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Ethical committee-role, Principal Investigator


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Ethical committee-role, Principal Investigator

  1. 1. Ethics in Research involving Human Subjects INSTITUTIONAL REVIEW BOARD/INDEPENDENT ETHICS COMMITTEE (IRB/IEC) Gayathri Devi R Pharm D V year January29,2015
  2. 2. Landmark Document • The Nuremburg Code Permissible Medical Experiments” Trials of War Criminals before the Nuermberg Military Tribunals under Control Council Law No. 10, 1949 • Helsinki Declaration World Medical Association General Assembly, Edinburgh, Scotland, October 2000 • Belmont Report of 1979 Report of the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, DHEW, April 1979 January29,2015
  3. 3. Helsinki Declaration The World Medical Association (WMA) has developed the Declaration of Helsinki as a statement of ethical principles for medical research involving human subjects, including research on identifiable human material and data. The first version was adopted in 1964 and has been amended six times since, most recently at the General Assembly in October 2008. The current (2008) version is the only official one. January29,2015
  4. 4. Other International Guidelines • 1982 - International Ethical Guidelines for Biomedical Research Involving Human Subjects by World Health Organization (WHO) and Council for International Organizations of Medical Sciences (CIOMS) • This 2002 text supersedes the 1993 Guidelines. It is the third in the series of biomedical-research ethical guidelines issued by CIOMS since 1982. Its core consists of 21 guidelines with commentaries. January29,2015
  5. 5. The FourPrinciplesof Ethics 1- Autonomy (Respect for the person) 2 - Beneficence (Do Good) 3 - Non-malfecience (Do No Harm) 4 - Justice January29,2015
  6. 6. Institutional Review Board (IRB) • Also called, Ethical Review Board (ERB) is a committee that has been formally designated to approve, monitor, and review biomedical and behavioral research involving humans with the aim to protect the rights and welfare of the research subjects. November14,2013
  7. 7. Composition collectively have the qualifications and experience to review and evaluate the science, medical aspects, and ethics of the proposed trial. • At least five members. • At least one member whose primary area of interest is in a non scientific area. • At least one member who is independent of the institution/trial site. January29,2015
  8. 8. • Only those IRB/IEC members who are independent of the investigator and the sponsor of the trial should vote/provide opinion on a trial-related matter. • A list of IRB/IEC members and their qualifications should be maintained. • The members must have enough experience, expertise, and diversity • If the IRB works with studies that include vulnerable populations, the IRB should have members who are familiar with these groups. January29,2015
  9. 9. The IRB/IEC • should perform its functions according to written operating procedures • should maintain written records of its activities and minutes of its meetings • should comply with GCP and with the applicable regulatory requirement(s). • should make its decisions at announced meetings at which at least a quorum, as stipulated in its written operating procedures, is present. • may invite non members with expertise in special areas for assistance. January29,2015
  10. 10. Need for IRB/IEC • Risks to study participants are minimized • Risks are reasonable in relation to anticipated benefits • Selection of study participants is equitable • Informed consent is obtained and appropriately documented for each participant • Adequate provisions for monitoring data collection to ensure safety of the study participants • Participant privacy and confidentiality is protected January29,2015
  11. 11. IRB Responsibilities • Conducting initial review • Conducting continuing review • Notifying the investigators about IRB decisions • Determining which studies require review more often than annually • Review and approval of changes in research activities • Determining which device studies pose significant or non-significant risk January29,2015
  12. 12. IRB Responsibilities (Cont.) • Ensuring that changes in approved research are not initiated without IRB review and approval except where necessary to eliminate apparent immediate hazards • Ensuring prompt reporting to appropriate institutional officials, regulatory agencies and funding sources of: • unanticipated problems involving risks to subjects or others • serious or continuing noncompliance with federal regulations • suspension or termination of IRB approval January29,2015
  13. 13. IRB Authority  The IRB reviews, and has the authority to approve, require modification in, or disapprove all research activities, including proposed changes in ongoing, previously approved, human subject research.  The IRB has the authority to suspend or terminate the approval of ongoing, previously approved research that is not being conducted in accordance with the IRB's requirements or that has been associated with unexpected, serious harm to subjects. January29,2015
  14. 14. Continuing Review  The IRB conducts continuing review of ongoing, approved research at intervals appropriate to the degree of risk, but not less than once per year.  For approved research, the IRB determines which activities require continuing review more frequently than every twelve months.  Continuing IRB reviews are preceded by receipt of appropriate progress reports from the investigator, including available, study-wide findings.  Continuing review must be substantive and meaningful. January29,2015
