Efficacy to Effectiveness (E2E)

Efficacy to Effectiveness (E2E) is an approach to clinical trial design that addresses the effectiveness and safety gaps that often occur in standard randomized controlled trials. E2E trials are designed prospectively, whereby an effectiveness trial would commence seamlessly upon completion of the efficacy trial. This approach offers an opportunity for improved understanding of how a treatment will work in more usual real-world clinical settings.

Reasons for adopting an E2E trial design:

  • To provide a broader understanding of the treatment
  • To allow understanding heterogeneity of treatment effects for special patient groups
  • Greater evidence for physicians, payers, providers, and patients
  • Better translation of research results into an impact on the public
  • Potential for wider target population

The JHU-Tufts Trial Innovation Center (JHU-Tufts TIC) works with CTSA investigators nationally to develop the E2E concept and understand the challenges and potential solutions for better linking efficacy and effectiveness trials. Through consultations and workshops we will work with investigators to design the logistics and features of a specific intervention, including site selection, inclusion and exclusion criteria, data issues, engagement of industry, and regulatory matters related to approval for marketing.

The team at Tufts working on this project includes highly experienced comparative effectiveness researchers, trialists, clinical epidemiologists, statisticians, pharmacologists, and experts in drug development and testing, from academics, industry, and the FDA.

The JHU-Tufts TIC, in collaboration with MIT’s NEWDIGS program hosted a series of Design Labs to discuss the considerations and challenges of designing phase 2 or phase 3 E2E multisite clinical trials that support the generation of robust efficacy and effectiveness data. These DesignLabs brought together physicians, payers, industry, regulatory agencies, and patient groups for structured and open conversation under strict confidentiality agreements. One of the earliest projects the NEWDIGS team helped bring to fruition was adaptive licensing, which is now part of the regulatory pathway in Europe (link to PDF).

For more information on NEWDIGS, visit their website at https://newdigs.mit.edu.

Investigators are invited to apply for an initial consultation at the Trial Innovation Network website: https://trialinnovationnetwork.org/e2e-consultations.

Read more about E2E here: