ICH/GCP Guidelines Self-Evaluation Questionnaire

THE QUALITY ASSURANCE JOURNAL, VOL. 2, 74 82 (1997) ICH/GCP Guidelines Self-Evaluation Questionnaire The questionnaire below has been designed as a diverting, internal training tool by a group of employees at PPD Pharmaco. It is intended to evaluate the reader s awareness of the Good Clinical Practice guidelines recently published by the International Conference on Harmonisation (Document EMEA, step 4, Consolidated Guidelines 1.5.96) Whether you feel truly confident or less comfortable with the detail of these guidelines, running the test should not take you more than 1 hour (unless you need too frequent checks of your answers with the ICH/GCP sections indicated between parentheses ). Reproduced with the kind authorization of PPD Pharmaco. SECTION 1: GLOSSARY 1.1 What is the Difference Between an Adverse Event (AE) and an Adverse Drug Reaction (ADR)? Both terms mean the same An ADR has some recognized causal relationship with the medicinal product that an AE does not have An ADR is seen with a marketed product whereas an AE is seen with an experimental drug Answer in 1.1 and 1.2 1.2 An Audit Certificate is: A declaration that the study was conducted according to GCPs A declaration that the investigational site meets regulatory requirements A declaration that an audit has taken place Answer in 1.7 PPD Pharmaco Postfach 4904, 76032 Karlsruhe, Germany 1.3 A Clinical Study Report must be paginated in the top right corner contain the names of the EC members fully integrate clinical and statistical data into one single document Answer in 1.13 1.4 Good Clinical Practice is a standard that provides assurance that The Ethnics Committee will approve the study The results are of good quality and that the patients rights are protected The experimental drug will obtain a marketing approval Answer in 1.24 1.5 An Independent Ethics Committee (IEC) Must review the suitability of the protocol, investigators, facilities and the informed consent process Must have at least two lay members (nonscientific, non-medical members) Must meet at least every 6 weeks and return their opinion within 8 weeks of receipt of the documents Answer in 1.27 1.6 An Investigational Product is An active ingredient used in a clinical trial An active ingredient or a marketed product used in a clinical trial An active ingredient or a marketed product or a placebo used in a clinical trial Answer in 1.33 1.7 Monitors Responsibilities Include Checking compliance with the protocol- + SOPs + GCPs + applicable Regulations is the responsibility of the Auditor) Taking the Investigator out for dinner from time to time Checking compliance with the protocol only

Self-Evaluation Questionnaire 75 (checking compliance with SOPs + GCPs + applicable Regulations Answer in 1.38 1.8 What is a Nonclinical Study A biomedical study performed outside a Clinic (e.g. at a general practitioner or in a Phase I center) A biomedical study not performed on human subjects A biomedical study performed in health volunteers Answer in 1.41 1.9 For an Adverse Event or an Adverse Drug Reaction, Serious Includes Death, Life-threatening, Hospitalization, Disability/Incapacity, Congenital Anomaly/Birth Defect but not Cancer and Overdose. All of the above plus Cancer and Overdose Death and Life-Threatening only. Answer in 1.50 1.10 An Adverse Drug Reaction is Unexpected When The investigator did not think it might happen The monitor did not think it might happen The nature or severity of the ADR is not consistent with the Product Information Answer in 1.60 SECTION 2: THE PRINCIPLES OF ICH/GCP 2.1 A Trial Should be Initiated and Continued Only if: The risks are reasonable The anticipated benefits justify the risks The benefits are greater than the anticipated risks Answer in 2.2 2.2 The Subjects Identity is: Published upon Sponsor or IRB request Communicated at project meetings Protected respecting privacy and confidentiality Answer in 2.11 2.3 All Clinical Trial Information Should be: Kept with hospital records Stored in a locked room Accurately recorded, handled and stored Answer in 2.10 2.4 In a Clinical Trial the Most Important Considerations are: The interests of science and society The rights, safety and well-being of the trial subjects The investigators requests Answer in 2.3 2.5 Each Individual Conducting a Trial Should be: Over 40 years old Qualified by Education, training and experience Intelligent and multilingual Answer in 2.8 2.6 Every Subject Should Freely Give his Informed Consent Before the first study medication treatment Prior to clinical trial participation After the first examination required by the protocol Answer in 2.9 2.7 A Trial Should be Conducted: In compliance with the protocol approved by the IRB or IEC According to the investigators availability In compliance with the patients requests Answer in 2.6 2.8 The medical Care and Decisions Made Should be of: A qualified physician or dentist A hospital nurse, when appropriate Patients parents or relatives Answer in 2.7 2.9 The Available Nonclinical and Clinical Information on an Investigational Product Should be: Almost Sufficient to support the proposed clinical trial Not given in too much detail

