Expert consensus on clinical research nurse management in China

Objective With the rising number of clinical trials conducted in China, the role of Clinical Research Nurses (CRNs) within clinical trial organizations has become increasingly crucial. However, in the absence of industry guidelines, the management of CRNs lacks clarity. This study aims to address this gap by establishing a consensus on CRN management. Methods The IACRN-Shanghai Chapter assembled a panel of experts to develop a consensus on the management of clinical research nurses. This consensus was formulated through an extensive literature review, expert evaluations, and collaborative conference discussions. Results The consensus document offers a comprehensive professional definition of CRNs and provides detailed insights into their management. It covers aspects such as job settings, qualifications, responsibilities, training, assessment, workload management, staffing allocation, performance evaluation, and career progression. Conclusions Establishing a professional definition for CRNs creates a standardized reference point for clinical trial institutions to effectively manage these professionals. Consistency in CRNs’ roles, training, staffing, and corresponding assessments is essential for promoting their sustainable and healthy development within the field of clinical research.


Introduction
Clinical research in China has flourished over the past few years, and an increasing number of medical institutions have begun to stress quality and efficiency when conducting clinical research.It is imperative to organize a well-trained research team to ensure the smooth progress of clinical research in medical institutions and high project quality.In general, research teams are comprised of research doctors, pharmacists, clinical research nurses (CRNs), and clinical research coordinators (CRCs).CRNs are gradually becoming essential core participants in clinical research and are responsible for the coordination and manage-ment of clinical research projects and to carry out subject treatment according to the research plan. 1 Because a record-keeping system has been implemented in clinical trial institutions, 2 more and more medical institutions will begin to train full-or part-time CRNs.The initial group of CRNs in China joined the International Association of Clinical Research Nurses (IACRN) and established the China (Shanghai) branch.The IACRN-Shanghai Chapter regularly holds academic exchanges and training activities to discuss the progress of clinical research and nursing work with international peer experts.To promote the healthy development of clinical research nursing in China, the IACRN-Shanghai Chapter assembled expert teams to discuss the management problems of CRNs

Draft of consensus
According to the retrieved literature, the writing team summarized, sorted, analyzed, screened, and refined the six key themes of CRN management, as follows: "role definition;" "position setting and qualification;" "responsibilities and tasks;" "training and assessment;" "job quantification and manpower allocation;" and "performance assessment and promotion."The members of the writing team are responsible for writing one of the topics first, then three members summarize the topic.The writing group has conducted two rounds of group discussions on the first draft of the consensus.The first draft of the consensus is mainly about discussion, and the argumentative expression requires readers to take time to understand.After sorting out the internal relevance among the six themes, the writing team made a structured list of the content of each part in the second draft to more clearly demonstrate the intrinsic relevance of each topic in postmanagement.In the second round of discussion, the writing group will discuss the specific content of each topic one-by-one, and the corresponding items shall be reserved and adopted for expression, which shall be agreed upon by the writing group, and finally form a consensus draft.

Expert discussion
After the first draft of the consensus is formed, it will be sent to five experts by mail for review.Five experts put forward opinions on each theme, including four opinions on the first-level theme and 25 opinions on each content under the first-level theme.According to expert opinions, the order and mode of first-level theme expression are adjusted, the second-level theme expression is streamlined, and the consensus content is adjusted.

Soliciting opinions
Two rounds of meetings and discussions will be held within the IACRN Association.The annual meeting will be held in the form of an online meeting of the IACRN-Shanghai Chapter on October 20, 2020.The participants include 70 members of the IACRN-Shanghai Chapters.The participants discussed the official content of the consensus together and collected four opinions for modification.At the annual meeting held in Nanjing, China, on October 30, 2021, the clinical nursing managers of the annual meeting clarified the corresponding concepts and answered the participants' questions.

CRN definition
A CRN refers to a member of the nursing staff with a nursing professional education background and nursing practice qualifications who participates in clinical research-related work (ie, engaged in clinical research project management and coordinating research parties, and performing subject treatment in accordance with the research protocol).CRNs work primarily in clinical trial institutions, placing a focus on the balance between subject protection and research protocol adherence, and solving issues involving clinical care feasibility and clinical research compliance. 1

Postsetting of a CRN
Medical institutions conducting clinical research are suggested to subdivide the nursing team and set up full-or part-time CRNs, with reference to the training of specialist nurses. 17According to the hospital or department management mode, the number and complexity of clinical research, the population demographics of research subjects and other aspects, and the number of personnel who need to set up CRNs is determined. 20

Part-time
Departments or hospitals with a small number of clinical studies require part-time CRNs who are usually clinical nurses. 17

Full-time
Departments or hospitals with complex or considerable clinical research projects require full-time CRNs who are external recruitment/ separate professional CRNs from existing caregivers and can be classified in one of three management modes as follows.
1) managed by professional groups or departments; 2) managed by the institution office/clinical research center; and 3) managed by the nursing department.

