药物临床试验伦理审查工作指导原则-EN

药物临床试验伦理审查工作指导原则（2010-11-02）Guidelines for Ethical Review Work of Drug Clinical Trials

Chapter I General Provisions

Article 1 For the purpose of strengthening the guidance and administration of ethical review of drug clinical trials, and standardizing the activities of the ethical review of ethics committee so as to ensure that drug clinical trials meet the requirements of science and ethics, the guidelines are formulated in accordance with the Good Clinical Practice for Pharmaceutical Products (GCP), the Declaration of Helsinki of the World Medical Association, and the International Ethical Guidelines for Biomedical Research Involving Human Subjects of the Council for International Organizations of Medical Sciences.

Article 2 An Ethics Committee reviews the scientific merits and ethical rationality of drug clinical trials in order to protect research participants’ dignity, safety, rights and interests, to promote the development of drug clinical trials in a healthy and scientific way, and to gain the public’s trust and support in drug clinical trials.

Article 3 It must be under the premise of abiding by the State constitution, law, regulations and relevant stipulations that ethics committees conduct ethical review of drug clinical trials independently and shall accept the instructions and administration by drug regulatory departments.

Article 4 The drug regulatory departments shall establish the procedures for inspecting and assessing the activities of committees’ ethical review of drug clinical trials, and shall instruct and administer the activities of ethical review.

Chapter II Organization and Management of

the Ethics Committee

Article 5 The establishment of an ethics committee should comply with the applicable administrative stipulations of the State. An ethics committee should constitute the members with backgrounds in multiple disciplines, including professionals related to medicine, professionals not related to medicine, legal, expert and the persons independent from the research/trial institution, at least five people and in the even ratio of gender. It should ensure that the members have the experience and qualifications to jointly review and assess a trial’s scientific merits and ethical rationality. The constitution and activities of an ethics committee should be free from the influence of any participants involved in trials.

Article 6 There should be documents in writing, which define an ethics committee’s

organizational structure, competent department, responsibilities, member qualification requirements, conditions and term for serving, work responsibilities of its office, establishment of procedures for selection and appointment of the member and office secretary and so on.

Article 7The institution/department that establishes an ethics committee should provide it with essential support, set up an independent office with necessary facilities for office work so as to ensure the communication with sponsors and the confidentiality of relevant documents.

Article 8 A member of an ethics committee may be engaged, recommended persons, etc. The committee has a director and several deputy-directors who are elected by the committee members.

Article 9Any committee members should consent to make public their names, occupations and affiliations, and sign a confidentiality agreement on review subject, research participants’ information and relevant matters, and sign a declaration of conflict of interest.

Article 10 The ethics committee may engage an independent consultant or appoint an executive one. By request of the committee, the independent consultant contributes consultancy to certain issues of a trial protocol, but the consultant has no vote on the ethical review. The consultant may be an expert in ethics, law, special diseases or methodology, or a representative of a population of a special disease, a special region population/ethnic group or other bodies with special interests.

Article 11 The ethics committee should establish a training mechanism of continuing education targeting new committee members and members, and organize the training of GCP etc of relevant law and regulations, the skills required by the ethical review of drug clinical trials, and standard operating procedures of the ethics committee.

Article 12 The ethics committee should formulate standard operating procedures and system to ensure the criteria and consistency in ethical review. At minimum, the content should include the following aspects:

1.the formulation of standard operating procedures and guide for ethical review

application;

2.the ethics committee’s organization and management: the establishment of the

ethics committee, the means to maintain the confidentiality of ethical review, the management of conflict of interest, the training of committee members and its office staff, the engagement of independent consultants;

3.the methods of ethical review: scheduled meeting review and ad hoc meeting

review, fast review;

4.the ethical review flow procedure: accepting and processing an ethical review

application, preliminary review, follow-up review and passing on review

decision;

5.Meeting management: meeting preparation, meeting procedure, meeting

minutes;

6.document and file management: making up files, archiving, retrieval and

photocopying.

Chapter III Responsibilities of the Ethics Committee Article 13The ethics committee should continuously improve its organizational management and system construction according to the need of ethical review, and perform its responsibility of protecting research participants’ safety, rights and interests.

Article 14 The ethics committee should independently, fairly, justly and timely conduct the review of ethical issues in the drug clinical trials submitted by applicants. Apart from review and supervision of the drug clinical trials undertaken by its institution, the ethics committee may conduct the ethical review of drug clinical trials entrusted by other institutions.

Article 15 When the ethics committee, conducts review and supervision of drug clinical trials, it may exercise the following power:

1.approve/not approve a drug clinical trial;

2.conduct follow-up review of an approved clinical trial; or

3.terminate or suspend an approved clinical trial.

Article 16 After an ethics committee is established, it should timely submit relevant documents to the State Food and Drug Administration and its provincial food and drug regulatory department for the record. The documents submitted for the record are as follows: name list of the director and members (their resumes attached) of the ethics committee, the constitution of the ethics committee, and its relevant working procedures and system.

Article 17 The ethics committee should report its annual situations of ethical review to the State Food and Drug Administration and its provincial food and drug regulatory department.

Chapter IV Application for Ethical Review and Its Acceptance Article 18 The ethics committee should provide the applicants of ethical review with consultant services for the matters involved in the ethical review, and with application form, informed consent form and formats of other documents needed by application for ethical review; it should formulate clear stipulations for matters related to

accepting an application for ethical review.

1.should specify the document list that must be submitted and the number of

copies of document needed for review;

2.should define primary requirements, form, criteria, timeline and procedure for

accepting an application for review;

3.should define primary requirements for submission and acceptance of an

amendment application and a supplementary application, timeline, procedure ,

conditions and requirements of a dossier, etc.

Article 19 After receiving an application from an applicant of ethical review, for the documents submitted for review that are incomplete or fail to meet the requirements, the ethics committee should give the applicant one-off notice of all content to be supplemented and corrected.

After accepting an ethical review application, the ethics committee should inform the applicant of the scheduled time that the ethical review meeting is to be held. Article 20 An applicant of ethical review must submit the application for ethical review to the ethics committee according to its stipulations and requirements. The application documents submitted for ethical review include (but not limited to the followings):

1.an application form of ethical review (it should be signed and dated);

2. a protocol of clinical trial (version no. and date should be noted );

3.an informed consent form (version no. and date should be noted);

4.relevant materials for recruitment of research participants;

5.the case report form;

6.the investigator’s brochure;

7.the resumes of principle investigators;

8.the Approval Letter of Drug Clinical Trial of the State Food and Drug

Administration;

9.other ethics committee’s statements of their crucial decisions on the

application for the clinical trial, the justification for previous negative conclusion should be presented; and

10.the testing report for passing of the investigational drug.

Article 21 The ethics committee should decide the review methods for the accepted application, and choose its principle review member. An independent consultant may be engaged when necessary.

Chapter V Ethical Review of the Ethics Committee Article 22 The ethics committee should stipulate the quorum required for convening an ethical review meeting. The committee members attending a meeting should at least exceed half of the total and be no less than five. The attending members should

include professionals related and not related to medicine, the person independent from the research/trial institution and, of both genders.

Article 23 The director (or an authorized person) will chair the ethical review meeting. An independent consultant may be invited to attend the meeting to provide advices when necessary; the principle investigator/sponsor may participate in the meeting to present the protocol or explicate special issues. The secretary of the ethics committee should summarize the meeting’s discussion and review decision to form the meeting records. The meeting records should have a procedure to get it approved.

