Need for large, fixed and dedicated sample sizes to independently address each research question or intervention in separate studies

Fixed study duration

Lack of generalisability of data from homogeneous study cohorts to real-world populations

Equally likely for patients to receive control or active treatment

Limited incentive to design head-to-head trials of approved treatments

Site related:

• Infrastructural barriers to conducting clinical trials in a broad and diverse geographical area, particularly in small centres and under-resourced settings (reduced equity)

Sponsor related:

• High operational costs, including costs to build study infrastructure for each trial and support extensive tests that fall outside patient care

Study related:

• Lack of open data

• Slow identification of new successful interventions

• Delays in translating results into clinical practice

Extensive inclusion and exclusion criteria and disease-specific focus (reducing opportunities to participate and equity of access to new treatments/interventions)

Burden of patient schedule, including additional travel requirements

Limited access to trials and increased inequality due to frequent focus on only a few specialist trial sites