Education background and professional requirements
A college degree or above is required with a major in clinical nursing, a nurse qualification certificate, and registration in medical institutions.

Language requirements
An ability to read and write in Chinese and English to meet the needs of clinical research is required.

Office software capability
The necessary skills in using office software and office equipment, and proficiency in using EXCEL, WORD, and other office software are required.

Responsibilities and task framework of CRNs
Clarifying the job responsibilities and tasks of CRNs established the basis for the training, manpower allocation, and performance evaluation.One CRN job responsibility category has 15 responsibilities under several tasks. 17,22The second category involves the clinical research development stage 21 and has five stages, including basic work, before start-up, start-up stage, project implementation, and close-out.At each stage, the CRN should undertake different responsibilities and tasks.Based on the CRN responsibilities and task framework table, all the categories of CRN responsibilities are listed, and the work tasks of research nurses in different research processes are specified (Table 1).

Setting principles of the responsibilities of CRNs
1) The work tasks undertaken by CRNs should be delegated by the principal investigator (PI).
2) The duties of CRNs shall not exceed the scope of nursing qualifications.

Factors influencing the responsibility setting of CRNs
Clinical study type In all types of clinical research, the work of CRNs should be subjectcentered, with equal emphasis on nursing care and research implementation management.CRNs also have different focuses in different types of research.In phase I clinical research, the work of CRNs paid more attention to the medication compliance of subjects, sample collection and management, and observation and collection of adverse events. 8,23In phase II/phase III/phase IV trials, the data management workload of CRNs was larger. 9

Management of clinical trial institutions/departments
The management mode selected by the respective institution/ department and its development stage are different, and there is a significant difference in the job responsibilities and tasks undertaken by CRNs in different institutions.In general, CRNs managed by clinical wards/departments focus on the nursing work of clinical research (eg, subject sample collection and administration).Central CRNs managed by the institutional office/clinical research center place a focus on the entire process management of the project and coordinate with all departments in the hospital.Moreover, CRNs, under the centralized management of the nursing department, will account for the entire process management of the project and the nursing work (eg, drug administration and sample collection) during the subject study while paying attention to the development of the clinical nursing discipline.

Knowledge and ability of CRNs
Five types of knowledge and abilities are required for CRNs, including medical nursing, statistical skills, subject protection, compliance with laws and regulations, research management expertise, project implementation practical skills, and professional quality. 17The content covered by the above five types of knowledge and abilities, and their corresponding learning resources are listed in the CRN knowledge and ability framework model of this consensus.For more details, please refer to Table 2.

Medical, nursing, and statistical skills
In addition to acquiring the basic knowledge of medicine and nursing, CRNs should master clinical research knowledge in the field of diagnosis and treatment of diseases and special nursing skills, and acquire the knowledge of clinical research design and methods in biological statistics, as well as the basic knowledge and concept of clinical research data management.

Subject protection and regulatory compliance
It is necessary to master the domestic laws, regulations, and international guidelines regarding subject protection and clinical research, including the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) guidelines, Helsinki Declaration, "Quality Management Specification for drug clinical trials," "ethical review measures for biomedical research involving human beings," "regulations of the People's Republic of China on the administration of human genetic resources," and "measures for the administration of drug registration."

Research management expertise
Research management expertise comprises equipment management, planning and implementation, subject management, subject education, safety management, investigational product management, sample collection, data management, contract and cost management, document management, material management, communication, and coordination, as well as project nursing.

Practical skills of project implementation
The practical skills of CRN project implementation are detailed as starting basic work, project review application and follow-up, project start-up, subject recruitment practice, subject screening and informed consent, subject enrollment visit, subject visit management, project conclusion management, CRF entry, as well as research-related nursing skills.

Professional quality of clinical research nurses
The following professional quality training is required for qualified new CRNs to ensure competency. 15,17mmunication and coordination skills.CRNs should communicate and coordinate with researchers, clinical nurses, sponsors, central laboratories, subjects, CRC, and a wide range of departments in the hospital to ensure the implementation of clinical research.Spirit of cautious independence.CRNs should operate in strict accordance with the plan and different standard operating procedures when implementing the clinical research plan.CRNs should operate in accordance with the relevant procedures of the research report when there are significant differences between the plan and the clinic, and they cannot do it at will.