Article 24The ethics committee may establish a “principal review system”. The committee may designate one to two principal members for a trial review according to the principle of specialty related and ethical issue related.

Article 25 The ethics committee takes the scheduled meeting review as the major method of review. A fast review may be conducted for any one of the following circumstances:

1. the clinical trial protocol that has been approved by the ethics committee with

minor modification, which does not impact on the risk-benefit ratio of the trial;

2. the trail that has not yet enrolled any research participants or the

annul/periodical follow-up review of a trial that has completed its intervention

measures; or

3. the review of the anticipated serious adverse events.

Article 26 The fast review is handled by one to two members. A trial approved by a fast review should be reported at the next meeting of the ethical committee members.

A fast review should be transformed to a meeting review if there exists any one of the following circumstances:

1.negation is the review opinion;

2.the two handling members do not have an agreeable conclusion; or

3.the members propose a meeting review.

Article 27 When the research participants’ safety is threatened by a severe or serious problem that occurs during a trial, the ethics committee should convene an ad hoc meeting to review the circumstance and take response measures to protect the research participants’ safety, rights and interests when necessary.

Article 28 The main content of an ethical review (Annex 1):

1.the design and implementation of the trial protocol;

2.risks and benefits of the trial;

3.the recruitment of research participants;

4.the details given by the informed consent form;

5.the process of informed consent;

6.the medical treatment and protection of the research participants;

7.privacy and confidentiality; and

8.the trials involving vulnerable persons.

Article 29For the purpose of ensuring the quality of ethical review and its review meeting, the ethics committee should manage and control the quality of ethical review. The meeting of ethical review should be conducted following the stipulated procedure and agenda. Sufficient deliberation should be given for reviewed documents so as to ensure that the committee members are able to sufficiently present different opinions on their own.

Article 30The ethics committee should specifically pay attention to such issues as trial’s scientific merits, safety, fairness, the protection of research participants, the informed consent form and the process of informed consent, conflict of interest, etc. Article 31For a multi-center clinical trial, the ethical review should take the consistent and timely completion as the primary principle. A multi-center clinical trial may establish a work procedure for the coordination of conducting reviews:

1.the ethics committee of the head institution in conducting the multi-center

trial is responsible for reviewing the scientific merits and ethical rationality of

the trail protocol;

2.under the premise that all ethics committees of the participating institutions

accept the review opinion of the ethics committee of the head institution, they

are responsible for reviewing the feasibility of the trial to be conducted in

their institutions including the qualifications and experience of the investigators, and whether they have enough time to take part in the clinical

trial, study members staffed and conditions of facilities. The ethics committee

of each participating institution is entitled to approve or disapprove the trial

proposed to be conducted in its institution；

3.once an ethics committee of a participating institution makes a proposal that a

trial protocol must be amended, a document in writing should be compiled

and reported to the sponsor or the trial institution responsible for the whole

plan of trial for its consideration and forming a consistent opinion for the

amendment so as to ensure that all trial institutions have the same trial

protocol to follow;

4.the ethics committee of every institution should conduct follow-up review of

the trial undertaken by its institution. If any serious adverse event occurs, the

ethics committees of all institutions should be responsible for reviewing them

in time and inform the sponsor of the review opinion. Based on the consideration of research participants’ safety, the ethics committee of every institution should be entitled to terminate the trial undertaken by its institution;

5.the institution heading the trial should give follow-up review opinion of the

clinical trial timely to every participating institution for the record.

Chapter VI Resolution and its Delivery of Ethical Review

Article 32 The ethical review meeting takes a vote on resolution and votes by over half number of attending members is deemed as review resolution of the ethics committee.

Article 33 When the ethics committee passes a review resolution, the following conditions should be met:

1.the application dossier is complete;

2.the number of attending members reaches the quorum required;

3.the review procedure is followed; the key review points are comprehensively

examined and sufficiently discussed.

4. While discussing and voting, the sponsor and the committee members with

conflict of interest are cleared off the meeting; and

5. absent member is not permitted to vote by proxy of other members.

Article 34Any clinical trial to be approved must at least meet the following criteria:

1.the risk-control response measures have been prepared for the anticipated

risks in the course of the trial;

2.the risks to the research participants are relatively reasonable against their

benefits;

3.the selection of the research participants is fair and just;

4.the information in the informed consent form are sufficient and the process of

getting informed consent meets the stipulations;

5.when necessary, the trial protocol should possess adequate data and safety

supervision plan to ensure the safety of the research participants;

6.protect privacy of research participants and secure confidentiality of data; and

7.there are relevant special protective measures for the trials involving

vulnerable persons .

Article 35 There are several outcomes for the review opinion of an ethics committee:

1.agree;

2.agree after necessary amendments are made;

3.re-review after necessary amendments are made;

4.disagree; or

5.termination or suspension of an approved clinical trial.

Article 36The secretary of the ethics committee should timely summarize the meeting minutes after the meeting and compile the opinion/approval letter of ethical review based on the meeting minutes and review conclusion. The opinion/approval letter of ethical review should be signed by the director (or the authorized person) and

stamped with the seal of the ethics committee. The details of the opinion/approval letter of the ethics committee include:

1. primary information

1)the information of a trial: name of the trial, sponsor, review opinion / serial no.

of approval letter ;

2)the clinical trial institution and investigators;

3)meeting details: meeting time, location, the form of review, and documents

reviewed, of which version number and date of both clinical trial protocol and

informed consent form, should be noted.

4)the dates for issuing the approval letter /opinion of ethical review; and

5)the contact person and contact method of the ethics committee;

2. Review opinion and resolution;

1) when the review resolution is “agree”, the ethics committee’s requirements for

conducting follow-up review is notified at the same time as the review resolution is informed;

2) when the review resolution is “agree after necessary amendments are made” or

“re-review after necessary amendments are made” the detailed opinion for amendments is explicated, and the requirements and re-submission flow for the protocol are informed;

3) when the ethical resolution is “disagree” or “termination or suspension of an

approved clinical trial”, sufficient justification must be given and the sponsor is informed that it may either clarify the matters concerned or lodge an appeal against the resolution.

Article 37 After the ethical review opinion/approval letter verified and signed by the director (or the authorized person) of the ethics committee, it should be timely delivered to the applicant.

Chapter VII Follow-up Review after Ethical Review

Article 38The ethics committee should conduct follow-up review for all approved clinical trials until they are accomplished;

Article 39 The review of protocol amendment refers to the review of any amendment made to an ongoing trial protocol in the course of the trial. Any amendment made to the trial protocol being implemented should be submitted to the ethics committee to be reviewed for approval before it can be carried out. The ethics committee should request the sponsor and/or investigator to submit the details regarding to the amendment including (but not limited to) the followings:

1.the amended content and the justification of the amendment;

2.impact of amended protocol on anticipated risks and benefits; and

3.impact of amended protocol on the rights and benefits, and safety of research

participants.

Mainly targeting the trial risks and benefits of the amended protocol, the ethics committee conducts a review of them and gives a review opinion. For the protocol amended in order to avoid an urgent harm to the research participants, the investigator may carry out the amendment prior to the review for approval by the ethics committee, and the amendment should be then reported to the ethics committee in writing timely.

