Protocol_Development flashcards

Page 1: Introduction to Protocol Development

  • UCL Protocol Development

    • Involvement of UCL MRC CTU

    • Presenter: Shiva Taheri, PhD Student, UCL MRC CTU

    • Contact: s.taheri@ucl.ac.uk

Page 2: Learning Objectives

  • Understand the Importance of Clinical Trial Protocols

    • Need for a clinical trial protocol

    • Different uses of a protocol

  • Formulate a Construction Plan

    • Plan for creating a clinical trial protocol

  • Identify Stakeholders

    • Involvement of various personnel in protocol development

  • Content Importance

    • Key elements to include in protocols and reasons why

  • Quality of Protocol Comparison

    • Differences between "good" and "bad" protocols

  • Consequences of Protocol Quality

    • Benefits of a well-written protocol

    • Risks associated with poorly written protocols

Page 3: Trial Protocol Definition

  • What is a Trial Protocol?

    • An essential document; often referred to as the "Holy Book" of the trial

    • Can greatly influence trial success or failure

  • Elements of Essential Documents

    • Aid in evaluating trial conduct, participant safety, and data quality

    • Provides full description of trial, outline rules including eligibility, safety reporting, rationale, and roles

    • Helps with clinical decision-making

Page 4: Protocol Importance

  • ICH GCP Guidelines

    • First produced June 1996

    • International standard ensuring ethical and scientific quality

    • Must be scientifically sound and backed by evidence

Page 5: Stakeholder Involvement

  • Collaboration is Key

    • Chief Investigator's role

    • Importance of clinical input

  • Consideration for Roles and Infrastructure

    • Roles involved in trial execution

    • Locations and infrastructure availability

  • Active Groups to Include

    • Functional (Data Science, Clin Ops, etc.)

    • Oversight groups (IDMC, TSC, TMG)

    • Patient and Public Involvement (PPI)

  • Review Committees

    • Protocol Review Committees (PRC) and Peer Review

Page 6: Essential Sections of a Protocol

  • Required Components

    • Introduction: Justification of the trial (facts, stats, clinical benefits)

    • Trial Design: E.g., double-blind, randomized

    • Aims and Objectives: Primary and secondary outcomes

    • Eligibility Criteria: Justification of criteria

    • Specifics on Intervention: Risk/benefit, side effects (IB and SmPC)

    • Comparator Justification: Placebo or sham, associated risks

Page 7: Additional Protocol Sections

  • Safety Section

    • Definitions, timelines, and pharmacovigilance requirements

  • Health Economics

  • Data Management

    • Collection, storage, sharing, analysis methods

    • Questionnaires and outcome coverage, licenses

  • Participant Timeline

    • Assessments, checks, and follow-ups

  • Statistics

    • Sample size, power, attrition factors, randomization

  • Teams List

    • Identify sponsors, oversight, PPI involvement

Page 8: Protocol Integration

  • Protocols Not Used in Isolation

    • Importance of SOPs and working practice instructions

    • Investigators Brochure (IB), Statistical Analysis Plans, and Patient Information Sheets

  • Uniformity Requirement

    • Necessity for consistency across all trial documents

Page 9: Protocol Templates

  • Template Usage

    • No mandatory template, organizations develop their own

    • Examples: CCTU template, Health Research Authority (HRA) template, SEPTRE template

  • Grant Application Reference

    • Use grant information for consistency and reduced workload

Page 10: Characteristics of a Good Protocol

  • Key Features

    • Clear, well-structured, and operationally feasible

    • Compliance with ethical/regulatory guidelines

    • Tailored to specific trial needs, incorporating expert opinions

    • Avoid vagueness and ensure easy navigation

  • Importance of Detail

    • Define eligibility, aims, and justifications with precision

Page 11: High-Quality Protocol Benefits

  • Benefits to Trial Operations

    • Facilitates appraisal of scientific, ethical, legal considerations

    • Supports high-quality data collection and management

    • Reduces workload due to clarity and conciseness

    • Enhances implementation and minimizes amendments/deviations

Page 12: Risks of Poor Protocols

  • Consequences of Poor Design

    • Need for protocol rewrites post-ethics/regulatory review

    • Increased risk to patient safety and trial integrity

    • Higher withdrawal rates, impacting study power

  • Additional Workload

    • Complications in the trial due to misinterpretation of information

Page 13: Protocol Usage

  • Users of the Protocol

    • Regulatory bodies (REC/HRA/MHRA), funders, intervention suppliers

    • Trial oversight groups, public interest entities, and medical journals

    • Trial teams at sponsors' offices and site teams conducting research

Page 14: Clinical Staff Usage

  • Role in Clinical Decision Making

    • Guidance on eligibility, tests, randomization, treatment delivery

    • Aids in understanding treatment modifications and follow-up scheduling

Page 15: Protocol Submission & Approval

  • Necessary Approvals

    • Protocol requires ethical approval from a REC

    • HRA approval combines governance and ethical compliance processes

    • Unified application process in the UK for trials in England and Wales

Page 16: Regulatory Authority Approval

  • Regulatory Oversight

    • MHRA controls trials on investigational medicinal products (CTIMPs)

    • Overview of the application process via the Integrated Research Application System (IRAS)

    • Local site R&D approvals required prior to starting trials

Page 17: Protocol Amendments

  • Types of Amendments

    • Substantial: Significant changes impacting scientific value or safety

    • Non-substantial: Minor changes that do not affect core trial integrity

    • Importance of documenting and justifying changes

Page 18: Careful Protocol Changes

  • Considerations for Protocol Changes

    • Rationale for changes must be explicitly described

    • Rarely should changes alter the direction of the original trial

    • Must undergo oversight group review and resubmission

Page 19: Protocol Deviations

  • Definition and Impact

    • Any change or departure from approved study design/procedures

    • Important deviations can adversely affect participant safety or trial results

Page 20: Reporting Deviations

  • Importance of Reporting

    • Essential for trial management and to maintain protocol adherence

    • Transparency across sites is crucial for trial integrity

Page 21: Publishing Clinical Trial Protocols

  • Need for Transparency

    • Protocols should be made publicly available on trial websites and registries

    • Publication must comply with funder and supplier agreements

Page 22: Summary of Protocol Essentials

  • Core Takeaways

    • Protocol is essential for clinical trials, supported by SOPs

    • The complexity of trials warrants clarity and thoroughness

    • Importance of involving all relevant parties from the outset

    • Adherence to ethical, legal, and funding guidelines

    • A well-written protocol lays the foundation for reliable trials

Page 23: Guided Learning Resources

  • Standards and Tools for Protocols

    • SPIRIT statement and SEPTRE resources for trial protocol guidance

    • MRC CTU clinical trials monitoring toolkit

Page 24: Questions

  • Final Page: Q&A Section

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