Characteristics and Principles of Master Protocols#

Presenter : Sang Ho Park

Introduction#

  • Master protocol is a overarching protocol dealing with multiple research questions.

  • In general, one research question requires one clinical trial.

  • We need to answer multiple research questions utilizing ‘Master Protocol’ in a coordinated, efficient, and sustainable manner.

  • There are issues with nomenclature of platform trials, basket trials, and umbrella trials.

    • We follow U.S. Food and Drug Administration (FDA)’s definition.

Important Concepts and Terminologies of Master Protocols#

  • Basket trial : one or more interventions on multiple diseases

  • Umbrella trial : two or more interventions on a single disease

  • Master protocol : A single overarching protocol dealing with multiple intervention hypotheses.

  • Platform trial : Allows addition of new interventions. New interventions were not pre-specified in the design stage.

  • Procedures and plans in master protocol can be updated over time.

  • Master protocol can be adaptive but adaptive design is not necessary.

Motivation for Master Protocol#

  • Traditional classification of disease is based on clinical evaluation and histology.

  • In modern approach, molecular classification utlizes genetic and other biomarkers related to therapeutic responses to targeted therapies.

  • Traditional International Classification of Diseases (ICD) classifications and molecular classifications are combined.

  • Performing clinical trials become complicated and costly.

    • Recruting a molecular-defined disease population is difficult.

Principles of Master Protocols#

Common Screening and Trial Systems#

  • Numbers of genomic test procedures and patients screened will be greater than number of patients recruited.

  • Accumulative total cost of genomic tests can be a substantial amount.

  • Having a single protocol can result in screening efficient and reduction of trial cost.

    • Also, master protocol can improve operational feasibility in the trial.

Establishment of Standardised Operating Procedures (SOP) for Common Trial Infrastructure#

  • In clinical trials, establishment of SOP is essential.

  • SOP : A guide for research staff (ex: administrative, clinical, data, laboratory, and pharmacy management and procedures)

    • SOP can prevent having important variations among different institutions.

Centralised Governance and Decision Making#

  • Adoption of a formal governance structure.

    • Composition of different committees should be outlined.

      • General membership and their roles and responsibilities.

  • Having common governing committees can lead to fewer resources.

    • ex: Data and Safety Monitoring Board (DSMB)

      • Require a large number of experienced personnel.

    • Having a single DSMB that monitor the progress of multiple sub-studies and interventions is more efficient than having multiple independent DSMBs.

SecondaryUse of Collected Data#

  • Master protocol enable collection of high-quality data, often in large quantity.

    • It can be utilized other researches than primary research question.