​Inexpensive medicines used to save lives by 100,000 new patients every year fall into a crisis of out of stock

At least one or two weeks later, Li Xiang (pseudonym) will see one or two messages about finding medicine in the patient group
.

Unlike the frequently searched "expensive medicine" news reports, Li Xiang's patients often need low-priced "old medicine
.

"

These "old medicines" are generally not expensive, mostly only a few hundred yuan, and the cheapest ones are even a few yuan, and they can often be reimbursed through medical insurance
.

But the clinical "life-saving medicine" that these patients can afford is difficult to buy for various reasons
.

Behind the frustration Li Xiang described is related to the approximately 100,000 new lymphoma patients in China each year

Unlike other malignant tumors, lymphoma has complex and diverse types, difficult to diagnose and easy to relapse, which has almost become its label
.

At the same time, compared with other solid tumors, lymphoma has the characteristics of good prognosis and longer survival time

Yang Qingming, chief physician of the Department of Tumor Biotherapy at the PLA General Hospital, told the health community that the treatment of lymphoma is very important
.

After the patient's first-line treatment, if the condition cannot be effectively controlled, it may turn into a drug-resistant case, and subsequent treatment will be more difficult

However, the reality is that patients may not be able to obtain sufficient and complete first-line treatment due to lack of drugs or even the suspension of production
.

It is actually difficult to provide cheap life-saving drugs

Old medicine, not enough

Old medicine, not enough

Witnessing the development of China's lymphoma medical career for decades, Yang Qingming is not only happy to see new and innovative drugs for lymphoma, but also suffers from the lack of "cheap old drugs"
.

"Many old drugs have very good effects in the process of tumor treatment
.

We consume a lot of them every month in the clinic

Most of the "old medicines" in his mouth are commonly used drugs in standard chemotherapy regimens for lymphoma
.

For example, nitrogen mustard and bleomycin, which are commonly used in the treatment of Hodgkin's lymphoma, and vincristine, which is used in the treatment of non-Hodgkin's lymphoma, have been discontinued

The common feature of these drugs is "urgent clinical need and inexpensive
.

" "Nitrogen mustard only cost one or two yuan at the earliest, but now it has risen to around five yuan

For another example, the data provided to the health sector by Hanhui Pharmaceutical, a Chinese manufacturer of bleomycin, shows that before July 2020, the price of the drug has been around 122 yuan
.

Bleomycin is the standard drug in the first-line treatment program "ABVD" for Hodgkin's lymphoma
.

Each letter in ABVD corresponds to the name of a chemotherapeutic drug, which are Doxorubicin (Adriamycin), Bleomycin (Bleomycin), Vincristine (Vincristine), and Dacarbazine
.

Under the standard plan, ABVD requires two medications for a course of treatment, with one bleomycin each time
.
Based on this estimate, even if medical insurance reimbursement is not included, the cost of bleomycin for patients using ABVD is only about 244 yuan per course of treatment
.

This affordable treatment cost made Gu Hongfei, a former Hodgkin lymphoma patient, deeply touched
.

Gu Hongfei is the founder of the patient communication platform "Lymphoma Home" and a beneficiary of the ABVD program
.

In 2010, Gu Hongfei, who was still in graduate school, was diagnosed with Hodgkin's lymphoma and went to Shanghai Cancer Hospital for treatment
.

"At that time, I didn’t have the money to see a doctor when I went to school with a student loan
.
Fortunately, the ABVD program was very cheap.
At that time, the total cost of medicine for a course of treatment was about 2,800 yuan
.
Because I was a student, the school could still reimburse me, and I only paid for each course of treatment.
Two or three hundred dollars
.
"

Although Gu Hongfei had a sufficient supply of bleomycin during treatment
.
However, his treatment plan also faces the episode of "drug shortage
.
"

Gu Hongfei recalled that because vincristine was out of stock at the time, it had to be replaced with vinorelbine
.
"At that time, the doctor asked me if I would like it, and I said that there is no way.
I can't wait for a certain medicine
.
"

Fortunately, Gu Hongfei has recovered for many years with a good prognosis
.

