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    Home > Active Ingredient News > Drugs Articles > The Health and Health Commission first mentioned "off-indication use", is the commercialization of tumor drugs ready for a turnaround?

    The Health and Health Commission first mentioned "off-indication use", is the commercialization of tumor drugs ready for a turnaround?

    • Last Update: 2022-04-27
    • Source: Internet
    • Author: User
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    A past event long forgotten by the media and the public, but because of the "2022-2024 Action Plan for Improving the Quality of Cancer Diagnosis and Treatment in Beijing" issued by the Beijing Municipal Health Commission on March 23, the "net open side" for off-label medication , is mentioned again
    .

    This is a lose-lose story
    .

    In June 2020, surgeon Lu Wei, who is in his prime, saw Ma Jincang, a patient with advanced gastric cancer who had no way to seek medical treatment and lost the best chance for surgery
    .


    In the case that chemotherapy combined with PD-1 treatment was ineffective, Lu Wei changed the treatment plan and gave a radical treatment plan that did not meet the diagnosis and treatment guidelines - using capecitabine, oxaliplatin, pemetrexed Serum, Anlotinib, Tamoxifen and other drugs


    This plan caused an uproar in the future, and was bombarded by another colleague, Zhang Yu, the attending physician of the Department of Oncology and Chemotherapy at Peking University Third Hospital— pemetrexed, anlotinib, breast cancer drugs for the treatment of lung cancer The cancer drug tamoxifen is an off-label drug and has no indication for treating gastric cancer
    .

    Pemetrexed and Anlotinib for the treatment of lung cancer, and tamoxifen for breast cancer are off-label drugs and have no indication for the treatment of gastric cancer
    .


    Off-label use refers to the situation where a certain drug has not been approved by the Food and Drug Administration because of its safety and effectiveness, but has been put into clinical use
    .

    The treatment of advanced tumors is a highly controversial field because of the widespread use of off-label drugs and new technologies.
    Some believe that this is the "last ditch" of adventurous clinicians to save patients, while others believe that this It is the way for unscrupulous doctors to make money
    .

    The truck driver, Ma Jincang, spent all his savings and did not save his life
    .


    Lu Wei took the stigma of "unscrupulous doctor" and "deliberately deceiving patients"


    Under the banner of exposing the shady history of China's medical care, Zhang Yu became famous in the first battle
    .


    He became an "inspector" in the field of tumor treatment, but fell into trouble in the "Liaocheng Fake Drug Case" and was eventually expelled from the Third Hospital of Peking University


    Less than a week after Zhang Yu was expelled, on March 1, 2022, the "Physician Law of the People's Republic of China" will be officially implemented
    .


    This new doctor is highly appreciated by many doctors.


    In special circumstances such as no effective or better treatment methods, physicians can use drugs that are not specified in the drug insert but have evidence-based medical evidence to implement treatment after obtaining the patient's explicit informed consent


    Because of its special status, the Beijing Municipal Health Commission is often regarded as one of the wind vanes of the National Health Commission
    .


    This official release of the use of off-label clinical indications not only reduces the legal risks of doctors in the use of some special drugs, but also, to a certain extent, is a disguised “acceleration of approval” for innovative drugs when looking at the pharmaceutical industry


    According to an industry insider, this change will benefit many local pharmaceutical companies
    .


    "For example, a new drug has only been approved for one indication, and now it can be expanded to other indications


    But inevitably, it will also make some companies that invest heavily in indications feel frustrated.
    "We spend a lot of money on indications that are honest.
    Once this policy is released, some companies that do not honestly make indications will benefit
    .


    " People in the clinical departments of foreign companies are a little frustrated


    "We spend a lot of money on the indications honestly, and as soon as this policy comes out, some companies that do not honestly do the indications will benefit
    .
    "

    For him, "in special circumstances such as there is no better treatment", this statement is used in the field of oncology, which is somewhat subjective, leaving some pharmaceutical companies the possibility of exploiting loopholes
    .

    - 01 -

    - 01 -

    Freeing the shackles of the clinician

    Freeing the shackles of the clinician

    For doctors, this plan of the Beijing Health and Health Commission is equivalent to their "shangfang sword" in clinical off-label drugs
    .

