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A seminar                  On        GOOD CLINICAL PRACTICE                (GCP)Prepared by :PARTH Patel       GUIED BY:MR...
OBJECTIVES Review research and development process Review trial design measurements IND drugs Early stopping rules Go...
RESEARCH & DEVELOPMENTPROCESS Includesall of the activities required to move the Investigational Product from discovery t...
KEY PLAYERS IN A CLINICAL TRIAL Sponsor Investigation Site Team IRB/IEC Regulatory Authority/Competent Authority Subj...
TRIAL DESIGN:MEASUREMENTS Safety Efficacy Primary endpoint/objective Secondary endpoint/objective
TRIAL DESIGN:BLIND OR OPEN   Blind     SingleBlind     Double Blind   Open or open-label     All parties know the ide...
TRIAL DESIGN:RANDOMIZATION   Treatment assigned by some element of chance.   Treatment groups may be stratified (divided...
TRIAL DESIGN:SAMPLE SIZE                 Anadequate                 sample includes a                 population large   ...
CLINICAL TESTING:TIMELINEStage/Phase     Time to CompletePreClinical                 4 YearsPhase I                     1....
IND REQUIREMENTS Must show the drug is safe for clinical trials Required for all clinical trials, except     Drugs not ...
STOPPING THE CLINICAL TRIAL   Development can be stopped at any time     Safety     Efficacy     Business   Reasons/$$...
INTERNATIONAL CONFERENCEON HARMONIZATION (ICH)
OBJECTIVES OF ICH GUIDELINES Provide a unified standard EU; US; Japan To facilitate mutual acceptance of clinical data...
GOOD CLINICAL PRACTICEDefinition “ a standard for the design, conduct, performance, monitoring, auditing, recording, analy...
GCP is not a wallpaper youpaste over your ClinicalDevelopment; it is to be builtinto the Structure.
GCPs       FDA                   OHRP                  ICH21 CFR                                      International       ...
PRINCIPLES OF ICH GCP Conduct trials according to GCP Weigh risks vs. benefits Protect the subjects Have adequate info...
FORM FDA 1572 Contract between FDA and the Investigator Includes logistics such as names and addresses Section 9     C...
ICH GCP Glossary Principles of ICH GCP Information regarding     IRB/IEC     Investigator     Sponsor     Protocol ...
GCP-ICH-GLOSSARY: DEFINITIONSRELATED TO CLINICAL STUDYISSUES   Investigator           Case Report Forms (CRF)   Monitor...
GCP-ICH-GLOSSARY: DEFINITIONSRELATED TO SAFETY ISSUES Adverse drug reaction (ADR) Adverse events (AE) Serious adverse e...
GCP-ICH-GLOSSARY: DEFINITIONSRELATED TO REGULATORY ISSUES Amendments               Good clinical practice Applicable re...
GCP-ICH-GLOSSARY: DEFINITIONSRELATED TO ETHICAL ISSUES Confidentiality         Independent ethics Contract             ...
GCP-ICH-GLOSSARY: DEFINITIONSRELATED TO COMPLIANCE/AUDITINGISSUES Audit Audit certificate Audit report Compliance (in ...
HOW TO COMPLY WITH ICH GCP Use qualified support staff Obtain informed consent Record information appropriately Protec...
InvestigatorResponsibilities
INVESTIGATOR RESPONSIBILITIES * Ensure   the study is conducted according  to the investigator statement/agreement,  prot...
INVESTIGATOR RESPONSIBILITIES Maintenance  of records Investigator Qualifications and  Agreements Adequate Resources M...
REGULATORY AUTHORITIES WILLINQUIRE ABOUT: Source of study subjects Did they have the disease under study Did the meet t...
COMMON FINDINGS VIA FDA ANDOHRP   Failures to adhere to protocol     Eligibility                criteria     Randomizat...
COMMON FINDINGS VIA FDA ANDOHRP   Failures to maintain adequate/accurate records     Data changed to could not be verifi...
