Toolbox: Methods to generate evidence on effectiveness

A Toolbox was developed by GetReal to display the key outputs and methodological tools under a common conceptual framework and using structured decision-making.

The Toolbox:

  • provides an understanding of effectiveness, including how to measure it both before and during a new medicine’s launch while minimising the risk of confounding bias
  • maps study design parameters and analytical options to assess effectiveness during the medicines development process and complement traditional study designs.

How was it developed?

The Toolbox was derived from more than 12 studies that addressed the following questions:

  1. How the efficacy-effectiveness gap can be understood and anticipated?
  2. What is the impact of the absence of evidence on effectiveness on health technology assessment (HTA) decisions?
    • A review of 68 post-registration studies requested by the French HTA agency (Haute Autorité de Santé) was conducted.
  3. How can literature reviews, experts interviews and data analyses be used to identify potential drivers of effectiveness before launch?
    • Three case studies were performed to explore the opportunities and limitations of different methods.
  4. Are there any RCTs performed before authorisation that have investigated effectiveness?
    • A review of the literature identified pre-authorisation RCTs specifically aimed at providing information on effectiveness in addition to evidence of efficacy.
  5. Can I enrich my trial population to better predict effectiveness without increasing the sample size and compromising my chances of success?
    • A simulation study was performed to explore how the enrichment of a typical RCT population may improve the prediction of effectiveness, using the RCT results.
  6. What are the key statistical issues related to the conduct of pragmatic trials?
  7. What are the key statistical issues related to the conduct of observational effectiveness studies just after market authorisation?
    • Various case studies explored time-varying confounding channeling bias which may be present after a medicine’s launch.

The Toolbox

Figure. Toolbox on methods to generate evidence on effectiveness before launch

Methods to generate evidence on Effectiveness before launch