Resolution based on the results of the V annual scientific-practical conference "RWD/RWE. Possible and real"

Introduction

On September 19, 2024, in Moscow (Russian Federation), the Association of Health Technology Assessment Specialists, the Association of Clinical Pharmacologists, and the St. Petersburg Division of the International Society for Pharmacoeconomic Research and Scientific Analysis organized and held the 5th annual scientific and practical conference with international participation "RWD/RWE. Possible and Real". The topic of the conference brought together leading specialists in the field of RWD/RWE.

A separate symposium "Digital Transformation in Medical Research: Possibilities of Data Science, AI and Engineering Approaches in RWE" was held within the framework of the V conference.

The conference participants discussed tools for researching RWD/RWE, the growing importance of RWE in modern medicine, legislation, as well as global prospects in the world, Russian Federation and the EAEU. A total of 28 reports were presented at the conference.

We invite you to familiarize yourself with the Conference Resolution.

RESOLUTION

This Resolution based on the results of the V annual scientific and practical conference with international participation "RWD/RWE. Possible and Real", which occurred on September 19, 2024, Moscow (Russian Federation).

The conference participants noted the significant progress made since the previous meetings. Thus, within the framework of the EAEU working group, a group of experts developed a whole series of guidelines (roadmap) for the EAEU in the field of collecting, analyzing and using RWD, and Order of the EEC Board No. 155, "General approaches to the development of regulation of the circulation of medicines within the Eurasian Economic Union in terms of collecting, analyzing and using RWD" were adopted.

At the same time, the state, the expert community, public organizations, and the industry are faced with a number of systemic issues that require urgent solutions, which were brought up for discussion by the conference participants.

During the conference, the following limitations were identified for the implementation of RWD/RWE obtained on their basis:

Legal framework in Russia at the national level:

1. The absence of norms at the legislative level regulating the procedures for collecting and analyzing RWD, including developed approaches to ensure quality of the data obtained and the representativeness of the final conclusions based on the collected data.
2. The absence of developed regulatory approaches regarding the implementation of RWD and/or evidence obtained based on the analysis of RWD, and their use together with the results of clinical trials.
3. The absence of tools to compare data on a specific drug with patient data sources in which information on patients is collected (or from which information can be obtained) do not interact with monitoring systems.
4. There is no possibility of accessing anonymized data for their reuse for organizations conducting scientific and research work, taking into account the protection of personal data.
5. The confidentiality of information remains the most pressing causing discussions among the expert community, as well as the ethical aspects of conducting research.

Using RWD/RWE in assessing health technologies in Russia at the national level:

1. The absence of legal frameworks governing the procedure for using RWD does not allow for the widespread use of data in decision-making when assessing health technologies.
2. According to the Rules for the formation of lists of drugs for medical use and the minimum range of drugs required to provide medical care, approved by RF Government Resolution No. 871 of 28.08.2014, in terms of the scale for assessing the reliability and persuasiveness of evidence, the provision of real-world study (RWS) results leads to a lower score than in the absence of such.
3. As part of the comprehensive assessment procedure for drugs when included in the list of vital and essential drugs (and other lists), it is permissible to provide the results of observational studies, which, in fact, are carried out under RWD conditions. Nevertheless, the lack of developed regulatory approaches to conducting such studies complicates the process of obtaining data and evidence and gives rise to mistrust of the results obtained.

Using RWD/RWE in the development of clinical guidelines in Russia at the national level:

1. There is no established mechanism for taking into account the results of real-world studies in the development/updating of clinical guidelines.
2. There are no special regulations that allow the use of RWD contained in information systems in the healthcare sector by professional non-profit organizations in the development/revision of clinical guidelines.

Using RWD/RWE in the implementation of innovative models of drug provision in Russia at the national level:

1. The absence of the RWD/RWE paradigm in the domestic healthcare system, which does not allow the implementation of a value-oriented approach and innovative drug provision models. At the same time, to launch pilot projects for the implementation of innovative models of drug provision, it is necessary, among other things, to analyze data on the clinical efficacy of a drug for the implementation of public procurement (for example, according to the risk-sharing model).

Using patient-reported outcome data:

1. There are still unresolved issues with collecting and analyzing patient-reported outcome (PRO) data — data on health status, treatment, and outcomes reported directly by patients, including symptoms, functional status, health-related quality of life, satisfaction with medical care, and adherence — which leads to insufficient disease and symptom control, decreased adherence, and decreased patient quality of life and survival.
2. The undeniable advantages of studying patient-reported outcome measures (PROMs) are improved physician-patient communication, timely detection of symptoms of disease progression and adverse events from therapy, and patient involvement in the clinical decision-making process.

When implementing information systems as a source of RWD in Russia at the national level:

1. The low quality of data collected by medical information systems of medical organizations, including clinical, statistical, and other data, and their incompatible format do not allow for the systematic processing and use of RWD when making decisions in the healthcare system.
2. There are no legal regulations that allows for the safe collection and analysis of anonymized data from information systems in the healthcare sector, which slows down research, developing, and ultimately, the availability of RWD.
3. The issue of the objectivity of published medical and statistical data and their compliance with RWD remains open.
4. There is no regulated mechanism for access to RWD for medical specialists, experts, scientists, non-governmental, and commercial companies, taking into account the legislative requirements for the protection and processing of personal data.

Obtain RWD from registers in Russia at the national level:

1. The Federal register combines data on individual categories of patients (listed nosologies and persons entitled to receive state social assistance).
2. The absence of a single register of patients receiving medical care within the state healthcare system, i.e., a register that would combine all registers.
3. The need to adjust the legal framework in the field of personal data processing and ensuring access to them by third parties is noted.

Protection and processing of personal data:

1. Confusing the concepts of "anonymization of personal data" as the responsibility of the personal data operator upon achieving the goal of processing personal data, which reasonably implies irreversibility (clause 7 of Article 5 of the Federal Law "On Personal Data" dated 27.07.2006 No. 152-FZ), and as an action that implies reversibility and subsequent protection of personal data obtained as a result of anonymization ("Requirements and methods for anonymization of personal data", approved by the Order of Roskomnadzor dated 05.09.2013 No. 996).
2. The absence of the concept of "anonymization of personal data" and regulation regarding work with anonymized data and anonymization of data in a simplified manner compared to personal data obtained because of anonymization.
3. The lack of the ability to interact between organizations conducting scientific and clinical research, developing and selling medical drugs, medical equipment, and medical products with information systems in the field of healthcare and medical organizations, including in accordance with the Decree of the Government of the Russian Federation of 12.04.2018 No. 447, the lack of a unified system containing data from RWD/RWE available for use by the above-mentioned organizations.

Legal framework at the EAEU level:

1. Methodological approaches to obtain data on efficacy and safety based on relevant RWD/RWE data are the final stage of development.
2. Guidelines have been prepared for discussion with authorized bodies of the EAEU member states at the Eurasian Economic Commission: on biostatistics; conducting non-interventional studies in RWD/RWE; ensuring the quality of RWD/RWE obtained on the basis of RWD analysis for making regulatory decisions when regulating the circulation of drugs.
3. Guidelines on general issues related to data collection, analysis and application of data from RWD/RWE under the approval process of the EEC.

During the conference, the following solutions were proposed for the implementation of the RWD/RWE:

Legal framework in Russia at the national level, it is necessary to:

