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Professor Yao Chen and Mr. Ge Yongbin had an in-depth conversation on "Compliance and Challenges of Real-World Data Research"!

 Last Update: 2023-02-03
 Source: Internet
 Author: User

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From April 7 to 10, 2023, CMAC will hold the "China Innovative Drug (Device) Medicine Conference and CMAC Annual Conference" at Suzhou International Expo Center, with the theme of "Innovation and Departure, Medicine Runs Through the Process", the scale of the conference will reach a new high, with a lineup of 1000+ speakers and more than 100 sub-forums
.
In the future, CMAC will conduct exclusive interviews with the leaders of each sub-forum to discuss hot topics in the medical field, and at the same time let CMAC readers better understand the characteristics
of each forum.
The following is a wonderful conversation between Mr.
Yao Chen and Mr.
Ge Yongbin, the leaders of the sub-forum of "Medical Compliance and Data Governance and Protection"!

Yao Chen (Director of Medical Statistics Office, Peking University First Hospital / Vice President of Hainan Real World Data Research Institute)

Ge Yongbin (Senior Partner, Zhong Lun Law Firm)

Q1: In terms of real-world data compliance, as far as the two teachers know, what are the foreign countries that we can learn from?

Ge Yongbin

Foreign regulations in this regard are mature, such as the 21st Century Cure Act in the United States and the Use of Real-World Evidence to Support Medical Device Regulatory Decisions, the Guidelines for the Use of Electronic Health Record Data in Clinical Research, the Framework of the Real-World Evidence Program, and the Use of Real-World Data and Real-World Evidence to Submit Drug and Biologics to FDA, all of which provide rules and guidelines
for the practical application of real-world research.
In the European Union Medicines Agency (EMA), it has also issued the "Scientific Guidelines for Post-Market Effectiveness Evaluation of Drugs" and "Guidelines for Pharmacovigilance Management Practices
".
The Japan Medicines and Medical Devices Agency (PMDA) has also issued relevant documents such as the Basic Principles on the Use of Health Information Database for Post-Market Monitoring of Medical Products, General Steps for Post-Market Drug Research Plans, and Amendments to Post-Market Drug Research Specifications, which put forward many requirements
for the use of real-world data for post-marketing safety evaluation of drugs.
So my understanding is that in foreign countries, there are already many relevant regulations in this regard, and the application practice of real-world data is also very extensive
.

China's CDE has also launched the Guiding Principles for Real-World Evidence to Support Drug R&D and Review (Trial), as well as the Technical Guidelines for Real-World Research to Support Children's Drug R&D and Review (Trial), and the Technical Guidelines for Real-World Data for Clinical Evaluation of Medical Devices (Trial
).
However, in the basic laws in the field of drug supervision, such as the Drug Regulatory Law and the Measures for the Administration of Drug Registration, the relevant content
of real-world data has not been fully reflected.
Therefore, many legislative experts are calling on us to gradually improve the regulatory system of real-world data at the legislative level, and provide regulatory guidance and guidance
for the compliant application of real-world data.

Chen yao

I think the relevant foreign laws and regulations mentioned by Mr.
Ge just now from the level of regulations are relatively perfect, in fact, China is basically in
the first square in this regard and the world.
Although I am not familiar with the specific regulations, I am already aware of this problem
.
Around New Year's Day 2021, I discussed with Dean Shen Weixing of Tsinghua University Law School how to achieve the reasonable use of data in the real world, as well as some issues
of data right confirmation.
From the legal level to ensure the compliance and legal development of real-world data research, most of the domestic information technology security laws and regulations in this area are gradually introduced from other fields, which is a good phenomenon
.
But many people now lack a deep understanding
of the compliance issues of real-world data research.
The Personal Information Protection Law of the People's Republic of China (PIPL) came into effect on November 1, 2021, and we need to popularize legal knowledge
among clinical researchers.
I think that in terms of real-world data research, the country's laws and regulations have been gradually improved, and the "PIPL" can be said to be the highest legal guarantee
for the legality of real-world data research.

Q2: Mr.
Yao, do you think Hainan still has any challenges in terms of compliance and security of real-world research data in the Lecheng Pilot Zone? What are the unique features?

Chen yao

Real-world data research actually emphasizes the characteristics of real-world data, because real-world data is mainly derived from daily routine medical data
.
In order to facilitate patients, the state has introduced many corresponding policies in this regard, and in order to make it convenient for patients to seek medical treatment or medical insurance, many places have now carried out the "three-doctor linkage" plan
.

