CommentaryPRECIS-2 in perspective: what is next for pragmatic trials?
Introduction
The PRECIS-2 tool has been introduced to support trialists in making design choices consistent with the intended purpose of the trial, be it explanatory or pragmatic [1]. Using PRECIS-2, a multidisciplinary team can score a trial design in a four-step process on nine domains to determine if the trial design matches the intended use of the trial results. This is an important advancement of the original PRECIS tool [2], now providing a guidance article with optimized domains. As the authors state in their article, tools such as PRECIS-2 will not provide the one “correct” answer, but they can help trial designers to explicitly match design decisions to the intended use of the trial results and assist in obtaining consistency in decision making. We fully endorse the thinking behind the PRECIS-2 tool and the importance of making design choices for trials more explicit and see the PRECIS-2 tool as an important addition to the literature on pragmatic and explanatory trials.
In this commentary, we would like to raise three discussion points with regard to PRECIS-2 and present our vision on how to bring this tool even further, from the drawing board into the practice of trial conduct.
Section snippets
Is a good match between trial and usual care conditions always necessary?
Quote: “If trialists are aiming for high applicability (that is, a pragmatic approach to design decisions), then we would expect the match between trial and usual care to be very good.”
This is indeed often the strategy chosen to ensure high generalizability of the results of a pragmatic trial. But what drives generalizability? Any clinical or nonclinical characteristic of a patient that has an impact on the benefit or risk of a treatment (modifiers of drug response) and may be differently
Can we leave comparator choice out of the PRECIS-2 equation?
Quote: “In pragmatic trials the comparator is usual care. In explanatory trials it may not be. In PRECIS-2, the domains are based on the assumption that the trial is two armed, one of which is usual care with no changes.”
The comparator choice is not discussed in PRECIS-2 but is assumed to be usual care as a single arm in which no changes are made. Although conceptually straightforward, the way this is interpreted or realized in trials may vary substantially [4], [5], [6], [7], [8]. In pragmatic
How suitable is PRECIS-2 when aiming to take an explanatory approach?
Quote: “PRECIS is a tool to help trialists make design decisions consistent with the intended purpose of their trial” where 9 domains are “scored from 1 (very explanatory) to 5 (very pragmatic).”
PRECIS-2 is not solely about pragmatic trails but about the design choices meeting the research question, be it pragmatic or explanatory. However, for most domains, the pragmatic approach is well explained, whereas the explanatory approach (e.g., why score methods to monitor and ensure patient
From the drawing board into the practice of trial conduct
Quote: PRECIS-2 “does not remove the need for judgement (of design decisions) because there is no single ‘correct’ answer. The advantage of PRECIS-2 is that it makes these judgements explicit and therefore able to be discussed by the trial team”; it “raises awareness of the need to explicitly consider the match between design decisions (and the consequences of these) and the usefulness of the future results to the intended audience.”
PRECIS-2 is a valuable tool in assessing the theoretical match
Acknowledgments
The work leading to these results has received support from the Innovative Medicines Initiative Joint Undertaking under grant agreement no (115546), resources of which are composed of financial contribution from the European Union's Seventh Framework Programme (FP7/2007/2013) and EFPIA companies in kind contribution. The research leading to these results was conducted as part of the GetReal consortium. For further information, please refer to http://www.imi-getreal.eu/. This article only
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PRECIS-2 for retrospective assessment of RCTs in systematic reviews
2020, Journal of Clinical EpidemiologyA prospective cohort and extended comprehensive-cohort design provided insights about the generalizability of a pragmatic trial: the ProtecT prostate cancer trial
2018, Journal of Clinical EpidemiologyCitation Excerpt :The ProtecT findings are likely to be most relevant for men with low- and intermediate-risk PCa and fit for treatment, who represent a large proportion of cases diagnosed in the UK, and even higher proportions in many parts of Europe and North America where higher levels of PSA testing occur. The PRECIS-2 tool provides support for trialists to discuss intentions to be more or less pragmatic and be clearer about the influence of design choices on applicability [6], but some have suggested that, although useful, this is only the first stage, and that operational challenges (and solutions) during trial conduct can have a greater impact on a trial's generalizability [10,13]. The ProtecT and CAP RCTs were designed long before these tools/guidelines were available.
Scientific integrity includes the rigour of the methods
2018, Journal of Clinical EpidemiologySeries: Pragmatic trials and real world evidence: Paper 5. Usual care and real life comparators
2017, Journal of Clinical EpidemiologyCitation Excerpt :Our series of eight articles in this journal (see Box 1) aims to extend this work by describing potential challenges and solutions in conducting trials that address the relative effectiveness of drugs in real-world clinical practice, specifically before or shortly after a drug is licensed and launched on the market. In this paper, we discuss the choice of the usual-care comparator, which is a central issue in pragmatic relative effectiveness research but is largely missing from PRECIS-2 [7]. We describe the operational and methodological challenges in pragmatic trials pertaining to defining and comparing treatment strategies and the choice of suitable usual-care comparator(s) for drug evaluation [8].
Designing pragmatic trials—what can we learn from lessons learned?
2017, Journal of Clinical EpidemiologySeries: Pragmatic trials and real world evidence: Paper 4. Informed consent
2017, Journal of Clinical EpidemiologyCitation Excerpt :The degree to which these challenges lead to actual impracticability will depend on the particulars of a specific pragmatic trial. For example, a good match between trial consent and consent in the real world may not always be strictly necessary to ensure high generalizability; only if consent is a relevant modifier of the treatment response, will such a match be required [29]. However, in a number of cases, it will remain unclear to what extent informed consent procedures actually affect treatment outcomes.