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