Release date: 2016-08-22
Cancer patients go to the United States behind the "being a white mouse"
Three years ago, the orthopedic surgeon Li Minglei felt that the pain in his left chest was getting heavier and he decided to have a CT examination. After finding a nod of about 4 cm in the lungs, he diagnosed himself - cancer.
Just last weekend, Li Minglei ran 5 kilometers on the Charles River in Boston, USA. Two years ago, he was pushed off the plane by his wife. After being diagnosed with stage IV lung cancer, a doctor in Beijing told him that his life may be only half a year left.
Today, Li Minglei regularly comes to the Massachusetts General Hospital affiliated with Harvard University to treat cancer. The improvement of his condition may not be called a medical miracle, but a common case among many patients who go to the United States to treat cancer. Of course, he was also fortunate enough - the EGFR19 gene mutation allowed him to enter the third-generation targeted drug clinical trial, and two weeks after the start of the trial, the turnaround appeared.
According to market research results of the Shenguo family, a Beijing-based medical service provider, there are about 3,000 patients in China who go to the United States each year, 70% of whom are cancer patients. Participation in clinical trials is not the first choice for patients with existing drugs. However, once patients become resistant to anti-tumor drugs, clinical trials of new drugs in the United States are likely to be their last fight.
At the famous MD Anderson Cancer Center in the United States, hundreds of clinical trials are conducted every day. More than 90% of cancer patients will take the initiative to ask doctors: “Can I participate in clinical trials of new drugs?†Today, there are also many from China. Referral to patients with advanced cancer for treatment.
67% of treatment options were changed
When 38-year-old Li Minglei was visiting a well-known top three hospital in Beijing, the doctor here told him that he belonged to “stage IV of lung cancer and could only be treated conservatively and had no chance to undergo surgeryâ€. He knows that the staging given by the doctor means that he is suffering from advanced lung cancer with distant metastasis. This made him fall into despair. In the next two courses of chemotherapy, Li Minglei's body was weakened by chemotherapy drugs, and eventually he could not turn over himself.
According to the World Health Organization (WHO) report, lung cancer is the most common malignant tumor in the world, accounting for 19.4% of cancer deaths. Lung cancer is also the leading cause of death of malignant tumors in China due to poor tobacco control and other reasons. It is estimated that by 2025, the number of lung cancer patients in China will reach 1 million, making it the country with the largest number of lung cancers in the world.
Although the 5-year survival rate of lung cancer in China is 16.1%, which is very close to 17% in the United States, in terms of the overall level of cancer treatment, the incidence of cancer in China is close to the world level, and the mortality rate is higher than the world level. The data show that the 5-year survival rate of cancer patients in the United States is 60% to 70%, while the 5-year survival rate of Chinese cancer patients is only about 30%.
Biopsy and genetic testing for Li Minglei found the exact cause of cancer - EGFR19 gene mutation. He said: "In the country, this situation is almost unresolved. But in the United States, there was already a second-generation specific drug, afatinib against the EGFR19 gene mutation, and the third-generation drug AZD9291 has also been clinically tested. Period." So, he decided to go to the United States to "take a chance."
After a series of very professional medical records, Li Minglei chose to visit the Massachusetts General Hospital, which is among the best in the United States. After going to the United States according to the appointment time, he went to the hospital to see the doctor the next day after arriving in Boston. The American doctor called him "Dr. Li" and got up and shook hands with him. The oncologist also gave him a chest surgeon to discuss the treatment plan.
Different from the opinions of domestic doctors, American doctors told Li Minglei that after the targeted drug treatment was effective, the remaining primary lesions could be treated again.
Cai Qiang, founder and chairman of Shengnuo, told China Newsweek (WeChat ID: china-newsweek) that 67% of Chinese patients' treatment plans were changed after going to the United States for medical treatment. One of the reasons is that clinical medicine in the United States is developing in the direction of “precise medical careâ€. A patient is often treated by doctors from multiple disciplines. Under this concept, they believe that “the treatment plan for any two lung cancer patients is identical".
Another reason for the change in treatment options is the difference in medicines. “A large number of cancer patients have chosen a new treatment plan in the United States because our latest drug is listed in the US in 2011, the United States in 2012, 2013... We did not have the drug until 2016.â€
For example, Cai Qiang said that they introduced a skin cancer patient to the United States to see a doctor. As a result, doctors in the United States found that the medicine used in China was 30 years ago in the United States.