Continuous learning ability.
With the development of new drugs in extensive fields and the continuous emergence of novel treatment schemes, CRNs are required to constantly learn and update their knowledge system to solve various problems in clinical research.
Team spirit.Clinical research requires the cooperation of CRNs and researchers, CRC, clinical nurses, inspectors, and many other members to ensure the smooth progress of clinical research with quality and quantity.

Training methods
Training methods include self-study, centralized teaching, practice with teaching, as well as selecting one or more ways based on different knowledge and skills to complete the corresponding content of training and learning.

Applicable objects
CRNs with different professional titles require different knowledge and abilities to facilitate hierarchical training and evaluation of CRN post-abilities (eg, primary, intermediate, and advanced).CRNs who master intermediate or advanced knowledge and skills can reserve personnel for the management of clinical trial institutions.Table 3 lists the job skill requirements of research nurses with different professional titles.

Training reference resources
Training resources are made available in the field of clinical research.

CRN job quantification
Quantifying CRN work can be calculated from three levels (macro, micro, and accurate calculation).Macroquantitative indicators include the number of trials and enrollments, which are easy and convenient to calculate.Microquantitative indicators include the number of screenings, enrollments, treatment visits, and follow-up visits, which can quantify the workload of CRNs more specifically.More accurate quantitative indicators take the number of tasks as the indicator to count the specific workload completed by CRNs during a specific period (eg, the number of informed consents, the amount of document management, the amount of sample collection and processing, the number of SAE reports, as well as the number of CRF filling).The precise calculation of the CRN workload is dependent on a mature management system or a powerful information management system.CRN workload calculation takes on a critical significance in reasonable manpower allocation. 18,20

Human resource allocation of CRNs
(1) To reasonably calculate the manpower allocation of CRNs, the job responsibilities should be reasonably divided according to the specific situation.Although Part 4 of this consensus lists the job responsibilities and tasks of CRNs in detail, various institutions can define the scope of work suitable for CRNs in each institution according to their own management mode.The scope of the work is different, and the CRNs are different.( 2) planning of the CRN fixed workload cannot be done.It is imperative to motivate personnel to bear the load beyond the standard workload, as well as to set the workload and performance incentive mechanism.

Performance evaluation indicators
Postevaluation of CRNs includes postcompetency and job performance evaluations.The evaluation of postcompetence involves basic medical knowledge and clinical research specialist knowledge, work skills, and professional quality, which is primarily completed during posttraining.Postperformance evaluation comprises the evaluation of the workload, work quality, and work progress of CRNs.

Workload
The workload of CRNs can evaluate the workload of different CRNs by comprehensively calculating the number of trials, number screenings, number enrollments, treatment visits, sample collection, number of processing visits, and SAE reports over a period.

Work quality
The work quality evaluation indicators of CRNs focus on the project quality, which can be determined by each institution according to the management direction.The indicators to evaluate the quality of the project include authorization error rate, number of missing trainings, number of protocol violation, medication compliance, and SAE report delay rate, as shown in Table 4.

Work progress
It should also be an auxiliary target for the work evaluation of CRNs.The main evaluation indicators involve project approval progress, ethics committee review, follow-up progress, contract review progress, and data entry progress.

Evaluation method
The workload of CRNs is evaluated through manual statistics or a management system summary.The work quality can be evaluated by reporting to the ethics committee or by indicators (eg, the incidence of protocol deviations, SAE report delay rate, and data entry delay rate obtained during the quality inspection).

Evaluation personnel
In general, the personnel management department is responsible for the workload evaluation, and the work quality and progress are primarily evaluated by the PI or the directly affiliated management department.

Title promotion
In general, clinical nursing title is divided into primary, intermediate, and senior, which are nurses, deputy director of nurses, and director of nurses, respectively.Each institution has different requirements for professional title evaluation.It is suggested that CRN title should be included in the professional title evaluation system of clinical nursing series, and the corresponding evaluation system should be established.Due to the employment mode, if it cannot be included in the nursing professional title evaluation system, the promotion channels can be set according to the primary, intermediate, and senior levels.The evaluation of CRNs with different professional titles/levels is listed in Table 5.

Position promotion
As the institutions of full-time CRN team gradually grow, each clinical trial institutions can set the corresponding management positions according to the respective management to provide competent CRNs promotion space (eg, team leader and head nurse position) and set the corresponding evaluation requirements according to different positions.

