“After decades of off-label use of drugs, a conclusion has finally been reached.” Sun Zhongyi, an expert from the National Rational Drug Use Monitoring Office of the Chinese Hospital Association, expressed emotion to the Health Knowledge Bureau.
From March 1, 2022, the “Physician Law of the People’s Republic of China” will be implemented, and the new version of the Physician Law will for the first time include the “off-label medication” under the diagnosis and treatment guidelines and evidence-based medicine into the law.
Article 29 of the New Physician Law first affirms that physicians should “follow the guidelines for clinical application of drugs, guidelines for clinical diagnosis and treatment, and drug instructions for rational drug use”, but when there is no effective or better Under special circumstances such as treatment methods, “after obtaining the patient’s explicit informed consent”, the drug usage that is not specified in the drug insert but has evidence-based medical evidence can be used for treatment.
This means that the mature usage of some drugs that have been approved abroad may be formally clinically applied in China. For immune drugs such as PD-1, it will be able to legally expand the scope of application.
Sun Zhongshi thinks: “The introduction of the new version of the Physician Law is very good, I agree with both hands, and the doctors are relieved.”
Give the doctor a peace of mind
Ai Fen, director of the emergency department of Wuhan Central Hospital, still remembers a lost lawsuit in the hospital: a certain contraindication was marked on the drug insert, but the doctor chose to use it beyond the instructions after weighing it, and finally the patient had an accident Yes, the two sides went to court.
Many doctors have been in the dock for off-label use. Sun Zhongshi introduced that in this case, hospitals generally choose to pay medical expenses to settle.
Off-label drug use includes off-indication, off-target population, off-dose, route of administration, etc., also known as off-limit medication. This is very common in clinical practice, and some medicine doctors who have used it for many years have their own usage.
Jiang Fan, an attending physician in the Department of Hematology of Beijing Jingdu Children’s Hospital, gave an example. Hematologists would let some patients take gentamicin injection before hematopoietic stem cell transplantation to clean up intestinal bacteria. This is an off-label drug on the route of administration; ruxolitinib, which is used to treat myelofibrosis, will be given to patients during anti-rejection, which is an off-label drug.
For innovative drugs, off-label use is more common.
Sun Zhongshi introduced that, in order to get approval faster and save money, new drugs generally only do clinical trials for one or two indications, and the pursuit is fast launch. But in terms of pharmacology, these drugs can theoretically treat a variety of diseases, and doctors can often find more curative effects and use them clinically in combination with the actual situation.
In the past, these usages were illegal on closer inspection. Article 14 of the “Measures for the Administration of Prescriptions” issued by the former Ministry of Health stipulates that: Physicians shall issue prescriptions according to the needs of medical treatment, prevention and health care, in accordance with the standards of diagnosis and treatment, the indications and pharmacological effects of drugs in the drug inserts.
The gap between law and practice is too great, putting off-label drug use at legal risk. Especially after 2018, a large number of innovative drugs were launched, and off-label medication was widely available in major hospitals in China. After adverse drug reactions, patients sued doctors or hospitals from time to time, which made off-label medication a topic of controversy in the medical community. .
“In order to cure patients, many doctors will take risks. But if there is a problem and they want to sue, they will sue.” Jiang, chief physician of the Department of Hematology, Beijing Jingdu Children’s Hospital Fan told the Health and Knowledge Bureau.
Sun Zhongshi learned that in order to reduce risks, some hospitals are cautious, and some doctors are afraid to take a step forward.
The United States, Germany and other countries have long had legislation related to off-label drug use. Sun Zhongshi believes: “Increasing an indication in the clinic is equivalent to developing a new drug, which is a major event that is beneficial to the country, the people, and the society.”
Ai Fen told the Health and Knowledge Bureau that after the implementation of the new Physician Law, if off-label medication with evidence-based medical evidence leads to legal conflicts, doctors can get better protection.
Clinical opportunities for innovative drugs
Drug instructions lag behind in the face of ever-changing treatment regimens, which is the understanding of many doctors.
“The new regulations are very realistic and should have come out a long time ago.” Ruan Xiangyan, director of the Department of Endocrinology, Beijing Obstetrics and Gynecology Hospital affiliated to Capital Medical University, believes that her hospital has always had specific regulations on off-label medication. Management methods and process requirements need to be filed in advance, and patients or their family members must sign an informed consent form.
However, these measures are only to prevent risks as much as possible and have no legal basis. Doctors have long expected legal protections for off-label drug use.
Innovative drug companies are more looking forward to the moderate liberalization of off-label drug use. Take PD-1 as an example. This type of drug has the reputation of “broad-spectrum anti-cancer drug”. All have certain curative effects, and many varieties have been approved for a large number of indications in Europe and the United States and other countries. However, when it is used clinically in China, there are still risks for doctors to use “super-appropriate” drugs.
Although the law has been liberalized, there are still strict requirements for off-label use. Wu Jinchang, the head of the oncology department of the Second Affiliated Hospital of Xuzhou Medical University, introduced that there are two prerequisites for off-label drug use: first, the medication plan is reasonable and the interests of the patient are the premise; second, the medication behavior conforms to pharmacology,The therapeutic value is higher than other programs.
In April 2021, Zhang Yu of Peking University Third Hospital questioned Dr. Lu Wei’s treatment plan of Shanghai Xinhua Hospital, arousing public attention. In the end, the Shanghai Municipal Health Commission and the Shanghai Changning District Health Commission imposed administrative penalties on Lu Wei, Shanghai Xinhua Hospital and the institutions involved respectively.
In this incident, one of the reasons for Lu Wei’s administrative punishment was “failure to fulfill the obligation of notification according to regulations”. The basis of punishment is consistent with the legislative spirit of “doctors obtain explicit informed consent of patients” in the new Physician Law. Sun Zhongshi believes that the new Physician Law solves the disputes between Zhang and Lu from a legal perspective: just by comparing the laws and regulations, it can be clear which practices are legal.
But the release of off-label drug use, after all, has opened a new window for drug companies. Sun Zhongshi emphasized that doctors themselves should deepen their studies and improve their theoretical level; pharmaceutical companies should also actively carry out new research on the basis of more clinical experience.
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