COMMON FINDINGS VIA FDA ANDOHRP Failures to report concomitant therapy Failures to maintain drug acct. records Failures...
COMMON FINDINGS VIA FDA ANDOHRP IRB failed to review the research at a convened  meeting Investigators failed to promptl...
COMMON FINDINGS VIA FDA ANDOHRP IRB did not ensure additional protections for  vulnerable subjects IRB members inappropr...
Informed Consent Process
INFORMED CONSENT An agreement  between  researchers and  participants A mutual  commitment   Both   parties agree   to…
ICH GCP PRINCIPLES OF THEINFORMED CONSENT PROCESS The investigator must comply with all applicable  regulations The inve...
INFORMED CONSENT PROCESS The investigator must provide ‘want to know”  information to participant, including risks and  b...
INFORMED CONSENT PROCESS Subjects must understand that they are able to  withdraw consent at any time The informed conse...
INFORMED CONSENT DOCUMENT Templates  are  provided by the  sponsor (MH, or  pharmaceutical  companies) Templates may be ...
INFORMED CONSENT DOCUMENT Must contain elements of informed consent  relevant to your clinical trial Protocol title Ver...
INFORMED CONSENTREVIEW/APPROVAL IRB must approve the form prior to use by any  subject IRB must approve of all informati...
SIGNATURES Participants must sign and date the most current  IRB approved form The person administering the consent sign...
SPECIAL CIRCUMSTANCES   Vulnerable participants     May   have a legal representative   Underage participants     Must...
COMMON CONSENTINGERRORS State and local requirements for legally  authorized representatives are not  adhered to Informe...
COMMON CONSENTINGERRORS Subject not signing informed consent prior  to administration of protocol required  procedures. ...
AE/SAE/EAEAdverse Events/Serious Adverse Events/Expedited Adverse Events
ADVERSE EVENTS   What are Adverse Events?     Any  untoward medical occurrence in a clinical trial      participant who ...
ADVERSE EVENTS Why is complete, accurate reporting of AE data important?  Allows  timely methodical evaluation of clinic...
INTENSITY OF THE EVENT All adverse events will be assessed by a sponsor  and/or protocol defined grading system The foll...
INTENSITY OF THE EVENT  Moderate: events result in a low level of  inconvenience or concern with the therapeutic  measure...
INTENSITY OF THE EVENT  Lifethreatening: any adverse drug experience that   places the patient or subject in the view of ...
RELATIONSHIP TO STUDY PRODUCTS Alladverse events must have their relationship to study product assessed using the followi...
ASSOCIATION WITH STUDY PRODUCT Determination of association with the study  product must be done by a qualified staff mem...
SAE DEFINITION ANY  adverse event that at any dose:  Results   in death  Is life threatening  Requires inpatient   hos...
SAE DEFINITION Results  in persistent or significant  disability/incapacity Is a congenital anomaly or birth defect Imp...
REPORTING TIMEFRAMES Per   MH IRB   Internal   AE –unexpected and related-report in    10 days   External AE-serious an...
RESOLUTION OF EVENT   All AE/SAE should be followed:     Untilevent has stabilized     Condition returns to baseline   ...
TRENDS    Adverse  events and serious adverse     events are reviewed throughout the     course of all clinical trials fo...
SAUMMARY/INVESTIGATORRESPONSIBILITIES Report all SAEs per sponsor/protocol defined  timelines Notify IRB of AEs/SAEs per...
Source Documentation
WORKING DEFINITION OF SOURCEDOCUMENTS   All written and printed documents that are    pertinent to a research participant...
DEFINITIONS   Source Documents are “original documents,    data, and records” and may include:       Hospital records, c...
DEVIATIONS FROM PROTOCOL Referred to as Protocol Violations and/or  Protocol Deviation/Departures Occur when there is no...
ELECTRONIC MEDICAL RECORDS Monitors are permitted at MH to have direct  access into the Epic system if a DRA amendment  h...
