Synthesising quantitative and qualitative evidence to inform guidelines on complex interventions: clarifying the purposes, designs and outlining some methods

Taking a complexity perspective

The first paper in this series17 outlines aspects of complexity associated with complex interventions and health systems that can potentially be explored by different types of evidence, including synthesis of quantitative and qualitative evidence. Petticrew et al17 distinguish between a complex interventions perspective and a complex systems perspective. A complex interventions perspective defines interventions as having “implicit conceptual boundaries, representing a flexible, but common set of practices, often linked by an explicit or implicit theory about how they work”. A complex systems perspective differs in that “complexity arises from the relationships and interactions between a system’s agents (eg, people, or groups that interact with each other and their environment), and its context. A system perspective conceives the intervention as being part of the system, and emphasises changes and interconnections within the system itself”. Aspects of complexity associated with implementation of complex interventions in health systems that could potentially be addressed with a synthesis of quantitative and qualitative evidence are summarised in table 2. Another paper in the series outlines criteria used in a new evidence to decision framework for making decisions about complex interventions implemented in complex systems, against which the need for quantitative and qualitative evidence can be mapped.16 A further paper18 that explores how context is dealt with in guidelines and reviews taking a complexity perspective also recommends using both quantitative and qualitative evidence to better understand context as a source of complexity. Mixed-method syntheses of quantitative and qualitative evidence can also help with understanding of whether there has been theory failure and or implementation failure. The Cochrane Qualitative and Implementation Methods Group provide additional guidance on exploring implementation and theory failure that can be adapted to address aspects of complexity of complex interventions when implemented in health systems.19

It may not be apparent which aspects of complexity or which elements of the complex intervention or health system can be explored in a guideline process, or whether combining qualitative and quantitative evidence in a mixed-method synthesis will be useful, until the available evidence is scoped and mapped.17 20 A more extensive lead in phase is typically required to scope the available evidence, engage with stakeholders and to refine the review parameters and questions that can then be mapped against potential review designs and methods of synthesis.20 At the scoping stage, it is also common to decide on a theoretical perspective21 or undertake further work to refine a theoretical perspective.22 This is also the stage to begin articulating the programme theory of the complex intervention that may be further developed to refine an understanding of complexity and show how the intervention is implemented in and impacts on the wider health system.17 23 24 In practice, this process can be lengthy, iterative and fluid with multiple revisions to the review scope, often developing and adapting a logic model17 as the available evidence becomes known and the potential to incorporate different types of review designs and syntheses of quantitative and qualitative evidence becomes better understood.25 Further questions, propositions or hypotheses may emerge as the reviews progress and therefore the protocols generally need to be developed iteratively over time rather than a priori.

Following a scoping exercise and definition of key questions, the next step in the guideline development process is to identify existing or commission new systematic reviews to locate and summarise the best available evidence in relation to each question. For example, case study 2, ‘Optimising health worker roles for maternal and newborn health through task shifting’, included quantitative reviews that did and did not take an additional complexity perspective, and qualitative evidence syntheses that were able to explain how specific elements of complexity impacted on intervention outcomes within the wider health system. Further understanding of health system complexity was facilitated through the conduct of additional country-level case studies that contributed to an overall understanding of what worked and what happened when lay health worker interventions were implemented. See table 1 online supplementary file 2.

There are a few existing examples, which we draw on in this paper, but integrating quantitative and qualitative evidence in a mixed-method synthesis is relatively uncommon in a guideline process. Box 2 includes a set of key questions that guideline developers and review authors contemplating combining quantitative and qualitative evidence in mixed-methods design might ask. Subsequent sections provide more information and signposting to further reading to help address these key questions.

Questions as anchors or compasses

Questions can serve as an ‘anchor’ by articulating the specific aspects of complexity to be explored (eg, Is successful implementation of the intervention context dependent?).27 Anchor questions such as “How does intervention x impact on socioeconomic inequalities in health behaviour/outcome x” are the kind of health system question that requires a synthesis of both quantitative and qualitative evidence and hence a mixed-method synthesis. Quantitative evidence can quantify the difference in effect, but does not answer the question of how. The ‘how’ question can be partly answered with quantitative and qualitative evidence. For example, quantitative evidence may reveal where socioeconomic status and inequality emerges in the health system (an emergent property) by exploring questions such as “Does patterning emerge during uptake because fewer people from certain groups come into contact with an intervention in the first place?” or “are people from certain backgrounds more likely to drop out, or to maintain effects beyond an intervention differently?” Qualitative evidence may help understand the reasons behind all of these mechanisms. Alternatively, questions can act as ‘compasses’ where a question sets out a starting point from which to explore further and to potentially ask further questions or develop propositions or hypotheses to explore through a complexity perspective (eg, What factors enhance or hinder implementation?).27 Other papers in this series provide further guidance on developing questions for qualitative evidence syntheses and guidance on question formulation.14 28