Discussion
CRNs have a developing role in China, which is different from the clinical research experience in European and American countries and  regions.CRNs in European and American countries are employed by clinical research institutions or PIs.4][5] In China, however, most clinical research institutions are public hospitals and the employment of personnel is limited by the quota.At first, research institutions or PIs employed CRNs to help manage clinical research.Due to the rapid growth in the amount of clinical research in the past 5 years, the quota cannot be provided.There are enough institutions to employ CRNs.A large number of externally employed CRC are used in clinical research, which makes the role of nurses in clinical research unclear. 25,26hinese hospital managers have gradually found that the external employment CRC has relatively large mobility and began to reexplore the experience of using CRNs.Inexperienced hospital managers are generally confused about the definition of responsibilities of CRNs and ordinary clinical nurses, CRC, and how to cultivate them.Inexperienced hospital managers also pay more and more attention to the deep-seated problems of "survival" in positions, such as job assessment, human cost accounting, and performance evaluation. 18In different clinical research institutions, the actual management situation is very different, which makes CRNs, as new posts, face different difficulties in their development.
We hope to systematically summarize the existing explorations of clinical research nursing researchers and introduce the practical experience of pioneers by drawing up a consensus.In the consensus, there is internal correlation among various topics and most of the clinical research environment in China should be considered as far as possible.We do not think that CRNs must have the same responsibilities in all scenes.Hospital managers can choose the responsibilities of CRNs matching the management mode according to actual needs, and their training, issues such as workload assessment and manpower allocation should be set around the selection of responsibilities.
It is suggested that hospital managers and nursing managers should see that nurses can play an advantageous role in clinical research, develop more important roles of nurses in scientific research, and promote the development of nursing departments.As a framework blueprint, we will guide the follow-up work of the association and look forward to promoting the specialized development of clinical research and nursing.
Project initiation application and follow-up √ Ethics committee review application and follow-up √ Human genetic resources application and follow-up √ √ √ Contract review application and follow-up √ Assist investigator to organize research teams according to project needs √ Work coordination and application of relevant departments in the research center √ (eg, pathology examination imaging and pharmacy) Assist in preparing, organizing, and holding kick-off meetings √ Confirm that the members of the research team have been trained and authorized Develop and continuously optimize worksheets √ √ Assist the research team in discussing drug combinations and treatment plans √ Record and report the scheme violations and continuously optimize the implementation process √ Submission of annual reports 24 √ Submission of protocol and revision of informed consent √ √ Review/submit CRF, drug test report, IB, and other projectrelated documents in the recruitment of subjects √ Assist in screening subjects √ Informed consent in the scope of professional qualification √ Check the eligibility of subjects √ Complete the randomization/enrollment procedure of subjects √ Appointment and arrangement of visit procedures (eg, examination, treatment, and follow-up of subjects) √ Offsite communication and follow-up via telephone or other means of communication √ Tracking and recording of combined treatment and medication of subjects in the study period √ Carefully observe the tracking and recording of the subjects' condition changes √ Survival follow-up √ 5 Subject education Instruct subjects to comply with the protocol for follow-up √ Instruct the subjects to use the trial drug √ Educate the subjects on prohibited drugs and treatment √ Instruct the subjects about diet, exercise, and other diseaserelated knowledge √ Instruct the subjects to use the relevant equipment for the test √ Instruct subjects to complete diaries and questionnaires √ (continued on next page)

Table 1
Responsibilities and tasks of clinical research nurses.

Table 1
(continued ) √Manage materials according to hospital regulations, report registration, as well as use records√ √Regularly check inventory and effectiveness and timely replenish√ √ √Timely liquidation and return of relevant materials √ (continued on next page) Ability to plan, organize, and manage.CRNs participate in all aspects of clinical research, organize project preparation and start-up, subject screening, enrollment and follow-up, and supervision, inspection and onsite verification of superior competent departments during clinical research to ensure the orderly progress of the project.Education ability.CRNs, facing subjects, clinical nurses, and CRC, are required to conduct education regarding clinical research (eg, the possible adverse reactions of experimental drugs, the drug administration process of clinical research, as well as the process of hospital and department work system).Evaluation thinking.CRNs should evaluate the feasibility of the research plan based on their own clinical experience, legal and ethical principles, and medical theoretical knowledge and propose opinions to facilitate the smooth implementation of clinical research.

Table 4
Requirements for job performance indicators.

Table 5
Evaluation and promotion conditions of clinical research nurses with different professional titles.