Li Huafang: Hospital drug clinical trial institutions are also in pain.

Read: What are the biggest challenges facing hospital clinical trials? I have been working at the Shanghai Mental Health Center since I graduated from the Department of Medicine of Shanghai Medical University in 1990.
doctor for more than twenty years, "medical teaching and research" has always been the main content of my work.
first, drug clinical trials are routine, and then I'm going to do translational medicine in conjunction with current trials.
I have three clinics a week, sometimes go to the ward to check the room, in addition, as a teacher, I also want to participate in medical students, graduate students, doctors and so on.
since 1997, I have been working with Professor Gu Niufan in clinical pharmacology research and clinical trials in the psychiatric field, where I have mainly conducted clinical trials of imported drugs.
Between 1990 and 2000, there were more new psycho-drugs around the world, foreign enterprises came to China to do clinical trials, after 2000, I was heavily exposed to imported drugs in international multi-center clinical trials, but also more understanding of GCP and ICH-GCP, training their own international clinical research concept, which is my fastest growing stage.
, a large number of domestic generic drugs emerged, foreign what, domestic imitation of what, and is swarming up.
pharmaceutical companies for registration purposes to do clinical trials, the same drug even five or six pharmaceutical companies at the same time to find us to lead the trial.
some manufacturers in this field is not familiar with, or even a little professional knowledge, only want to get the production batch.
at that time, domestic enterprises were rarely able to undertake the task of the whole process from programme design to clinical summary reporting, and the very complex system engineering of clinical trials, from the beginning to the end, generally no two or three years is not complete.
and some companies are requiring a registered clinical trial of an antidepressant or antipsychotic in three to four months, which I think is against the law and almost impossible.
our organization's philosophy is to ensure the quality of the test, so our organization will not undertake such projects.
I often say to my colleagues, "Only if the subjects are safe, we are safe, the subjects are not safe, we, including the bid, are not safe."
we insist on the highest quality within our capabilities in order to ensure the safety of the subjects, ensure the safety of the tests and hope to reach a consensus with the bid.
the CFDA's clinical trials, I think it's generally a good thing for the country and the people.
drug with the same generic name, but the effect is quite different is no accident.
I personally in the clinical process, if the patient's financial conditions permit, it is recommended to choose the original drug.
the historical legacy of generic drugs should be resolved, but it is best not to one-size-fits-all, after all, there are many seriously done clinical trials of good drugs, but incomplete or irregular data.
I think it would be appropriate for the bid party to make a final decision on its own terms if it is necessary to select some drugs with greater clinical needs, determine whether they can verify their effectiveness and safety based on the actual situation of existing clinical trials, and make a request for further research or additional evidence, and then make a final decision according to their own conditions."
Li Huafang, Director of Shanghai Mental Health Center, on Clinical Trials Reporter: What are the biggest challenges facing clinical trials in hospitals? Li: Since "7.22", hospital managers have been more cautious about accepting clinical trials and demanding higher demands, fearing damage to the hospital's reputation.
PI and physician motivation is limited, first, doctors' daily medical teaching and research work is stressful and has no time to take into account clinical trials;
In addition, there is now more and more emphasis on research and development of innovative drugs, but for most enterprises or research and development institutions, are "big girl on the car - the first time" for the institution is also inexperienced, although we have been in contact with many multinational companies, but the clinical trials, relatively late-stage research, mainly for the FDA, EMA or CFDA registration to provide PHASE III trial or validation test data.
, early clinical trials, such as POC or Phase I. and II.
: Why do clinical trials become validation trials? Li: At present, when the bid party declares to CDE, most of them specify the adaptation certificate, and then conduct clinical trials for the adaptation certificate.
, however, for innovative drugs, clinical trials are an ongoing process that requires multiple POC trials, with N in Phase I and N in Phase II.
clinical trials are designed to answer questions about effectiveness and safety through trials, and one trial does not answer all of them, inevitably involving more trials.