    The problem of off-label drug use is in many cases a lag in approval, that is to say, the results of clinical studies in the real world or in other countries have proven that the drug is effective for a certain disease, but the State Food and Drug Administration has not yet approved it
    .
    With the continuous progress of medical disciplines and the continuous exploration of new uses of old drugs, doctors are often the first to discover new indications for old drugs
    .

    With the continuous progress of medical disciplines and the continuous exploration of new uses of old drugs, doctors are often the first to discover new indications for old drugs
    .

    Many doctors told Shenlanguan that, on the one hand, for the clinical needs of patients, off-label drugs have been widely used in practice for many years, especially in the treatment of some "difficult and miscellaneous diseases", but off-label drugs have not been adopted.
    It is legally recognized that there are risks for doctors to use off-label drugs
    .

    "For example, oxaliplatin has been used in gastric cancer for more than ten years, but its indication for gastric cancer was not approved until this month
    .
    " On March 26, Professor Li Jin, director of the Department of Oncology, Shanghai Dongfang Hospital affiliated to Tongji University, introduced, Oxaliplatin was launched globally in 1996.
    It was initially registered for colorectal cancer, but it has been clinically proven to be effective against a variety of cancers, including gastric cancer.
    In the standard guidelines for tumor diagnosis and treatment, this has formed a situation where the legal provisions and clinical guidelines "contradict themselves"
    .

    When this kind of contradiction appears in the clinic, it is easy to form a contradiction between doctors and patients
    .
    Li Jin has dealt with many such conflicts between doctors and patients, all of which are due to the ineffectiveness of standard treatment for tumor patients.
    The doctor prescribed off-label medication, which was expensive, but the medication was also ineffective.
    The patient then filed a complaint
    .

    In most cases, the starting point of the doctor's off-label medication is good, but the patient may not understand or accept the final invalid result
    .
    Li Jin said that although off-indication medication is mostly in line with the norm in tumor treatment, when off-indication medication is in a gray area, it is inevitable that doctors do not operate well and their interests are opaque.
    The off-label drug was used, but a domestic drug was used.
    At that time, there were better imported drugs of the same type that could be used.
    In this case, the patient complained and the doctor was judged to need compensation
    .
    "

    On the other hand, although it is not uncommon to use off-label use of tumor drugs in clinical practice, different regions, medical institutions and doctors have different restrictions on the use of off-label anti-tumor drugs
    .

    An oncologist who lives in the west and has been practicing for a long time said that her department has strict control over the use of off-label anti-tumor drugs, "First, we must consider the restrictions of laws, regulations and guidelines, and secondly, senior doctors are more Freedom to prescribe
    .
    "

    "It is not up to every physician to decide whether to use off-label drugs
    .
    " Ma Jun, director of the Harbin Institute of Hematology and Oncology, said that the clinical application of tumor drugs is strictly controlled, and there are still no specific implementation rules and management methods for off-label drugs.
    When it is introduced, in clinical discussions, it is generally by the chief physician or above, or the administrative director or above, at least an expert at the deputy chief physician or above, to formulate off-indication drug regimens
    .

    In clinical discussions, generally above the chief physician, or above the administrative director, at least the deputy chief physician or above, can formulate off-label drug regimens
    .

    "It should be comprehensively evaluated according to the doctor's law, ethics, whether the patient benefits, as well as the safety and efficacy of the drug, especially for combination therapy outside of some indications, which should be used with caution
    .
    " Ma Jun added
    .

    Oncologists who have been on the front line of clinical practice for a long time have also explored various ways to treat patients' conditions while exempting themselves from responsibility
    .

    Li Jin told Shenlanguan that when PD-1 had not been approved in China, he was convinced that it was effective for cancer patients after obtaining evidence from his own channels, and many patients had the conditions and channels to purchase imported PD-1 from outside the mainland 1.
    However, oncology medication needs to be monitored by clinicians, and patients cannot use it privately
    .

    Therefore, if there was a patient request or need to use PD-1 at that time, Li Jin would still use it.
    At the same time, he also summed up three conditions, all of which must be met before the drug can be used.
    The first is to have a copy of the prescription issued by a foreign doctor; The second is that the patient must have a PD-1 purchase ticket from a formal overseas medical institution; the third is the patient's drug swab informed consent
    .