In fact, Chinese doctors have no mistakes in formulating treatments based on domestically marketed drugs, but the drugs are not advanced enough. In the case of backward development of new drugs, it is difficult for Chinese doctors to have no shortage of rice. After a patient achieved satisfactory treatment in the United States, he said: "It is like the United States is using the iPhone6. We are still using the iPhone 3. Of course, this is just an inappropriate metaphor. On the mobile phone, the Chinese are completely Unwilling to fall behind."
Zhang Tianyin, a patient with cutaneous melanoma, was treated in a top three hospital in Beijing. His doctor, Li Tao, suggested that he could consider going to the United States for clinical trials. Li Tao, who just attended the full annual oncology conference, told China Newsweek (WeChat ID: china-newsweek): "At the time we knew that the United States had a new drug for melanoma, and was doing phase III clinical trials, and I The results of Phase II and Phase II trials show that the results are very good. However, there are no drugs or clinical trials in China. For patients who are eligible to go abroad for medical treatment, I would recommend them to go abroad to choose the latest drug treatment."
Fortunately, Zhang Tianyin meets the admission criteria for clinical trials. After entering the trial group, he has been receiving treatment. Now, for six or seven years, he is very satisfied with the results. Now, he does not feel that he is undergoing trials and treats this process as a complete treatment plan.
Approval of backlog of 17,000 pieces
The backwardness of the development of new drugs in China is an indisputable fact. According to the US Clinical Trial Registry, as of October 2015, there were 201149 clinical trials registered worldwide, of which 48.53% were conducted in the United States, and only 9.75% of clinical trials were conducted in China.
Taking anti-lung cancer drugs as an example, the United States has begun clinical trials of the fourth-generation targeted drugs, while China still stays on the first-generation targeted drugs. This means that once a patient develops resistance, patients treated in China will have no other medicine to choose from.
The first step in the approval of new drugs in China is to approve clinical trials. The “Regulations on the Administration of Drug Registration†issued in 2007 has time limits for each examination and approval process. The time for approval of clinical trials of new drugs should not exceed 90 days, but in fact, it comes from the State Food and Drug Administration (hereinafter referred to as food and medicine). According to the data of the Bureau of Supervision, in 2014, the average evaluation time for clinical trials of Chinese 1.1 new drugs, 3.1 new drugs and 6 new drugs was 14 months, 28 months and 28 months.
In the United States, after the applicant filed a new drug clinical trial application with the US Food and Drug Administration (hereinafter referred to as the FDA), if the FDA did not receive a decision to suspend the clinical study within 30 days, it would mean approval.
Compared with the US “extension and strictness†approval system, China is just the opposite. The applicant must pass the two-level examination and approval of the national and provincial drug regulatory authorities, and the clinical trial can only be carried out after obtaining the approval.
Chinese clinical trials require more detailed information on the applicant's pharmaceutical research data. All materials should be submitted before the Phase I clinical trial and all materials should be filled in one time within 4 months. But in fact, for clinical trials of new drugs, many research data are difficult to submit before Phase I clinical trials. In the United States, this information can be submitted gradually as the research plan progresses.
In order to improve the efficiency of FDA work and the quality of drug review and approval, the United States issued the "Prescription Drug Reporter Payment Act" in 1992, which requires: new drug applicants can pay a certain application fee to the FDA, the annual fee for the prescription drug production site, etc. It also requires the FDA to complete the review and approval work within a limited time. This revenue allows FDA to hire more experts and reviewers in different fields and update information technology facilities, greatly reducing approval time.
The FDA, with more than 9,300 employees, is one of the largest government agencies in the US federal government. But it is different from the semi-commercial model of the United States. According to public data, in 2014, the administrative establishment of the China Food and Drug Administration was 345, of which only 10 were auditors. Although the Food and Drug Administration receives certain fees when accepting applications for drug registration, all of these costs are turned over to the state treasury and cannot be used to optimize the review resources.
According to the “2015 Drug Evaluation Report†issued by the Food and Drug Administration, although about 120 drug testing center staff completed the 9601 review tasks in 2015, there are still 17,000 backlogs.
In the case of insufficient manpower, new drugs, vaccines, and medical devices in the Chinese market lag behind Europe and the United States. For example, the first HPV vaccine to prevent cervical cancer was approved by the FDA in 2006 and entered the market in many countries. However, due to the delay in the approval of the vaccine in China, many Chinese women choose to leave the country to vaccinate in private clinics. . Until July 18 this year, the first HPV vaccine was approved for listing in China, and this approval process has been going on for nearly 10 years.
In order to speed up the review of drugs for the treatment of critical illness, the FDA has established four special approval channels, including fast-track, priority review, accelerated approval, and breakthrough therapy. Cai Qiang said that these special channels "the speed of approval is much faster than the conventional, sometimes only three months."
