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To propose a tool to assist trialists in making design decisions that are consistent with their trial's stated purpose. Randomized trials have been broadly categorized as either having a pragmatic or explanatory attitude. Pragmatic trials seek to answer the question, “Does this intervention work under usual conditions?,” whereas explanatory trials are focused on the question, “Can this intervention work under ideal conditions?” Design decisions make a trial more (or less) pragmatic or explanatory, but no tool currently exists to help researchers make the best decisions possible in accordance with their trial's primary goal. During the course of two international meetings, participants with experience in clinical care, research commissioning, health care financing, trial methodology, and reporting defined and refined aspects of trial design that distinguish pragmatic attitudes from explanatory. We have developed a tool (called PRECIS) with 10 key domains and which identifies criteria to help researchers determine how pragmatic or explanatory their trial is. The assessment is summarized graphically. We believe that PRECIS is a useful first step toward a tool that can help trialists to ensure that their design decisions are consistent with the stated purpose of the trial.

The pragmatic explanatory continuum indicator summary (PRECIS) tool, initially published in 2009 and revised in 2015, was created to assist trialists to align their design choices with the intended purpose of their randomised controlled trial (RCT): either to guide real-world decisions between alternative interventions (pragmatic) or to test hypotheses about intervention mechanisms by minimising sources of variation (explanatory). There have been many comments, suggestions, and criticisms of PRECIS-2. This summary will be used to facilitate the development of to the next revision, which is PRECIS-3. We used Web of Science to identify all publication types citing PRECIS-2, published between May 2015 and July 2023. Citations were eligible if they contained ‘substantive’ suggestions, comments, or criticism of the PRECIS-2 tool. We defined ‘substantive’ as comments explicitly referencing at least one PRECIS-2 domain or a concept directly linked to an existing or newly proposed domain. Two reviewers independently extracted comments, suggestions, and criticisms, noting their implications for the update. These were discussed among authors to achieve consensus on the interpretation of each comment and its implications for PRECIS-3. The search yielded 885 publications, and after full-text review, 89 articles met the inclusion criteria. Comments pertained to new domains, changes in existing domains, or were relevant across several or all domains. Proposed new domains included assessment of the comparator arm and a domain to describe blinding. There were concerns about scoring eligibility and recruitment domains for cluster trials. Suggested areas for improvement across domains included the need for more scoring guidance for explanatory design choices. Published comments recognise PRECIS-2's success in aiding trialists with pragmatic or explanatory design choices. Enhancing its implementation and widespread use will involve adding new domains, refining domain definitions, and addressing overall tool issues. This citation review offers valuable user feedback, pivotal for shaping the upcoming version of the PRECIS tool, PRECIS-3. •The paper summarises user feedback from trialists relating to the pragmatic explanatory continuum indicator summary (PRECIS)-2 design tool and points toward considerations, which may be needed to develop and refine the next version of the tool.•Developers should consider adding assessments of blinding and comparator arm design decisions.•Further detail should be given to guide explanatory approaches to design decisions to address the current imbalance, which favors a more pragmatic approach.•Further consideration and research is needed to supplement these review findings to provide guidance for the use of the PRECIS tool for retrospective assessment of design choices.