At that time, when we designed the real-world research platform of Hainan Province, we also invited experts from the Hainan Provincial Big Data Bureau, believing that these medical data could be directly used
through the "three-doctor linkage".
But using this data to conduct real-world research actually faces an important compliance issue, and that is ethical guidelines
.
In 2016, the International Committee of Medical Science Organizations and the World Health Organization developed the International Ethical Guidelines for Health-Related Research Involving People (the Guidelines), of which Guideline 12 specifically refers to the collection, storage and use of data in health-related research, with particular emphasis on the need for institutions to establish a management system for the use of such data for future research, so as to obtain authorization from the data source for the use of such data in future research, and the researcher must not harm the personal rights and well-being
of the data source.
This is a very important request
.
This implies the "personality rights" of the data source (such as patients), because if the patient's data is used for research in addition to treatment, many non-medical professionals may be involved, which inevitably leads to personal privacy issues
.
Therefore, if we want to use these data for research, we must pay attention to the issue of
informed consent.

Informed consent can be divided into pan-informed consent and individual informed consent
.
Informed consent is often used in medical care, for example, in medical informed consent, which may mention that the data may be used for medical research
in the future.
However, universal informed consent does not mean that individual informed consent can no longer be done in the future
.
As a medical research, the data is not only limited to the hospital, but also includes additional data collected according to the purpose of the study, especially follow-up data, when it is not enough to have universal informed consent, but also to explain it clearly to the data provider, because they have the individual right to
know.

In addition, the Guidelines also mention the opt-out procedure, that is, to clarify the existence of this procedure in the PIC and make patients aware of the existence of this procedure, and to provide sufficient information to inform patients of their right to withdraw their data
.
If you directly use the data in the "three-doctor linkage" database for research, in fact, there is a lack of a clear path to obtain informed consent, which must be considered
.

Of course, the PIPL also specifically specifies that when processing personal information, there should be a clear and reasonable purpose, it should be directly related to the purpose of processing, adopt a method that has the least impact on personal rights and interests, and the collection of personal information should be limited to the minimum scope of achieving the purpose of processing, and excessive collection of personal information
must not be allowed.
This means that collecting all the data together without a clear research purpose at first is actually not in compliance with the Personal Information Protection Law
.

This is a real-world research platform in Hainan Province, using "three-doctor linkage" data to do real-world research, which I think is debatable
.
I don't know what kind of attitude
you have, Lawyer Ge.

Ge Yongbin

Thank you Mr.
Yao for sharing
.
After the introduction of the "Personal Insurance Law" and the Data Security Law, the state's law enforcement in this regard is very strong, and it is understandable that everyone is under pressure
.
Real-world research is really valuable, so it's
a must to move this forward.
The country is now also studying the issue
of data ownership that Mr.
Yao just mentioned.
Worldwide, there is no clear theory
of data ownership that is acceptable to everyone.

Just now, Teacher Yao talked about the issue
of pan-informed consent.
In fact, in Europe and the United States, pan-informed consent can be accepted
.
They felt that if they made a general informed general consent when collecting data at the beginning, it would be no problem
to use it within a certain range.
Of course, the data provider has the right to modify, delete or withdraw the data at any time, as well as to know how the data is used, and the information subject must be provided with a convenient link without any additional trouble, which is a basic right
.

Our country also has a relevant law "Measures for the Ethical Review of Biomedical Research Involving Humans", article 39 of which stipulates that the donor of biological samples has signed an informed consent form, and if the donor sample and related information can be used for all medical research, the informed consent can be exempted from signing the informed consent
form with the approval of the Ethics Committee.
Therefore, the donation of biological samples can be done in a pan-informed approach
.
In practice, we are also discussing that if data is collected prospectively for future real-world research, it is also possible
to obtain prior ethical consent and general knowledge.
However, retrospective data, whether it is medical treatment, medical insurance or individual data in medicine, involves informed consent, because the previous informed consent may not be complete in itself and does not fully reach the level of general knowledge; In addition, the quality of the data may be poor, many of the filling is not standardized, and it is difficult
to complete.
So I think for data to really be used for research, it needs to be de-identified and even desensitized
.

Just now, Mr.
Yao said that many places are now doing regional research hospital platforms, which are also for the data collected in the future, and how to solve informed consent and how to clean up the existing data and retrospective data is still a problem
.
Moreover, this big data in the process of cleaning, formatting and anonymization, will involve the traceability of data, which needs to be further improved
both at the process and technical level.
There are many challenges
to retrospective data.

But we have been suggesting that hospitals start to establish regional networks or data alliances for new data now, and slowly unify data entry standards, so that sharing data or using data within the alliance can be done with general informed consent
.
Teacher Yao, listen to your opinion
as well.