The reform plan has become a regret forever

The reform plan has become a regret forever

According to the head of the content of Lymphoma Home, Kongquehe (a pseudonym), there are not a few patients who have changed their plans due to lack of drugs
.
"Bleomycin was replaced with expensive PD-1, vincristine was replaced by vindesine or vinorelbine, teniposide was replaced with high-dose methotrexate.
.
.
"

What impressed Kongquehe was the eternal regret caused by changing the medication plan
.

In 2013, Kongquehe's mother was diagnosed with lymphoma.
After a period of treatment, she developed brain metastases in 2014 and went to a well-known top three hospital in Beijing for treatment
.

At that time, the treatment plan given by the doctor included a drug called Teniposide
.
This is a chemotherapeutic drug that can directly act on the nerve center and is often used in the treatment of malignant lymphoma
.

The effect of the first course of treatment was very good, Kongquehe recalled, “The tumor shrank by more than half quickly, and the mother’s symptoms of compression of the limbs were also significantly improved
.
” However, during the second course of treatment, the doctor told the teniposide to stop the drug.
Switch to methotrexate, which has a similar effect
.

This time, the effect did not continue
.
"In the second course of treatment, my mother's tumor grew rapidly.
After the doctor discovered the problem, he told me that methotrexate was not suitable for my mother.
We wanted to find a way to see if we could buy teniposide
.
"

Unfortunately, due to the resistance of chemotherapy, the teniposide found failed to exert its miraculous effect
.
The state of Kongquehe's mother was worsening every day, and the unused teniposide was eventually transferred to other patients
.

This time the dressing change became a regret that Kongquehe could never make up for.
“I actually blamed the doctor a little bit.
Why didn’t I just ask me to go to Teniposide when there was no medicine for the second course of treatment?”

The health community has learned from patients and clinicians that teniposide has long been discontinued and is almost unavailable now
.
In clinical practice, the treatment of central lymphoma is generally high-dose methotrexate
.

A study from the Lymph and Hematological Oncology Branch of the Chinese Society of Geriatric Oncology showed that teniposide can treat primary central lymphoma, and the curative effect is not less than that of high-dose methotrexate, and the side effects and ease of operation are better than high-dose.
Methotrexate
.

With professional knowledge, doctors often know the importance of cheap life-saving medicines more clearly than patients
.
However, due to the cheap prices of medicines, pharmaceutical companies often do not set up special medical representatives, and patients are limited in finding medicines
.

Wang Sheng (a pseudonym), a lymphoma expert at a large tertiary hospital, told the health industry that around 2010, he felt that some medicines were often out of stock
.
Some are in the drug factory, but it is difficult to enter the hospital, and some are out of production and cannot be bought
.

"Pharmaceutical factories can't directly deliver to our doctors.
They must go through the hospital
.
But the prices of these medicines are too cheap, and the number of patients is relatively small.
For various reasons, hospitals may not be able to introduce these medicines
.
" Wang Sheng said, once there was.
For a period of time, he entrusted a primary hospital in Zhangjiakou to help purchase these medicines, such as 100 bottles of nitrogen mustard hydrochloride at a time
.
The other party sent it to Wang Sheng's department by express delivery.
When the patient needed it, he sold it to the patient at the original price, saving many people
.
"But I think this approach is not necessarily legal and compliant
.
"

Why is it so difficult to get cheap life-saving medicine?

Why is it so difficult to get cheap life-saving medicine?

Asked about the reasons for the difficulty in accessing cheap life-saving medicines, clinicians, patients, and patient organizations all agreed that this is due to "the price of medicines is too cheap
.
" However, it seems difficult for everyone to explain the specific reasons
.

"I heard that because the price of medicines is too low, pharmaceutical companies can't make much money
.
There is also the problem of raw material supply caused by the epidemic
.
" Li Xiang told the health industry
.