VERIFYING SOURCE DOCUMENTS Ensure  that  source data are  complete,  accounted for,  follow a logical  sequence of events...
PROTOCOL REQUIREDDOCUMENTATION Allinclusion/exclusion criteria be  addressed Clinical trial required tests and  procedur...
RESOURCES 21 CFR 11 21 CFR 312.62 ICH section 4.9,5.5 FDA form 3500A Medwatch 21 CFR 312.32 ICH section 4.11, 5.16, ...
.!!THANKYOU.!!
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Gcp 112070804017

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Gcp 112070804017

  1. 1. A seminar On GOOD CLINICAL PRACTICE (GCP)Prepared by :PARTH Patel GUIED BY:MR.Musir I.MansuriM.pharm-(SEM-1)Quality AssuranceRoll no:09APMC College of Pharmaceutical Education And Research.
  2. 2. OBJECTIVES Review research and development process Review trial design measurements IND drugs Early stopping rules Good clinical practice
  3. 3. RESEARCH & DEVELOPMENTPROCESS Includesall of the activities required to move the Investigational Product from discovery to market  Discovery  Pre-clinical testing  Permission to test in humans  Phase I, II, III testing  Process & interpret the data  Obtain approval to market the product  Market the product  Phase IV testing
  4. 4. KEY PLAYERS IN A CLINICAL TRIAL Sponsor Investigation Site Team IRB/IEC Regulatory Authority/Competent Authority Subject/Participant Contract Research Organization
  5. 5. TRIAL DESIGN:MEASUREMENTS Safety Efficacy Primary endpoint/objective Secondary endpoint/objective
  6. 6. TRIAL DESIGN:BLIND OR OPEN Blind  SingleBlind  Double Blind Open or open-label  All parties know the identity of the subject’s treatment
  7. 7. TRIAL DESIGN:RANDOMIZATION Treatment assigned by some element of chance. Treatment groups may be stratified (divided) into different sub-groups based on characteristics such as age, gender, and race.
  8. 8. TRIAL DESIGN:SAMPLE SIZE  Anadequate sample includes a population large enough to make generalizations from the data.  Statisticians will help answer question
  9. 9. CLINICAL TESTING:TIMELINEStage/Phase Time to CompletePreClinical 4 YearsPhase I 1.3 YearsPhase II 2.1 YearsPhase III 1.5-Several YearsPhase IV Total Time to Complete Testing 15 Years
  10. 10. IND REQUIREMENTS Must show the drug is safe for clinical trials Required for all clinical trials, except  Drugs not subject to pre-market approval  Approved drugs
  11. 11. STOPPING THE CLINICAL TRIAL Development can be stopped at any time  Safety  Efficacy  Business Reasons/$$$ Clinical trial can be halted at one site or all Clinical trial can be halted by the PI, IRB/IEC, Sponsor, or the CRO
  12. 12. INTERNATIONAL CONFERENCEON HARMONIZATION (ICH)
  13. 13. OBJECTIVES OF ICH GUIDELINES Provide a unified standard EU; US; Japan To facilitate mutual acceptance of clinical data Developed in accordance with existing standards in US, EU, Australia, Canada, Nordic Countries, and WHO
  14. 14. GOOD CLINICAL PRACTICEDefinition “ a standard for the design, conduct, performance, monitoring, auditing, recording, analyses, and reporting of clinical trials that provides assurance that the data and reported results are credible and accurate, and that the rights, integrity and confidentiality of trial subjects are protected.” (ICH GCP)
  15. 15. GCP is not a wallpaper youpaste over your ClinicalDevelopment; it is to be builtinto the Structure.