Article 40Annual/periodical follow-up review. When conducting preliminary review, the ethics committee should decide the frequency of the annual/periodical follow-up review, at least once a year, depending on the degree of the trial risks. The ethics committee should request the investigator to timely submit the report. The details of the annual/periodical follow-up review report include (but not limited to) the followings:

1.the progress of the trial;

2.the number of cases enrolled of research participants, cases finished, cases

of attrition, etc.;

3.confirmed serious adverse events reported in time and properly treated; and

4. any event or new information that might impact on the trial’s risks and

benefits.

After reviewing the research progress, the ethics committee shall reassess the trial’s risks and benefits.

Article 41The review of serious adverse events refers to the review of the serious adverse events reported by the sponsor/or investigator including their degree and range, the impact on the trial’s risks and benefits, and research participants’ medical protective measures.

Article 42 The review of non-compliance/violation of protocol refers to the review of the event, occurring in a clinical trial, that the protocol is not followed or violated. The ethics committee should request the sponsor/or investigator to explain the cause

of the event, its impact and handling measures, and investigate whether the event impacts on the safety, rights and benefits of the research participants and on the trial’s risks and benefits.

Article 43 The review of the early termination of a trial refers to the review of a trial that is prematurely aborted by the sponsor/investigator. The ethics committee should request the sponsor/investigator report the justification for the early termination and the subsequent treatment of the research participants, and check whether their safety, rights and benefits are ensured.

Article 44 The review of trial completion refers to the review of the completion report

of a clinical trial. The ethics committee should request the sponsor and/or investigator

to report the situation of the trial accomplishment and review the protection of the research participants’ safety, rights and benefits.

Article 45The resolution and justification of follow-up review should be informed the applicant in time.

Chapter VIII Management of Documents of the Ethics Committee

Article 46The ethics committee should possess an independent file management system. The ethics committee’s documents for making up files and archiving include documents in management and in trials for review.

Article 47 The management documents of the ethics committee include (but not limited to) the followings:

1.its working procedures, post responsibilities, standard operating procedures

and the guide for ethical review application;

2.the appointment documents of the committee members, their resumes and

training records, and signed confidentiality agreement and the declaration of

conflict of interest; and

3.its annual work plan and summation.

Article 48The ethics committee’s documents in review of trials include the followings:

1.all dossiers submitted by the investigators/sponsors for review;

2.working form of ethical review, meeting attendance sheet, vote sheet, meeting

minutes, the committee’s approval letter/opinions and related letters of correspondence;

The ethical review documents should be kept with care for five years after the clinical trial is completed, or the keeping period is extended according to relevant requirements. The archiving document list is seen in annex 2.

Article 49 The ethics committee should formulate relevant stipulations for retrieval and photocopying of the documents so as to ensure security and confidentiality of documents and files.

Chapter IX Supplementary Provisions

Article 50The mechanism of information exchange and work cooperation may be established between and by ethics committees so as to facilitate capability of ethical review.

Article 51Ethics committees established prior to implementation of the guidelines should, within one year from the date of implementation of the guidelines, improve their organizational management and system construction according to relevant requirements of the guidelines, and report to the State Food and Drug Administration and their provincial food and drug regulatory departments for the record.

Article 52 This guidelines shall be implemented from date of its promulgation.

Annex 1

Main Content of Ethical Review

1The design and implementation of a trial protocol.

1.1 The trial meets the scientific principle commonly-recognized, and based on

literatures, sufficient laboratory study and animal experiments.

1.2 The rationality of trial design and establishment of control group related to trial

aims.

1.3 The criteria of research participants’ early withdrawal from a trial and the criteria

of suspension or termination of a trial.

1.4 The inspection and audit plan of an ongoing trial including the establishment of an

independent data and safety monitoring board when necessary.

1.5 The investigators’ qualifications and experience, and sufficient time available for

conducing the clinical trial, study members staffed and the conditions of the facilities etc meet the trial’s requirements.

1.6 Clinical trial result report and the way to publish it.

2 The risks and benefits of the trial

2.1 The assessment of the nature of the trial’s risks, magnitude and occurring

likelihood.

2.2 The minimization of the risks within the possible range.

2.3 The anticipated benefit assessment: the research participants’ benefits and social

benefits.

2.4 The rationality of the trial’s risks and benefits:

2.4.1 For the trial with the prospect of direct benefits to the research participants, the

anticipated benefits and risks should at least be equivalent to those of the current alternative treatment available. In terms of the anticipated benefits of the research participants, the trial’s risks must be rational.

2.4.2 For the trial without the prospect of direct benefits to the research participants,

the risks must be rational in terms of anticipated social benefits.

3 The recruitment of research participants

3.1 The characteristics of the research participants (including gender, age, and race

etc).

3.2 The fair and just distribution of the trial’s benefits and risks among the targeted

disease population.

3.3 The mode and method of recruitment to be used.

3.4 The way used to inform the research participants or their representatives of the

information related to the trial.

3.5 The criteria of inclusion or exclusion of a research participant.

4 The details notified by the informed consent form.

4.1 The objectives of the trial, the procedures that the trial should follow (including all

invasive operations), trial period.

4.2 The anticipated risks and inconvenience of the research participants.

4.3 The anticipated benefits. The research participants should be informed when they

do not directly benefit from the trial.

4.4 The alternative treatment available for the research participants and its important

potential risks and benefits.

4.5 Whether the research participants receive any compensation.

4.6 Whether research participants participating in the trial need bear any expense.

4.7 The degree of confidentiality of the relevant records by which research

participants can be identified and the explanation statement that the sponsor of the trial study, the members of ethics committee, and governmental regulatory departments, when necessary, may access the information of the research participants according to the stipulations.

4.8 The treatment and corresponding compensation that research participants may

obtain if harm related to the trial has done to them.

4.9 It has been stated that the participation of the trial is voluntary or that the

participants may reject the participation of the trial or be entitled to withdraw from the trial at any phase without being discriminated or avenged and without affecting their medical treatment, rights and benefits.

4. 10 When the issue of the rights of the trial study or research participants is raised or

the injury occurs related to the trial, there are the contact person and contact number available for dealing with the circumstance.

5 The process of informed consent.

5.1 The informed consent should meet the principle that the participant is fully

informed, sufficiently understand and at liberty choose participation in the trial. 5.2 The statement for informed consent should be popular and easy to be understood

and suitable for the understanding level of the research participant population.

5.3 There is a detailed description stating that how the informed consent is obtained,

including who is in charge of obtaining it, and the stipulations for the signature of the informed consent form.

5.4 When planning to enroll the research participants who are unable to give their

consent, justifications for that should be sufficient, and there must be a detailed statement indicating how to obtain their consent or the consent from their authorized representatives.

5.5 There are the stipulations for hearing the opinions or replying to the questions

raised by the research participants or their representatives in the course of the trial.

6 The medical treatment and protection of the research participants.

6.1 The qualifications and experience of the investigators should be relevant to the

trial’s requirements.

6.2 The justification for not giving the conventional treatment due to the trial’s aims. 6.3 The medical care security provided for the research participants during and after

the trial.

6.4 Appropriate medical care monitoring, psychological and social supports provided

for the research participants.

6.5 The means to be taken to deal with the circumstance that a research participant

voluntarily withdraws from the trial.

6.6 The criteria for providing the investigational product for extending use,

emergency use or for sympathetic reason.

