What you need to know about cancer treatment: Experts explain the use of off-label drugs in detail
A few days ago, Leng Jiahua, director of the Medical Insurance Department of Peking University Cancer Hospital and a surgeon at the Gastrointestinal Cancer Center, said at a media communication meeting held by the China Medical Insurance Association that the drug instructions are legally effective and doctors should prescribe drugs in accordance with the drug instructions, but The phenomenon of using drugs beyond the instructions is not uncommon in actual clinical work, and it cannot be said to be wrong behavior.
Recently, public opinion focused on the problem of overtreatment in tumor treatment, which also involves the category of off-label medication.
The "Prescription Management Measures" formulated in accordance with the "Professional Physician Law" and "Drug Administration Law" and other relevant laws and regulations clearly stipulate that physicians should follow the medical, preventive, and health care needs, follow the diagnosis and treatment specifications, and the drug indications and pharmacological effects in the drug inserts , Usage, dosage, contraindications, adverse reactions and precautions.
Why does the law clearly stipulate that doctors should prescribe drugs according to the drug inserts, but there are off-label medications in the clinic?
To this end, reporters from China Youth Daily and China Youth Daily interviewed many experts in the industry, and conducted preliminary discussions on the rationality of off-label use of drugs, possible problems and related supervision methods.
Why off-label medication cannot be avoided
In April 2015, the "Adverse Drug Reactions" magazine published the "Expert Consensus on Off-label Drug Use" (hereinafter referred to as "Expert Consensus") formulated by the Drug Risk Management Group of the Therapeutic Drug Monitoring Research Professional Committee of the Chinese Pharmacological Society. , Off-label medication refers to the usage of the drug, such as the indication, dosage, course of treatment, route, or population, that is not within the scope of the drug specification approved by the drug regulatory authority.
As for the reasons for the existence of off-label drugs, Leng Jiahua said that the revision of the legally effective drug label is the same as the revision of the law. It takes a certain period of time. Sometimes it is difficult to synchronize with clinical medication, especially difficult to synchronize with some new indications. development of.
For example, during the fight against the new crown pneumonia epidemic, when there was no indication for the use of the virus at the time, preliminary clinical evidence found that some traditional old drugs may be effective against the new crown virus and can be used clinically. "This is the so-called off-label drug." A situation.
Shao Qinshu, Honorary Director and Chief Physician of Gastrointestinal Surgery Department of Zhejiang Provincial People’s Hospital, and member of China’s First National Colorectal Tumor Quality Control Expert Committee, said frankly in an interview with a reporter from China Youth Daily and China Youth. realistic".
Regarding off-label medication in tumor treatment, Shao Qinshu said that at present, the pathogenesis of tumors is not clear in the medical community. It is only known that it is caused by multiple factors such as lifestyle, genetics, and environment, but which factor is the dominant factor. Not sure.
This has led to the fact that the drugs used to treat tumors often fail to meet clinical treatment. Shao Qinshu said: "Therefore, when treating tumors, there is currently no drug that is 100% effective, and chemotherapy is only effective for 30% to 60% of patients."
One situation is that when the existing drugs cannot meet the actual clinical needs, some doctors will try to use the drugs off-label.
Shi Luwen, a professor in the Department of Pharmaceutical Affairs and Clinical Pharmacy of Peking University School of Pharmacy and director of Peking University’s International Research Center for Pharmaceutical Management, said that doctors are also helpless. There are not many diseases that humans can really cure, exceeding 10% of existing diseases. The doctors are dealing with a complicated person, not a separate organ, nor a special object. They also want to do everything possible to help the patient relieve the pain. That's why there are some doctors' off-label medications."
In addition, Shao Qinshu also introduced that most drugs will be further optimized and explored after they are marketed, which causes a disconnect between clinical practice and drug instructions, and the approval of newly explored indications requires clinical trials that meet the registration requirements. This clinical trial The cost is high, and companies often lack motivation to apply.
Another situation is that some drug inserts are incomplete or unclear, and even the inserts of the same drug produced by different companies are not the same, which is also an objective reality that leads to the occurrence of off-label use of drugs.
Shao Qinshu said that when some foreign-developed drugs enter the Chinese market, because of practical considerations, companies often only declare part of the indications to the State Food and Drug Administration, and the undeclared indications limit the scope of clinical use.
Off-label medication is common
Shao Qinshu gave an example to reporters from China Youth Daily and China Youth Daily about his off-label use of drugs in the process of treating tumor patients: For example, a drug commonly used in the treatment of pancreatic cancer, paclitaxel, is very effective.
Both the cancer treatment guidelines formulated by the National Comprehensive Cancer Network and the treatment guidelines formulated by the Chinese Clinical Oncology Association recommend albumin paclitaxel for the treatment of pancreatic cancer, "the level of evidence is also very high."
However, the scope of indications marked in the paclitaxel instructions is only for breast cancer treatment.