  15. 15. The IRB/IEC should obtain the following documents –Trial protocol(s)/amendment(s), – Written informed consent form(s) –Consent form updates that the investigator proposes for use in the trial –subject recruitment procedures (e.g., advertisements), written information to be provided to subjects, Investigator's Brochure (IB), January29,2015
  16. 16. – Available safety information, – Information about payments and compensation available to subjects, the investigator's current curriculum vitae and/or other documentation evidencing qualifications, – Any other documents that the IRB/IEC may need to fulfill its responsibilities. January29,2015
  17. 17. Procedures The IRB/IEC should establish, document in writing, and follow its procedures, which should include: • Determining its composition(names and qualifications of the members) and the authority under which it is established. • Scheduling, notifying its members of, and conducting its meetings. Conducting initial and continuing review of trials. Determining the frequency of continuing review, as appropriate January29,2015
  18. 18. • Providing, according to the applicable regulatory requirements, expedited review and approval/favourable opinion of minor change(s) in ongoing trials that have the approval/favourable opinion of the IRB/IEC, Specifying that no subject should be admitted to a trial before the IRB/IEC issues its written approval/favourable opinion of the trial. • Specifying that no deviations from, or changes of, the protocol should be initiated without prior written IRB/IEC approval/favourable opinion of an appropriate amendment, except when necessary to eliminate immediate hazards to the subjects January29,2015
  19. 19. Specifying… Investigator should promptly report to the IRB/IEC: • Deviations from, or changes of, the protocol to eliminate immediate hazards to the trial subjects • Changes increasing the risk to subjects and/or affecting significantly the conduct of the trial • All adverse drug reactions (ADRs) that are both serious and unexpected. • New information that may affect adversely the safety of the subjects or the conduct of the trial. January29,2015
  20. 20. Ensuring that… The IRB/IEC promptly notify in writing the investigator/institution concerning: (a) Its trial-related decisions/opinions. (b) The reasons for its decisions/opinions. (c) Procedures for appeal of its decisions/opinions. January29,2015
  21. 21. IRB Documentation • All correspondence (e.g. e-mails, submission…) between investigators /study staff and HRC • IRB Initial approval • IRB continuing review • Amendments • Violations/deviations (including sponsor- approved protocol deviations) January29,2015
  22. 22. IRB Minutes Minutes of IRB meetings must include: • attendance at the meetings • actions taken by the IRB • the vote on these actions including the number of members voting for, against, and abstaining • the basis for requiring changes in or disapproving research • documentation of specific findings required by the regulations, and • a written summary of the discussion of debated issues and their resolution January29,2015
  23. 23. IRB Records  copies of all research proposals reviewed, scientific evaluations, if any, that accompany the proposals, approved sample consent documents, progress reports submitted by investigators, and reports of injuries(if any) to subjects;  minutes of IRB meetings;  records of continuing review activities;  copies of all correspondence between the IRB and the investigators;  a list of IRB members;  written procedures for the IRB  statements of significant new findings provided to subjects January29,2015
  24. 24. Universal Ethics Committee c/o Aurous HealthCare R&D India Private Limited, No. G2 RR Villa, 180/109 Rangarajapuram Main Road, Kodambakkam, Chennai - 600024. India. Phone: +91 9551050612; +91 9840909155 EMail id:, Website: About Us Universal Ethics Committee, a Chennai based, OHRP registered (Office of Human Rights Protection, United States - No. IORG0007234) It is a unit of Aurous HealthCare Research and Development India Pvt. Ltd, has commenced its operations since early 2012, Initiated by Dr. V.T. Sriraam, MD (Pharmacology), a medical graduate, researcher and the founder of Aurous HealthCare, who has over 10 years of experience in clinical research. The committee is chaired by Dr. C. ARUN BABU MS(Gen.Sur.), MRCS (Edin.) January29,2015
  25. 25. • Institutional Ethics Committee IC& SR Building 2nd Floor, IIT Madras, Chennai 600 036 Phone: +91 (44) 2257 4929 EMail: • Dr. Anju Chadha Member Secretary, IEC Professor, Laboratory of Bioorganic Chemistry Department of Biotechnology and National Center for Catalysis Research IIT Madras, Chennai 600 036 Phone: +91 (44) 2257 4106; Fax 4102 January29,2015
  26. 26. Helpful Websites • FDA - http:// • NIH - http:// • OHRP- • FDA IRB Guidance document - http:// • Code of Federal Regulations - http:// search.html January29,2015
  27. 27. The Relationship B/w the Investigator and the IRB The IRB More supporting documents needed!!! App/disapp/app with changes Oh joy! The P.I. January29,2015
  28. 28. Then…. Have a nice trip! See you next time!! Finally!The IRB The P.I. January29,2015
  29. 29. Principal Investigator: FDA Regulations • An individual who actually conducts a clinical investigation, i.e., under whose immediate direction the test article is administered or dispensed to or used involving, a subject, or, in the event of an investigation conducted by a team of individuals, is the responsible leader of that team. January29,2015