1. Together with authorized executive authorities and the pharmaceutical industry, we prepared amendments to the Federal Law of 12.04.2010 No. 61-FZ "On the Circulation of Medicines" to include in the provisions of this federal law terms adopted at the Eurasian Economic Union level for the purpose of further developing the national regulatory framework in the field of collecting, analyzing, and using RWD to resolve issues not regulated at the EAEU level.
2. RWD and/or RWE obtained on the basis of RWD analysis and their use together with the results of clinical trials should, in the future (in the medium or long term), have the opportunity to become a scientific basis for making regulatory decisions related to the competence of national federal authorized bodies, taking into account the regulatory requirements developed at the EAEU level.
3. The need to support the national register of observational and other studies as a public source of information on RWD/RWE studies.
4. Establishment of a body (committee) to monitor the quality of methods and tools for collecting and processing data from RWD/RWE.
5. Together with authorized executive bodies and the pharmaceutical industry, we will prepare amendments to Article 2 of Law No. 152-FZ defining the term "anonymized personal data". Possible approach: anonymized personal data is a set of structured and unstructured anonymized (including through anonymization and pseudonymization) personal data in large volumes, characterized by a high rate of variability, that are subject to automatic processing using computer algorithms to identify certain correlations, trends, and patterns.
6. Together with authorized executive bodies and the pharmaceutical industry, we prepare amendments to paragraph 2 of Article 3 of Law No. 152-FZ, a direct exception indicating that the person to whom anonymized personal data concerning the state of health is transferred for the purpose of processing within the framework of the functioning of medical decision support systems is not the operator of personal data.
7. Together with authorized executive bodies and the pharmaceutical industry, we will prepare amendments to paragraph 9.1 of Part 1 of Article 6 of Law No. 152-FZ to indicate that the subject's consent to the processing of anonymized personal data for scientific and/or medical purposes related to the creation of systems to support medical decision-making is not required.
8. Together with authorized executive bodies and the pharmaceutical industry, prepare corresponding amendments to No. 323-FZ and other legislative and bylaws, including in terms of harmonization with the legislation of the EAEU.

Using RWD/RWE was based on the assessment of healthcare technologies in Russia at the national level:

1. Together with authorized executive bodies and the pharmaceutical industry, preparing amendments to paragraph 55 of Article 4 of the Federal Law of 12.04.2010 No. 61-FZ "On the Circulation of Medicines" "... analysis of information on the comparative clinical efficacy and safety of a medicinal product, including on the basis of real-world data."
2. Together with authorized executive bodies and the pharmaceutical industry, amendments to the Rules for the formation of lists of medicinal products for medical use and the minimum range of medicinal products necessary for the provision of medical care were approved by RF Government Resolution of 28.08.2014 No. 871, in terms of taking into account evidence of RWD/RWE in conducting a comprehensive assessment of medicinal products. As a basic option, it is proposed to introduce into the scale for assessing the reliability and persuasiveness of evidence of RWS designs with the assignment of points sufficient to reach the threshold value (in accordance with the general requirements set out in the EAEU regulations on obtaining and using RWD/RWE data, as well as subject to the formation of positive law enforcement practice).
3. Together with the authorized executive bodies and the pharmaceutical industry, prepare amendments to the Rules for the formation of lists of medicinal products for medical use and the minimum range of medicinal products necessary for the provision of medical care, approved by RF Government Resolution No. 871 of 28.08.2014, in terms of ensuring the possibility of inclusion in the lists subject to the conclusion of risk-sharing/ conditional compensation agreements (with the collection of RWD/RWE) (in accordance with the general requirements set out in the EAEU regulations on obtaining and using RWD/RWE data, as well as subject to the formation of positive law enforcement practice).
4. Together with authorized executive bodies and the pharmaceutical industry, prepare to work out the issue of amending the Rules for the formation of lists of medicinal products for medical use and the minimum range of medicinal products required to provide medical care, approved by RF Government Resolution No. 871 of 28.08.2014 on the inclusion of an additional assessment criterion "Availability of data indicating the effectiveness of the use of a medicinal product in RWD/RWE in the Russian Federation" in the Scale for quantitative assessment of additional data on a medicinal product.
5. It is necessary to create industry guidelines that can ensure the quality of RWD/RWE study and the reliability of the results provided for conducting a comprehensive assessment of medicinal products.

Using real-world study results in the development of clinical guidelines in Russia at the national level:

1. Together with authorized executive bodies and the pharmaceutical industry, preparation of amendments to Appendix 1 to the Order of the Ministry of Health of Russia dated 28.02.2019 No. 103n "On approval of the procedure and terms for the development of clinical guidelines, their revision, the standard form of clinical guidelines and requirements for their structure, composition and scientific validity of the information included in clinical guidelines" in terms of the possibility of expanding the consideration of RWD in the formation of clinical guidelines, as well as the use of such data by professional non-profit organizations in the development / revision of clinical guidelines (in accordance with the general requirements enshrined in the regulatory acts of the EAEU on obtaining and using RWD, as well as subject to the formation of positive law enforcement practice).