Wang Sheng analyzed that some medicines for niche groups have a short storage period, which is also a burden for hospitals
.
"I know that there is a pharmaceutical company in Shanghai that has the goods.
Which hospital asks him to order the goods.
He will deliver the goods to him.
However, doctors are not allowed to buy directly.
For prescriptions, the hospital charges a 15% price difference
.
When a medicine is only a few dollars, the hospital can only make a few cents, and the profit margin is particularly low, so it is not active
.
"

This phenomenon makes it impossible for the pharmaceutical factory to watch the drugs produced, but not many sold, and they can't keep losing money and making money
.

The health sector interviewed Hanhui Pharmaceutical on the issue of drug supply
.
The company is a Chinese manufacturer of vincristine and bleomycin, and is also the only Chinese pharmaceutical company that produces bleomycin (the bleomycin sold in China comes from two companies, and one is Nippon Kayaku Co.
, Ltd.
)
.

The relevant person in charge of Hanhui Pharmaceuticals told the health industry that a clinically necessary or even urgently needed drug has experienced a shortage of supply, and even the suspension of production and supply.
The common cause is the long-term price "inflated" caused by the unreasonable price system
.
For small part of the demand for low-cost life-saving drugs, the "market regulation is a failure」
.

The person in charge also said that in addition to price factors, the shortage of medicines may also be due to various production and process issues, such as environmental protection issues, process optimization, improved quality standards, and reduced occupational exposure and occupational exposure requirements
.

"Solving these problems requires a large amount of capital investment, and the price limit caused by the online price inversion has actually returned to the price problem
.
" The person in charge explained
.

So is the ``price adjustment'' expected to ensure the stable supply of ``life-saving drugs''?

From the patient's point of view, it seems that an affirmative answer can be obtained
.
Kongquehe told the health industry that taking bleomycin as an example, the price has increased in recent years.
According to the feedback from patients of Lymphoma Home, the lack of medicine has been alleviated
.

Huang Shan (pseudonym), who just received an ABVD treatment program at a cancer hospital in Guangzhou, said that the Guangzhou pharmaceutical market has a sufficient supply of bleomycin
.
I heard that patients from other places bought bleomycin for more than 100 yuan, 200 yuan, and 300 yuan
.
"

The response of the relevant person in charge of Hanhui Pharmaceutical also partially confirmed this point.
"The supply of bleomycin has been stable after the price increase.
Some time ago, due to the official audit of the European Union, the supply of raw materials in the API production line was upgraded and the market was suspended for a period of time.
The normal supply has been restored since July 2.

"

But only raising prices may not be enough
.
The data shows that the price of bleomycin in Nippon Kayaku Co.
, Ltd.
is 150 yuan in 2019, and it will increase to 246 yuan in 2020
.
The corresponding product supply has increased from approximately 20,000 in 2019 to approximately 25,000 in 2020
.

In other words, the price has increased by 64%, and the supply volume has not increased as expected, but only increased by 25%
.

The person in charge of Hanhui Pharmaceutical said that a reasonable increase in prices can guide companies to resume production, but the output of industrial products and costs are inversely proportional.
In an era of soaring prices, scale can only dilute costs
.
However, such national-level drugs in short supply are often in a small market, and the actual amount is not large.
The room for price increases does not bring much profit to the company
.

According to the data provided by Hanhui Pharmaceutical, the current supply of bleomycin to the market is about 10,000 bottles per month
.

Change is happening

Change is happening

In 2017, "mercaptopurine tablets", an essential drug for the treatment of childhood acute lymphoblastic leukemia, formed a "drug shortage" in many parts of the country, and some places were even out of stock for more than half a year
.
At that time, mercaptopurine was about 1 yuan per tablet, and many children only needed to take 1/4 tablet each time, and the clinical dosage was relatively small
.

It is understood that there are 6 companies in the country that have the qualifications for the production of mercaptopurine tablets, and 3 have stopped production for many years, and 3 have stopped production between 2015 and 2017
.

"Life-saving drugs" are in short supply, and many parents of children have to choose high-priced imported drugs as alternative drugs
.
However, the purchase channels are not transparent, and the authenticity of medicines cannot be guaranteed, and there are huge security risks
.