  30. 30. INVESTIGATOR Investigator's Qualifications and Agreements - The investigator(s) should be qualified by education, training, and experience to assume responsibility for the proper conduct of the trial, should meet all the qualifications specified by the applicable regulatory requirement, and should provide evidence of such qualifications through up-to-date curriculum vitae and/or other relevant documentation requested by the sponsor, the IRB/IEC, and/or the regulatory authority(is). January29,2015
  31. 31. Investigators’ Responsibilities • Regulatory Documentation • Medical care of subjects • IRB Correspondence • Informed Consent Process • Recruitment Procedures • Subject Selection Criteria • SAE Reporting • Drug/Device Accountability • CRF/Source Documentation • Record Keeping • Allocation of Responsibilities January29,2015
  32. 32. Medical Care of Trial Subjects: • A qualified physician (or dentist, when appropriate), who is an investigator or a sub-investigator for the trial, should be responsible for all trial-related medical (or dental) decisions. • -During and following a subject's participation in a trial, the investigator/institution should ensure that adequate medical care is provided to a subject for any adverse events, including clinically significant laboratory values, related to the trial. • The investigator/institution should inform a subject when medical care is needed for intercurrent illness(es) of which the investigator becomes aware. January29,2015
  33. 33. Compliance with protocol: • The investigator should conduct the trial in compliance with the protocol agreed to by the sponsor and, if required, by the regulatory authorities and which was given approval/favourable opinion by the IRB/IEC. • The investigator/institution and the sponsor should sign the protocol, to confirm agreement. • Investigator, or person designated by the investigator, should document and explain any deviation from the approved protocol. January29,2015
  34. 34. Drug Dispensing and CRF Drug/Device Dispensing Accountability: • Dispensing log • Shipping/receiving CRF/SD: • Consistency • Dated signature /initials • Cross-outs January29,2015
  35. 35. Informed Consent of Trial Subjects: • In obtaining and documenting informed consent, the investigator should comply with the applicable regulatory requirement(s), and should adhere to GCP and to the ethical principles that have their origin in the Declaration of Helsinki. • Prior to the beginning of the trial, the investigator should have the IRB/IEC's written approval/favourable opinion of the written informed consen form and any other written information to be provided to subjects. January29,2015
  36. 36. • The written informed consent form and any other written information to be provided to subjects should be revised whenever important new information becomes available that may be relevant to the subject’s consent. • The subject or the subject’s legally acceptable representative should be informed in a timely manner if new information becomes available that may be relevant to the subject’s willingness to continue participation in the trial. The communication of this information should be documented. January29,2015
  37. 37. Contd… • None of the oral and written information concerning the trial, including the written informed consent form, should contain any language that causes the subject or the subject's legally acceptable representative to waive or to appear to waive any legal rights. • The language used in the oral and written information about the trial, including the written informed consent form, should be as non-technical as practical and should be understandable to the subject or the subject's legally acceptable representative and the impartial witness, where applicable. January29,2015
  38. 38. Contd… • Before informed consent may be obtained, the investigator, or a person designated by the investigator, should provide the subject or the subject's legally acceptable representative ample time and opportunity to inquire about details of the trial and to decide whether or not to participate in the trial. All questions about the trial should be answered to the satisfaction of the subject or the subject's legally acceptable representative January29,2015
  39. 39. Both the informed consent discussion and the written informed consent form and any other written information to be provided to subjects should include explanations of the following: • That the trial involves research. • The purpose of the trial, trial treatment(s) and the probability for random assignment to each treatment. • The trial procedures to be followed, including all invasive procedures. • The subject's responsibilities. January29,2015
  40. 40. • The reasonably foreseeable risks or inconveniences to the subject and, when applicable, to an embryo, fetus, or nursing infant. • The alternative procedure(s) or course(s) of treatment that may be available to the subject, and their important potential benefits and risks. • The compensation and/or treatment available to the subject in the event of trial-related injury. • The anticipated expenses, if any, to the subject for participating in the trial. January29,2015
  41. 41. • That the subject's participation in the trial is voluntary and that the subject may refuse to participate or withdraw from the trial, at any time, without penalty or loss of benefits to which the subject is otherwise entitled. • That the monitor(s), the auditor(s), the IRB/IEC, and the regulatory authority(ies) will be granted direct access to the subject's original medical records for verification of clinical trial procedures and/or data, without violating the confidentiality of the subject, to the extent permitted by the applicable laws and regulations. January29,2015
