Section A Intervention. What is the problem and its derived questions?

This section helps you to better define the question of interest and consider the potential variations of this question (e.g. related to the population, to the intervention and comparators). When considering all its potential variations more than one relevant question could be identified. Developing that questions in a structured format (e.g. population, intervention, comparator, and outcome or PICO) will facilitate not only the evidence search but it will also help to identify which question is a priority for a “living evidence” approach.

To adequately complete the steps in this section, it is desirable to work it with content experts in the subject of interest (i.e. the panel in the context of GPC development or group of experts in the context of HTA)

If you have already worked on definition of the question of interest and its derived PICOs in line with your organisational methods or processes, you may skip Section A. If you have not done yet you may find it useful to follow this section guidance. 

Step 0. Defining the relevance of the problem or main question

If your answer to all the above questions is NO, at this stage you may reconsider to setting up a living evidence synthesis approach for this problem

Step 1. Defining the context

This step seeks to help you define the context in which the evidence will be applied. Think about the type of decision you want to support with this evidence synthesis (i.e., clinical decisions, decisions to generate recommendations in CPGs, coverage decisions, institutional or public health policies).

Step 2. Definition of the population of interest

Define the population of interest, considering whether variations in practice, due to differences in disease presentation, stages, severity or other patient characteristics may warrant evaluation of the evidence by subgroups.

Step 3. Definition of the intervention of interest

This step seeks to help you define the intervention of interest. Consider the type of intervention (i.e., prophylactic, secondary prevention, therapy, and rehabilitation), its characteristics and possible variations of interest.

Step 4. Definition of the comparator (s) of interest.

This step seeks to help you define the comparator (s) of interest. To answer the questions below, please think about other intervention alternatives that are routinely used for the treatment of the condition of interest, whether it is a pharmacological or non-pharmacological intervention

Step 5. Definition of outcomes of interest

This step seeks to help you define the expected benefit or potential harm of the study intervention and its comparator(s). Following the recommendation of the GRADE working group, consider up to six outcomes (critical or important) including efficacy and safety outcomes. Work with experts to identify the most relevant outcomes for decision-making.

Step 6. Structure of the question(s) in PICO format.

Define the PICO format question(s) that make up the health problem of interest, based on your answers to the previous questions (steps 2 to 5).

Take the population of interest (and the subgroups of this population), as well as the intervention (and the intervention subgroups, if any), the comparators of interest, and the relevant outcomes for decision-making in each case. At this point you must consider the relevance of subgroups for decision making.

Step 7. Carry out a pragmatic search

To define how pertinent it is to setting up a living evidence synthesis for the identified PICO questions, (which is going to be addressed in Section B of the Framework) at this point you should carry out a pragmatic search aimed at identify the gross evidence that exists to answer them. Running a preliminary search at this step can also help you refine the PICO. For this purpose, we suggest to start by identifying summarized evidence (e.g., systematic reviews) and then, in a stepwise manner, searching for primary studies. To rapidly identify systematic reviews, use the Epistemónikos database, and for randomized controlled trials (RCTs) as primary studies, you can conduct your search in the Cochrane Central Register of Controlled Trials (CENTRAL), complete the information by searching clinical trial registries.