6.7 The statement of whether the investigational product is continuously provided for

the research participants after the trial is completed.

6.8 The statement explaining the expenses that the research participants need to pay. 6.9 The compensation provided for the research participants (including cash, services

and/or presents).

6.10 The compensation and medical treatment provided for the research participants

due to the trial-related injuries/disability/death. .

6.11 Insurance and compensation for injuries.

7 Privacy and confidentiality

7.1 The stipulations for persons who may consult the personal information of the

research participants (including medical records, biological samples).

7.2 The measures to ensure the confidentiality and security of personal information of

the research participants.

8 The trial involving .

8.1 Only vulnerable persons are used as research participants, can the trial be well

conducted.

8.2 The trial targets on the disease or health problem that is unique to vulnerable

persons.

8.3 As the trial does not provide the possibility of direct benefits for research

participants of vulnerable persons, the trial’s risks generally are not allowed to be larger than the minimal risks, unless the ethics committee consents to the marginal increase in degree of the risks.

8.4 When a research participant is unable to give sufficient informed consent, the

informed consent from his or her legal representative should be obtained and, at the same time, consent s hould still be obtained from the research participant if possible.

9 The trial involving a special disease population, a special region population/ethnic

group.

9.1 The trial’s impact on a special disease population, a special region

population/ethnic group.

9.2 The external factors that influence an individual’s informed consent.

9.3 The plan for the consultation of the said population/group during the trial.

9.4 The trial is beneficial to the local development, for instance, the enhancement of

the local medical and health services and the improvement of research capability and the capability to cope with the demand of the public health.

Annex 2

The List of Archiving Documents of the Ethics Committee

1 The type of management documents

1.1 The work procedures and persons’ responsibilities of the ethics committee.

1.2 The professional resumes and appointment documents of the ethics committee’s

members.

1.3 The training documents of the ethics committee’s members.

1.4 The guidance for the application for ethical review.

1.5 The standard operating procedures of the ethics committee.

1.6 The technical guidance for the major ethical issues pertaining to clinical trials.

1.7 The documents and records of expenditure management.

1.8 Annual work plan and summation.

2 The type of trial review documents.

2.1 The dossiers submitted by the applicants.

2.2 The acceptance notice of application.

2.3 The review work forms of the ethics committee.

2.4 The agendas of the ethics committee’s meetings.

2.5 The meeting attendance forms of the ethics committee.

2.6 The vote sheets of the ethics committee.

2.7 The meeting minutes of the ethics committee meetings.

2.8 The opinion/approval letters of ethical review.

2.9 The liability declaration of the ethical review applicants.

2.10 The correspondence between the ethics committee and applicants or other

relevant persons regarding to the issues of application, review or follow-up review.

2.11 The relevant documents of the follow-up review.

Annex 3

List of Terms

1. A special disease population or a special region population/ethnic group: the

population or group that possesses similar a characteristic and the characteristic can be the same/similar region, the same value, the common interest or the same disease suffered from.

2.Confidentiality: to prevent all the ownership information or individual

identification information from being leaked to the unauthorized.

3.Conflict of interest: it is because that the ethics committee member has a related

interest with the trial for review, which would undermine his or her impartiality and independency to conduct the review from the perspective of protecting the research participants. A conflict of interest usually happens when the ethics committee member has an interest relation with the trial for review in the aspect of economy, material, institution, and social relations.

4.Data and Safety Monitoring Board: an independent data and safety monitoring

board that sponsor is responsible for setting up. Its responsibility is to regularly assess trial progress, analyze safety data and important indexes of effects, and make proposal to the sponsor of the trial’s continuation, modification, or early termination.

5.Ethics committee: an independent organization consisting of medical

professionals, legal expert and non-medical persons. Its responsibility is to review the clinical trial protocol and the annexes if they are conformed to morals, and to

provide public assurance for ensuring protection of research participants’ safety, health, rights and interests. The composition of the committee and its all activities are free from the intervention or influences of the clinical trial organization and implementers in the trial..

6.The informed consent: refers to the process that, after informed of every aspect of

a trail, a prospect research participant voluntarily confirms to content participation

in the clinical trial, and the participant shall sign and date an informed consent form as a proof document.

7.The informed consent form: a proof document that a research participant

voluntarily participates in a trial. The investigator shall tell the research participant the nature, aims, possible benefits and potential risks of the trial, alternative treatments available, and the research participant’s rights and obligations which are conformed to the Declaration of Helsinki so as to enable the research participant to fully understand the trial before confirming his or her willingness. 8.minimal risk: refers to that an anticipated risks’ possibility and degree are not

greater than those in daily life, a regular physical examination, or psychological test.

9.Multicenter trial: refers to a clinical trial that follows the same protocol, is

conduced in multiple trial sites and taken charge by several investigators who implement and accomplish the trial respectively.

10.Non-compliance/violation: refers to the circumstances of the deviation of the trial

protocol approved by the ethics committee, and the deviation not approved by the committee in advance or non-compliance/violation of the stipulations for human subjects protection and the requirements of the ethics committee.

11.Protocol amendment: refers to a written revision of or clarification to the protocol,

and other documents and information that related trial organizations implement. 12.Quorum: refers to the stipulated number and qualifications of the committee

members attend a meeting to review a trial and make a resolution, i.e. for an effective meeting, the number and qualifications of the committee members should be required.

13.Research participant: an individual who participates in biomedical research may

be in treatment group, control group or observation group, including a healthy volunteer or a volunteer no direct correlation with the population targeted by the trial, or a patient from the disease population targeted by the trial.

14.Standard Operating Procedure (SOP): detailed operating instructions in writing

formulated to ensure the consistence of implementation so as to achieve the special aims.

15.Serious adverse event: the event occurs in the course of a clinical trial, and causes

inpatient hospitalization for treatment, or the prolongation of existing hospitalization, injuries, disability or incapacity for work, life-threatening, or death or a congenital anomaly defect and so on.

16.Unanticipated adverse event: the nature, degree of seriousness or frequency of the

adverse event, different from those of the anticipated risks depicted by the set protocol or other relevant documents (such as investigator’s brochure and

investigational drug insert sheet).

17.Vulnerable persons: the population relatively (or absolutely) have no ability to

maintain their own interests, usually referring to the people whose ability or freedom is restricted and are unable to give their consent or dissent, such as minors, the psychotic etc of the persons who are unable to give their informed consent.

