2024-09-17
한어Русский языкEnglishFrançaisIndonesianSanskrit日本語DeutschPortuguêsΕλληνικάespañolItalianoSuomalainenLatina
judging from the online listing situation, the hotly discussed online "large-scale withdrawal of original research drugs from the domestic network" does not match the actual situation. the three dosage forms of imported azithromycin are still listed normally in most provinces. visual china | picture
a "net celebrity" original drug actually "disappeared" in a public hospital?
in early september 2024, as schools across the country opened, respiratory infectious diseases increased. many parents of sick children discovered that a commonly used drug for children's mycoplasma pneumonia had "disappeared" - some public hospitals could only prescribe domestically produced azithromycin, and were unable to prescribe the imported azithromycin "xistomycin".
azithromycin was first developed by the yugoslav company sourpliva (now part of croatia) was developed in 1980. later, pfizer of the united states obtained the global development rights of azithromycin and launched it to the global market. a number of domestic companies such as shijiazhuang pharmaceutical group, sunflower pharmaceutical, puli pharmaceutical, china resources sanjiu, and federal pharmaceutical have produced domestic azithromycin, which has relatively high popularity and sales.
the last time azithromycin was "out of the circle" was 8 months ago. after the mycoplasma pneumonia pandemic at the end of 2023, "zithromax", which has the halo of "imported original research, global manufacturer", was written by many bloggers into the list of original research drugs that "must be recognized" and "must be stocked up by families".
"it is surprising and unexpected that such an 'old drug' that has long been replaced by domestic products has caused so much doubt and discussion on the internet." jiang changsong, director of the price procurement office of the national healthcare security research institute of capital medical university, told southern weekend reporters.
southern weekend reporters found that due to factors such as centralized procurement, online listing, and medical insurance assessment, some original research drugs have indeed decreased or even "disappeared" from public hospitals. however, some of these "disappeared" original research drugs have voluntarily withdrawn due to strategic adjustments, while others have been forced out due to loss of competitiveness. however, they can still be purchased at one's own expense through retail and e-commerce channels outside the hospital.
for example, roche pharmaceuticals' star product xeloda - used to treat colorectal cancer, gastric cancer andbreast cancerthe basic drugs of astrazeneca have been withdrawn from public hospitals due to failure to win the bid.anastrozole）、eli lilly's zyprexa (olanzapine), selectstar (atomoxetine hydrochloride capsules), eisai's polytetracycline (rabeprazole sodium enteric-coated tablets）、merck's ennis (desloratadine), bayer's bayer glucoside (acarbose) and other medicines have similar situations.
jiang changsong pointed out that under the resource constraints of limited medical funds, imported original drugs are not "disappearing", but are undergoing a structural optimization adjustment - after the patent expires, a large number of approved generic drugs selected in centralized procurement will replace original drugs, and the money saved will be used to give more innovative drugs. "this drug patent cliff is an inevitable trend, and it is the same all over the world."
mycoplasma infection is one of the common causes of upper respiratory tract diseases in children. if the disease is delayed, it may develop into mycoplasma pneumonia. children with persistent high fever and severe dry cough often make parents "break down" - can they use imported medicine and give them intravenous drips as soon as possible to get better faster?
according to the "guidelines for the diagnosis and treatment of mycoplasma pneumonia in children (2023 edition)" issued by the national health commissionhereinafter referred to as the "guidelines"), macrolide antibiotics are the first choice of treatment, and azithromycin is the most widely used one. the imported azithromycin in this public opinion storm is from pfizer's zithromax.
it is worth noting that, judging from the online listing situation, the hotly discussed online issue of "large-scale withdrawal of original research drugs from the domestic market" does not match the actual situation.
gu hai, director of the health policy and management research center of nanjing university, told southern weekend that the three dosage forms of imported azithromycin are still sold online normally in most provinces: the injection is sold online in 26 provinces across the country, and not in 5 provinces; the dry mixed suspension is sold online in 23 provinces across the country, and not in 8 provinces; tablets are sold online in 30 provinces across the country, and only shanghai is not listed online.
at present, all provinces have built a medicine procurement platform as the main channel for buying and selling medicines between public hospitals and enterprises. its role is similar to that of an e-commerce platform. enterprises display their medicines on the platform, and public hospitals place orders for purchases from the platform. this process is generally referred to as "online procurement."
jiang changsong specifically pointed out that in zhejiang, where the public opinion originated, because the economic consumption capacity of residents leads the country, xishumi injection, dry mixed suspension and tablets have been kept online normally and have not been removed from the online market.
according to data from minenet, the total sales of 116 domestic azithromycin manufacturers in 2022 was approximately rmb 1.37 billion, while the sales of pfizer-branded products reached rmb 652 million, accounting for 48% of the total sales of azithromycin, far ahead of other companies. among them, the sales of azithromycin dry suspension exceeded rmb 600 million, of which pfizer's products accounted for 93.19%.