This issue of people's livelihood has attracted the attention of the country
.
Premier Li Keqiang issued a special instruction on this matter, requesting special affairs to be handled specially to alleviate the "medicine pain" of families with children
.

At the end of 2017, Zhang Feng, then deputy director of the National Health and Family Planning Commission's Drug Policy and Essential Drug System Department (Pharmaceutical Administration Department), introduced that in order to quickly restore the supply of mercaptopurine, multi-sectoral coordination has accelerated the GMP certification and approval process
.
Zhebei Pharmaceutical, which was forced to stop production due to GMP certification, has resumed production and supply
.
The first batch of 2.
95 million tablets produced can basically meet the national one-year clinical dosage
.

In recent years, many ministries and commissions have promoted measures such as the "Ministry-level Joint Response Mechanism for Shortage Drugs", "Short Drugs Early Warning System", "Small Variety Centralized Production Bases", and "Small Variety Supply Guarantee Consortium"
.
The shortage of low-cost life-saving drugs, this international problem, can be alleviated under the national top-level design
.

The health community has learned from relevant sources that teniposide is expected to resume production in 2021 and be put on the market in the second half of the year
.
In this regard, the health sector sought confirmation from the relevant persons of the Teniposide pharmaceutical company "China Resources Double Crane", and the other party informed that it would not be convenient to reply
.
However, some clinical experts said that if teniposide can really resume production, it will provide another option for clinical treatment
.

In addition, the development of new drugs has been accelerating
.
Some old drugs have also shown a tendency to be replaced
.

Taking vincristine, a commonly used drug for chemotherapy of lymphoma, as an example, in some treatment scenarios, it has been replaced by vindesine, which has a similar mechanism of action
.
The consensus of Chinese lymphoma treatment experts clearly states that for patients with high risk factors for neurotoxicity (such as diabetes, etc.
), pay attention to reducing the use of vincristine or using vindesine instead
.

"Vincristine can easily cause more severe peripheral neuritis, but the side effects of vindesine are much smaller
.
Correspondingly, the price of vindesine is also much higher
.
" Yang Qingming introduced
.

In recent years, the anti-cancer drug PD-1, which has attracted much attention in recent years, is also a bright star in the flood of drug replacement
.
Clinical studies have shown that the PD-1 monoclonal antibody combined with AVD has a good effect in the first-line treatment, and can be used to replace the bleomycin in the ABVD standard regimen
.

When Li Xiang, who had recovered, was treated at a hospital in Zhejiang Province, he used the ABVD regimen, but because the bleomycin was out of stock, he used Xindali's PD-1 product-Sintilizumab injection instead
.
At that time, the drug had just been included in the medical insurance, and the indication was relapsed and refractory Hodgkin's lymphoma
.

Li Xiang, who was diagnosed with lymphoma in 2017 and moved to three hospitals before and after, happened to be eligible for reimbursement
.
In the end, the medicine with the original price of 5,686 yuan, after the medical insurance reimbursement, will cost more than 1,000 yuan at one's own expense
.

"I heard that bleomycin outages have always been serious.
The doctor said that PD-1 was used.
I learned that the effect was good, so I used it
.
But at the time, if bleomycin could be used, I would be financially The pressure on you will definitely be much less
.
" Li Xiang said
.

After three years of fighting cancer, Li Xiang finally recovered
.
After the medical insurance was reimbursed, the treatment still cost about 400,000 yuan of savings
.
"I am cured, and my savings are almost spent
.
"

Different from patients with other solid tumors, lymphomas mostly occur in the youth or old age, with a higher cure rate, longer survival period, and no recurrence, the patient's prognosis is good
.
It is precisely because of this that the health community felt in the interview that patients with lymphoma are more active in both their mental and psychological states
.

"In terms of therapeutic value, it is still necessary to ensure the treatment of lymphoma patients as much as possible
.
After they are cured, they can also bring great value to society, families, and individuals
.
" Yang Qingming said
.