    "This was illegal at the time, but my first starting point was to save people
    .
    " Li Jin added that he has many tumor patients who have failed standard treatment, and come from all over the country.
    Through this method, he has made many The patients achieved good clinical results
    .

    "It was illegal at the time, but my first starting point was to save people
    .
    "

    - 02 -

    - 02 -

    Off-label use, moderate freedom under supervision

    Off-label use, moderate freedom under supervision

    Get adapted to get the world
    .

    To a certain extent, the more indications, the larger the market size
    .
    Take Humira, the “King of Medicines”, whose sales will exceed US$20 billion in 2021, as an example.
    It has more than a dozen indications worldwide
    .
    The rising star PD-1 inhibitor K drug (Keytruda) has been approved for more than 20 indications, and its sales in 2021 will exceed 17 billion US dollars
    .

    Some people in the industry have revealed to the media that due to lax drug supervision, the revenue from off-label use of some drugs can account for 40% of the total revenue
    .
    Pharmaceutical giants such as Roche, Johnson & Johnson, Pfizer, and Eli Lilly have all been fined billions of dollars for off-label promotions around the world
    .
    However, even under such penalties, it still brings huge profits to the relevant pharmaceutical companies
    .

    The huge commercial interests behind it make off-label drug use a "stubborn disease" in the medical industry
    .
    The off-label medication mentioned here refers to off-label medication
    .
    Previously, the United States, Germany, Japan, India and other countries have legislated against such drugs
    .

    Last year, after the "Lu Wei medical incident" in China, the "off-label drug use" that was hidden in the dark is now exposed to the spotlight
    .
    This incident has made doctors more cautious about off-label drug use.
    In fact, how to grasp the boundaries of patients' rational drug use has always been a difficult problem in the industry
    .

    When doctors refer to guidelines (clinical practice guidelines), they sometimes face the conflict of human ethics and medical technology
    .
    For example, some patients are not suitable for the first- and second-line programs in the guidelines.
    Should doctors break through the guidelines and adopt personalized treatment? If it is just blindly tightened, an extreme situation is that the doctor does not consider the special situation of the patient and still uses the standard treatment plan in the guideline
    .
    Physicians are exempted from responsibility, but patient outcomes come second
    .

    However, the "off-label drug use" has indeed produced a gray area before - the phenomenon of pharmaceutical companies giving rebates and other benefits to doctors
    .

    ——The phenomenon of pharmaceutical companies giving rebates and other benefits to doctors
    .

    In fact, the Drug Administration Law allows pharmaceutical companies to increase drug indications, but each application for a new indication requires several years of clinical research.
    Once the research and development fails, the time and money invested will be overwhelmed.
    Therefore, some companies choose to take risks.
    Using "off-label" to promote new drugs is an effective way to expand sales
    .

    In this context, clear legislation on "off-indication medication" is urgently needed, but there are also relevant conditions for off-indication use
    .
    From March 1 this year, the "Physician Law of the People's Republic of China", the description of the use of off-label use, is the first time that the guidelines for diagnosis and treatment and off-label use of drugs under evidence-based medicine are written into the law
    .

    In addition, the document of the Beijing Health and Health Commission also expressly stipulates that "off-label drug use": in principle, the clinical application of anti-tumor drugs must follow the clinical application guidelines, clinical diagnosis and treatment guidelines, and drug instructions
    .
    In special circumstances such as no better treatment, medical institutions may use drugs that are not specified in the drug insert but have evidence-based medical evidence after obtaining the patient's explicit informed consent
    .

    In principle, the clinical application of antitumor drugs must follow the clinical application guidelines, clinical diagnosis and treatment guidelines, and drug instructions
    .

    The levels of evidence adopted for the use of antineoplastic drugs under special circumstances are as follows: usage approved in the drug inserts of other countries or regions, diagnosis and treatment specifications issued by international authoritative associations or organizations, clinical diagnosis and treatment guidelines, diagnosis and treatment specifications issued by national associations, clinical diagnosis and treatment guidelines Diagnosis and treatment guidelines and clinical pathways,
    etc.

    This document followed by the Beijing Health and Health Commission means that there is a clear industry basis for off-label use of drugs, which will undoubtedly accelerate the clinical use of anti-tumor drugs and ensure medical quality and medical safety
    .