"before centralized procurement, imported and domestic products were evenly matched, with each accounting for roughly 50% of the market share. after centralized procurement, the usage of domestic azithromycin has exceeded that of imported products, accounting for more than 60% of the national market share," said jiang changsong.
although there was no large-scale withdrawal from the market, it is an indisputable fact that xishumei was not selected in the centralized procurement. the main reason for the failure was that the price was too high.
taking dry mixed suspensions, the most commonly used medicine for children, as an example, in november 2023, the state organized centralized bulk procurement for 42 types of drugs including azithromycin dry mixed suspension, and 11 domestic and foreign companies participated in the bidding for azithromycin dry mixed suspension.
according to the rules of the "national drug centralized procurement document" issued in october 2023, the top 9 bidders with the lowest prices were selected. cialis offered a price of 5.58 yuan per bag, which was about 4.7 times higher than the 9th bid of 0.98 yuan per bag, ranking last and failing to be selected. in the fifth batch of national centralized procurement in june 2021, cialis injection was also not selected.
in some provinces (city) regarding the listing rules for drugs that failed to be selected in the centralized procurement, products of multinational pharmaceutical companies such as "xishumei" can continue to be listed if their prices are not higher than the median level of typical developed countries and regions in the world. in other words, it is equivalent to being listed in the eight provinces that withdrew from the network (city) the platform's listing price needs to be reduced from 5.58 yuan/bag to 4.47 yuan/bag.
"the national medical insurance administration negotiated with the company at the time, hoping to further reduce the price." hu xin, director of the pharmacy department of beijing hospital, told southern weekend that the company would rather remove xishumei from the platform.that is, the previously displayed drug information is removed from the platform, and the drug cannot be purchased through the platform.), nor are they willing to appropriately lower the prices they supply to local public hospitals.
like "zithromax", it has become a common phenomenon that original research drugs are difficult to be selected in the centralized procurement due to their high prices. according to data from the national medical insurance administration, 1,583 domestic generic drugs and 70 imported original research drugs were selected in the first nine batches of centralized procurement, with generic drugs accounting for more than 95%.
gu hai showed a set of data to the southern weekend reporter: the price of 5 mg of the antihypertensive drug norvasc is 3.26 yuan per tablet in china, 1 yuan per tablet in japan, 1.3 yuan per tablet in italy, and 0.9 yuan per tablet in portugal; the price of 20 mg of the lipid-lowering drug lipitor is 5.8 yuan per tablet in china, 0.3 yuan per tablet in the uk, 1.45 yuan per tablet in australia, and 1.39 yuan per tablet in belgium.
it can be seen that the domestic prices of some imported original drugs are significantly higher than the international prices, which are basically 3-5 times the prices in some developed countries. "china is still a developing country, and it is obviously unacceptable for imported original drug companies to give such prices," said gu hai.
many experts interviewed said that after the patent cliff arrives, domestic generic drugs will replace imported drugs, and the market share, price and volume of original drugs will drop significantly. this is a normal trend, and the same is true in europe and the united states. the public should slowly accept this trend.
jiang changsong provided a set of data to the southern weekend reporter: the scale of prescription drug use in the united states is about 600 billion us dollars each year. from the perspective of usage, 90% are generic drugs that have passed the patent period, and 10% are patented innovative drugs; from the perspective of expenditure, 90% is spent on patented innovative drugs, and generic drugs account for only 10%. germany and japan account for 80% of the usage of generic drugs and 20% of the amount. "this is a huge price scissors gap."
iqvia, a biopharmaceutical r&d service providera research report shows that the sales of domestic innovative drugs will increase from 2.1 billion yuan in 2020 to 3.5 billion yuan in 2022, while the sales of imported innovative drugs will increase from 2.3 billion yuan to 4.4 billion yuan.
jiang changsong said that most of the money saved from the procurement of mature drugs has been used for innovative drugs and patented drugs. "in many regions, the sales scale of negotiated drugs has exceeded that of centralized procurement drugs. multinational companies are focusing on introducing patented innovative drugs with higher prices and higher profits, and the market for mature drugs that have been sold for 20 years has gradually been ceded to domestic generic drugs."
although some original research drugs were not selected in the centralized procurement, in theory, as long as the drugs are still "online", hospitals can still place orders for purchases according to their own needs. previously, medical insurance bureaus in many places also required medical institutions not to "stop using unselected drugs across the board."
however, southern weekend reporters found that according to the local guidance on centralized procurement of drugs for public hospitals, for the winning products of centralized procurement, the hospital's volume purchase is to purchase at least 70%-80% of the actual amount of drugs used in the previous year. failure to complete this may affect the allocation of medical insurance funds for the next year.