76 ICH/GCP Guidelines Adequate to support the proposed clinical trial Answer in 2.4 2.10 Clinical Trials Should be: New and interesting Described in a clear and detailed protocol Scientifically sound and described in a clear and detailed protocol Answer in 2.5 2.11 Investigational Products are: Manufactured, handled and stored according to GMP Kept with the hospital drugs Stored by the patients Answer in 2.12 SECTION 3: INSTITUTIONAL REVIEW BOARD/INDEPENDENT ETHICS COMMITTEE (IRB/IEC) 3.1 An IRB/IEC Should Safeguard Rights, Safety and Well Being of: All trial subjects Particularly vulnerable subjects only All subjects who have not participated in a previous trial Answer in 3.1.1 3.2 An IRB/IEC, at Minimum, Should Obtain and Review: The trial protocol and amendments and Investigator Brochure Written information to be provided to subjects Information about payments and compensation available to subjects All the above Answer in 3.1.2 3.3 An IRB/IEC Should Review a Proposed Clinical Trial and Document its Views in Writing: Within 2 weeks Within 1 month Within a reasonable time Within 6 weeks of submission to the committee Answer in 3.1.2 3.4 An IRB/IEC Should Continue Review of Each Ongoing Trial: During each meeting At least every three months When every member of the committee are present At intervals appropriate to the degree of risk to subjects Answer in 3.1.4 3.5 In Certain Indications Where Pre-consent to Enter a Trial is not Possible, an IRB/IEC Should Determine that the Protocol and/or Other Documents Adequately: A. Contain details of all food to be consumed throughout the study B. Addresses ethical concerns C. Meets applicable regulatory requirements B and C A and B Answer in 3.1.7 3.6 An IRB/IEC Should Ensure Payments to a Subject: Are prorated Are wholly contingent on completion of the trial Are sufficient to influence and ensure subjects complete the trial Are prorated by each day of the study completed Answer in 3.1.8 3.7 An IRB/IEC Should Ensure it has: Written procedures Twelve members Equal male and female representation All of the above Answer in 3.2.2 3.8 In Order for All Ethical and Medical Issues to be Addressed, an IRB/IEC Should Include: A. One member whose primary area of interest is cardiovascular B. One member who is independent of the institution/trial site C. One member whose primary area of interest is non-scientific A and B B and C

