Advancing ‘real-world’ trials that take account of social context and human volition
Hansen and Jones Trials
Advancing 'real-world' trials that take account of social context and human volition
Anders Blaedel Gottlieb Hansen 0
Allan Jones 1
0 Strategic Research and Development Support, Metropolitan University College , Tagensvej 18, Copenhagen N 2200 , Denmark
1 Bachelor's Degree in Global Nutrition and Health, Faculty of Health and Technology, Metropolitan University College , Sigurdsgade 26, Copenhagen N 2200 , Denmark
Background: The recent paper in Trials by Porter and colleagues highlights the utility of applying a critical realism approach in randomised trials, an approach central to the Medical Research Council's (MRC) Framework for the Development and Evaluation of Complex Healthcare Interventions. The MRC framework offers a pragmatic step towards a more open systems approach that bridges randomised evaluation with social context and human agency in an effort to improve the generalisability of trial outcomes. Main body: The MRC framework has contributed to the proliferation of a more open systems approach in health research; however, the broader acceptance of the realist approach to health research does not seem to be emulated by norms in research fund allocation, which largely prioritises laboratory-based research. Conclusion: This commentary is simply a plea, to those who make the strategic decisions regarding allocation of research funding, to support all phases of health intervention research in complex systems that contribute to the development of effective, translational and sustainable interventions in the promotion of health.
Complex interventions; External validity; Research funding
The dissemination over a decade ago of the Medical
Research Council’s (MRC) Framework for the
Development and Evaluation of Complex Healthcare
], and appeals by researchers for more
research to be conducted on interventions in complex
] has contributed to the proliferation of
research in more open systems, i.e. in ‘real-world’
settings (for an example, see the INCLUSIVE study –
]). The MRC framework advocates a mixed-method
approach, including: qualitative research – such as
process evaluation of implementation of an
intervention and of contextual factors that could lead to
variability in outcomes [
]; causal modelling approaches,
that can provide information on the process and
outcome of an intervention and that may lead to design
changes prior to implementation, e.g. [
]; and a range
of experimental methods for evaluating effectiveness,
with preference given to randomised designs
(randomised controlled trials – RCTs), wherever possible or
appropriate, for optimisation of internal validity [
The mixed-method approach is an attempt to
supplement the randomised trial with procedures embedded
in realism that take the complexity of social context
and human volition into account, and to shift the
focus from identifying causality to explaining
causality, or in other words, to explaining how intervention
components interact with different populations and in
different contexts [
]. Moore and Evans [
demonstrate the importance of context by describing how
an intervention nearly two decades ago, that
effectively reduced smoking in young people by prohibiting
smoking on school premises and thereby challenging
norms surrounding smoking behaviour, may not prove
as effective today. Norms surrounding smoking that
existed 15–20 years ago (e.g. high prevalence rates
and social acceptance) have changed, and
consequently, so have the mechanisms that predict smoking
behaviour in young people [
The combination of positivist and realist approaches
found in the MRC framework, which Porter et al. [
and others [
] refer to as realist RCTs, has given rise to
]. Central to the debate is whether
randomised and realist evaluation can be consolidated. While
critics argue that the realist RCT design found in the
MRC framework does not fully take complexity into
account , the MRC framework does offer a
pragmatic step towards a more open systems (real-world)
approach that bridges, to a degree, randomised evaluation
with social context and human agency [
]. The recent
paper in Trials by Porter and colleagues highlighting the
utility of applying a critical realism approach [
] and the
ongoing debate exploring the utility between realist and
randomised evaluations [
] are welcome and
important steps towards the development and refinement of a
usable open systems approach.
A plea for more research funding aimed at supporting
health interventions in complex systems
While incremental steps are being made as evidenced by
the MRC complex framework, the broader adoption of a
more open systems approach in health research does not
seem to have penetrated the orthodoxy of applying a
traditional positivist epistemological and ontological
(bio-medical) approach to evaluating research and, by
extension, to deciding how research funds are allocated
]. For example, an overview of research-fund
allocation from the Medical Research Council, The
Wellcome Trust, British Heart Foundation, and Cancer
Research UK, showed that across the four
researchfunding agencies, 85% of funds on average were
allocated to laboratory-based research . A recent
review of funding trends within diabetes research
illustrated that the proportion of funded studies that
included social context and human volition was small
compared to the proportion of funded bio-medical
studies, with an estimated mean ratio of 17:1 [
uptake of a non-linear, or real-world conception of
causality by funding agencies seems, therefore, to be a slow
burn. There is no doubt that the closed linear system
approach, so pervasive in bio-medical and health
research, has been effective in solving health-related and
other issues. However, researchers, including those
within bio-medicine, are increasingly asking whether the
documented efficacy of an intervention, gained from
identifying causality in a closed part of a larger or open
system (traditional reductionist approach), is robust
enough to reproduce the recorded effects reliably in
real-world settings [
]; or if successionist models of
causality alone are adequate in solving the complex
health issues of our time [
It is estimated that as much as 85% of research
investment can be categorised as waste (i.e. not benefitting
society/patients) due largely to avoidable weaknesses in
research design and production [
]. Lack of
external validity in the experimental research designs
employed is one of the main reasons why
laboratorybased and randomised clinical trial outcomes often fail
to translate into benefits for the patient, as the
robustness of probabilities in different contexts (what
works best for whom and in which setting) is uncertain
12, 18, 19, 21, 28
]. Laboratory and clinical trials that do
not take higher-level concepts, such as social context
and human volition, into account are, therefore,
vulnerable when attempting to replicate intervention effects in
real-world settings. As stated by Rothwell: “Government
expenditure should provide value for money, and medical
research is no exception” .
The MRC framework is an attempt to increase the
external validity of evaluations while still preserving
internal validity. The availability of more research funds
that support health interventions and practice-orientated
research in complex systems may result in more robust
and sustainable interventions and lead to reduced waste
in research investment.
Since the introduction of the MRC framework, complex
interventions are increasingly being developed in an
attempt to solve the continually expanding burden of
health-related issues. This commentary is, therefore, a
plea to policy-makers, and those who make the strategic
decisions regarding allocation of research funding, to
support to a greater degree all phases of real-world trials
that take into account social context and human volition
as advocated by the MRC framework, rather than to
automatically allocate research funds on the basis of
MRC: Medical Research Council; RCTs: Randomised controlled trials
No sources of funding to declare.
Availability of data and materials
Not applicable (no empirical data involved)
ABGH and AJ drafted the document, ABGH and AJ revised it critically for
important intellectual content. Both authors have given final approval and
agreed to be accountable for it.
Ethics approval and consent to participate
Not applicable (as this is not an empirical study, it involved no participants
and does not require ethics approval).
Consent for publication
Not applicable (no individual data included).
The authors declare that they have no competing interests.
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