For anchor and compass questions, additional application of a theory (eg, complexity theory) can help focus evidence synthesis and presentation to explore and explain complexity issues.17 21 Development of a review specific logic model(s) can help to further refine an initial understanding of any complexity-related issues of interest associated with a specific intervention, and if appropriate the health system or section of the health system within which to contextualise the review question and analyse data.17 23–25 Specific tools are available to help clarify context and complex interventions.17 18

If a complexity perspective, and certain criteria within evidence to decision frameworks, is deemed relevant and desirable by guideline developers, it is only possible to pursue a complexity perspective if the evidence is available. Careful scoping using knowledge maps or scoping reviews will help inform development of questions that are answerable with available evidence.20 If evidence of effect is not available, then a different approach to develop questions leading to a more general narrative understanding of what happened when complex interventions were implemented in a health system will be required (such as in case study 3—risk communication guideline). This should not mean that the original questions developed for which no evidence was found when scoping the literature were not important. An important function of creating a knowledge map is also to identify gaps to inform a future research agenda.

Table 2 and online supplementary files 1–3 outline examples of questions in the three case studies, which were all ‘COMPASS’ questions for the qualitative evidence syntheses.

Review team level

In a guideline process, it is common for syntheses of quantitative and qualitative evidence to be done separately by different teams and then to integrate the evidence. A practical consideration relates to the organisation, composition and expertise of the review teams and ways of working. If the quantitative and qualitative reviews are being conducted separately and then brought together by the same team members, who are equally comfortable operating within both paradigms, then a consistent approach across both paradigms becomes possible. If, however, a team is being split between the quantitative and qualitative reviews, then the strengths of specialisation can be harnessed, for example, in quality assessment or synthesis. Optimally, at least one, if not more, of the team members should be involved in both quantitative and qualitative reviews to offer the possibility of making connexions throughout the review and not simply at re-agreed junctures. This mirrors O’Cathain’s conclusion that mixed-methods primary research tends to work only when there is a principal investigator who values and is able to oversee integration.9 10 While the above decisions have been articulated in the context of two types of evidence, variously quantitative and qualitative, they equally apply when considering how to handle studies reporting a mixed-method study design, where data are usually disaggregated into quantitative and qualitative for the purposes of synthesis (see case study 3—risk communication in humanitarian disasters).

Question formulation

Clearly specified key question(s), derived from a scoping or consultation exercise, will make it clear if quantitative and qualitative evidence is required in a guideline development process and which aspects will be addressed by which types of evidence. For the remaining stages of the process, as documented below, a review team faces challenges as to whether to handle each type of evidence separately, regardless of whether sequentially or in parallel, with a view to joining the two products on completion or to attempt integration throughout the review process. In each case, the underlying choice is of efficiencies and potential comparability vs sensitivity to the underlying paradigm.

Searching

Once key questions are clearly defined, the guideline development group typically needs to consider whether to conduct a single sensitive search to address all potential subtopics (lumping) or whether to conduct specific searches for each subtopic (splitting).36 A related consideration is whether to search separately for qualitative, quantitative and mixed-method evidence ‘streams’ or whether to conduct a single search and then identify specific study types at the subsequent sifting stage. These two considerations often mean a trade-off between a single search process involving very large numbers of records or a more protracted search process retrieving smaller numbers of records. Both approaches have advantages and choice may depend on the respective availability of resources for searching and sifting.

Screening and selecting studies

Closely related to decisions around searching are considerations relating to screening and selecting studies for inclusion in a systematic review. An important consideration here is whether the review team will screen records for all review types, regardless of their subsequent involvement (‘altruistic sifting’), or specialise in screening for the study type with which they are most familiar. The risk of missing relevant reports might be minimised by whole team screening for empirical reports in the first instance and then coding them for a specific quantitative, qualitative or mixed-methods report at a subsequent stage.