  16. 16. GCPs FDA OHRP ICH21 CFR International 45 CFR 46•Electronic •Glossary •IRBs•Documents •Principles •Informed Consent•Informed Consent •IRBs •Women•Financial Disclosure •Investigator •Prisoners•IRBs •Sponsor •Children•IND Regulations •Essential Documents
  17. 17. PRINCIPLES OF ICH GCP Conduct trials according to GCP Weigh risks vs. benefits Protect the subjects Have adequate information to justify trial Write a sound protocol Receive IRB/IEC approval Use qualified physicians
  18. 18. FORM FDA 1572 Contract between FDA and the Investigator Includes logistics such as names and addresses Section 9  Commitments of the Investigator
  19. 19. ICH GCP Glossary Principles of ICH GCP Information regarding  IRB/IEC  Investigator  Sponsor  Protocol  Investigator’s Brochure  Essential Document
  20. 20. GCP-ICH-GLOSSARY: DEFINITIONSRELATED TO CLINICAL STUDYISSUES Investigator  Case Report Forms (CRF) Monitoring  Clinical study report Monitoring report  Clinical trial Multicenter trial  Coordinating investigator Nonclinical study  Identification code (of trial Protocol subjects) Randomization  Interim clinical study report Sponsor  Investigational product Sponsor-initiated  Subject Subinvestigator  Trial Site
  21. 21. GCP-ICH-GLOSSARY: DEFINITIONSRELATED TO SAFETY ISSUES Adverse drug reaction (ADR) Adverse events (AE) Serious adverse events Unexpected adverse drug reaction
  22. 22. GCP-ICH-GLOSSARY: DEFINITIONSRELATED TO REGULATORY ISSUES Amendments  Good clinical practice Applicable regulatory  Institution (medical) requirement  Investigator Brochure Contract Research  Legally acceptable Organization (CRO) representative Direct access  Standard operating Documentation procedures
  23. 23. GCP-ICH-GLOSSARY: DEFINITIONSRELATED TO ETHICAL ISSUES Confidentiality  Independent ethics Contract committee (IEC) Impartial witness  Informed consent Institutional review  Minimal risk board (IRB)  Opinion  Vulnerable subjects  Well-being
  24. 24. GCP-ICH-GLOSSARY: DEFINITIONSRELATED TO COMPLIANCE/AUDITINGISSUES Audit Audit certificate Audit report Compliance (in relation to trials) Inspection Quality assurance Quality control Source data Source documents
  25. 25. HOW TO COMPLY WITH ICH GCP Use qualified support staff Obtain informed consent Record information appropriately Protect confidentiality Handle investigational products appropriately Implement quality systems
  26. 26. InvestigatorResponsibilities
  27. 27. INVESTIGATOR RESPONSIBILITIES * Ensure the study is conducted according to the investigator statement/agreement, protocol and regulatory requirements Ensure the protection of the participant’s rights, safety and welfare. Ensure the control of investigational drug. Obtain informed consent  *(21 CFR 312.60 and 312.61)
  28. 28. INVESTIGATOR RESPONSIBILITIES Maintenance of records Investigator Qualifications and Agreements Adequate Resources Medical Care of Subjects Communication with IRB Compliance with protocol Investigational product Randomization Informed Consent
  29. 29. REGULATORY AUTHORITIES WILLINQUIRE ABOUT: Source of study subjects Did they have the disease under study Did the meet the eligibility criteria Was the protocol precisely followed Were AE’s reported appropriately
  30. 30. COMMON FINDINGS VIA FDA ANDOHRP Failures to adhere to protocol  Eligibility criteria  Randomization  Required efficacy tests  Changes unauthorized by the sponsor
  31. 31. COMMON FINDINGS VIA FDA ANDOHRP Failures to maintain adequate/accurate records  Data changed to could not be verified  Records destroyed or otherwise missing  Medical course not documented
  32. 32. COMMON FINDINGS VIA FDA ANDOHRP Failures to report concomitant therapy Failures to maintain drug acct. records Failures to obtain proper consent  Verbal  Obtained after admission
  33. 33. COMMON FINDINGS VIA FDA ANDOHRP IRB failed to review the research at a convened meeting Investigators failed to promptly report unanticipated problems involving risks to subjects to IRB, OHRP, and sponsor Continuing review of research was NOT substantive nor meaningful
  34. 34. COMMON FINDINGS VIA FDA ANDOHRP IRB did not ensure additional protections for vulnerable subjects IRB members inappropriately participated in new and continuing review of protocols of which they had a conflicting interest
  35. 35. Informed Consent Process
  36. 36. INFORMED CONSENT An agreement between researchers and participants A mutual commitment  Both parties agree to…
  37. 37. ICH GCP PRINCIPLES OF THEINFORMED CONSENT PROCESS The investigator must comply with all applicable regulations The investigator must obtain prior written IRB/IEC approval of the consent form, and any other information given to the participant The informed consent process must be free of any coercion or undue influence
