3. The Objectives of Clinical Research To Contribute to Public Health To Contribute to Health Science To Contribute to Economic Development
4. Good Clinical Practice A Set of Responsibilities ‘a process that makes all parties to a study responsible for patient safety and study quality’
5. US & EU Objectives inHarmonizing GCP(3 August 2009, Launch of a Bilateral GCP Initiative) To achieve common understandings and practices To share standards and methodologies To share knowledge To share resources To improve human subjects protections
6. Challenges to GCP Harmonization The extensive reach of clinical trials The complexity of law and regulation Lack of an internationally agreed code of ethics for human research protections The progress of medical science The lack of appropriately representative platforms
7. Current Ethical Challenges to GCP in Clinical Trials (1) The use of control arms (placebo) ‘Standard of care’ Informed consent process Community consultation Individual and community access to research The role & responsibility of ethics committees (IRBs/ECs) Compensation for trial injury Patient/Participant Confidentiality and Privacy Locating phase I, II, and III trials Pharmacovigilance
8. Current Ethical Challenges to GCP in Clinical Trials (2) Medical treatment during the course of research Product availability Sponsorship Liability & Insurance Tissues Stem Cell Research Data Protection Monitoring (DMCs) Data Ownership Proprietary Information/Knowledge Publishing Clinical Trial Information and Results Botanical/Traditional Medicines
9. Dimensions of GCP General Frameworks WHO GCP ICH GCP Regional/Applied Frameworks EU GCP US CFR National/Applied GCP Guidelines China, India, Russia, Singapore, Malaysia, Indonesia, South Korea Argentina, Brazil, Mexico, South America, South Africa, Turkey
10. The Way Forward for GCP Further National & Regional Development(e.g., CTTI, The AfroGuide Project) A Broader Scope to Include All Health Research Modernizing Guidance to Meet New Developments (e.g., Registries, Results Publication, DMCs, Insurance, Regulatory Science) Appropriate National, Regional, & International Platforms A Broad and Comprehensive Vision Complimented by Small Steps
12. CI Responsibilities Guidance Supervision of the Conduct of a Clinical Investigation What Is Appropriate Delegation of Study-Related Tasks? What Is Adequate Training? What Is Adequate Supervision of the Conduct of an Ongoing Clinical Trial? What Are an Investigator’s Responsibilities for Oversight of Other Parties Involved in the Conduct of a Clinical Trial? Protecting the Rights, Safety, and Welfare of Study Subjects
52. Overview The typical reaction to a finding from a Good Clinical Practice (GCP) audit or inspection is a quick fix to: Update the wording in a Clinical Standard Operating Procedure (SOP), or Provide more training But this does not guarantee that the: Process will be more effective, SOPs will be followed, or that Activities will prevent similar issues from occurring
53. Overview To have sustainable compliance across clinical trials, a set of underlying mechanisms should be in place for: Building effective clinical processes, Managing continuous improvement, and Holding staff accountable for day to day quality and compliance
54.
55. not intended to imply actual costsPrevention Costs + Detection Costs + Rework Costs = Total Cost of Quality
56. The Focus – Clinical Trial Operations 33 Compliance Activities Implementation Activities Foundation Processes Process Management Activities Clinical / Service Processes Training SOPs Monitoring TMF
57. The Foundation Processes Mar 30, 2010 How to manage initiatives and process changes effectively Process Mgmt Activities How to proactively build lessons learned, improvements, new skills, management involvement and measures of success into organization How to collect, report, trend and prioritize issues and propose changes / resolutions on global basis Plan Assess Implementation Activities Compliance Activities Do
58. Roles and Accountabilities Quality Control (QC): Daily hands on activities to ensure operations and associated deliverables meet quality standards and metrics Quality/Compliance: Oversight for process development, inspection readiness, compliance oversight, continuous improvement, quality metrics, compliance communications and engine for QMS Management Support / Governance/CI: Oversight of strategic direction of compliance activities, tactical assessments, priority of issues, measurement/ enforcement of compliance and implementation of CAPA/process improvements Research into, implementation of and support for compliance issues, proposed changes and expected outcomes Audit: Independent examination by sponsor or contracted resource to determine whether the sampled trial activities were conducted, recorded, analyzed and reported according to all requirements Oversight of regulatory inspections
59. Roles: Governance/CI Teams Clinical/Service Processes Foundation Processes Assessment Board Process Team Process Team Process Team Process Team Process Team Process Team Process Team Process Team Process Team Process Team Process Team Process Team Process Team Initiatives CAPAs Policies SOPs GDs Systems Training Process Team Initiatives CAPAs Policies SOPs GDs Systems Training Mgmt Sponsor Process Lead(s) = = Process SMEs Training Rep Executive Governance Quality Cost Time
74. Structured Investigation Method 1. Define the performance problem (DEFINE) 2. Collect Existing Data (MEASURE) 3. Identify Possible Causes (ANALYZE) 4. Test Possible Causes (ANALYZE) 5. Identify Root Causes (ANALYZE) 6. Determine Best Solution (IMPROVE) 7. Verify Solution (CONTROL)
75.
76. Usually a team activity; allows for different points of view
77. Expands the scope of the investigation; mitigates against focusing / targeting too soon
78. Identifies areas that need further analysis (e.g., review of data, experimentation); does not pinpoint root cause.40
79. Fishbone Diagram - Example Major cause categories Process Training No adequate training to staff regarding the new lab kits Validation done at Lab Supplies, Lab kits sent from distribution for re-assembly and distribution Wrong Kits assembled and sent to investigation sites Miscommunication between sites Inattention to work order requirements Human Root cause 41
As described in slide 14, the 3 basic steps of Cause mapping can further be broken up in identifiable steps and can be serve as a easy to follow Root Cause Analysis Process.*DEFINE*Step One: Define the Problem (DEFINE)What do you see happening?What are the specific symptoms?*ANALYZE*Step Two: Collect Data What proof do you have that the problem exists?How long has the problem existed?What is the impact of the problem?You need to analyze a situation fully before you can move on to look at factors that contributed to the problem. To maximize the effectiveness of your Root Cause Analysis, get together everyone who understands the situation.Step Three: Identify Possible Causal FactorsWhat sequence of events leads to the problem?What conditions allow the problem to occur?What other problems surround the occurrence of the central problem?During this stage, identify as many causal factors as possible. You don’t want to simply treat the most obvious causes – you want to dig deeper. Use the following suggested tools to identify causal factors:5xWhys and Fishbone Diagram (Cause and Effect Diagrams)Step Four: Identify the Root Cause(s)Why does the causal factor exists?What is the real reason the problem occurred? Use the same tools you used to identify the causal factors in step 3 to look at the roots of each factor. *PREVENT*Step Five: Recommend and Implement SolutionsWhat can you do to prevent the problem from happening again?How will the solution be implemented?Who will be responsible for it?What are the risks of implementing the solution?Identify the changes needed for various systems. It is also important to plan ahead to predict the effects of your solution. This way, you can spot potential failures before they happen.
This slide indicates some of the tools available to be utilized during Root Cause analysis. Only four will be explained in this presentation nl. Brainstorming, Fishbone Diagram/ Cause and Effect diagram, Why-Why Analysis and the Force Field Analysis.
When you use the fishbone diagram, you just list the causes under the Major cause categories Major categories is more a system level, for example, process, procedure, human, instrument, facility, training etc.The category with most causes is the root cause. So in this case, human error is the root cause that led to the issue.Just a side note that, when you develop the CAPA plans, u will have to consider the root cause, and also other causes that led to the issue.