Downloaded 1,979 times
Uploaded byTamer Hifnawy
Clinical trials flow process
This document discusses the clinical trials process from protocol development through study completion. It covers developing the protocol, regulatory documents, patient recruitment, safety reporting, interim reports, and end of study activities. Key aspects include writing an approvable protocol, establishing an investigator site file, screening and enrolling suitable patients, maintaining safety oversight, and conducting closeout procedures. The goal is to provide guidance on managing all stages of a clinical trial.
More Related Content
Similar to Clinical trials flow process
Clinical trials flow process
- 1. Clinical Trials FlowProcess: The life Cycle of Clinical Trials Tamer Hifnawy MD. Dr. PH Associate Professor Public Health & Community Medicine Faculty of Medicine – BSU- Egypt College of Dentistry Taibah University- KSA Vice Dean For Quality, Development & International Affairs Certified Trainer for International Research Ethics
- 2. Objectives Developing/Writing aprotocol. Developing an Investigator Site File (ISF) – Regulatory Binder. Screening, Recruitment, Enrollment and Retention. Safety reporting (SAE &AE) SUSARS. Interim and Annual Reports. End of Study Visit.
- 4. The great tragedyof science.. the slaying of a beautiful hypothesis by an ugly fact. Thomas Henry Huxley
- 5.
- 6.
- 7.
- 8.
- 9. Preparation of trial Serology + CRF Monitoringvisits Pre-Study Activities Clinical Trials IP
- 10. Monitoring visits Serology CRF Data analysis+ Development Plan Preparation of trial Study report Registration file Scientific publications IP Pre-Study Activities End of study activity Clinical Trials
- 11.
- 12. General Information Protocoltitle, and date. Name and address of the Investigator & sponsor Name, title, address, and telephone number(s) of the sponsor's medical expert for the trial.
- 13. Background Information Nameand description of the investigational product(s). A summary of findings from nonclinical studies that potentially have clinical significance and from clinical trials that are relevant to the trial. Summary of the known and potential risks and benefits, if any, to human subjects. Description of and justification for the route of administration, dosage, dosage regimen, and treatment period(s).
- 14. Background Information Astatement that the trial will be conducted in compliance with the protocol, GCP and the applicable regulatory requirement(s). Description of the population to be studied. References to literature and data that are relevant to the trial, and that provide background for the trial.
- 15. Trial Objectives andPurpose A detailed description of the objectives and the purpose of the trial.
- 16. Trial Design Primarysecondary endpoints, if any, to be measured during the trial. A description of the type/design of trial to be conducted (e.g. double-blind, placebo-controlled, parallel design) and a schematic diagram of trial design, procedures and stages. A description of the measures taken to minimize/avoid bias, including: (a) Randomization. (b) Blinding. A description of the trial treatment(s) and the dosage and dosage regimen of the investigational product(s
- 17. Selection and Withdrawalof Subjects Subject inclusion criteria. Subject exclusion criteria. Subject withdrawal criteria (i.e. terminating investigational product treatment/trial treatment) and procedures.
- 18. Assessment of Efficacy Specification of the efficacy parameters. Methods and timing for assessing, recording, and analysing of efficacy parameters.
- 19. Assessment of Safety Specification , methods & timing of safety parameters. Procedures for eliciting reports for recording and reporting adverse event. The type and duration of the follow-up of subjects after adverse events.
- 20. Statistics Statistical methodsto be employed, and planned interim analysis(ses). Sample size & its justification (Power). The level of significance to be used. Criteria for the termination of the trial.