Assessment of methodological limitations in primary studies

Within a guideline process, review teams may be more limited in their choice of instruments to assess methodological limitations of primary studies as there are mandatory requirements to use the Cochrane risk of bias tool37 to feed into Grading of Recommendations Assessment, Development and Evaluation (GRADE)38 or to select from a small pool of qualitative appraisal instruments in order to apply GRADE; Confidence in the Evidence from Reviews of Qualitative Research (GRADE-CERQual)39 to assess the overall certainty or confidence in findings. The Cochrane Qualitative and Implementation Methods Group has recently issued guidance on the selection of appraisal instruments and core assessment criteria.40 The Mixed-Methods Appraisal Tool, which is currently undergoing further development, offers a single quality assessment instrument for quantitative, qualitative and mixed-methods studies.41 Other options include using corresponding instruments from within the same ‘stable’, for example, using different Critical Appraisal Skills Programme instruments.42 While using instruments developed by the same team or organisation may achieve a degree of epistemological consonance, benefits may come more from consistency of approach and reporting rather than from a shared view of quality. Alternatively, a more paradigm-sensitive approach would involve selecting the best instrument for each respective review while deferring challenges from later heterogeneity of reporting.

Data extraction

The way in which data and evidence are extracted from primary research studies for review will be influenced by the type of integrated synthesis being undertaken and the review purpose. Initially, decisions need to be made regarding the nature and type of data and evidence that are to be extracted from the included studies. Method-specific reporting guidelines43 44 provide a good template as to what quantitative and qualitative data it is potentially possible to extract from different types of method-specific study reports, although in practice reporting quality varies. Online supplementary file 5 provides a hypothetical example of the different types of studies from which quantitative and qualitative evidence could potentially be extracted for synthesis.

The decisions around what data or evidence to extract will be guided by how ‘integrated’ the mixed-method review will be. For those reviews where the quantitative and qualitative findings of studies are synthesised separately and integrated at the point of findings (eg, segregated or contingent approaches or sequential synthesis design), separate data extraction approaches will likely be used.

Where integration occurs during the process of the review (eg, integrated approach or convergent synthesis design), an integrated approach to data extraction may be considered, depending on the purpose of the review. This may involve the use of a data extraction framework, the choice of which needs to be congruent with the approach to synthesis chosen for the review.40 45 The integrative or theoretical framework may be decided on a priori if a pre-developed theoretical or conceptual framework is available in the literature.27 The development of a framework may alternatively arise from the reading of the included studies, in relation to the purpose of the review, early in the process. The Cochrane Qualitative and Implementation Methods Group provide further guidance on extraction of qualitative data, including use of software.40

Synthesis and integration

Relatively few synthesis methods start off being integrated from the beginning, and these methods have generally been subject to less testing and evaluation particularly in a guideline context (see table 1). A review design that started off being integrated from the beginning may be suitable for some guideline contexts (such as in case study 3—risk communication in humanitarian disasters—where there was little evidence of effect), but in general if there are sufficient trials then a separate systematic review and meta-analysis will be required for a guideline. Other papers in this series offer guidance on methods for synthesising quantitative46 and qualitative evidence14 in reviews that take a complexity perspective. Further guidance on integrating quantitative and qualitative evidence in a systematic review is provided by the Cochrane Qualitative and Implementation Methods Group.19 27 29 40 47

Types of findings produced by specific methods

It is highly likely (unless there are well-designed process evaluations) that the primary studies may not themselves seek to address the complexity-related questions required for a guideline process. In which case, review authors will need to configure the available evidence and transform the evidence through the synthesis process to produce explanations, propositions and hypotheses (ie, findings) that were not obvious at primary study level. It is important that guideline commissioners, developers and review authors are aware that specific methods are intended to produce a type of finding with a specific purpose (such as developing new theory in the case of meta-ethnography).48 Case study 1 (antenatal care guideline) provides an example of how a meta-ethnography was used to develop a new theory as an end product,48 49 as well as framework synthesis which produced descriptive and explanatory findings that were more easily incorporated into the guideline process.27 The definitions (box 5) may be helpful when defining the different types of findings.

Bringing mixed-method evidence together in evidence to decision (EtD) frameworks

A critical element of guideline development is the formulation of recommendations by the Guideline Development Group, and EtD frameworks help to facilitate this process.16 The EtD framework can also be used as a mechanism to integrate and display quantitative and qualitative evidence and findings mapped against the EtD framework domains with hyperlinks to more detailed evidence summaries from contributing reviews (see table 1). It is commonly the EtD framework that enables the findings of the separate quantitative and qualitative reviews to be brought together in a guideline process. Specific challenges when populating the DECIDE evidence to decision framework15 were noted in case study 3 (risk communication in humanitarian disasters) as there was an absence of intervention effect data and the interventions to communicate public health risks were context specific and varied. These problems would not, however, have been addressed by substitution of the DECIDE framework with the new INTEGRATE16 evidence to decision framework. A d ifferent type of EtD framework needs to be developed for reviews that do not include sufficient evidence of intervention effect.