Clarify the issues

Clarify and understand the potential issues (or ‘effectiveness issues’) you may have in establishing the relative effectiveness of a medicine. For a definition of effectiveness issues, see Effectiveness Issues: Challenges in Demonstrating Effectiveness.

This section explains the main terminology of relevance, and then takes you through a series of considerations, questions and examples about the different aspects of PICO: relevant population or patient group, intervention, comparator, and outcome.

  • Consider the questions for your medicine of interest.
  • Explore and identify the effectiveness issues, which may be addressed using real-world evidence (RWE).

When you have clarified the issues, go to Find RWE Options.

How does effectiveness differ from efficacy?

See the GetReal glossary for definitions of efficacy and effectiveness from the High Level Pharmaceutical Forum (2008). The definitions in the box below have been developed to highlight the differences between key aspects of efficacy and effectiveness in the population, intervention, comparator and outcomes (PICO).

Box. Definitions of efficacy, relative efficacy and relative effectiveness

Efficacy – The change in a key clinical measure compared to placebo in a cohort of well-defined patients under a standardised care protocol.

Relative efficacy – The change in a key clinical measure compared to a standard alternative in a cohort of well-defined patients under a standardised care protocol.

Relative effectiveness – The change in a variety of endpoints of interest to patients and providers compared to the usual care provided in the population of patients identified as eligible for treatment by clinicians under the normal care provided by the healthcare system, subject to free and variable clinician and patient behaviour.

What is the efficacy-effectiveness gap?

The observed discrepancy between the effects of a health intervention in routine clinical practice (effectiveness) compared with the effects demonstrated in randomised controlled trials (efficacy) is increasingly known as the efficacy‑effectiveness gap (Eichler et al., 2011).

A narrative review was undertaken by the GetReal project on the background and conceptualisation of the efficacy‑effectiveness gap – see Background and Current Conceptualisation of the Efficacy-Effectiveness Gap.

What are the drivers of effectiveness?

The concept of ‘drivers of effectiveness’ has been developed to help understand the difference between efficacy and effectiveness and the efficacy-effectiveness gap. Drivers of effectiveness are contextual factors that interact with the medicine’s pharmacological effect in the real world; if they are not properly accounted for in study design or analysis, they may influence the effect of the medicine as reported in a trial or other study. For more information, see Drivers of Effectiveness.

Clarify and understand the issues

The differences between efficacy and effectiveness for each aspect of PICO and the reasons for these differences are described in more detail in the subsequent pages. These pages also take you through a serious of planning questions designed to help you to anticipate any effectiveness issues that may arise when undergoing health technology assessment (HTA), as well as specific methods to explore these issues. The questions may be helpful for pharmaceutical companies to consider when constructing an evidence development plan for a medicine, for HTA organisations when giving scientific advice or when scoping a new appraisal, or for patients to understand what considerations are important when designing studies for new medicines.

While the questions are presented separately for each aspect of the PICO framework, these elements are usually interconnected. Consider all of the aspects and note how these may be relevant to your medicine of interest. Use this when considering different options to address the issues (Find RWE Options).

Select an aspect of the PICO framework below:

Explore issues related to POPULATION Explore issues related to INTERVENTION  Explore issues related to COMPARATOR Explore issues related to OUTCOME

Note: In addition to methods and questions specific to each aspect of PICO, there are some general methods that may be used to explore what issues may be relevant for a particular medicine. See the box below.

Box. General methods to explore potential effectiveness issues

· Explore patient perspectives (See Patient Perspectives in Medicines Development)

· Use scientific advice processes (See Scientific Advice Processes)

· Examine existing health technology assessment reports (See Existing Health Technology Assessments)

· Understand care pathways (See Understand the Care Pathway/Patient Journey)