药物临床试验的一般考虑指导原则

药物临床试验的一般考虑指导原则 一、概述 药物临床试验的一般考虑指导原则（以下称指导原则），是目前国家食品药品监督管理总局关于研究药物在进行临床试验时的一般考虑。制定本指导原则的目的是为申请人和研究者制定药物整体研发策略及单个临床试验提供技术指导，同时也为药品技术评价提供参考。另外，已上市药品增加新适应症等进行临床试验时，可参照本指导原则。本指导原则主要适用于化学药物和治疗用生物制品。 二、临床试验基本原则 （一）受试者保护 1．执行相关法律法规 药物临床试验必须遵循世界医学大会赫尔辛基宣言，执行国家食品药品监督管理总局公布的《药物临床试验质量管理规范》等相关法律法规。 2．应具备的安全性基础 开展任何临床试验之前，其非临床研究或以往临床研究的结果必须足以说明药物在所推荐的人体研究中有可接受的安全性基础。 在整个药物研发过程中，应当由药理毒理专家和临床专家等动态地对药理毒理数据和临床数据进行评价，以评估临床试验可能给受试者带来的安全性风险。对于正在或将要进行的临床试验方案，也应进行必要的调整。 参与药物临床试验的有关各方应当按各自职责承担保护受

试者职责。 （二）临床试验基本方法 1．临床试验一般规律 药物研发的本质在于提出有效性、安全性相关的问题，然后通过研究进行回答。临床试验是指在人体进行的研究，用于回答与研究药物预防、治疗或诊断疾病相关的特定问题。通常采用两类方法对临床试验进行描述。 按研发阶段分类，将临床试验分为Ⅰ期临床试验、Ⅱ期临床试验、Ⅲ期临床试验和Ⅳ期临床试验。 按研究目的分类，将临床试验分为临床药理学研究、探索性临床试验、确证性临床试验、上市后研究。 两个分类系统都有一定的局限性，但两个分类系统互补形成一个动态的有实用价值的临床试验网络（图1）。 图1. 临床研发阶段与研究类型间的关系 （实心圆代表在某一研发阶段最常进行的研究类型，空心圆代表某些可能但较少进行的研究类型）概念验证（Proof of Concept，POC）是指验证候选药物的药理效应可以转化成临床获益，一般在早期临床研究阶段进行，用以探索安全耐受剂量下有效性的信号，降低临床开发风险。 本指导原则采用以研究目的分类为主线对临床试验进行描述。 临床药理学研究的目的是评价耐受性，明确并描述药代动力学及药效学特征，探索药物代谢和药物相互作用，以及评估药物活性。 探索性临床试验的研究目的是探索目标适应症后续研究的给药方案，为有效性和安全性确证的研究设计、研究终点、方法

第二类体外诊断试剂临床试验指导原则

北京市第二类体外诊断试剂临床试验 指导原则 由于体外诊断试剂产品具有发展快、专业跨度大、临床使用目的各异的特点，不同使用目的的产品，临床研究方法及内容不尽相同。申请人应在完成产品分析性能评估，拟定产品标准后，方可申请体外诊断试剂产品的临床评价。临床评价开始前，申请人应根据产品特点及使用目的，确定临床评价的项目、方法，制定合理的临床评价方案，合理、系统地评价申报产品的临床性能。本方案仅用于指导体外诊断试剂检测方法一致性临床研究，并对临床试验机构的选择、样本要求、检测前的准备、临床试验数据的分析等具体操作提出了一般性要求。 申请人应根据国家法律、法规、标准及技术指导原则的要求建立更加可靠、可重复的临床评价方案，合理评价产品的安全性、有效性。 一、临床试验机构的选择 临床评价开始前，申请人应根据申报产品特点选择临床试验机构。临床试验机构应当具有与申报产品相适应的人员、场地、设备、仪器和管理制度，试验机构的选择应符合以下标准要求：

本方案将申报产品的检测系统称为试验系统，所选择的对照检测系统称为对照系统。 （一）应选择至少2家（含两家）省级卫生医疗机构，特殊使用的产品可在市级以上的疾病控制中心、专科医院或检验检疫所、戒毒中心等临床机构。临床机构的检验实验室（简称实验室）应符合《医疗机构临床实验室管理办法》要求；应优先考虑经CNAS-CL02《医学实验室能力认可准则》(ISO 15189:2007)认可或GB17025标准认可的实验室。 （二）实验室所釆用的检测系统应为完整、有效的, 检测系统包括申报产品的检测系统和所选择的对照检测系统。对照检测系统的试剂、校准品、仪器等应是经注册批准的；其主要分析性能指标（如准确性、精密度、线性范围、参考区间、测量范围等）满足临床要求。 申报产品的检测系统与所选择的对照检测系统最好为同一类型的检测方法（如同为酶联免疫反应、同为化学发光免疫反应等），如为非同一类型的检测方法，尽可能选择分析性能较近似的方法。 （三）实验室应有完善的室内质控程序；应优先选择连续两年以上室间质量评价结果为满意的实验室。 （四）实验室的该项目检测人员应具有相应资质（项目

药物临床试验数据现场核查要点 注释版

附件 填写说明：在如下填写说明中： 蓝色字体为说明性文字，作为自查过程的参考； 凡发现不符合条目中要求的情况，须将每个问题详细描述在各个条目下方。 药物临床试验数据现场核查要点 序号现场核查要点 一、Ⅱ、Ⅲ期临床试验、人体生物等效性(BE)/人体药代动力学(PK)试验、疫苗临床试验数据现场核查要点——通用内容 1.临床试验条件与合规性（含各方在临床试验项目中职责落实） 1.1* 临床试验单位承担药物临床试验的条件与合规性： 1.1.1临床试验须在具有药物临床试验机构资格的医院内进行（含 具有一次性临床试验机构资格认定的批件），落实临床试验条件是 否支持试验项目实际的实施过程。 查看CFDA临床试验机构资格认定证书或公告，以确认该试验进行时机构具备资格，确认资 质认定证书包含该试验的专业。 1.1.2具有合法的《药物临床试验批件》。 核对药物临床试验批件，核对所列试验与实际试验方案是否完全一致（包括试验药物的剂型、 剂量等）；批件中特别提出的建议是否有在方案体现等。 1.1.3核对项目开始实施时间与国家食品药品监督管理总局《药物 临床试验批件》时间相符性。 核对CFDA批件日期和中心启动（SIV）日期，SIV时间需在CFDA批件日期之后； 1.2 伦理审查批件及记录的原始性及完整性： 1.2.1有出席伦理审查会议的签到表和委员讨论的原始记录。 签到表可以通过查看伦理批件确认，核查签到表人数及组成是否符合GCP要求。 由于委员讨论的原始记录属于伦理委员会内部文件并且可能不一定提供给监查员查看，因此 须向机构或伦理负责人员确认委员讨论原始记录是否存档，然后备注：“经与xx（职位，如 机构秘书）确认，委员讨论的原始记录为伦理委员会内部文件，已按规定保存完整。”如可 能，请提供存档负责人的联系方式。 1.2.2委员表决票及审查结论保存完整且与伦理审批件一致。 查看伦理委员会批件，其中须包含委员最终投票结论（表决意见）和审查结论；

抗肿瘤药物临床试验技术指导原则

抗肿瘤药物临床试验技术指导原则 一、概述 恶性肿瘤是严重威胁人类生命的一类疾病，尽管现有治疗手段取得了一定疗效，但多数肿瘤患者生存时间有限，缺乏有效的可以治愈的药物，亟需开发新的药物来满足需要。在抗肿瘤药物的风险效益评估中，医护人员和患者可能愿意承受相对较大的安全性风险，所以抗肿瘤药物的临床研究除遵循一般药物临床研究原则外，还应考虑其特殊性。由于肿瘤生物学研究的进展，一些新的作用机制、作用靶点的抗肿瘤药物不断涌现，呈现出不同于以往传统细胞毒类药物的安全性和有效性特点；肿瘤疾病的药物治疗也从以往的单纯追求肿瘤缩小向延长患者的生存期、提高生存质量转变，这些改变使抗肿瘤药物临床疗效评价终点指标也出现较大改变。因此，传统的抗肿瘤药物开发模式已经变得不适宜，需要更多地探索能加快和促进开发进程的临床研究策略。 本指导原则将对抗肿瘤药物临床研究一般考虑进行阐述，重点阐述在不同临床研究阶段中需要重点考虑的问题，旨在为抗肿瘤药物临床研究的设计、实施和评价提供方法学指导。申请人在进行临床研究时，还应当参照国家食品药品监督管理局（以下简称SFDA）既往发布的相关指导原则和《药物临床试验质量管理规范》（GCP）要求进行，对于一般药物临床研究需要遵从的原则以及与其他指导原则重复内容在本文中不再赘述。 本指导原则主要适用于抗肿瘤新化合物的临床研究，抗肿瘤生物制品也可参考部分内容，不适用于中药制剂。药物类别上主要针对细胞毒

