君，藥害救濟法淺析，台灣本土法學雜誌第14期，2000年9月，頁200-215
謝幸燕，藥商、醫院與醫師的處方決策：醫療制度與組織面之脈絡分析，臺灣社會學刊第34期，頁59-114，2005年6月。

(三) 學位論文
宋家桾，藥品標示外使用之定性與損害責任研究，國立清華大學科技法律研究所碩士論文，2007年。
吳志正，醫療契約論，東吳大學法學院法律學系法律專業碩士班碩士論文，2005年。
何愛文，特別公課之研究-現代給付國家新興之財政工具，國立台灣大學法律研究所碩士論文，1994年。
林恩萱，Carbamazepine藥品核准標示外使用（off-label use）之研究，國立陽明大學衛生福利研究所碩士論文，2004年。
陳俞潓，臺北地區醫學中心醫師對藥品核准標示外使用的認知、態度與使用概況，國立台灣大學衛生政策與管理研究所碩士論文，1999年。
張永健，論藥品、健康食品、食品之管制，國立台灣大學法律學研究所碩士論文，2003年。
辜仲明，特別公課規範概念及基本原則之研究，中原大學財經法律學系碩士論文，2001年。
黃崇呈，使用仿單核准適應症外處方之責任，國立清華大學科技法律研究所碩士論文，2006年。
廖建瑜，論醫師之說明義務，國立成功大學法律學研究所碩士論文，2005年。

(四)網路資料
1、歷年藥害救濟申請、調查、審議之成果及分析(1999/01-2007/12)
http://www.tdrf.org.tw/article.asp?channelid=A29&serial=201&click，最後瀏覽日：2008年9月24日。
2、藥師週刊電子報1549期，「只因別人都是這樣做」？
http://ys34485257.ncc.to/b/index.php-act=view&nid=270.htm，最後瀏覽日：2008年10月28日。
3、財團法人藥害救濟基金會96年年報http://www.tdrf.org.tw/e-Portal/Publish/uploadfile/AR/Annual%20Report%202007.pdf，最後瀏覽日：2008年12月7日。

、外文參考資料

(一) 書籍
Chapman, G.B., Sonnenberg, F.A. Decision making in health care- theory, psychology, and applications, Cambridge University Press (2000).
Graham, D. The law and ethics of the pharmaceutical industry, Elsevier (2006).
Katz, J. The silent world of doctor and patient. Johns Hopkins University Press, (2002).
Lee, A. Adverse Drug Reactions, Pharmaceutical Press (2006).
Lewis, M.A., Tamparo, C.D. Medical law, ethics, and bioethics in the medical office. F.A. Davis Company (1993).
Loughlin, K. and Generali, J. Prescription Drugs: Alternative Uses, Alternative Cures: Over 1,500 New Uses for FDA-Approved Drugs, Pocket Books (2007).
Manson,N.C., O’Neill, O. Rethinking informed consent in bioethics. Cambridge University Press (2007).
Parker,M., Dickenson,D. The Cambridge medical ethics workbook. Cambridge University Press (2003).
Santoro, M.A., Gorrie, T.M. Ethics and pharmaceutical industry. Cambridge University Press (2005).
Scott, R.W. Promoting legal awareness in physical and occupational therapy, Mosby (1997).