Using RWD/RWE when implementing innovative drug provision models in Russia at the national level:

1. Improving antitrust legislation to eliminate the risks of unjustified application of existing regulations to innovative models of drug provision.
2. Implementing a mechanism for taking into account RWD when assessing the effectiveness of treatment in the model of a payment agreement based on the results of therapy (in accordance with the general requirements set out in the regulatory acts of the EAEU on obtaining and using data from RWD/RWE, as well as subject to the formation of positive law enforcement practice).

When receiving RWD during the operation of information systems in the healthcare sector in Russia at the national level:

1. Implement security measures to control the quality of data collected and entered within the framework of information systems in the healthcare sector, including medical information systems.
2. Together with authorized executive authorities and the pharmaceutical industry, prepare and develop a set of national standards and unified normative and reference information for coding medical information and medical records to ensure compatibility and improve the interoperability of RWD collected from medical information systems.
3. Create and use a national register of observational and other studies that will allow the publication of data on studies and their results to increase the availability of RWD.

Use of patient-reported health and outcome data:

1. Developing a methodology for collecting and analyzing patient-reported outcome measures (PROMs) for diseases and conditions in which there is a possibility of symptom or condition correction.
2. Developing mechanisms for prompt feedback of collected data.
3. Implement programs to train physicians on the use of PROMs and their effective implementation in clinical practice.

When implementing information systems as a source of RWD:

1. Implementation of safeguards to control the quality of data collected/entered within the framework of information systems in the field of healthcare, including medical information and other systems, including clinical data, information on the provision and payment for medical care and other data characterizing the methods and volumes of provision and payment for medical care, statistical data.
2. Harmonization of the activities of experts and expert institutes participating in the development of RWD methodologies and structured electronic medical documents and reference books.
3. Together with authorized executive bodies and the pharmaceutical industry, the issue of regulating access to third-party data, subject to ensuring the protection of personal data, including as one of the solutions, would be possible to consider the introduction of a regulated institute of data intermediaries.

When receiving real-world data during the analysis/maintenance of registers in Russia at the national level:

1. Review approaches to maintaining registers to improve the quality and availability of sources of reliable scientific information on the patient population, prescribed and applied therapy, treatment outcomes, etc.
2. Develop and implement a single register for all nosologies, including the procedure for interdepartmental interaction for the purpose of maintaining and processing the data of such a register, as well as the possibility of providing limited access for the formation of RWD by the medical and scientific community, non-profit, and commercial organizations.
3. Establishment of mandatory use of registers within the framework of health technology assessment.
4. Within the framework of the RF Government Resolution “On the Unified State Information System in the Sphere of Healthcare”, it is advisable to provide for the procedure for collecting, storing and accessing the RWD, as well as organizing a system of access to the RWD (and not to its individual subsystems) for medical specialists, experts, scientists, non-governmental and commercial companies (IT-sector, pharmaceutical industry, manufacturers of medical and diagnostic equipment) by developing a separate mechanism providing such access and ensuring effective protection of personal data.

To improve the protection and processing of personal data:

1. Together with the authorized executive authorities and the pharmaceutical industry, we will prepare amendments to Article 2 of Law No. 152-FZ defining the term "anonymization of personal data" and "anonymized data", and distinguishing between the concepts of "anonymization" and "depersonalization". Possible approach: "anonymization of personal data" is a method of data processing that results in the aggregation of data that excludes their correlation with directly or indirectly determined or determinable individuals, "anonymized data" is data obtained as a result of the anonymization of personal data.
2. Together with the authorized executive authorities and the pharmaceutical industry, we will prepare amendments to paragraph 2 of Article 1 of Law No. 152-FZ, directly excluding the effect of Law No. 152-FZ on anonymized data. Possible approach: "This Federal Law shall not apply to relations arising from the processing of anonymized data or data obtained because of anonymization."
3. Simplify access to information systems in the field of healthcare for operators that are not medical or pharmaceutical organizations but are engaged in the development and supply of drugs and medical products (equipment), scientific and clinical research in the field of medicine and pharmacology.
4. Together with authorized executive bodies and the pharmaceutical industry, we prepare amendments to Law No. 152-FZ on a specific procedure for depersonalizing personal data on health status and constituting a medical secret, providing for the indication of categories of information subject to mandatory depersonalization, allowing for the unlimited use of the data obtained by operators for statistical, scientific, and research purposes, including for the purpose of processing within the framework of the functioning of medical decision support systems.
5. Expand the range of possibilities for processing special category personal data without obtaining the consent of the subject (clause 2, Article 10 of Law No. 152-FZ), providing for the possibility of such processing by operators that are not medical or pharmaceutical organizations, but are engaged in the development and supply of medical drugs and products (equipment), scientific and clinical research in the field of medicine and pharmacology, for statistical, scientific and research purposes, including for the purpose of processing within the framework of the functioning of systems to support medical decision-making.

Legal framework at the EAEU level:

1. Submit for consideration to the Working Group on the Formation of Common Approaches to the Regulation of Medicines Circulation within the Eurasian Economic Union proposals on the definition of the concept of real-world study (RWS) to establish a watershed between "pivotal" registration studies and RWS, since the requirements and scope of application differ, and also to create regulatory requirements for conducting RWS, obtaining high-quality data, generating evidence, and using it to make regulatory decisions.
2. Submit for consideration to the Working Group on the Formation of Common Approaches to the Regulation of Medicines Circulation within the Eurasian Economic Union proposals on the standardization of approaches to the implementation of RWD/RWE obtained on the basis of RWD analysis, and their use together with the results of clinical studies for scientific justification and making relevant regulatory decisions.
3. Submit for consideration by the Working Group on the Formation of Common Approaches to the Regulation of Medicines Circulation within the Eurasian Economic Union proposals on a unified approach to the collection, analysis and use of RWD, by developing at the EAEU level additional relevant guidelines regarding the use of electronic medical records as a source of RWD, the quality and transformation of RWD, the application of biostatistics principles in research, conducting research based on RWD and their designs, and the use of RWD for decision-making in the healthcare system.
4. Assistance is needed to accelerate the adoption of international requirements for the ICH GCP E6 rules. Currently, the Decision of the EEC Council dated 3.10.2016 No. 79 "On Approval of the Good Clinical Practice Rules of the Eurasian Economic Union" complies with ICH GCP E6 R1. Changes corresponding to version R2 are under consideration.
5. Submit for consideration by the Working Group on the Formation of Common Approaches to the Regulation of Medicines Circulation within the Eurasian Economic Union proposals on the need to develop special approaches to the use of RWD/RWE obtained on the basis of RWD analysis in conducting post-authorisation clinical trials and/or in organizing pharmacovigilance. It is necessary to develop regulatory requirements for the conduct and publication of non-interventional studies. In the context of conducting post-authorisation efficacy studies (PAES) and post-authorisation safety studies (PASS), it is necessary to comply with the “best practices” for collecting, managing, and analyzing data with a high level of quality and transparency. Monitoring of the efficacy and safety of drugs should be continued throughout the entire life cycle of a drug. PASS and PAES are important tools for identifying any additional risks or assessing the uncertainty regarding the benefit/risk of drugs.

Recommendations for patient communities:

1. Take direct part in the development of recommendations regarding new and effective methods of collecting evidence from RWD.

Organizing interdepartmental and expert interaction:

1. Create working groups to address the above issues in order to quickly implement the RWD approach and implement measures to increase the level of application of RWD.
2. Organize interaction between experts and expert institutions in terms of harmonizing the developed RWD methodology with approaches to electronic medical document management, data collection and processing within the framework of digital transformation.

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19.09.2024, Moscow, Russian Federation