Chen yao

The PIPL only emphasizes the protection of personal information, and the scope of protection does not include anonymized information
.
So what is anonymized information? For example, after everyone does a study together, cleans up the data according to a certain research purpose, and forms a standard database, then the personal information can be completely removed, that is, anonymized, so that the information in the database can be shared within a multi-center scope, forming a multi-center research shared database
.
In this way, the data can also be exchanged externally or uploaded to the databases of the various alliances
, which are now so-called.
But how do you become an anonymized database or a research database? In fact, the PIPL has clearly stipulated that Article 6 specifically mentions that when processing personal information, there should be a clear and reasonable purpose, it should be directly related to the purpose of processing, the method with the least impact on personal rights and interests should be adopted, the collection of personal information should be limited to the minimum scope of achieving the purpose of processing, and excessive collection of personal information
should not be allowed.
This one is important
.
The processing of this personal information is also the process of
turning this original information into anonymized data.
Article 7 also mentions that the rules for the processing of personal information shall be disclosed in accordance with the principle of openness and transparency, and the purpose, method and scope
of the processing shall be clearly stated.
Article 8 also emphasizes that when processing personal information, the quality of personal information should be ensured to avoid adverse effects
on personal rights and interests due to inaccurate and incomplete personal information.
This means that this information should faithfully reflect the actual situation
of the patient.
Article 9 also mentions that the processor of personal information shall be responsible for its personal information processing activities and take necessary measures to ensure that the personal information processed is secure
.

If these rules are met, I believe that the shared research information will be safe and legal and compliant
.
To do that, I think it's important to be clear about source data and research data base).

Source Data Be sure to include personal information for future research data traceability; But the data that becomes a database that can be studied should be cleaned up, standardized and structured data
.
In this way
, future research data can no longer be restricted by the "PIPL".
Therefore, we should change the existing thinking when doing research, and the data shared by each center should be the research data
formed according to the unified scheme.
As for the raw data of each patient, it should be stored in each hospital to avoid leakage of personal information
.

Ge Yongbin

It is indeed necessary to reasonably turn the source data into data base for everyone to study and share
.
Anonymization is the most difficult step
.
Under the premise of high data quality, the technical level is not difficult
.
At present, there is no clear determination of the rights and interests of data and the distribution of benefits, and the collection, storage and subsequent confidentiality of data by hospitals is more for medical obligations
.
After the epidemic, many hospitals began to pay attention to clinical research, and in the process of collecting data, not only doctors need to actively cooperate, but also the entire system needs to be adjusted
as a whole.
So there are two main problems here, one is to make the medical staff of the medical system interested and willing to enter data according to the standard format; One is to at least be informed
from the beginning of data entry.
Coupled with the technical solutions introduced by Mr.
Yao, it is not difficult to meet the requirements of the "PIPL", and there is no problem
at the regulatory level.
So can hospitals clean up data with current data quality? Please introduce Teacher Yao
.

Chen yao

Okay, I'd like to share my views
on that.
I know the work of the hospital very well, indeed as Mr.
Ge said, first of all, the issue of confirming rights, I published "Information Security Challenges of Real-World Data Research" in the journal "China Food and Drug Administration" some time ago, in this paper I specifically talked about the promulgation of the Shenzhen Special Economic Zone Data Regulations in July 2021, in this regulation mentioned several concepts, I think you can refer to
.

The first is the "personality right", which is a right
to protect the privacy of patients.
The collection of patient information in the hospital can only serve the patient, but the individual service
.
But medicine is not only to solve the problem of individual pain, but to solve the overall problem
of similar patients through medical research.
From a statistical point of view, from an individual to a group, there must be a scientific law
of medical formation.
At this time, doctors should process the patient's data to form a research database, and at the same time accumulate certain cases to study and analyze and derive scientific laws
.

This process is actually a processing process, once the data is removed from the specific identified individual data, it becomes de-anonymized research data, which should be given "property rights"
.
Property rights embody its value and are tradable
.
For example, if we do a randomized controlled drug clinical trial, the sponsor needs to pay the hospital for clinical research, including the corresponding remuneration for CROs and researchers, which are actually through the so-called concept of "property rights", I don't know if I understand it correctly
.

Ge Yongbin

You understand very well and indeed should be
.
A person's name, etc.
has no direct value in itself, and only has a certain "property right"
when it is used by others.
There is no doubt that the anonymized data rights are not the original data subject
.
But who exactly does the right belong to? In general, it should be attributed to the hospital
.
Because the hospital put in the labor in
the process.
It also includes other participants who have joint rights
to control, process, process and research of data.
The State may use this data
in the public interest under certain conditions.
Hospitals, pharmaceutical companies, and various data made by the clinical research sponsor company itself can also bring benefits and form property rights
after desensitization.
I couldn't agree
more.
But there is a difference, that is, as far as I know, now real-world patient data, on the one hand, for medical research, on the other hand, may also be used for patient recruitment and DTP pharmacy, which has to be traced back to individuals through data, and this process should be particularly careful, because this model is the most direct way to cash out medical big data, but there must be a compliant solution
.