  42. 42. • That records identifying the subject will be kept confidential and, to the extent permitted by the applicable laws and/or regulations, will not be made publicly available. If the results of the trial are published, the subject’s identity will remain confidential. • That the subject or the subject's legally acceptable representative will be informed in a timely manner if information becomes available that may be relevant to the subject's willingness to continue participation in the trial. January29,2015
  43. 43. • The person(s) to contact for further information regarding the trial and the rights of trial subjects, and whom to contact in the event of trial-related injury. • The foreseeable circumstances and/or reasons under which the subject's participation in the trial may be terminated. • The expected duration of the subject's participation in the trial. • The approximate number of subjects involved in the trial. January29,2015
  44. 44. Safety reporting All serious adverse events (SAEs) should be reported immediately to the sponsor except for those SAEs that the protocol or other document (e.g., Investigator's Brochure) identifies as not needing immediate reporting. • The immediate reports should be followed promptly by detailed, written reports. The immediate and follow-up reports should identify subjects by unique code numbers assigned to the trial subjects . • The investigator should also comply with the applicable regulatory requirement(s) related to the reporting of unexpected serious adverse drug reactions to the regulatory authority(ies) and the IRB/IEC. January29,2015
  45. 45. • Adverse events and/or laboratory abnormalities identified in the protocol as critical to safety evaluations should be reported to the sponsor according to the reporting requirements and within the time periods specified by the sponsor in the protocol. • For reported deaths, the investigator should supply the sponsor and the IRB/IEC with any additional requested information (e.g., autopsy reports and terminal medical reports). January29,2015
  46. 46. Progress Reports • The investigator should submit written summaries of the trial status to the IRB/IEC annually, or more frequently, if requested by the IRB/IEC. • The investigator should promptly provide written reports to the sponsor, the IRB/IEC and, where applicable, the institution on any changes significantly affecting the conduct of the trial, and/or increasing the risk to subjects. January29,2015
  47. 47. Records and reports 1. Source Documentation 2. Lab Documentation 3. Investigator Brochure 4. NIH Progress Report/DSMB 5. Curriculum Vitae (CVs) 6. Study Logs 7. Eligibility Criteria Checklist 8. Consent Form Issues 9. Protocol deviations, violations 10. Record Keeping January29,2015
  48. 48. Records and reports • The investigator should ensure the accuracy, completeness, legibility, and timeliness of the data reported to the sponsor in the CRFs and in all required reports. • Data reported on the CRF, that are derived from source documents, should be consistent with the source documents or the discrepancies should be explained. January29,2015
  49. 49. • Any change or correction to a CRF should be dated, initialed, and explained (if necessary) and should not obscure the original entry (i.e. an audit trail should be maintained); this applies to both written and electronic changes or corrections . • Sponsors should provide guidance to investigators and/or the investigators' designated representatives on making such corrections. Sponsors should have written procedures to assure that changes or corrections in CRFs made by sponsor's designated representatives are documented, are necessary, and are endorsed by the investigator. The investigator should retain records of the changes and corrections. January29,2015
  50. 50. Premature Termination or Suspension of a Trial • If the trial is prematurely terminated or suspended for any reason, the investigator/institution should promptly inform the trial subjects, should assure appropriate therapy and follow-up for the subjects, and, where required by the applicable regulatory requirement(s), should inform the regulatory authority(ies). January29,2015
  51. 51. Contd.. • If the investigator terminates or suspends a trial without prior agreement of the sponsor, the investigator should inform the institution where applicable, and the investigator/institution should promptly inform the sponsor and the IRB/IEC, and should provide the sponsor and the IRB/IEC a detailed written explanation of the termination or suspension. January29,2015
  52. 52. Contd.. • If the IRB/IEC terminates or suspends its approval/favourable opinion of a trial , the investigator should inform the institution where applicable and the investigator/institution should promptly notify the sponsor and provide the e sponsor with a detailed written explanation of the termination or suspension January29,2015
  53. 53. Helpful Websites (Cont.) • OHRP Compliance Oversight • • OHRP Compliance Findings & Guidance • • OHRP Education Materials • • FDA Warning Letters • • ICH HARMONISED TRIPARTITE GUIDELINE ; GUIDELINE FOR GOOD CLINICAL PRACTICE E6(R1) Current Step 4 version dated 10 June 1996 January29,2015
  54. 54. Helpful Websites (Cont.) • Registration of Ethics Committees to become mandatory for clinical trials; Ramesh Shankar, Mumbai, Thursday, October 13, 2011, 08:00 Hrs [IST] • FDA Information Sheets • w • FDA MedWatch (AE Reporting) • • PRIM&R • • Bioethics Resources • January29,2015
  55. 55. Thanks for your endurance!!!! January29,2015