Continuum Trial in Clinical Research
A continuum trial refers to a clinical research approach that studies interventions across the full spectrum of disease progression, from preclinical stages through symptomatic disease, rather than focusing on a single disease stage. This design is particularly relevant when disease-modifying treatments are hypothesized to be more effective when initiated earlier in the disease course.
Definition and Context
The continuum trial concept has emerged most prominently in Alzheimer's disease research, where the disease progresses along a continuum from preclinical disease (characterized by normal cognition with abnormal brain biomarkers) to mild cognitive impairment and then to clinically apparent dementia 1. This framework recognizes that interventions may have differential effects depending on when they are initiated along the disease trajectory.
When Continuum Trials Are Considered
Continuum trials should be considered when:
Disease-modifying treatments are being developed that are hypothesized to work better early in disease progression - Many phase 3 clinical trials enrolling patients with symptomatic disease have failed, leading researchers to believe that disease-modifying treatment is more likely to demonstrate benefit when utilized early in the disease continuum 1
The disease has well-defined biomarker-driven stages - The Research Framework to define and stage disease continuum, along with FDA guidance on study design in early disease stages, has advanced the feasibility of such trials 1
There is a need to assess treatment effects across multiple disease stages simultaneously - This allows for evaluation of whether earlier intervention provides superior outcomes compared to later treatment initiation 1
Key Design Considerations
The continuum approach requires:
Development of measurement scales suitable for early disease stages where traditional outcome measures may not be sensitive enough to detect change 1
Biomarker-driven patient selection and stratification to ensure appropriate disease staging 1
Longer follow-up periods to capture disease progression and treatment effects across stages 1
Distinction from Other Trial Designs
The continuum trial differs from traditional stage-specific trials by enrolling patients across multiple disease stages within a single protocol, allowing direct comparison of treatment effects based on timing of intervention 1. This contrasts with the approach described in oncology guidelines where treatment recommendations represent "a continuum of care in which lines of treatment are blurred rather than discrete" 2, which refers to sequential treatment strategies rather than a specific trial design.
Regulatory and Practical Implications
Recent advances supporting continuum trial implementation include: