A study of regulations for Off –Label Uses of prescription drugs in Taiwan

• Main Authors: Chien-YuLiao, 廖建瑜
• Other Authors: Ing-Ling Hou
• Format: Others
• Language: zh-TW
• Published: 2013
• Online Access: http://ndltd.ncl.edu.tw/handle/43037820250964240985

博士 === 國立成功大學 === 法律學系 === 101 === In the United States, Japan, and Taiwan, the drug administration authority（FDA, PMDA, TFDA）only allows new drugs in the market after pharmaceutical industries prove that they are both safe and effective. The agency does not approve a new drug for general use. Therefore pharmaceutical manufacturers must provide full three-phased clinical trial reports of investigations into the drug's safety and effectiveness, the comp onents and production methods used to manufacture the drug, and specimens of the labeling proposed to be used for the drug.The drug administration authority reviews the proposed “labeling” for the drug, which includes indications, usages, patient populations, contraindications, warnings, dosages, side effect, pharmacology and other drug data, all proposed claims about the drug's risks and benefits. If the agency agrees that a new drug is safe and effective for its intended use, as reflected in the marketing application, it approves the application and the drug's professional labeling. The uses that are approved by the agency are sometimes referred to as “on-labeled uses” because they appear in the drug's approved labeling. Uses that do not appear in the labeling and are not approved by the agency are referred to as “off-label use”. Once a drug has been approved by the agency and placed on the market, physicians may prescribe it for any purpose. The use of a drug “off-label use” is therefore common in and accepted as beneficial by the health care community. Examples of off-label uses include using a drug to treat a condition for which it is not indicated, treating an indicated condition with different doses than those specified on the label, and prescribing a drug for a different patient population than that indicated. Off-label uses are especially prevalent when the cancer (such as lung cancer) has reached an advanced stage. These uses are also particularly prevalent among conditions commonly diagnosed in children (if a drug has only been approved to treat adults), where pharmaceutical manufacturers are justifiably reluctant to subject children to experimental clinical trials. This article argues that physicians may have clinical freedom, exercising reasonable medical judgment, to prescribe drugs for off-label use, which fosters innovation, leading to the development of new treatments. Besides, according to characters of off-label use of prescribing drugs, off-label uses of drugs should not be regarded as a “new drug （or investigational drug）or human experiment ” that falls under Pharmaceutical Affairs Acts regulation in Taiwan. However, in some instances, scholars have investigated off-label uses and found them to be ineffective or dangerous. Therefore, a physician who engages in off-label uses has the responsibility to be well informed about the drug, and to base the decision to use it on evidence-based medicine. In Taiwan, Department of Health claims that physicians have a legal obligation to inform their patients about the material risks associated with the drug, including the use of a drug in a manner that was not approved by the TFDA. The remarkable differences related to the scope of disclosure that physicians prescribe off-label uses between our current regulations and judicial cases are made to compare with those of the United States. In addition, compare to Japan’s Adverse Drug Reaction Relief System, section 13（h）of the Drug Hazard Relief Act of 2011 still inappropriately constitutes restriction against the remedy for adverse drug reactions of prescribing drugs off-label in Taiwan. Next, although proof of a departure from the recommendations in a drug's labeling is not alone sufficient to prove a breach of the standard of care, this article adopt that a drug’s label can provide significant assistance in identifying the physician's standard of care in a medical malpractice case. Accordingly, this article argues that a prescription drug's labeling is admissible to assist the judge to determine whether the off-label use of prescription drugs presented an unacceptable risk to the patient. As mentioned above, however, because innovative off-label medication use（defined as prescribing with reasonable rationale for use, but insufficient evidence to allay safety and effectiveness）is not a standard therapy and a common challenge to medical practice, such use is easily considered as a violation of the standard of care. This article argues that courts shall apply the respectable minority rule in evaluating a physician's prescribing off-label use of drugs. On the other hand, by the development of pharmacogenomics, physicians also may be subject to malpractice liability for failing to to provide pharmacogenomic screening tests to ascertain the safety of off-label use. Pharmacogenomics has become a tool to evaluate the safety and effectiveness of off- label use of prescription drugs. Finally, in Taiwan, Pharmaceutical industries have had close financial ties to physicians. They create financial relationships that influence physicians’ independent judgment and rational prescribing by offering physicians financial incentives to prescribe their drugs. They reimburse attending physicians for registration fees and travel expenses（such as meals, hotel expenses） for professional meetings and continuing medical education; and provide gifts（such as pens, sample drugs, medical and office supplies）to physicians as enticements for writing prescriptions for their drugs for both approved and off-label uses. They also attempt to promote prescription Drugs for off-label uses through CME and professional meetings by choosing topics they support. Taiwan lacks a statute that oversees gifts and Pharmaceutical industries funding for all physicians. It relies on voluntary medical organization conflict of interest guidelines and Pharmaceutical Research and Manufacturers Association codes of conduct. This Article proposes using various strategies to solve conflicts of interest. It can create clearly ethical standards to guide conduct; or disclose conflicts of interest. In addition, physicians have a contractual obligation（or fiduciary duty）for their patients to disclose that they have received gifts or compensation from Pharmaceutical industries. By recognizing this legal duty, physicians will ensure that the well-being of their patients remains their focus and thereby return the practice of medicine to what should be its patient-centered focus. Taiwan lacks to impose constraints that affect off-label use through enforcement actions under the False Claims Act (“FCA”) against pharmaceutical manufacturers for off-label marketing practices This article also discusses that the control strategy - based on the False Claims Act and regulation off-label promotion. As such, regulation revision proposals should be considered appropriate solutions to Off-Label promotion and marketing problems.