If the first qualification of the adaptation certificate, and then according to I., II., III. clinical process, it may be in the early exploration of new drugs, especially other adaptation certificates are not thorough enough, can not compare the advantages and disadvantages of new drugs to different adaptation certificates.
from an enterprise perspective, in order to save time in clinical trials, foreign pharmaceutical companies usually develop a detailed research and development plan, doing different trials simultaneously or doing similar trials in different regions, of course, this is very expensive.
domestic enterprises have limited funds, often to complete one experiment, and then do another experiment, which will extend the research and development time, we all know that time is money.
reporter: What are the disadvantages of this clinical trial? Li: One of the biggest differences in the early stages of clinical trials at home and abroad is the exploration of adaptive evidence.
, for example, the same compound, the domestic direct declaration of antidepressants, and only do this one adaptation of clinical trials.
and foreign countries will do a lot of preliminary research on the compound, because the adaptation certificate is unknown, so the exploration process is diversified, can develop a number of related adaptation certificates at the same time, will also design some very small-scale experiments to explore the initial effects.
focus on an adaptation that is most likely to succeed.
not all drugs go into Phase III clinical trials, and not all compounds become drugs.
The current domestic drug development is often "only child", on a compound, the certificate of adaptation is also set, placed too much hope, limited ability to bear risks, which is very high pressure on research and development-related personnel.
: What is the gap between the level of the bid and the CRO and the requirements of current clinical trials? Li: In theory, the entire clinical trial is led by the bid party, which is responsible for initiating, organizing, implementing the whole process, and even the submission of materials.
institutions and researchers are just one of them, commissioned to complete clinical trial subject recruitment, group entry, data collection, effectiveness and safety assessment, as well as professional counseling, and so on.
our cooperation with foreign enterprises, often by the other side to provide pilot programs, generally complete, mature.
researchers can propose changes according to the actual situation, but generally do not need major changes and changes.
addition, their teams are well-formed and work together, with staff from the Medical Department, the CRA Department, the Drug Alert Department, the Statistical Analysis Department, and even the Marketing Department.
In contrast, some domestic enterprises, usually one or two people in charge of a new product, they assume the job functions of several departments, in fact, is the role of liaison, not enough professionalism, this is the status quo.
in the concept, expertise can not keep up with the situation, the regulatory authorities on the quality of clinical trials more and more demanding, such a contrast will naturally appear mismatch.
fact, there are some things we can do to assist or even replace the bidders, such as helping to design the scheme, but some of them are not, such as CRA's responsibilities.
The current rapid development of domestic CRA, business needs are large, the overall level can not keep up with the requirements of clinical trials, many CROs have not been professionally trained, do not have a medical background, even pharmaceutical background is not, and liquidity is great, a project replacement of three or four CRA is also the norm.
addition, in the previous decade, CRO companies had low-cost competition, many drugs attempted to save money, delegated to the CRO, and did not regulate them, which is a great risk for clinical trials.
of course, I also see some large enterprises with the increase in investment, research and development varieties increase, awareness and ability is slowly increasing, the research team is gradually reasonable.
: "722" clinical verification on the impact of clinical institutions? Li: The overall impact is certainly good, and there are concerns.
in general, is a long over over time to do a good thing, absolutely bring positive energy to the industry! Such requirements and regulation are more fair and just for all parties.
the importance and responsibilities of the bidders.
but there are some concerns, first of all, it is not conducive to increasing the enthusiasm of hospitals to participate in clinical trials.
the entire clinical trial, CRO and the bid party are direct stakeholders, and the hospital is an important "supplier" to complete the trial in accordance with the aforementioned cooperation agreement.
hospitals do more clinical trials, especially for innovative drugs, which mean greater responsibility and risk, and while I know we can't fake them ourselves, there's no guarantee that every trial will be perfect, flawless, and not missing.
no one can guarantee that there will be no mistakes, which is the general rule of clinical trials.
if hospitals' reputations are to suffer as a result of clinical trials, hospitals will need to be more careful in assessing whether it is worth taking risks to conduct clinical trials.
it's harder for organizations and PIs to withstand this pressure.
from the perspective of PI, most of the senior chief physicians, professors, now become directly responsible, the responsibility is great, like the hospital, to undertake the project will be more cautious.