  38. 38. INFORMED CONSENT PROCESS The investigator must provide ‘want to know” information to participant, including risks and benefits Clinical trial information must be presented in a way that ensures understanding Subjects must have adequate time to ask questions and get answers
  39. 39. INFORMED CONSENT PROCESS Subjects must understand that they are able to withdraw consent at any time The informed consent form/process must contain no language that implies the waiver of rights The consenting process must be clearly documented in the subject’s chart
  40. 40. INFORMED CONSENT DOCUMENT Templates are provided by the sponsor (MH, or pharmaceutical companies) Templates may be modified by the site to meet the local requirements
  41. 41. INFORMED CONSENT DOCUMENT Must contain elements of informed consent relevant to your clinical trial Protocol title Version date of the consent form Page numbers Participant signature line
  42. 42. INFORMED CONSENTREVIEW/APPROVAL IRB must approve the form prior to use by any subject IRB must approve of all information provided to participants including written material such as handouts or brochures, verbal instruction and videotapes
  43. 43. SIGNATURES Participants must sign and date the most current IRB approved form The person administering the consent signs and dates the form The investigator and/or a witness may sign and date Participants are given a copy of the consent form and the originals are filed with the participants’ records
  44. 44. SPECIAL CIRCUMSTANCES Vulnerable participants  May have a legal representative Underage participants  Must have a parent or legal guardian sign the consent form  Depending on the age of the subject, assent may be required Problems with literacy A witness must be present
  45. 45. COMMON CONSENTINGERRORS State and local requirements for legally authorized representatives are not adhered to Informed consent form is not properly signed and dated as indicated on the form and according to the regulations Subject signing informed consents that sections of the consent have been crossed out
  46. 46. COMMON CONSENTINGERRORS Subject not signing informed consent prior to administration of protocol required procedures. Subjects are provided the informed consent document, but are told to read and sign it without opportunity to ask questions or obtain clarification Document not approved by the IRB or is an outdated version
  47. 47. AE/SAE/EAEAdverse Events/Serious Adverse Events/Expedited Adverse Events
  48. 48. ADVERSE EVENTS What are Adverse Events?  Any untoward medical occurrence in a clinical trial participant who has received test article/intervention that may or may not have a causal relationship with this treatment
  49. 49. ADVERSE EVENTS Why is complete, accurate reporting of AE data important?  Allows timely methodical evaluation of clinical safety data for clinical trial participants both individually and as a group  Maximizes individual participation safety  Develops accurate drug toxicity profiles  Compliance with regulatory requirements
  50. 50. INTENSITY OF THE EVENT All adverse events will be assessed by a sponsor and/or protocol defined grading system The following guidelines are often used to quantify intensity  Mild: events require minimal or no treatment and do not interfere with the patient’s daily activities  Grade I
  51. 51. INTENSITY OF THE EVENT  Moderate: events result in a low level of inconvenience or concern with the therapeutic measures. Moderate events may cause some interterence with functioning  Grade II  Severe: events interrupt a patient’s usual daily activity and may require systemic drug therapy or other treatment. Severe events are usually incapacitating  Grade III
  52. 52. INTENSITY OF THE EVENT  Lifethreatening: any adverse drug experience that places the patient or subject in the view of the investigator, at immediate risk of death from the reaction as it occurred, i.e., it does not include a reaction that had it occurred in a more severe form, might have caused death  Grade IV  Death  Grade V
  53. 53. RELATIONSHIP TO STUDY PRODUCTS Alladverse events must have their relationship to study product assessed using the following terms:  DefinitelyRelated  Probably Related  Possibly Related  Probably Not Related  Not Related  Pending (temporary assignment for death)
  54. 54. ASSOCIATION WITH STUDY PRODUCT Determination of association with the study product must be done by a qualified staff member What makes someone qualified to assess association with a study product?