I think there is no problem at all when Mr.
Yao said that the data is cleaned and used for research, and I believe that China will agree at
the legislative level.
However, if it is used to track the personal information of the information subject, there is a compliance problem
.

Chen yao

Yes, that's subtle
.
From a research point of view, I think so
.
In addition, regarding how to motivate doctors or hospitals, I think there needs to be a management process
.
The specific work in the hospital is often the youngest low-level doctor, who has a heavy workload, but in the end does not show value in the paper
.
This brings up a big problem - how to evaluate the performance
of medical staff in scientific research.

Doctors in clinical research actually have to pay a lot of labor, specifically reflected in the treatment of patients, data collection, etc.
, so how much data each doctor collects, how to collect it, etc.
, there are many details here, if there is no corresponding tool to record, it is difficult to quantify, performance appraisal will be difficult to evaluate
.
I designed the source data logging tool ESR with this
in mind.
By recording the efforts of medical staff with electronic information technology, it is easy to convert performance and reflect the achievements of doctors who work specifically
.
The issue of authorship and contribution of future evaluation articles can also be quantified, and the performance evaluation of clinical research will be very fair
.

Another point is that doctors in clinical research and usual clinical treatment are actually two concepts, to do real-world research only relying on medical data is far from enough, can not achieve the goal of research, so real-world
research just to aggregate medical data is not enough.
Because clinical research often requires the derivation of causality and the follow-up data of patients, this part of the data is incomplete
in medical information systems.
Therefore, real-world research data cannot be completed simply from a medical data, and it still needs a lot of work
.
This requires the extra value of the doctor's work, which is very important
.

Ge Yongbin

I would like to add that regarding the KPI assessment of hospitals, I remember that Shanghai issued a regulation the year before last, that is, the clinical research of hospitals is used as an assessment indicator, and the number of clinical research projects completed by hospitals is also an important indicator
.
But I don't know if this was implemented
later.

Then back to the doctor, the daily diagnosis and treatment doctor is only responsible for medical treatment, the collection of data, fill in the integrity of various data information, if there are also assessment indicators, the doctor will also do a very good
job.
When research-oriented doctors participate in research, the data obtained directly will be of high quality
.
In this way, the back is also easy to clean and compliance can be easily achieved
.
But the key is that a lot of data because the ownership is not clear, the assessment is not in place, resulting in the daily diagnosis and treatment doctors have this idea: I don't participate in the research, you didn't pull me into the project, why should I be so detailed, I just treat the patient
.
They were also not motivated for out-of-hospital follow-up
.
So how can the assessment of the entire medical system improve the quality of data?

Chen yao

I think clinical research must be prospective, collect data
according to the requirements of the research purpose.
So the data from cohort studies, registry studies, and even effectiveness studies must have a very clear purpose
.
I'm working on design this time When the source data recording tool ESR binds the content of the program to the case, if the doctor does not write a piece in the process of writing, the computer will automatically remind to supplement this piece of data
.
This is a big role
that computer technology will play in future clinical research.

Q3: The two teachers are the chairs of the sub-forum "Medical Compliance and Data Governance and Protection", do you have any preliminary thoughts on the direction of the sub-forum?

Chen yao

For source data, many doctors have different understandings, and in real-world research, there are many methodological applications on medical compliance and data governance, and we need to change our concepts and explore
.
Therefore, I suggest that I first work with Mr.
Ge's team to design a questionnaire to investigate the current clinicians' understanding of relevant laws and understand everyone's current situation
.
Then Mr.
Ge will talk about medical compliance from a legal perspective, then I will talk about it from the perspective of data governance, and then invite guests to talk from
the perspective of management.

Ge Yongbin

Teacher Yao's advice is very good
.
First of all
, the requirement of unification is too important.
Because doing research without data, without real things, is just empty words
.
I completely agree with Teacher
Yao's thinking.
Second, I would also like to add that some start-up pharmaceutical sponsors often confuse QA with clinical compliance, thinking QA It's compliance
.
This is a big misunderstanding
.
In the process of clinical research, they are often not proficient in GCP and all relevant laws and regulations, including personal insurance law, data security law, etc
.
So the idea of the questionnaire survey is particularly good, and we can also add the opinions of the sponsors to see their perception
of compliance.

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