(二) 期刊文章
American Academy of Pediatrics Committee on Drugs. "Therapeutic orphans" and the package insert. 46 Pediatrics 811 (1970).
American Academy of Pediatrics, Committee on Drugs. Uses of drugs not described in the package insert (off-label uses). 110 Pediatrics 181 (2002).
Askin, D.F. Off-label therapies for newborns. Miracles or mistakes? 10 AWHONN Lifelines 160 (2006).
Beck, J.M. FDA, off-label use, and informed consent: debunking myths and misconceptions. 53 Food & Drug L.J. 71 (1998).
Bernardi, A., Pegoraro, R. The ethics of off-label use of drugs: oncology pharmacy in Italy. 33 J.Clin.Pharm.Ther. 95 (2008).
Berry, D.C., Michas, I.C., Gillie, T., et al. What do patients want to know about their medicines, and what do doctors want to tell them?: A comparative study. 12 Psychol. Health. 467 (1997).
Blumenthal, D. Doctors and drug companies. 351 N.Engl.J. Med. 1885 (2004).
Boos, J. Off label use-label off use？14 Ann. Oncol. 1 (2003).
Bradford, G.E., Elben, C.C. The drug package insert and the PDR as establishing the standard of care in prescription drug liability cases. 57 J. Mo. B. 233 (2001).
Casali, P.G. The off-label use of drugs in oncology: a position paper by the European Society for Medical Oncology (ESMO). 12 Ann.Oncol. 1923 (2007).
Choonara, I., Conroy, S. Unlicensed and off-label drug use in children: implications for safety. 25 Drug Saf. 1 (2002).
Christopher, W.L. Off-label prescription: filling the regulatory vacuum. 48 Food & Drug L.J. 247 (1993).
Cohen, J.S., Insel, P.A. The physicians’ desk reference- problems and possible improvements. 156 Arch. Intern. Med. 1375 (1996).
Conroy, S. Unlicensed and off-label drug use: issues and recommendations. 4 Pediatr. Drugs 353 (2002).
Cuzzolin, L., Zaccaron, A., Fanos, V. Unlicensed and off-label uses of drugs in paediatrics : a review of the literature. 17 Fundam. Clin. Pharmacol. 125 (2003).
Endejann, N. Is the FDA’s nose growing？: The FDA does not “exaggerate its overall place in the univers” when regulating speech incident to “off-label “ prescription drug labeling and advertising. 35 Akron L. Rev. 491 (2002).
Fritch, D.M. Speak no evil, hear no evil, harm the patient？Why the FDA needs to seek more, rather than less, speech from drug manufacturers on off-label drug treatments. 9 Mich. St. U. J. Med. & L. 315 (2005).
Gass, A., Wilson, J. Marketing off-label use to physicians: FDA’s draft (mis)guidance. 8 Am. J. Bioeth. 1 (2008).
Gazarian, M., Kelly, M., McPhee, J.R., et al. Off-label use of medicines: consensus recommendations for evaluating appropriateness. 185 Med. J. Aust. 544 (2006).
Gilhooley, M. When drugs are safe for some but not others: the FDA experience and alternatives for products liability. 36 Hous. L. Rev. 927 (1999).
Grimm, D.A. Informed consent for all! No exceptions. 37 N.M.L.Rev.39 (2007).
Gupta, M.A., Gupta, A.K. The use of antidepressant drugs in dermatology. 15 J. Eur. Acad. Dermatol. Venereol. 512 (2001).
Hall, R.F. Inconsistent government policies: why FDA off-label regulation cannot survive First Amendemnt review under greater new Orleans. 62 Food & drug L.J.1 (2007).
Hampton, T. Experts weigh in on promotion, prescription of off-label drugs. 7 J.A.M.A. 683 (2007).
Harbour, R., Miller, J. A new system for grading recommendations in evidence based guidelines. 323 B.M.J. 334 (2001).
Helm, K.A. Protecting public health from outside the physician’s office: a century of FDA regulation from drug safety labeling to off-label drug promotion. 18 Fordham Intell. Prop. Media & Ent.L.J. 117 (2007).
Henry, V. Off-label prescribing legal implications. 20 J. Legal Med. 365 (1999).
Hixson, T.J. Anti-depressants and children: suicidality, off-label use, and trial publication. 3 Ind. Health L. Rev. 201 (2006).
Jablow, V. Lawsuits fault off-label use of neurontin in suicide cases. 40-NOV Trial 12 (2004).
Johns, M.Z. Informed consent: requiring doctors to disclose off-label prescriptions and conflicts of interest. 58 Hastings L.J.967 (2007).
Johnson, S.H. Polluting medical judgment？False assumptions in the pursuit of false claims regarding off-label prescribing. 9 Minn. J.L. Sci. & Tech. 61 (2008).
Kairuz, T.E., Gargiulo, D., Bunt, C., Garg, S. Quality, safety and efficacy in the “off-label” use of medicines. 2 Curr. Drug Saf. 89 (2007).