In 2012, the United States revised the Prescription Drug Reporter Payments Act for the fifth time, emphasizing the improvement of the FDA's rapid approval channels, including the review of such drug reviewers, and the priority to review orphan drugs. The third-generation targeted drug AZD9291 was launched in November 2015, which relied on a rapid approval channel.
Sino-US clinical trials vary widely
On November 6, 2014, Li Minglei took the first second-generation targeted drug, afatinib, which was already in the US for one year and has not been introduced in China. Li Minglei clearly remembers that after 5 weeks of taking the drug, PET-CT showed that the metastatic lesions on the spine and ribs disappeared, and the primary lung lesions were also reduced by 60%.
But in less than a year, the doctor discovered that Li Minglei had developed resistance to afatinib, and the puncture showed that he had a mutation in the drug resistance gene. However, this coincides with the entry criteria for the AZD9291 clinical trial, when the trial was conducted to Phase III.
It took only one month for Li Minglei to apply for the trial and formally enrolled. Before the application, the doctor informed him of the risks and possible side effects of the drug. He did not hesitate to sign the authorization agreement.
This authorization agreement is also subject to review by a third-party ethics committee.
In China, the ethics committee is attached to the hospital and the review is also in the form. Cai Xuliu, general manager of Beijing Jingwei Legend Medical Technology Co., Ltd., told China Newsweek (WeChat ID: china-newsweek): "Sometimes, doctors will emphasize free medication, but not fully inform the risk of medication."
As the director of this third-party auditing company, Cai Xuliu found that some hospitals will group patients together, and a doctor will tell dozens of patients about the risks and benefits of the trial, and then let the patient decide whether to sign the authorization consent form. “Doing so may cause patients to influence each other.â€
In the United States, clinical trial medication is free, but the cost of patient examinations will be higher than usual. Therefore, patients participating in clinical trials often get more detailed consultations from doctors, and medical staff are willing to spend more time fully understanding patient compliance and fit. The doctor will also leave the patient with an emergency contact, and the nurse will call the patient from time to time to ensure that the patient's medication, adverse reactions, and help the patient fill out the test form.
However, in China, most of the leading clinical trials are doctors in qualified top three hospitals, who are usually chief physicians and the busiest group in the entire hospital. "In fact, as long as the researchers can fully participate in the clinical trials, they will do very well. But basically, they rarely have time to participate." Cai Xuliu said.
Since there are only more than 400 medical institutions in China that can conduct clinical trials, mainly the top three hospitals, and drug development and sales rely on hospitals, which makes Chinese pharmaceutical companies dare not offend these hospitals and doctors.
Unlike the weak position of pharmaceutical companies in China, most of the clinical trials in the United States are dominated by pharmaceutical companies. “Because any doctor in the United States can participate in clinical trials.†Wang Changyu told China Newsweek (WeChat ID: china-newsweek), who was the R&D director of the Pfizer Immunity Department in the United States.
Cai Xuliu said: "Many clinical trials in China rely on pharmaceutical R&D contract outsourcing services (CRO) and hospitals to design together, and some pharmaceutical companies are not as good as CRO." Some pharmaceutical companies may even contract with CRO. Note: Clinical trials must be guaranteed.
Today, Wang Changyu founded Huafu Biotechnology Co., Ltd. in Chengdu. He feels that trust is the biggest gap between Chinese and American clinical trials. "The United States pays attention to credit. The only review when filing is to look at the information you declare, conclusions, inferences about whether there are errors, and will not question your test procedures and results."
Because in the United States, once the trial protocol is determined, very minor changes in procedures need to be proactively reported to the FDA, even if a patient's infusion time changes from 1 hour to 2 hours. However, it is not uncommon for Chinese doctors to make up their signatures, post-repair records, and even post-tests.
Wang Changyu even heard, "What kind of data is needed for the drug companies, what kind of data the hospital can give you." According to an insider, some clinical trials will directly modify the original data in order to ensure the drug is effective. Some hospitals will “drop†the control group and the experimental group; some researchers will directly modify the patient's medical record; and some hospitals will “larger†the size of the tumor before the patient participates in the clinical trial. The final result When the evaluation is carried out, the amount of the drug is “small†and the efficacy of the drug is “appearedâ€.
Source: China News Weekly
Weighing Scale,Weighing Inidcator,Weighing Load Cell,Weighing Equipment,Electronic Scale,Weighing Controller
Changzhou Satidi Import and Export Co., Ltd. , https://www.guanjiejts.com