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Improving the external validity of clinical trials: the case of multiple chronic conditions

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Version 2 2022-03-25, 14:08
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journal contribution
posted on 2022-03-25, 14:08 authored by Martin Fortin, Susan SmithSusan Smith

The U.S. Department of Health and Human Services vision and strategic framework on multiple chronic conditions (MCCs) incorporates recommendations designed to facilitate research that will improve our knowledge about interventions and systems that will benefit individuals with MCCs (or multimorbidity). The evidence base supporting the management of patients with MCCs will be built both through intervention trials specifically designed to address multimorbidity and identification of MCCs in participants across the clinical trial range. This article specifically focuses on issues relating to external validity with specific reference to trials involving patients with MCCs. The exclusion of such patients from clinical trials has been well documented. Randomized control trials (RCTs) are considered the “gold standard” of evidence, but may have drawbacks in relation to external validity, particularly in relation to multimorbidity. It may, therefore, be necessary to consider a broader range of research methods that can provide converging evidence on intervention effects to address MCCs. Approaches can also be taken to increase the usefulness of RCTs in general for providing evidence to inform multimorbidity management. Additional improvements to RCTs would include better reporting of inclusion and exclusion criteria and participant characteristics in relation to MCCs. New trials should be considered in terms of how they will add to the existing evidence base and should inform how interventions may work in different settings and patient groups. Research on treatments and interventions for patients with MCCs is badly needed. It is important that this research includes patient-centered measures and that generalizability issues be explicitly addressed.


Martin Fortin is supported by the Canadian Institutes of Health Research (CIHR) and partners (CIHR Applied Health Services and Policy Research Chair on Chronic Diseases in Primary Care/Canadian Institutes of Health Research – Institute of Health Services and Policy Research, Canadian Health Services Research Foundation and Centre de santé et de services sociaux de Chicoutimi). Susan Smith is affi liated with the Health Research Board Primary Care Research Centre in Ireland.



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Published Citation

Fortin M, Smith SM. Improving the external validity of clinical trials: the case of multiple chronic conditions. Journal of Comorbidity. 2013;3:30-35.

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  • HRB Centre for Primary Care Research
  • General Practice

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