  55. 55. SAE DEFINITION ANY adverse event that at any dose:  Results in death  Is life threatening  Requires inpatient hospitalization or prolongs hospitalization 21 CFR 312.32
  56. 56. SAE DEFINITION Results in persistent or significant disability/incapacity Is a congenital anomaly or birth defect Important medical event Other conditions as specified in the protocol 21 CFR 312.32
  57. 57. REPORTING TIMEFRAMES Per MH IRB  Internal AE –unexpected and related-report in 10 days  External AE-serious and unexpected and related-report in 10 days Death-Report within 24 hours of discovery  Must be reported within 24 hours  If patient died within 30 days of participating and is deemed related to study
  58. 58. RESOLUTION OF EVENT All AE/SAE should be followed:  Untilevent has stabilized  Condition returns to baseline  Condition is resolved  Condition no longer meets the SAE criteria
  59. 59. TRENDS  Adverse events and serious adverse events are reviewed throughout the course of all clinical trials for potential trends  Review of these “data snapshots” allows for identification of potential trends which can be related to:  Concomitant medications  Toxicities  Secondary indications
  60. 60. SAUMMARY/INVESTIGATORRESPONSIBILITIES Report all SAEs per sponsor/protocol defined timelines Notify IRB of AEs/SAEs per IRB policy Comply with all applicable regulatory requirements related to the reporting of unexpected serious adverse events
  61. 61. Source Documentation
  62. 62. WORKING DEFINITION OF SOURCEDOCUMENTS All written and printed documents that are pertinent to a research participant’s:  Exposure to the investigational agents  Exposure to other treatments  Progress of the disease course  Response to therapy
  63. 63. DEFINITIONS Source Documents are “original documents, data, and records” and may include:  Hospital records, clinic charts, laboratory notes, memoranda, subject diaries, x-rays, subject file ICH 1.52
  64. 64. DEVIATIONS FROM PROTOCOL Referred to as Protocol Violations and/or Protocol Deviation/Departures Occur when there is non-adherence to Protocol All deviations from Protocol must be addressed in clinical trial subject source document The documentation should include the reasons for the deviation and all attempts to prevent or correct them
  65. 65. ELECTRONIC MEDICAL RECORDS Monitors are permitted at MH to have direct access into the Epic system if a DRA amendment has been approved by the IRB Copies of electronic medical records DO NOT need to be certified for the sponsors to accept them
  66. 66. VERIFYING SOURCE DOCUMENTS Ensure that source data are complete, accounted for, follow a logical sequence of events Ensure that source data support entries in CRF
  67. 67. PROTOCOL REQUIREDDOCUMENTATION Allinclusion/exclusion criteria be addressed Clinical trial required tests and procedures done on time or if not, why not Withdrawals, dropouts, lost to follow up AEs/SAEs properly documented/reported Endpoints of the clinical trial
  68. 68. RESOURCES 21 CFR 11 21 CFR 312.62 ICH section 4.9,5.5 FDA form 3500A Medwatch 21 CFR 312.32 ICH section 4.11, 5.16, 5.17 and 7.3 ICH E2A 21 CFR 50 21 CFR 312.60 ICH 4.8 ICH 5.18.4e 45 CFR 46
  69. 69. .!!THANKYOU.!!

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