Figure - PMC

Skip to main content

An official website of the United States government

Here's how you know

Here's how you know

Official websites use .gov
A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS
A lock ( ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

View full-text article in PMC

. 2022 Jun 13;10(7):700–714. doi: 10.1016/S2213-2600(22)00044-3

Search in PMC
Search in PubMed
View in NLM Catalog
Add to search

© 2022 Elsevier Ltd. All rights reserved.

Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

PMC Copyright notice

Enrolment and intervention delivery in explanatory and pragmatic trials

This figure serves to highlight the differences between explanatory and pragmatic trials (green arrows) and how they impact routine clinical care (black arrows). (A) Explanatory trials. Many hospitals do not have research teams capable of conducting explanatory clinical trials (community hospital, top). When there is uncertainty regarding the relative effectiveness of two therapies, arbitrary variation develops as part of usual care in the community hospital setting. Some treating clinicians (purple) choose to use one therapy (therapy A) as part of usual care and others choose to use a different therapy (therapy B). Because this practice, which applies to all patients (grey), is not incorporated into a clinical trial, it does not generate generalisable knowledge. Conversely, in hospitals capable of conducting explanatory trials (research hospital, bottom), members of a dedicated research team (red) perform screening, enrolment, randomisation, intervention delivery, and outcome assessment among a carefully selected, homogeneous group of patients (blue) while excluding most of the patients receiving those therapies as part of usual care (green and orange). Explanatory trials are typically underpowered to detect differences in patient-centred outcomes such as mortality, and therefore focus on biomarkers or other surrogate outcomes. (B) Pragmatic trials. In contrast to the explanatory trial, pragmatic trials embed screening, enrolment, intervention delivery, and outcome assessment into routine clinical care. Using these efficient methods, pragmatic trials can enrol enough patients to detect differences in patient-centred outcomes (eg, mortality), and by enrolling all patients receiving the therapy as part of clinical care (blue, green, and orange patients at community and research hospitals), pragmatic trials provide generalisable results. While some pragmatic trials such as the RECOVERY trial also leverage a platform design (to cycle in and out proposed interventions using a shared trial infrastructure) or Bayesian sequential analysis (to ensure that enrolment is continued until trial evidence is definitive for effectiveness or futility), these aspects of trial design can be combined with both pragmatic and explanatory trials. Furthermore, the separate research teams employed in explanatory trials might be the ideal method of evaluating trials of novel therapies for which the safety profile is unknown.