类抗肿瘤药物临床研究，由于非细胞毒类药物（如信号传导抑制剂，生物反应调节剂，激素类等）是目前新药开发的主要方向，本指导原则也将尽可能对此类别药物临床研究的不同之处进行阐述。 本指导原则中的观点仅代表SFDA当前对抗肿瘤药物临床研究的一般性认识，不能涵盖在新药研发中遇到的所有情况，申请人在研究中应始终坚持具体问题具体分析的原则。尤其应注意的是，抗肿瘤药物研究理论和技术的快速发展，很可能对将来抗肿瘤药物开发模式产生影响，因此申请人可以积极探索更为科学合理的研究方法，并及时寻求SFDA 药品注册部门的建议。 二、临床研究的总体考虑 抗肿瘤药物的临床研究过程通常分为Ⅰ期、Ⅱ期和Ⅲ期临床试验。Ⅰ期临床试验主要目的是对药物的耐受性、药代动力学进行初步研究，为后期研究给药方案的设计提供数据支持；Ⅱ期临床试验主要是探索性的研究，如给药剂量探索、给药方案探索、瘤肿有效性探索等，同时也观察安全性；Ⅲ期临床试验则在Ⅱ期基础上进一步确证肿瘤患者临床获益情况，为获得上市许可提供足够证据。 需要指出，这种临床研究的分期并不是固定的开发顺序。在本指导原则中，尽管对Ⅰ、Ⅱ期探索性试验和Ⅲ期确证性试验区别对待，但统计假设的建立和检验也可以成为Ⅱ期临床试验的一部分，同样，部分探索性研究也可能成为Ⅲ期临床试验的一部分。 由于Ⅲ期临床试验需要提供生存获益的疗效数据，试验周期较长，因此可以采用探索的开发模式，按照预定的中期分析计划，依据不断积累的信息，对临床试验方案进行调整。

药物Ⅰ期临床试验管理指导原则(试行)

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北京市第二类体外诊断试剂临床试验指导原则(2016年版)

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（五）临床试验必须获得临床试验机构伦理委员会的同意。 二、参比检测系统的选择 以下将申报产品的检测系统称为考核系统，所选择的对照检测系统称为参比系统。 （一）实验室应保证所用检测系统的完整性和有效性。考核系统和对照系统的主要分析性能指标（如准确性、精密度、线性范围等）应满足临床要求。 （二）参比系统的试剂、仪器、校准品均应已取得医疗器械注册证；考核系统的仪器、校准品应已取得医疗器械注册证或与考核试剂同步注册，且进度基本一致。 （三）参比系统应选择与考核产品方法学原理相同（如同为酶联免疫反应、同为化学发光免疫反应等）或相似的，其方法学分析性能应优于或近似于考核产品。 （四）对于定量产品，参比试剂的性能技术指标（如线性范围、精密度等）应与考核试剂近似或更优，两者的参考区间不宜差别过大；对于定性产品，两者检出限/临界值应基本一致；对于半定量产品，两者的分段区间应基本一致。 （五）定性产品可选性能更优的半定量或定量产品作为参比试剂（统计数据时应先将定量/半定量测试结果按照其自身说明书中确定的参考区间/临界值分别划归阴性、阳性结果后，再进行两个试剂测试结果间的等效性分析）。同理，半定量产品可选择定量产品作为参比试剂。 三、试验样本的选择 （一）应明确临床样本要求，考核系统与参比系统所用样本及其要求应一致。应注明样本采集、预处理、保存、输送的要求及条件（如明确采血管种类、抗凝剂要求等）。 注：推荐使用新鲜样本，如果使用贮存样本时，应注明贮存条件及时间，在数据分析时应考虑其影响并说明。

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第六条Ⅰ期试验研究室负责Ⅰ期试验的实施。研究者应遵循临床试验相关法律法规、规范性文件和技术指导原则，执行临床试验方案，保护受试者的权益与安全，保证临床试验结果的真实可靠。 第七条药物临床试验生物样本分析应在符合《药物临床试验生物样本分析实验室管理指南》（以下简称《实验室管理指南》）的实验室进行。从事药物临床试验生物样本分析的实验室均应接受药品监督管理部门的监督检查。 第八条伦理委员会应针对Ⅰ期试验的特点，加强对受试者权益与安全的保护，重点关注：试验风险的管理与控制，试验方案设计和知情同意书的内容，研究团队的人员组成、资质、经验，受试者的来源、招募方式，实施过程中发生的意外情况等。 第三章实施条件 第九条Ⅰ期试验研究室应设有足够的试验病房，也可以设有临床试验生物样本分析实验室（以下简称实验室）。试验病房应符合本指导原则的要求，实验室应符合《实验室管理指南》的要求。均应具备相应的组织管理体系、质量管理体系及能满足I期试验需要的场所和设施设备等。 第十条I期试验研究室应配备研究室负责人、主要研究者、研究医生、药师、研究护士及其他工作人员。所有人员应具备与承担工作相适应的专业特长、资质和能力。实验室人员应符合《实验室管理指南》的要求。 （一）研究室负责人。研究室负责人总体负责I期试验的管理工作，保障受试者的权益与安全。研究室负责人应具备医学或药学本科以上学历并具有高级职称，具有5年以上药