I think the new policy is deeply rooted in people's hearts and implementation is a step-by-step process, and the policy should also be "targeted treatment", in addition to punishing data counterfeiters, but also to encourage which serious, multi-do researchers and institutions, for example, in the verification of multi-center trials, the selection of verification centers, do not recommend each selection of more cases of the center.
, hospitals are reluctant to do more to avoid being checked.
, such as the establishment of institutions or PIs with good records, the establishment of verification-free measures are better.
: Some enterprises feel that PI is a school bully, very strong, what do you think? Li: Just as everyone has their own style, PI has a different style.
some of the PI may be "schoolboys", I believe some certainly not, and will not be very strong.
I personally believe that in clinical studies, it is not important to judge whether the other person is strong or not, it is important to be professional, scientific, committed, rigorous and responsible.
if the bid party really lacks professional ability, PI is really professional, then you may as well listen to PI's advice, he helps you come up with ideas, but also willing to assume this responsibility, which is a good thing.
strong is also good, not strong, it is important to be responsible for clinical trials, can communicate.
PI is selected by the bid party, the bid party sometimes also needs to use the strength of PI and his academic dominance to do the follow-up market.
other words, it is the bid party that knows it.
for clinical trials themselves, especially those with a large input and time span, choosing the right PI is a big decision, weighing the pros and cons and choosing carefully, especially the lead PI.
: How to choose the right PI? Li: Experienced, capable, able to communicate, good coordination.
to conduct clinical trials of innovative drugs, I, as a lead PI, wanted to help the bidders find as many professionals as possible.
Because everyone's experience and ability are limited, the entire clinical trial process is complex, a good PI should not only have their own professional ability, but also have the ability to discover all areas of the industry, and use these resources in clinical trials.
, some bidders like to find the dean to do PI, the bidders want to use their influence.
theory, this is a good choice, leaders have more resources and appeal, conducive to the experiment.
But in fact, clinical trials are a very detailed and complex systematic research, requiring researchers to pay close attention for a long time, require PI serious and responsible, have plenty of time to directly participate in and manage assistance projects, not just a name can be.
the "7.22" clinical trial verification, it is clear that PI as the person directly responsible, I believe that the bid will be more careful in selecting PI.
: What do you think is the method of clinical evaluation of generic drugs that is more in line with the law of clinical trials? Li: First of all, in line with China's relevant laws and regulations.
I think it is necessary to confirm pharmaceutical consistency and biological equivalent first, for foreign listed, domestic generic drugs not yet listed, whether multi-center clinical trials are needed, personal opinion needs to consider several factors: first, foreign applications and the support of the entire declaration data, which needs to be reviewed by CDE to determine whether it is sufficient;
When we do bioethics tests, we can get drug data, compared with foreign data, if the PK data are very different, there may be racial differences, which will affect the effectiveness and safety of the drug.
this requires clinical studies to test the problem.
food has an effect on drug absorption metabolism, it is also a factor that needs attention.
P450 enzymes, some of which are racially different, cannot be ignored.
, according to safety information, if there is a dose-related more serious AE, dose adjustment needs to be considered.
if these problems are not available, based on available information from abroad, and biological equivalent test data do not suggest that there may be risks, I do not think there is a need for multi-center clinical trials."
: What are your expectations for the future? Li: Now our hospital leads a number of new drugs that have been highly concerned by the industry, some have entered Phase III, some are ready to enter Phase III, and some are in Phase II.
main evidence of the disease is Alzheimer's disease and depression.
the risks of developing new drugs are high, they are still worth looking forward to.
expect success for all of us and be prepared to fail.
for myself.