in reality, many hospitals choose to "use less or even not purchase" some drugs that were not selected in the centralized procurement, and use a one-size-fits-all approach to meet the centralized procurement "hard indicators", and even tie cost control to the evaluation, performance, and reward and punishment mechanisms. a doctor told the southern weekend reporter that "for every box of original research drugs, two boxes of generic drugs are required to match them", "in the first half of the year, only centralized procurement drugs can be prescribed, and in the second half of the year, imported drugs can only be prescribed if there are indicators".
from the perspective of policy design, the centralized procurement of drugs accounts for about 70% of the final drug usage in hospitals, and the other 30% is centralized procurement of external drugs, leaving room for multi-level drug demand. however, in actual management, some hospitals are indeed relatively simplistic.
"hospitals are actually in a difficult situation. if other hospitals suspend the use of original drugs, and one hospital is more relaxed and can prescribe imported drugs, then patients who must use original drugs may go to that hospital and request a prescription. this hospital will face certain pressure to smoothly complete the use of the products selected in the centralized procurement," said jiang changsong.
jiang changsong pointed out that the proportion of drugs (the proportion of the total cost of buying medicine in the process of seeing a doctor) as an important assessment indicator for the national hospital performance ranking, almost all hospital managers are working hard to reduce the proportion of drug revenue and increase the proportion of medical service income. therefore, the cost-effectiveness of drugs must be taken seriously. under the same efficacy, reducing the use of high-priced original drugs has also become one of the hospital's management measures.
gu hai suggested that the health and medical departments should relax the restrictions on the number of drugs purchased by medical institutions to ensure that the selected drugs do not occupy the "one product, two regulations" (the same drug can only have two specifications in hospital drug procurement to prevent excessive backlog of the same drug and cause waste) to ensure that medical institutions’ purchase of imported original drugs is not restricted by the number of specifications in the hospital.
"at the same time, we can relax to a certain extent the various assessment requirements for medical institutions to use imported original drugs, and we can start the pilot project from special departments, such as pediatrics, geriatrics, and oncology," said gu hai.
this time, azithromycin has once again "gone viral" due to a viral article. the author of the article said that after his 6-year-old child was diagnosed with mycoplasma pneumonia, he still had a high fever after taking domestic azithromycin for 2 days, and he was cured after taking imported azithromycin on the 3rd day.
is there a huge difference in efficacy between domestic azithromycin and imported azithromycin? "since it was included in the centralized procurement in 2023, public hospitals have indeed used more and more domestic azithromycin. we have not seen a significant difference in the therapeutic effect in clinical practice." professor yin genquan, a member of the national health science popularization expert database and a professor at the guangzhou women and children's medical center, told southern weekend reporters.
regarding the claim that the patient's condition improved after taking imported azithromycin, yin genquan pointed out that mycoplasma pneumonia is self-limiting and may improve on its own after the course of the disease has progressed. it is not necessarily due to the switch to imported drugs.
in yin genquan's opinion, rather than worrying about the effectiveness of domestic or imported drugs, the more critical issue is whether comprehensive treatment is fully carried out based on clinical classification.
doctors should clarify the condition of the child's lung lesions and choose different treatment strategies based on different clinical symptoms, such as the duration of high fever, cough and wheezing, laboratory tests such as crp and d-dimer levels, chest x-ray or chest ct typing, etc., including whether to use bronchoscopy, hormones, anticoagulation, immunoglobulin, etc., or even combined anti-infection (in case of mixed infection), and select different comprehensive treatment plans according to the child's condition.
"normally, the children in our ward basically take azithromycin orally, without intravenous use, and most mycoplasma infections can be cured," said yin genquan.
from a clinical perspective, azithromycin resistance may be the root cause that further restricts the effectiveness of treatment.
“many treatments are ineffective or have become so severe that they causepneumoniawe generally do not recommend azithromycin for children with leukemia. whether it is imported or domestic, the effect is not good. "sun jie, former deputy chief physician of pediatrics at the shenzhen hospital of the university of hong kong and medical director of yihe clinic, told southern weekend reporters.
luo shujuan, a pediatrician and pediatric respiratory specialist at zhuozheng medical, a private mid-to-high-end comprehensive medical service institution, provided a set of data to southern weekend reporters: statistics from zhuozheng's 11 clinics across the country showed that in the targeted sequencing tngs tests of respiratory pathogens conducted from october 2023 to july 2024, among more than 3,000 cases of mycoplasma pneumoniae, the detection rate of drug-resistant genes was about 82%, of which 99% were a2063g gene mutations (this indicates that there is resistance to macrolide antibiotics such as azithromycin）。
luo shujuan once saw a patient who had been to many public hospitals with poor treatment results, but the doctor refused to agree to change the medication. the reason was that the second-line medication "tetracycline drugs" were not recommended for children under 8 years old because they might cause side effects such as enamel defects.
in the latest "guidelines" (2023 edition), it is clearly stated that doxycycline (a tetracycline drug) is relatively safe. there are no reports of permanent yellowing of teeth within the recommended dosage and treatment course.
