藥品仿單標示外使用（Off-Label Use）之民事責任與藥害填補機制

Civil Liability and The Relief Mechanism for Adverse Drug Reactions in Off－Label Use of Drugs

系所名稱：科技法律研究所 學位別：碩士 畢業學年：97年 指導教授：侯英泠 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.