    - 03 -

    - 03 -

    The gains and losses of pharmaceutical companies

    The gains and losses of pharmaceutical companies

    According to an industry insider, this change will benefit many local pharmaceutical companies
    .
    "For example, a new drug has only been approved for one indication, and now it can be expanded to other indications
    .
    In the past, I worked hard for several years to test for one (indication), but now it has been released.

    .
    "

    With the extrapolation of indications, the scope of use of drugs will expand, which will directly increase the sales and profits of pharmaceutical companies
    .
    Whether it is reducing development costs or improving drug accessibility, it has important implications
    .
    Now that there is a law to follow, the sales strategy of pharmaceutical companies may become more flexible
    .
    The above-mentioned industry insiders said frankly: "This gives some doctors the confidence to use drugs across indications, but this is also a double-edged sword.
    Some doctors and drug agents who have no bottom line may be more reckless
    .
    "

    "This gives some doctors the confidence to use drugs across different indications, but this is also a double-edged sword.
    Some doctors and drug agents who have no bottom line may be more reckless
    .
    "

    However, in the opinion of some people, the latest "Physician Law" and "Action Plan" are to a large extent to solve the contradiction between doctors and patients.
    Whether it can actually benefit pharmaceutical companies from off-label use requires follow-up observation.

    .

    "Some large hospitals still clearly stipulate that cross-indication drugs are not allowed
    .
    " A pharmaceutical company official pointed out that "better" in "better" in the field of oncology Subjective
    .
    Existing standardized treatment regimens with low effective rates and high adverse reactions are considered 'there is no better way'? "

    The 'better' in "in special cases where there is no better treatment" is more subjective in the field of oncology
    .
    Existing standardized treatment regimens with low effective rates and high adverse reactions are considered 'there is no better way'? "

    Regarding the determination of off-label drug use, Ma Jun explained: "There are three steps, one is to be decided by top doctors (professional experts above the chief doctor) according to the guideline consensus, the guiding principles of drug use and evidence-based medicine; the second is to decide Fully communicate with family members and patients to obtain their consent; third, it is best to pass the review of the ethics committee
    .
    "

    "From the point of view of registration, companies still need to do cross-indication clinical research, follow the path of review and approval, and appear in the (drug) instruction sheet after approval,
    " said a person from a pharmaceutical company
    .

    A doctor admitted that in the past two decades, he has seen many patients whose lives have been extended due to off-label medication
    .
    The use of some drugs "off-label" can indeed solve certain diseases
    .
    For example, for rare diseases, in the absence of effective drug treatment, trying "old drugs" may be the last straw for patients
    .
    This type of safe and effective personalized medicine is beneficial to patients, so strict supervision and protection are needed
    .

    From the perspective of drug R&D innovation, it cannot completely block off-indication drug use
    .

    According to the Journal of the American Medical Association, about 40% to 60% of prescription drugs in U.
    S.
    hospitals are used for "non-FDA-approved uses" each year
    .
    These unapproved new indications are called "old drugs for new uses", and after trials, some eventually change their past uses to save patients
    .
    Some successful examples include aspirin, an antipyretic and analgesic, used to thin the blood and prevent blood clots; the antidepressant, atomoxetine, used to treat ADHD in children
    .

    These unapproved new indications are called "old drugs for new uses", and after trials, some eventually change their past uses to save patients
    .

    In fact, for off-indication drugs to benefit from multiple parties, the joint efforts of regulatory authorities, medical institutions, clinicians and pharmaceutical companies are needed to find a dynamic balance
    .

    But in any case, under the current pressure of medical insurance for innovative drugs, commercial promotion itself requires a certain amount of investment.
    Sales team building, channel layout, and some clinical promotion are costs, which are separate from the research and development costs of innovative drugs
    .

    Whether the substantial price reduction in the medical insurance negotiation and the improved accessibility can cover the cost of commercialization is not very optimistic at present
    .
    The liberalization of off-label use can be seen as a "relaxation" policy for the commercialization of innovative drugs
    .

    However, an industry insider also said that this is unfair to some innovative pharmaceutical companies that have invested heavily in various indications and treatment areas
    .

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