"for clinicians, it may be better if they have sufficient room for drug selection based on the actual needs of clinical patients. especially for some acute or critically ill patients, it may be safer to use original drugs with more sufficient clinical evidence," said sun jie.
the director of the pediatric respiratory department of a well-known tertiary hospital in shanghai told southern weekend reporters that approved generic drugs can meet 90% of the needs of most patients, "but if patients insist on asking for imported drugs and the hospital system does not have them, sometimes it can even cause conflicts between doctors and patients and lead to complaints."
in fact, the "placebo effect" may also be the reason why original research drugs are more popular. some patients and even medical workers still have a "looking up" mentality towards imported original research drugs.
many clinicians said it was difficult to evaluate the actual situation of each generic drug because there are currently a large number of generic drugs and the products produced by different manufacturers are also different. but overall, the quality of drugs that have passed the generic drug consistency evaluation is still acceptable.
since 2016, china has required that all generic drugs included in the centralized procurement must pass the consistency evaluation. the national healthcare security administration has also conducted real-world studies on some of the drugs selected in the centralized procurement. the results showed that the clinical efficacy and safety of 14 drugs in the first batch of centralized procurement and 23 representative varieties in the second and third batches of national centralized procurement were comparable to those of original drugs.
gu hai suggested that the drug regulatory authorities should further strengthen the long-term monitoring of the quality and efficacy of selected generic drugs, encourage medical institutions to actively report the use of selected drugs in clinical practice, and pay attention to the incidence of adverse reactions.
jiang changsong found that in the vast majority of county, township and village medical institutions in the country, the proportion of high-priced imported original drugs that have passed the patent period for common and chronic diseases is very low, and the general public is more accustomed to using more cost-effective and approved generic drugs.
"it is true that the quality of original drugs that have passed the patent period is guaranteed. but it is also unreasonable to say that generic drugs that have passed the quality and efficacy consistency evaluation are not effective and cannot gain the trust of patients at all," said jiang changsong.
in the long run, it is necessary to reduce the prices of some mature drugs that have passed their patent period and are higher than those in developed countries through centralized procurement.
jiang changsong said that in recent years, the basic medical insurance fund has faced increasing payment pressure, with the increase in expenditure exceeding the increase in income. even a considerable number of pooling areas have not been able to cover their current expenditures, and the fund is facing the risk of "bottoming out". in 2023, the resident medical insurance for 960 million insured persons will have an income of 1,056.971 billion yuan and an expenditure of 1,045.765 billion yuan, with a current balance of 11.206 billion yuan, a surplus rate of only 1%, which deserves more attention and vigilance.
since the national healthcare security administration launched national, inter-provincial and provincial centralized procurement, by squeezing out the water in the drug circulation link, over the past five years, nine batches of centralized procurement have saved patients a total of more than 500 billion yuan.
behind the money savings is the fact that china's vast low-income groups can get cheap domestic generic drugs in the fields of hypertension and chronic diseases - and part of the saved medical insurance funds is still turned to more expensive "innovative drugs" that have passed drug negotiations.
"the total amount of medical insurance is so small, so we have to spend the money where it counts," said gu hai.
regarding the suggestion of returning prescription rights and drug use freedom to doctors and patients, in the short term, this can be solved through the outpatient market and prescription circulation. in the view of relevant experts, it took japan 50 years to achieve the separation of medicine and pharmacy, and the prescription outflow rate has reached 90%, while china's current dual-channel policy has just started, and the conditions in all aspects are not yet mature.
in the long run, it is necessary to innovate the payment standard management mechanism. for example, the selected products in the centralized procurement will be paid according to the centralized procurement price, while the original high-priced products that were not selected can be purchased at a certain out-of-pocket cost if the patient is willing to choose. medical insurance will unify the payment standards for the same centralized procurement products of different companies, which will be fairer and more reasonable for both insured persons and manufacturers.
"for example, if a selected drug in the centralized procurement costs 10 yuan and the medical insurance payment standard is set at 10 yuan, the selected drug will be fully included in the medical insurance reimbursement, with medical insurance paying 8 yuan and the patient paying 2 yuan. if you want to use an imported original drug that costs 30 yuan, that is also possible. medical insurance will include it in the reimbursement according to the payment standard of 10 yuan, and medical insurance will still pay 8 yuan. the excess 22 yuan will be borne by the patient. in this way, the needs of patients at different levels can be met, and the requirements and concepts of fair medical insurance can be implemented." jiang changsong said.
collect and organize the latest news information and make it available for free for everyone to read
