Talk:Pragmatic clinical trial

The section discussing the continuum from explanatory to pragmatic trial designs could be improved by updating the references to mention the development of the original PRECIS too and subsequent revision to PRECIS-2. I have put some suggested text in BOLD below:

"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. Work over the last decade has sought to formalise the design features upon which trials are more or less pragmatic. This includes the initial PRagmatic-Explanatory Continuum Indicator Summary (PRECIS) developed by Thorpe and colleagues . PRECIS included 10 domains with a visual scale to represent where the trial fell on each domain . PRECIS was later revised to PRECIS-2, which contains 9 domains each provided a 5 point likert-scale upon which a trial can be scored from very explanatory (1) to very pragmatic (5) However, most randomized controlled trials (RCTs) 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".[2] The movement toward supporting pragmatic randomized controlled trials (pRCTs) hopes to make sure that money spent on RCTs is well spent by providing information that actually matters to real-world outcomes,[2] regardless of conclusively tying causation to particular variables. This is the pragmatic element of such designs. Thus pRCTs are important to comparative effectiveness research,[2] and a distinction is often (although not always) made between efficacy and effectiveness, whereby efficacy implies causation proved by deconfounding other variables (we know with certainty that drug X treats disease Y by mechanism of action Z) but effectiveness implies correlation with outcomes regardless of presence of other variables (we know with certainty that people in a situation similar to X who take drug A tend to have slightly better outcomes than those who take drug B, and even if we think we may suspect why, the causation is not as important)."

A table could also be inserted showing the PRECIS-2 domains

PRECIS-2 domain	Description
Eligibility	To what extent are the participants in the trial similar to those who would receive this intervention if it was part of usual care? A more pragmatic trial would have criteria that ensure participants are essentially identical to those in usual care; a more explanatory approach would have lots of exclusions (e.g. those who don't comply, respond to treatment, or are not at high risk for primary outcome, are children or elderly), or uses many selection tests not used in usual care.
Recruitment	How much extra effort is made to recruit participants over and above what that would be used in the usual care setting to engage with patients? For example, a very pragmatic trial may have recruitment through usual appointments or clinic; a very explanatory trial may have targeted invitation letters, advertising in newspapers, radio plus incentives and other routes that would not be used in usual care.
Setting	How different is the setting of the trial and the usual care setting? For example, a very pragmatic trial may use identical settings to usual care; a very explanatory trial may include a single centre, or only specialised trial or academic centres.
Organisation	How different are the resources, provider expertise and the organisation of care delivery in the intervention arm of the trial and those available in usual care? For example, a very pragmatic trial may use identical organisation to usual care; a very explanatory trial may increase staff levels, give additional training, require more than usual experience or certification and increase resources.
Flexibility (delivery)	How different is the flexibility in how the intervention is delivered and the flexibility likely in usual care? For example, a very pragmatic trial may have identical flexibility to usual care allowing healthcare professionals to modify delivery of the intervention; a very explanatory trial may include a strict protocol, monitoring and measures to improve compliance, with specific advice on allowed co-interventions and complications
Flexibility (adherence)	How different is the flexibility in how participants must adhere to the intervention and the flexibility likely in usual care? For example, a very pragmatic trial may involve no more than usual encouragement to adhere to the intervention; a very explanatory approach may involve exclusion based on adherence, and measures to improve adherence if found wanting.
Follow-up	How different is the intensity of measurement and follow-up of participants in the trial and the likely follow-up in usual care? For example, a very pragmatic trial may have no follow up than would be the case in usual care; a very explanatory approach may have more frequent, longer visits, unscheduled visits triggered by primary outcome event or intervening event, and more extensive data collection.
Primary outcome	To what extent is the trial's primary outcome relevant to participants? For example, a very pragmatic trial would have an outcome is of obvious importance to participants; a very explanatory trial may use a surrogate, physiological outcome, central adjudication or use assessment expertise that is not available in usual care, or the outcome is measured at an earlier time than in usual care.
Primary analysis	To what extent are all data included in the analysis of the primary outcome? For example, a very pragmatic trial would use intention to treat with all available data; a very explanatory analysis may exclude ineligible post-randomisation participants, or include only completers or those following the treatment protocol

Adapted from Loudon K, Treweek S, Sullivan F, Donnan P, Thorpe KE, Zwarenstein M. The PRECIS-2 tool: designing trials that are fit for purpose. BMJ. 2015;350:h2147 and

SNicholls1979 (talk) 18:47, 22 February 2019 (UTC)Stuart G. Nicholls