Self-Evaluation Questionnaire 77 All of the above Answer in 3.2.1 3.9 An IRB/IEC May Invite Non-Members: To provide a non-biased review of clinical data To provide expertise in special areas To provide a buffet To vote when regular members are unavailable Answer in 3.2.6 3.10 Following Approval of a Trial, any Minor Changes to the Protocol Introduced Thereafter Should be: Reviewed expediently Reviewed during the regular IRB/IEC meetings Favourably approved by the IRB/IEC according to applicable regulations Given to the IEC/IRB for information only Answer in 3.3.5 3.11 The Investigator Should Promptly Report to the IRB/IEC: All protocol deviations, including administrative/logistical issues All adverse events Changes that increase risk to the subjects All of the above Answer in 3.3.8 3.12 The IRB/IEC Should Retain all Relevant Records, after Completion of the Trial For a period of at least 3 years For a period of at least 10 years When requested by the investigator When requested by the sponsor Answer in 3.4 SECTION 4: INVESTIGATOR 4.1 Who has the Responsibility for the Study Medication at a Site During the Study? The Sponsor The CRA The Investigator The Pharmacist Answer in 4.6 4.2 Under What Circumstances Would the Answer to Question 4.1 be the Pharmacist? Always Never When the task is delegated in writing by the investigator When there are too many tablets to account for Answer in 4.1.5 4.3 For How Long Should Essential Documents Remain at Site? At least 15 years after completion of the study At least 10 years after the product licensed Until the investigator moves At least 2 years after the last approval of a marketing application or discontinuation of clinical development Answer in 4.9.5 4.4 Verification of Data Against Source Documents? Must be in the investigator s native language Must be by direct access to trial related notes Must be using a back-to-back technique (indirect access) Is no longer required Answer in 4.9.7 4.5 Patient Information Sheets must be? A maximum of four pages long On three part carbon paper Signed by a witness Signed and personally dated by the patient (except in an emergency) Answer in 4.8.8 and 4.8.15 4.6 Changes or Corrections to the CRF should? Over-write the original entry Be in red ink in the margin Always be explained Endorsed by the investigator Answer in 4.9.3 4.7 Any Discrepancies Between Source Documents and CRF Should be? Highlighted in fluorescent pen Always amended to be consistent Explained Ignored Answer in 4.9.2

78 ICH/GCP Guidelines SECTION 5: SPONSOR 5.1 Which Responsibilities may be Transferred by the Sponsor to the Clinical Research Organization (CRO)? Difficult ones Easy ones All or any None Answer in 5.2.1 5.2 In a Contracted Trial, the Ultimate Responsibility for the Quality and Integrity of the Data Resides With? The CRO The Sponsor Quality Assurance Quality Control Answer in 5.2.1 5.3 How Must Trial-Related Duties be Transferred to, and Assumed by, a CRO? In writing By telephone By carrier pigeon Over lunch Answer in 5.2.2 5.4 At Which Stages Should Quality Control be Applied to Data Handling to Ensure Reliability and Correct Processing? Each stage First stage Final stage None Answer in 5.1.3 5.5 How May the Progress of the Clinical Trial be Assessed, Including Safety Data and Critical Efficacy End-Points, in Order to Determine Recommendations to Continue, Modify or Stop the Trial to be made? Arrange ad hoc meetings for informal discussions Read the final clinical/statistical report Establish an independent data-monitoring committee Seek the advice of the regulatory authorities Answer in 5.5.2 5.6 Who Must Inform the Investigator of the Need for Record Retention Requirements at the Investigational Site? The archivist, orally, in writing The Head of the Hospital/Institution Whoever remembers Answer in 5.5.12 5.7 What are the Primary Requirements in Selecting Investigators? Gracious hospitality Qualified by training and experience with adequate resources Personal recommendation Well travelled and knowledgeable Answer in 5.6.1 5.8 What Does the Potential Investigator Require Before Agreeing to Conduct a Trial? A protocol and up-to-date investigator s brochure Financial reimbursement A good lunch Nothing should be handed over before the agreement is signed Answer in 5.6.2 5.9 When Should Trial-Related Duties and Functions be Allocated? In the clinical study plan or master action plan prepared prospectively Prior to initiating the trial During the initiation visit After dinner Answer in 5.7 5.10 Who Should Provide Insurance or Indemnify the Investigator Against Claims Arising From the Trial (Excluding Malpractice and/or Negligence)? The CRO The hospital or institution The investigator s professional association Answer in 5.8.1