体外诊断试剂临床试验技术指导原则

体外诊断试剂临床试验技术指导原则 （征求意见稿） 一、概述 体外诊断试剂的临床试验（包括与已上市产品进行的比较研究试验）是指在相应的临床环境中，对体外诊断试剂的临床性能进行的系统性研究。 申请人应在符合要求的临床单位，在满足临床试验最低样本量要求的前提下，根据产品临床预期用途、相关疾病的流行率和统计学要求，制定能够证明其临床性能的临床试验方案，同时最大限度地控制试验误差、提高试验质量并对试验结果进行科学合理的分析。临床试验报告是对临床试验过程、结果的总结，是评价拟上市产品有效性和安全性的重要依据，是产品注册所需的重要文件之一。 本指导原则仅对体外诊断试剂临床试验提出了一般性的要求。由于体外诊断试剂产品具有发展快、专业跨度大、临床预期用途各异的特点，不同临床预期用途的产品的临床试验方法及内容不尽相同。申请人应根据产品特点及临床预期用途，制定合理的临床试验方案。国家食品药品监督管理总局也将根据体外诊断试剂发展的需要，适时修订本指导原则。 二、临床试验的基本原则 （一）基本要求 1．必须符合赫尔辛基宣言的伦理学准则。伦理考虑：研究者应考虑临床试验用样本，如血液、羊水、胸水、腹水、组织液、胸积液、组织切片、骨髓等的获得或试验结果对受试者的风险性，应提交伦理委员会的审查意见及受试者的知情同意书。对于例外情况，如客观上不可能获得受试者的知情同意或该临床试验对受试者几乎没有风险，可不提交伦理委员会的审查意见及受试者的知情同意书，但临床研究者应提供有关伦理事宜的说明。 2．受试者的权益、安全和意志高于临床试验的需要。 3．为受试者保密，尊重个人隐私。防止受试者因检测结果而受到歧视或伤害。 4．临床前研究结果支持进行临床试验。 （二）临床试验机构及人员的要求 1．体外诊断试剂的临床试验机构应获得国家食品药品监督管理总局资质认可。 2．申请人应根据产品特点及其预期用途，综合不同地区人种、流行病学背景、病原微生物的特性等因素选择临床试验机构。临床试验机构必须具有与试验用体外诊断试剂相适应的专业技术人员，及仪器设备，并能够确保该项试验的实施。 3. 申请人应当在临床试验前制定文件明确各方的职责分工，与各临床试验机构协商制定统一的临床试验方案，按照临床试验方案组织制定标准操作规程，并组织对参加试验的所有研究者进行临床试验方案和试验用体外诊断试剂使用的培训，以确保临床试验方案和试验用体外诊断试剂操作的一致性，并在临床试验过程中促进各研究者之间的沟通。 4．在临床试验开始前，申请人应与临床试验工作人员进行临床试验的预试验，使其熟悉并掌握该产品所适用的仪器、操作方法、技术性能等，以最大限度地控制试验误差。 5．在临床试验过程中，申请人应考虑吸收流行病学、统计学、临床医学、检验医学等方面专业人员（或知识），以保证临床试验科学、合理的开展。

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新药I 期临床试验申请技术指南 (草案) 国家食品药品监督管理总局（CFDA） 2016年9月

目录 一、前言 (1) 二、背景 (2) 三、与药审中心沟通交流 (3) 四、IND提交所需的特定信息 (4) （一）规定的表格 (4) （二）文件目录 (4) （三）介绍性说明和总体研究计划 (5) （四）研究者手册 (6) （五）方案 (8) （六）化学、生产和控制信息 (9) （七）药理毒理信息 (13) （八）研究药物既往在人体使用的经验 (16) （九）其他重要信息 (16) （十）相关信息 (17) 五、提交信息 (17) 六、IND过程和审评过程 (17) （一）临床试验暂停要求 (19) （二）IND修订 (20) 七、申请人的其他责任 (21)

（一）遵守法规伦理要求 (21) （二）监测正在进行的研究 (22) （三）研究药物的推销或付费 (22) （四）记录和报告 (22) （五）IND安全性报告 (22) （六）IND年度报告 (23) 八、撤回、终止、暂停或者重新启动IND (24) 附件 (26) 附件1：药品注册临床试验申报资料信息表 (26) 附件2：研究者声明表 (29) 附件3: 化药Ⅰ期临床研究CMC资料表 (32)

新药I期临床试验申请技术指南 一、前言 国家食品药品监督管理总局（CFDA）发布本技术指南旨在帮助新药研发申请人提交足够的临床试验研究申请（Investigational new drug，IND）材料，以提高新药研发与审评效率，并同时能保证药品的安全性、有效性和质量可控性。 本指导原则阐述了在中国将研究药品（包括已进行结构确证的治疗性生物工程类产品）开始用于人体研究时，所需要提供的数据。将申报资料的要求按照新药不同的研究阶段加以分类，在满足向CFDA提供评估拟进行研究所需要数据的同时，建立对同一类别IND申报的统一标准，增加IND申报要求的透明度、标准化，减少模糊性和不一致性，将有助于缩短新药批准进入临床试验的时间。 本指导原则的目的是：（1）针对I期临床试验确保有充足的数据提交给监管机构，以评价拟进行的临床研究的安全性和可行性；（2）结合IND阶段的沟通交流制度，优化IND申报流程。（3）通过规I期临床资料的数据要求，加快新药研发。通过优化申报流程与细化申报资料标准，本技术指南将促进申请人成功地提交IND。

医疗器械临床试验设计指导原则

医疗器械临床试验设计指导原则 （征求意见稿） 二〇一七年十一月

目录 一、适用范围 ..................... 错误!未定义书签。 二、临床试验的开展原则 ........... 错误!未定义书签。 三、医疗器械临床试验的设计原则和特点错误!未定义书签。（一）临床试验目的 ............... 错误!未定义书签。（二）器械临床试验设计需考虑的特殊因素错误!未定义书签。 1．器械的工作原理 ................ 错误!未定义书签。2．使用者技术水平和培训 .......... 错误!未定义书签。3．学习曲线 ...................... 错误!未定义书签。4．人为因素 ...................... 错误!未定义书签。（三）临床试验设计的基本类型和特点错误!未定义书签。1.平行对照设计 ................... 错误!未定义书签。（1）随机化 ...................... 错误!未定义书签。（2）盲法 ........................ 错误!未定义书签。（3）对照 ........................ 错误!未定义书签。 2.配对设计 ....................... 错误!未定义书签。 3.交叉设计 ....................... 错误!未定义书签。 4.单组设计 ....................... 错误!未定义书签。（1）与OPC比较 .................. 错误!未定义书签。（2）与PG比较 ................... 错误!未定义书签。

体外诊断试剂临床试验技术指导原则(16号)

附件 体外诊断试剂临床试验技术指导原则 一、概述 体外诊断试剂的临床试验（包括与已上市产品进行的比较研究试验）是指在相应的临床环境中，对体外诊断试剂的临床性能进行的系统性研究。 申请人应在符合要求的临床单位，在满足临床试验最低样本量要求的前提下，根据产品临床预期用途、相关疾病的流行率和统计学要求，制定能够证明其临床性能的临床试验方案，同时最大限度地控制试验误差、提高试验质量并对试验结果进行科学合理的分析。临床试验报告是对临床试验过程、结果的总结，是评价拟上市产品有效性和安全性的重要依据，是产品注册所需的重要文件之一。 本指导原则仅对体外诊断试剂临床试验提出了一般性的要求。由于体外诊断试剂产品具有发展快、专业跨度大、临床预期用途各异的特点，不同临床预期用途产品的临床试验方法及内容不尽相同。申请人应根据产品特点及临床预期用途，制定合理的临床试验方案。国家食品药品监督管理总局也将根据体外诊断试剂发展的需要，适时修订本指导原则。 二、临床试验的基本原则 （一）基本要求 1．临床试验必须符合赫尔辛基宣言的伦理学准则,必须获得临床试验机构伦理委员会的同意。研究者应考虑临床试验用样本，如血液、羊水、胸水、腹水、组织液、胸积液、组织切片、骨髓等的获得或试验结果对受试者的风险性，应提交伦理委员会的审查意见及受试者的知情同意书。对于例外情况，如客观上不可能获得受试者的知情同意或该临床试验对受试者几乎没有风险，可经伦理委员会审查和批准后免于受试者的知情同意。 2．受试者的权益、安全和健康必须高于科学和社会利益。 3．为受试者保密，尊重个人隐私。防止受试者因检测结果而受到歧视或伤害。 4．临床前研究结果支持进行临床试验。 （二）临床试验机构及人员的要求 1. 第三类体外诊断试剂申请人应当选定不少于3家（含3家）、第二类体外诊断试剂申请人应当选定不少于2家（含2家）临床试验机构，按照有关规定开展临床试验。 2．体外诊断试剂的临床试验机构应获得国家食品药品监督管理总局资质认可。 3．申请人应根据产品特点及其预期用途，综合不同地区人种、流行病学背景、病原微生物的特性等因素选择临床试验机构。临床试验机构必须具有与试验用体外诊断试剂相适应的专业技术人员及仪器设备，并能够确保该项试验的实施。 4. 申请人应当在临床试验前制定文件明确各方的职责分工，与各临床试验机构协商制定统一的临床试验方案，按照临床试验方案组织制定标准操作规程，并组织对参加试验的所有研究者进行临床试验方案和试验用体外诊断试剂使用的培训，以确保临床试验方案和试验用体外诊断试剂操作的一致性，并在临床试验过程中促进各研究者之间的沟通。 5．在临床试验开始前，申请人应与临床试验工作人员进行临床试验的预试验，