- 21. Quality Control andQuality Assurance Ethics Data Handling and Record Keeping Financing and Insurance
- 22. Objectives Developing/Writing aprotocol. Developing an Investigator Site File (ISF) – Regulatory Binder. Screening, Recruitment, Enrollment and Retention. Safety reporting (SAE &AE) SUSARS. Interim and Annual Reports. End of Study Visit. Key Players in Clinical Trials
- 23. Investigator Study File& Essential Documents
- 24. Definition Essential Documents: Documents whichindividually and collectively permit evaluation of the conduct of a study and the quality of the data produced
- 25. Sections Grouped in3 sections: 1) before the clinical phase of the trial commences, 2) during the clinical conduct of the trial, and 3) after completion or termination of the trial
- 26. • Investigator Brochure •Signed protocol, amendments, sample CRF • Informed consent and any other written information given to subject • Advertisement to recruit subjects • Financial aspects of trial • Insurance statement, where required • Signed agreement between involved parties Before clinical phase of trial commences INV SPO
- 27. • Dated, documentedEC favorable opinion • EC membership list / composition • Clinical Trial Authorization • CVs of investigator/sub-investigators • Laboratory normal values/ranges • Laboratory accreditation/certification • Sample of label(s) attached to IMP container Before clinical phase of trial commences INV SPO Where required
- 28. • Instructions forhandling IMPs & materials • Shipping records for IMPs & materials • Certificate(s) of analysis for shipped IMPs • Decoding procedures, if trial blinded • Master randomisation list • Pre-trial monitoring report (site suitable) • Initiation monitoring report Before clinical phase of trial commences INV SPO (or third party) (or third party)
- 29. • Effective commencementdate to CA, EC • IB updates • Revisions to protocol/amendment(s), CRF, informed consent form, other written info for subjects, advertisements, etc. • Dated, documented EC favorable opinion of substantial amendments • CA authorization of substantial amendments During trial INV SPO where required
- 30. • Updates ofCVs, CVs for new investigators • Updates to laboratory normal values/ranges • Updates to lab accreditation/certification • Documentation of IMP & materials shipments • Certificate(s) of analysis for new batches of IMPs • Monitoring visit reports INV SPO where required During trial
- 31. • Relevant communicationsother than site visits • Signed informed consent forms • Source documents • Signed, dated, completed CRFs • Documentation of CRF corrections • SAE reports (Investigator to Sponsor) INV SPO copy original copy original During trial
- 32. • Notification bysponsor to investigators of safety information • Interim or annual reports to EC & CA • Subject screening log • Subject identification code list INV SPO Where required During trial
- 33. • IMP accountabilityat site • Signature sheet • Record of retained body fluids/tissue samples (if any) INV SPO During trial
- 34. • IMP accountabilityat site • Documentation of IMP destruction • Subject identification code list • Audit certificate, if available • Close-out monitoring report After completion/termination of trial INV SPO if destroyed at site
- 35. • Treatment allocation& decoding info • Notification(s) of end of trial to CA, EC • Clinical study report • Final Study Report submission to CA, EC INV SPO returned to sponsor if applicable After completion/termination of trial
- 36. Objectives Developing/Writing aprotocol. Developing an Investigator Site File (ISF) – Regulatory Binder. Screening, Recruitment, Enrollment and Retention. Safety reporting (SAE &AE) SUSARS. Interim and Annual Reports. End of Study Visit. Key Players in Clinical Trials.
- 37. Patient Recruitment Determining thebest way to recruit for a particular study requires experience plus an understanding of the recruitment process.
- 38. Planning Determine whowill be involved? Discuss multiple strategies Establish goals and timelines Develop recruitment materials Ads, brochures, educational materials Plan to be flexible
- 39. Enrolment Enroll onlyindividuals who meet ALL of the Eligibility Criteria. Using individuals that do not meet each of the inclusion and exclusion criteria constitutes a protocol violation.
- 40. Barriers to Recruitmentand Retention Subject-related barriers Investigator-related barriers Protocol-related barriers Other barriers
- 41. Subject Barriers Longclinic waiting times Inconvenient appointment scheduling Dislike of uncertainty associated with the trial; prefer the doctor to make the decision about their treatment Perceived risks outweigh benefits Unrealistic expectations of the clinical trial Site accessibility barriers
- 42. Investigator Barriers Lackof enthusiasm for the design or aims of the study protocol Lack of time to recruit due to the investigator’s clinical workload and other duties Conflict of roles between caregiver and clinical investigator Investigator involved in too many clinical trials
- 43. Protocol Barriers Eligibilitycriteria that are so tight that potential study subjects do not qualify for entry Protocol too difficult to follow due to complex study designs Lengthy study periods or excessive visit schedules
- 44. Other Barriers Negativeinfluence of the media Social stigma associated with the research Lengthy ethical approval process may delay recruitment and trial commencement Multiple studies competing for same patients Lack of referrals from colleagues to the clinical trial Poor choice of study site by the sponsor Inaccurate estimate of patient population Not enough staff resources for the site
- 45. Methods for PatientRetention Don’t recruit “doubtful” patients Determine availability to attend visits Get as many contact details as possible: friends, family, caregiver, employer, usual medical practitioner
- 46. Methods for PatientRetention (cont.) Transportation money Be flexible Dignity and respect
- 47. Methods for PatientRetention (cont.) Clean and comfortable waiting area Tea, coffee, sandwiches Make patient feel special
- 48. Methods for PatientRetention (cont.) Serious adverse events – explain and make sure patient understand what is going on Always encourage communication by phone, email, letters Home-visits End of year party
- 50. Objectives Developing/Writing aprotocol. Developing an Investigator Site File (ISF) – Regulatory Binder. Screening, Recruitment, Enrollment and Retention. Safety reporting (SAE &AE) SUSARS. Interim and Annual Reports. End of Study Visit. Key Players in clinical trials
- 51. Adverse Events DEFINITION : Anadverse event is any undesirable/ untoward medical occurrence/ experience associated with the use of a medical product in a patient and which does not necessarily have a causal realtionship with this treatment. KINDS OF AEs: • Adverse event (AE) • Serious adverse event (SAE) • (Unexpected) adverse drug reaction (ADR) • Serious adverse drug reaction (SADR) Safety Reporting
- 53. Adverse event (AE) Any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment
- 54. Adverse drug reaction(ADR) A response to a drug which is noxious and unintended and which occurs at doses normally used in man for prophylaxis, diagnosis, or therapy of disease or for modification of physiological function
- 55. Unexpected adverse reaction (UAR) An adverse reaction, the nature or severity of which is not consistent with the applicable product information
- 56. Serious adverse event(SAE) Results in death Is life-threatening Requires hospitalisation or prolongation of existing hospitalisation Results in persistent or significant disability or incapacity Involves a congenital anomaly or birth defect Is medically significant !!!!!