Khamar, B. Off-label use of medicines: medical research and medical practice. 55 Indian J Ophthalmol 411 (2007).
Leghorn, J., Bropy, E., Rother, P.V. The first amendment and FDA restrictions on off-label uses: the call for a new approach. 63 Food & Drug L.J. 391 (2008).
Mitka, M. Critics say FDA’s off-label guidance allows marketing disguised as science. 299 J.A.M.A. 1759 (2008).
Morreim, E.H. Litigation in clinical research: malpractice doctrines versus research realities. 32 J.L. Med. & Ethics 474 (2004).
Nightingale, S.L. Off-label use of prescription drugs. 68 Am. Fam. Physician 425 (2003).
Noah, L. Informed consent and the elusive dichotomy between standard and experimental therapy. 28 Am. J.L. & Med. 361 (2002).
Oates, M. Facilitating informed medical treatment through production and disclosure of research into off-label uses of pharmaceuticals. 80 N.Y.U.L.Rev. 1272 (2005).
Ou Yang, C.W., Hung, H.I., Juo, C.G., et al. HLA-B*1502–bound peptides: Implications for the pathogenesis of carbamazepine-induced Stevens-Johnson syndrome. 120 J. Allergy Clin. Immunol. 870 (2007).
Pandolfini, C., Bonati, M. A literature review on off-label drug use in children. 164 Eur. J. Pediatr. 552 (2005).
Paulsen, N. The regulatory gap: off-label drug use in Canada. 63 U.T. Fac. L. Rev. 183 (2005).
Pinxten, W., Nys, H., Dierickx, K. Regulating trust in pediatric clinical trials. 11 Med. Health Care Philos. 439 (2008).
Politis, P. Transition from the carrot to the stick: the evolution of pharmaceutical regulations concerning pediatric drug testing. 12 Widener L. Rev. 271 (2005).
Psaty, B.M., Ray, W. FDA guidance on off-label promotion and the state of the literature from sponsors. 299 J.A.M.A. 1949 (2008).
Radley, D.C., Finkelstein, S.N., Stafford, R.S. Off-label prescribing among office-based physicians. 166 Arch. Intern. Med. 1021 (2006).
Ratner, M., Gura, T. Off-label or off-limits？ 26 Nat. Biotechnol. 867 (2008).
Riley, J.B., Basilius, P.A. Physicians' liability for off-label prescriptions. 21 Nephrol. News Issues 43 (2007).
Roberts, R., Rodriguez, W., Murphy, D., et al. Pediatric drug labeling: improving the safety and efficacy of pediatric therapies. 290 J.A.M.A. 905 (2003).
Roth, S.H. Drug use, the package insert, and the practice of medicine. 142 Arch. Intern. Med. 871 (1982).
Salbu, S.R. Off-label use, prescription, and marketing of FDA-approved drugs: an assessment of legislative and regulatory policy. 51 Fla. L. Rev. 181 (1999).
Stafford, R.S. Regulating off- label drug use- rethinking the role of the FDA. 358 N. Engl. J. Med. 1427 (2008).
Stoffelmayr, K.J. Products liability and “off-label” uses of prescription drugs. 63 U. Chi. L. Rev. 275 (1996).
Sutcliffe, A.G. Testing new pharmaceutical products in children. 326 B.M.J. 64 (2003).
Temple, R. Legal implications of the package insert. 58 Med. Clin. North Am. 1151 (1974).
Tietz, G.F. Informed consent in the prescription drug context: the special case. 61 Wash.L.Rev. 367 (1986).
Tomaszewski, C. Off-label: just what the doctor ordered. 2 J. Med. Toxicol. 87 (2006).
Turner, E.H., Matthews, A.M., Linardatos, E., et al. Selective publication of antidepressant trials and its influence on apparent efficacy. 358 N. Engl. J. Med. 252 (2008).
Turner, S., Nunn, A.J., Fielding, K., Choonara, I. Adverse drug reactions to unlicensed and off-label drugs on paediatric wards: a prospective study. 88 Acta Paediatr. 965 (1999).
Wagner, M. Off-label use of misoprostol in obstetrics: a cautionary tale. 112 B.J.O.G 266 (2005).
Waxman, H.A. The lessons of Vioxx-drug safety and sales. 352 N.Engl.J.Med. 2576 (2004).
Wilsker, J. A. One-half Phen in the morning/ One Fen before dinner: a proposal for FDA regulation of off-label uses of drugs. 6 J.L. & Plo’y 795 (1998).
Woolf,C.J., Mannion,R.J. Neuropathic pain: aetiology, symptoms, mechanisms, and management. 353 Lancet 1959 (1999).

(三)、網路資料
1、FDA information sheets, "Off-Label" and Investigational Use of Marketed Drugs, Biologics, and Medical devices, http://www.fda.gov/oc/ohrt/irbs/offlabel.html，最後瀏覽日：2008年9月26日。
2、Guidance for Industry: Good Reprint Practices for the Distribution of Medical Journal Articles and Medical or Scientific Reference Publications on Unapproved New Uses of Approved Drugs and Approved or Cleared Medical Devices，http://www.fda.gov/oc/op/goodreprint.html，最後瀏覽日：2008年11月29日。