Self-Evaluation Questionnaire 79 5.11 If Necessary, How Should Subjects Receive Compensation in the Event of Trial-Related Injuries? In compliance with applicable regulations In cash In perpetuity Patients should never be paid Answer in 5.8.3 5.16 When an Investigator s Participation in the Trial is Terminated Because of Serious or Persistent Non-Compliance, the Sponsor Should. Refuse to pay the investigator Notify promptly the regulatory authority/ies Notify Quality Assurance Answer in 5.20.2 5.12 When Should the Investigator s Brochure be Updated? At the end of the trial As significant new information becomes available Following marketing authorization The investigator s brochure should not be amended Answer in 5.12.2 5.17 In Multi-Centre Trials The responsibilities of the co-ordinating investigator(s) must be documented before the start of the trial All investigators must be paid the same honoraria A co-ordinating investigator must be identified in each participating country Answer in 5.23.3 5.13 To Whom Should Serious and Unexpected Adverse Drug Reactions (ADRs) be Reported? The investigator(s), the ethics committee(s) and regulatory authorities The specialized medical press An independent committee reviewing the safety of the drug Answer in 5.17.1 5.18 How should Investigational Product(s) be Packaged During Transport to, and Storage at, the Investigational Site? In a wooden crate To prevent tampering by using tamper-evident seals To prevent contamination and unacceptable deterioration Answer in 5.13.3 5.14 What is the Principal Characteristic of a Sponsor s Audit? It should be non-disruptive to the clinical operations It should be independent of, and separate from routine monitoring activities It should include a night at the opera Answer in 5.19.1 5.15 In the Event of Non-Compliance, the Sponsor Should Take prompt action to secure compliance Ignore it if it does not appear to have a significant effect on patient recruitment Request an amendment to the protocol or SOPs Answer in 5.20.1 5.19 What Does the Sponsor Require from the Investigator Before Supplying Investigational Product(s) to the Site? A signed request for clinical trial test products Written confirmation of adequate storage and record keeping facilities All required documentation including approvals from the independent ethics committee and regulatory authorities A list of proposed patients screened for enrolment Answers in 5.14.2 5.20 Access to Patient s Records (Source Data) The investigator must agree in writing to providing direct access The investigator may apply discretion as to which data or documents may be accessed Patient records should never be available to anyone other than the investigator The investigator may provide indirect (back to

80 ICH/GCP Guidelines back) access only to the source data or documents Answer in 5.15.1 No, if already available in the scientific literature Answer in 6.2.3 5.21 Who Must Consent in Writing to Direct Access to the Patient s Records? The patient The investigator The hospital director The monitor Answer in 5.15.1 and 5.15.2 6.3 Blinding Envelopes Are to be Opened By the investigator after a patient completed the study In the case of patient s death According to procedures described in the protocol Answer in 6.4.8 5.22 In Order to Confirm the Adequacy of the Review of the Proposed Trial by the Independent Ethics Committee, the Sponsor Should Obtain The written constitution and approved working practices of the independent ethics committee A statement from the independent ethics committee that it is organized and operates according to GCP and the applicable laws and regulations Answer in 5.11.1 SECTION 6: CLINICAL TRIAL PROTOCOL AND PROTOCOL AMENDMENT(S) 6.1 Please Check Which of the Following Elements (Only One) Does Not Need to be Mentioned in the Protocol (or in Other Documents Referenced in the Protocol) Name and address of the Sponsor Name and address of the Monitor Name and telephone number of the Sponsor s Medical Expert Name of participating investigators Name of the Independent Ethics Committee(s) Description of the study population Type of study (placebo-controlled, doubleblind) Description of the discontinuation criteria Identification of data to be recorded directly in the CRF (that will be considered source data) Answers in 6.1, 6.2, 6.3 and 6.4 6.4 Statistical Methods to be Employed During Study Are a part of the investigator s brochure Are a part of the protocol Are described separately Answer in 6.9.1 SECTION 7: INVESTIGATOR S BROCHURE 7.1 The Main Purpose of the Investigator s Brochure (IB) is to Provide: A list of potential investigators for project managers The investigators and others involved in the trial with the information to help them to understand key features of the protocol Promotional material from the sponsor on the investigational product Guidelines on conducting a clinical trial for investigators 7.2 Who Should Participate in the Editing of an IB? A medical writer A project manager A medically qualified person 6.2 Should Potential Risks and Benefits to Human Subjects, That Have Been Recognized During Other Studies With the Drug, be Mentioned in the Protocol: Yes, as a rule Yes, if in line with animal data 7.3 The Contents of the IB Should be Approved by: Regulatory affairs The disciplines that generated the described data A medically qualified person