- 57. Medically significant Anevent may be considered a SAE when, based upon appropriate medical judgment, it may jeopardize the patient or may require medical or surgical intervention to prevent one of the outcomes listed in the definitions for SAEs
- 58. SUSAR Suspected ,Unexpected Serious, Adverse drug Reactions associated with the use of the study medication,
- 59. AE/SAE evaluation INTENSITY CAUSALITY
- 60. INTENSITY Grade 1 -MILD Transient events, requiring no special treatment and not interfering with patient's daily activities Grade 2 - MODERATE Events introducing some level of inconvenience and may interfere with daily activities, but are usually ameliorated by simple therapeutic measures (may include drug therapy)
- 61. INTENSITY Grade 3 –SEVERE Unacceptable or intolerable events, significantly interrupting patient's normal life and requiring systemic drug therapy or other treatment
- 62. CAUSALITY (relationship to studydrug) CERTAIN A clinical event occurring in a plausible time relationship to drug administration, and which cannot be explained by concurrent disease or other drugs or chemicals.
- 63. PROBABLE A clinicalevent, including laboratory test abnormality, with a reasonable time sequence to drug administration, unlikely to be attributed to concurrent disease or other drugs or chemicals, and which follows a clinical plausible response on withdrawal (dechallenge)
- 64. POSSIBLE A clinicalevent with a reasonable time sequence to drug administration, but which could also be explained by concurrent disease or other drugs or chemicals. Information on drug withdrawal may be lacking or unclear
- 65. UNLIKELY A clinicalevent with temporal relationship to drug administration which makes a causal relationship improbable, and in which other drugs, chemicals or underlying disease provide more plausible explanations
- 66. UNASSESSABLE A reportsuggesting an adverse drug reaction, which cannot be judged because information is insufficient or contradictory and which cannot be supplemented or verified
- 67. NOT RELATED Anadverse event, which is definitely not related causally to drug administration
- 68. SAE/SUSAR reporting SAEsmust 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 investigator should also comply with applicable regulatory requirement(s) related to the reporting of unexpected serious adverse drug reactions
- 69. Reporting of SAEs- Timelines All Serious Adverse Events (Immediate Reportable Events) should be reported to the Sponsor within 24 hours after Detection of the Event. Initial and Follow-up reports as soon as possible after receipt of all the information needed As per Sponsor’s SOPs As per regulatory requirements Include reporting unexpected ADRs (SUSARs) OR
- 70. What to report? Subject number and initials Description of the event Severity Causal relationship Frequency Outcome Diagnostic tests Treatment procedures Medication administered
- 72. Objectives Developing/Writing aprotocol. Developing an Investigator Site File (ISF) – Regulatory Binder. Screening, Recruitment, Enrollment and Retention. Safety reporting (SAE &AE) SUSARS. Interim and Annual Reports. End of Study Visit. Key Players in Clinical Trials.
- 73. Reporting in ClinicalTrials Describe the Plan Report the Results Confess to Problems Interpret Objectively
- 74. End of StudyVisit To close down the study officially at the centre • Visit performed once all patients have completed the trial • Last opportunity to resolve all outstanding matters • To collect all unused material • A very last check
- 75. Close Out Visitis used to Remind the investigator of his continuing responsibilities The investigator should: - Inform the IRB/IEC on the end of the trial - Archive all study documentation for approx. 15 years
- 76. Did we “BRIDGETHE GAP”?
- 77. THANK YOU Tamer HifnawyMD. Dr PH. Associate Professor of Public Health & Community Medicine Faculty of Medicine, Beni Suef University, Egypt College of Dentistry Taibah University, KSA Certified Trainer on Ethics of Human Research Research Consultant Email: tamer.hifnawy@med.bsu.edu.eg thifnawy@taibahu.edu.sa thifnawy@yahoo.com Mobile: +201114130107 Egypt +966564356123 KSA