Pragmatic clinical trial


A pragmatic clinical trial, sometimes called a practical clinical trial, is a clinical trial that focuses on correlation between treatments and outcomes in real-world health system practice rather than focusing on proving causative explanations for outcomes, which requires extensive deconfounding with inclusion and exclusion criteria so strict that they risk rendering the trial results irrelevant to much of real-world practice.

Examples

A typical example is that an anti-diabetic medication in the real world will often be used in people with diabetes-induced kidney problems, but if a study of its efficacy and safety excluded some subsets of people with kidney problems, the study's results may not reflect well what will actually happen in broad practice. PCTs thus contrast with explanatory clinical trials, which focus more on causation through deconfounding. The pragmatic versus explanatory distinction is a spectrum or continuum rather than a dichotomy, but the distinction is nonetheless important to evidence-based medicine because physicians have found that treatment effects in explanatory clinical trials do not always translate to outcomes in typical practice. Decision-makers hope to build a better evidence base to inform decisions by encouraging more PCTs to be conducted.

Distinction from other forms of trials

The distinction between pragmatic and explanatory trials is not the same as the distinction between randomized and nonrandomized trials. Any trial can be either randomized or nonrandomized and have any degree of pragmatic and explanatory power, depending on its study design, with randomization being preferable if practicably available. However, most randomized controlled trials to date have leaned toward the explanatory side of the pragmatic-explanatory spectrum, largely because of the value traditionally placed on proving causation by deconfounding as part of proving efficacy, but sometimes also because "attempts to minimize cost and maximize efficiency have led to smaller sample sizes". The movement toward supporting pragmatic randomized controlled trials hopes to make sure that money spent on RCTs is well spent by providing information that actually matters to real-world outcomes, regardless of conclusively tying causation to particular variables. This is the pragmatic element of such designs. Thus pRCTs are important to comparative effectiveness research, and a distinction is often made between efficacy and effectiveness, whereby efficacy implies causation proved by deconfounding other variables but effectiveness implies correlation with outcomes regardless of presence of other variables.
Explanation remains important, as does traditional efficacy research, because we still value knowledge of causation to advance our understanding of molecular biology and to maintain our ability to differentiate real efficacy from placebo effects. What has become apparent in the era of advanced health technology is that we also need to know about comparative effectiveness in real-world applications so that we can ensure the best use of our limited resources as we make countless instances of clinical decisions. And it is apparent that explanatory evidence, such as in vitro evidence and even in vivo evidence from clinical trials with tight exclusion criteria, often does not help enough, by itself, with that task.