兽用中药、天然药物临床试验技术指导原则等5个技术指导原则

5个技术指导原则 兽用中药、天然药物临床试验技术指导原则 (3) 一、概述 (3) 二、兽用中药、天然药物临床试验的基本内容 (3) (一)靶动物安全性试验 (3) (二)实验性临床试验 (3) (三)扩大临床试验 (3) 三、兽用中药、天然药物临床试验的共性要求 (4) (一)以中兽医学理论为指导 (4) (二)试验设计原则 (4) (三)试验方案 (5) (四)试验记录 (6) (五)统计方法 (7) (六)结论推导 (7) (七)临床试验报告 (7) 四、靶动物安全性试验 (7) 五、实验性临床试验 (7) (一)—般性原则 (7) (二)人工发病或复制病证模型 (7) (三)自然病例的临床试验 (8) 六、扩大临床试验 (9) (一)一般性原则 (9) (二)试验设计 (9) 兽用中药、天然药物临床试验报告的撰写原则 (10) 一、概述 (10) 二、临床试验报告的结构与内容 (10) (一)报告封面或扉页 (10) (二)报告目录 (10) (三)缩略语 (10) (四)报告摘要 (10) (五)报告正文 (11) (六)附件 (13) 兽用中药、天然药物安全药理学研究技术指导原则 (14) 一、概述 (14) 二、基本原则 (14) 三、基本内容 (14) (一)受试物 (14) (二)生物材料 (14) (三)样本数和对照 (15) (四)给药途径 (15) (五)剂量或浓度 (15) (六)给药次数和检测时间 (15) (七)观察指标 (15) (八)结果及分析 (16)

四、名词解释 (16) 兽用中药、天然药物通用名称命名指导原则 (17) 一、基本原则 (17) 二、命名细则 (17) (一)药材命名 (17) (二)饮片命名 (18) (三)提取砌命名 (18) (四)成方制剂命名 (18) 兽用中药、天然药物质量控制研究技术指导原则 (20) 一、概述 (20) 二、处方及原料 (20) 三、制备工艺 (20) 四、质量研究及质量标准 (20) (一)质量研究的文献资料 (20) (二)质量研究的试验资料 (21) (三)质量标准草案及起草说明 (21) 1．质量标准制定前提 (21) 2．质量标准内容及起草说明 (21) 3．标准物质内容及要求 (23) 五、制剂稳定性试验要求 (24) 六、参考文献 (24)

关于印发药物Ⅰ期临床试验管理指导原则(试行的通知

关于印发药物Ⅰ期临床试验管理指导原则（试 行）的通知 国食药监注[2011]483号 各省、自治区、直辖市食品药品监督管理局（药品监督管理局），总后卫生部药品监督管理局： 为加强药物Ⅰ期临床试验的管理，有效的保障受试者的权益与安全，提高药物Ⅰ期临床试验的研究质量与管理水平，根据《中华人民共和国药品管理法》、《药品注册管理办法》和《药物临床试验质量管理规范》等有关规定，国家局组织制定了《药物Ⅰ期临床试验管理指导原则（试行）》，现予印发。请你局组织本行政区域内药物临床试验机构学习，参照执行。 附件：《药物Ⅰ期临床试验管理指导原则（试行）》起草说明 国家食品药品监督管理局 二O一一年十二月二日 药物Ⅰ期临床试验管理指导原则（试行） 第一章总则

第一条为加强药物Ⅰ期临床试验（以下简称I期试验）的管理，有效地保障受试者的权益与安全，提高Ⅰ期试验的研究质量与管理水平，根据《中华人民共和国药品管理法》、《药品注册管理办法》、《药物临床试验质量管理规范》等相关规定，参照国际通行规范，制定本指导原则。 第二条本指导原则适用于Ⅰ期试验，旨在为Ⅰ期试验的组织管理和实施提供指导。人体生物利用度或生物等效性试验应参照本指导原则。 第二章职责要求 第三条申办者应建立评价药物临床试验机构的程序和标准，选择、委托获得资格认定的I期试验研究室进行Ⅰ期试验。 第四条申办者应建立质量保证体系，对I期试验的全过程进行监查和稽查，确保临床试验的质量，保障受试者的权益与安全。 第五条申办者可以委托合同研究组织（CRO）执行I期试验中的某些工作和任务。委托前对合同研究组织的研究条件、能力、经验以及相应的质量管理体系进行评价。当合同研究组织接受了委托，则本指导原则中规定的由申办者履行的责任，合同研究组织应同样履行。申办者对临床试验的真实性及质量负最终责任。 第六条Ⅰ期试验研究室负责Ⅰ期试验的实施。研究者应遵循临床试验相关法律法规、规范性文件和技术指导原则，执行临床试验方案，保护受试者的权益与安全，保证临床试验结果的真实可靠。

Ⅰ期临床试验指导原则

药物Ⅰ期临床试验管理指导原则（试行） 2011年12月02日 发布 第一章 总则 第一条 为加强药物Ⅰ期临床试验（以下简称I期试验）的管理，有效地保障受试者的权益与安全，提高Ⅰ期试验的研究质量与管理水平，根据《中华人民共和国药品管理法》、《药品注册管理办法》、《药物临床试验质量管理规范》等相关规定，参照国际通行规范，制定本指导原则。 第二条 本指导原则适用于Ⅰ期试验，旨在为Ⅰ期试验的组织管理和实施提供指导。人体生物利用度或生物等效性试验应参照本指导原则。 第二章 职责要求 第三条 申办者应建立评价药物临床试验机构的程序和标准，选择、委托获得资格认定的I期试验研究室进行Ⅰ期试验。 第四条 申办者应建立质量保证体系，对I期试验的全过程进行监查和稽查，确保临床试验的质量，保障受试者的权益与安全。 第五条 申办者可以委托合同研究组织（CRO）执行I期试验中的某些工作和任务。委托前对合同研究组织的研究条件、能力、经验以及相应的质量管理体系进行评价。当合同研究组织接受了委托，则本指导原则中规定的由申办者履行的责任，合同研究组织应同样履行。申办者对临床试验的真实性及质量负最终责任。 第六条 Ⅰ期试验研究室负责Ⅰ期试验的实施。研究者应遵循临床试验相关法律法规、规范性文件和技术指导原则，执行临床试验方案，保护受试者的权益与安全，保证临床试验结果的真实可靠。

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