Self-Evaluation Questionnaire 81 7.4 An Extensive IB May Not be Necessary if: The trial is taking place only in Europe does not think it is needed The drug has not killed anyone The investigational product is marketed and its pharmacology is widely understood 7.5 Should an IB Specific to a New Indication of a Marketed Product be Prepared? Yes, always Yes, if there is time No If the sponsor thinks it is necessary 7.6 The IB Should be Reviewed and Revised, as Necessary, at Least: Monthly Annually Every 2 years At the end of the phase 2 programme 7.7 When Does Information Need to be Communicated to the Investigators, IRBs, IECs and Regulatory Authorities Without Waiting for a Revised IB? Never When relevant and sufficiently important If a patient dies during a clinical trial If the sponsor gives their permission 7.8 Who is Responsible for Providing an Up-to-Date IB to the Investigators? The monitor The project manager The medical writer 7.9 Who is Responsible for Providing an Up-to-Date IB to the Responsible IRBs/IECs? The monitor The project manager The investigators 7.10 The Title Page Should Include: The author s name The edition number and reference to the edition it supersedes s company logo A list of current clinical trials using the investigational product Answer in 7.2.1 7.11 The Clarity of the Non-Clinical Data Should be Enhanced by Including: Photographs Tables and/or listings Illustrations Non-clinical data is not included Answer in 7.3.5 7.12 The Clarity of the Clinical Data Should be Enhanced by Including: A summary of each completed clinical trial Data on only clinical trials when the product worked Only data approved by the sponsor Clinical data is not included Answer in 7.3.6 7.13 The IB Should Identify Countries Where the Investigational Product: Killed people Has been marketed or approved Did not work Is unlikely to be used Answer in 7.3.6c SECTION 8: ESSENTIAL DOCUMENTS FOR THE CONDUCT OF A CLINICAL TRIAL One or two answers can be correct. 8.1 Essential Documents for Clinical Trial Demonstrate compliance of the investigator, sponsor and monitor with the standards of GCP and regulatory requirements Are a part of the regulatory submission Should be available for Audits and Inspections Answer in 8.1

82 ICH/GCP Guidelines 8.2 Essential Documents are Generated Before the start of the trial Before, during and after the trial Regardless of the stage of the trial, but have to be completed before it is finished Answer in 8.1 8.3 Trial Master Files Are established at the sponsor s office only Are established both at the investigator s site and the sponsor s office Are subject to audits/inspections Answer in 8.1 8.4 EC Does Not Have to Review Advertisement for the subjects recruitment Subject compensation Evaluation report of the site Answer in 8.2.7 8.5 Before the Clinical Trial Commences, it is Usually Required: To have a regulatory approval/notification of the protocol To have the consent forms of the first patients signed To have the subject screening log Answer in 8.2 Certificates of analysis of new batches of the products should be added to the files Subject identification code list is to be filed with the sponsor Answer in 8.3 8.7 Subject Enrolment Log Has to be Filed On site In the office of the sponsor Both Answer in 8.3.22 8.8 After the Completion of the Trial Pre-trial documents have to be filed with the sponsor only There are specific rules on where to file each document Audit certificate has to be filed with the sponsor Answer in 8.4 8.9 Investigational Product(s) Accountability at Site Is necessary to document the use of the product according to the protocol Has to be filed with the investigator and the sponsor Is used only if the drug is destroyed on site Answer in 8.4.1 8.6 During the Clinical Trial It is necessary to submit certificates of analysis to the EC if updated