In addition, Shao Qinshu said that after major upper abdomen surgeries such as liver cancer and pancreatic cancer, patients often develop gastroparesis for unknown reasons (the stomach stops peristaltic—reporter's note), and can’t eat for more than one week for more than three months. So far, there is no effective treatment method. In clinical practice, fasting, gastrointestinal decompression, acupuncture, gastroscopy stimulation and other symptomatic treatment measures are often used. "In response to this situation, we clinically use erythromycin to stimulate the stomach and cause vomiting. Side effects, given to patients by intravenous infusion, have achieved obvious results for more than ten years. It has been highly recognized and widely promoted by colleagues, but this kind of treatment is indeed off-label medication."
The "Expert Consensus" clearly pointed out that in clinical drug treatment, off-label use of drugs is common.
A set of data is cited in the "Expert Consensus": In the United States, 21% of approved drugs have off-label use; this situation accounts for 7.5%-40% of adult drugs and 50% of pediatric drugs. 90%.
At the second fair drug use conference held in June 2012, Chen Xiaoyuan, the former senior reviewer of the Drug Evaluation Center of the National Medical Products Administration, also cited this set of data in the report.
Why is off-label medication in pediatrics so common?
Shi Luwen explained to a reporter from China Youth Daily and China Youth Daily that there are fewer drugs for children, because clinical trials for children’s drugs are more difficult to do, so there are not many children’s drugs that can be approved.
In addition, there are more cases of off-label medication in elderly patients, because elderly patients often have multiple organ disease, and the pathogenesis is more complicated. Sometimes, off-label medication may occur in order to rescue patients.
At the same time, the treatment of patients with rare diseases will also encounter off-label medication.
Shi Luwen said that less than 10% of patients with rare diseases can be accurately diagnosed, and even fewer are available if medicines are available. "But these patients can't be ignored and they have to be treated." It is inevitable to use drugs that are out of specification.
Experts call for the development of guidelines for off-label medication as soon as possible
Shao Qinshu told reporters that in addition to the above, there are some pharmaceutical companies that deliberately induce hospitals and doctors to use drugs beyond the instructions for commercial purposes. "Strict management of such behaviors is required." This is also one of the reasons why the use of off-label drugs is controversial. .
At present, only a few countries in the world, such as the United States, Japan, the Netherlands, and New Zealand, allow off-label drugs from the legal level. Most countries, including China, have no clear legal regulations for off-label drugs.
Shao Qinshu told reporters that the "Expert Consensus" is my country's first specification for the use of off-label drugs issued by a professional organization.
The "Expert Consensus" restricts the use of off-label drugs from five aspects: 1. The purpose of off-label use of drugs can only be for the benefit of patients; second, off-label use of drugs should weigh the pros and cons to maximize the benefits of patients; The use of drugs in the drug insert should be supported by reasonable medical evidence; 4. The use of drugs beyond the drug insert must be approved and filed by the relevant department of the hospital; 5. The use of drugs beyond the drug insert must protect the patient's right to know and respect their right to make decisions.
The reporter learned that, usually, the top three hospitals have a special supervision process for off-label drugs.
Shao Qinshu introduced to reporters the special management process of the Zhejiang Provincial People’s Hospital for off-label medication: the hospital’s Pharmaceutical Affairs and Medical Affairs Department drafted the off-label medication management system, and the clinical department filled out an application form for off-label medication, accompanied by corroborative medical evidence. At the same time, clinical pharmacists from the Pharmaceutical Affairs Department were invited to evaluate the level of evidence, and then submitted to the Pharmaceutical Affairs Committee for discussion.
After the discussion is passed, it needs to be filed in the hospital, and in actual clinical use, a written informed consent form must be signed with the patient.
If an unapproved off-label medication needs to be temporarily used due to the patient’s condition, the attending physician needs to consult a clinical pharmacist and superior physician, and then implement the specific implementation based on the unified opinion after the consultation.
In clinical practice, off-label use of drugs in the treatment of intractable diseases is more common, and basic hospitals may have limited solutions to intractable diseases. Historical records suggest that these intractable disease patients should be referred to higher-level hospitals. To deal with it, “large tertiary hospitals have sufficient technical capabilities to regulate off-label medication. In addition, if an accident occurs, they are also capable of rescue.” In other words, off-label medication should be restricted to high-level hospitals with sufficient technical capabilities as much as possible.
Shi Luwen added that to realize this plan requires a relatively complete referral process and the construction of a medical system, which also requires huge and systematic work to complete.
Although the country has not regulated the use of off-label drugs at the legal level, Shi Luwen believes that there is room for maneuverability at the technical level.
As a clinician, Shao Qinshu said that in order to protect patients’ medication safety and avoid occupational risks for medical institutions and medical staff, he hopes that functional departments will act as the main management body to organize relevant industry associations and academic institutions to provide reliable advice on off-label medication. According to medical evidence, formulate off-label medication guidelines, and issue government-level management principles or regulatory documents as soon as possible.
"In addition to off-label use of drugs, other diagnosis and treatment behaviors will also have unconventional exploration." Shi Luwen said that based on the consensus reached by some clinical experience, there will still be problems in the face of differentiated individuals.
Medicine is a highly practical subject, and it is in these unconventional explorations that medical science has made progress.
China Youth Daily·China Youth Daily reporter Liu Changrong Source: China Youth Daily