The Pragmatic-Explanatory Continuum Indicator Summary-2 (PRECIS-2) tool has been widely used to help investigators design randomized trials, facilitating the task of aligning design choices with an explanatory or pragmatic primary trial intention. PRECIS-2 is increasingly being used to retrospectively assess the degree of pragmatism or explanatoriness among published trials within reviews. There is little information on the interrater reliability of the tool and no consensus on the preferred method of achieving an accurate and reliable judgment of trial “pragmatism” when using PRECIS-2 retrospectively. The aims of this study were to assess the level of pragmatism or explanatoriness of trials that cite PRECIS-2 and to assess interrater reliability of PRECIS-2 using different scoring approaches. We compared agreement between two independent ratings within a single pair with agreement between consensus scores reached by two independent pairs of reviewers and whether widening the agreement criteria increased interrater reliability. Thirty randomized controlled trials (RCTs) were randomly selected from trials citing the PRECIS-2 tool. Two pairs of reviewers, a clinician paired with a methodologist in each case, were trained and independently scored each trial and reached a consensus score within pairs. Agreement between reviewers within pairs and between consensus scores across pairs was assessed using kappa statistics for each of the nine PRECIS-2 domains. RCTs citing PRECIS-2 had predominantly pragmatic design features. Interrater reliability within pairs was low across all domains, with the highest levels found in the two domains of analysis (0.32) and follow-up (0.33). Agreement across pairs on the consensus scores was similarly low. Agreement between reviewers and reviewer pairs was above 70% when agreement was reclassified as “within 1-point difference on the scoring scale” for eight domains, but no improvement was obtained for the remaining domain. Trials citing PRECIS-2 tend to have predominantly pragmatic design features. When using PRECIS-2 to retrospectively score trial publications, agreement between consensus scores across pairs of reviewers was no better than agreement within pairs. Reconfiguring the PRECIS scoring scale and improving scoring guidance may provide a more meaningful, easily interpreted measure of “pragmatism” for trialists wishing to use PRECIS-2 as a review tool. The Pragmatic-Explanatory Continuum Indicator Summary-2 (PRECIS-2) tool is designed to help researchers match their design decisions to the intended purpose of their trial. The intention of a trial can be “explanatory,” which improves our understanding of how an intervention works, or “pragmatic,” which supports decision-making in health care. Increasingly, the tool has been used for a secondary purpose: in systematic reviews. Here the tool is used to judge the level of “pragmatism” or “explanatoriness” of trials included in the review to aid the understanding of trial results. However, there is debate on the most reliable means of making this judgment. Sometimes judgements are made using one reviewer; other times, multiple reviewers. Our study evaluated interrater reliability of two methods of scoring trial publications using PRECIS-2: individual reviewer scores and pairs of reviewers agreeing on a consensus score. We also found that neither method we tested produced a reliable judgment using PRECIS-2, and the scores from two reviewers agreeing on a consensus were no more reliable than scores from a single reviewer. We performed an additional analysis that showed that simplifying the scoring from the original five-point scale to a three-point scale may give a more reliable judgment of the “pragmatism” or “explanatioriness” of published trials. This simpler method of scoring should be encouraged for retrospective use of PRECIS-2 in systematic reviews. •There is ongoing debate as to the most reliable method to assess “pragmatism” in published trials.•The reliability of PRECIS-2 in judging published trials is poor, regardless of number of reviewers•Reliability improves by moving to a 3-point scoring scale when scoring published trials

Introduction Pragmatic randomized controlled trials (RCTs) mimic usual clinical practice and they are critical to inform decision-making by patients, clinicians and policy-makers in real-world settings. Pragmatic RCTs assess effectiveness of available medicines, while explanatory RCTs assess efficacy of investigational medicines. Explanatory and pragmatic are the extremes of a continuum. This debate article seeks to evaluate and provide recommendation on how to characterize pragmatic RCTs in light of the current landscape of RCTs. It is supported by findings from a PubMed search conducted in August 2017, which retrieved 615 RCTs self-labeled in their titles as “pragmatic” or “naturalistic”. We focused on 89 of these trials that assessed medicines (drugs or biologics). Discussion 36% of these 89 trials were placebo-controlled, performed before licensing of the medicine, or done in a single-center. In our opinion, such RCTs overtly deviate from usual care and pragmatism. It follows, that the use of the term ‘pragmatic’ to describe them, conveys a misleading message to patients and clinicians. Furthermore, many other trials among the 615 coined as ‘pragmatic’ and assessing other types of intervention are plausibly not very pragmatic; however, this is impossible for a reader to tell without access to the full protocol and insider knowledge of the trial conduct. The degree of pragmatism should be evaluated by the trial investigators themselves using the PRECIS-2 tool, a tool that comprises 9 domains, each scored from 1 (very explanatory) to 5 (very pragmatic). Conclusions To allow for a more appropriate characterization of the degree of pragmatism in clinical research, submissions of RCTs to funders, research ethics committees and to peer-reviewed journals should include a PRECIS-2 tool assessment done by the trial investigators. Clarity and accuracy on the extent to which a RCT is pragmatic will help understand how much it is relevant to real-world practice.

To systematically review and characterize the literature on using the pragmatic-explanatory continuum indicator summary (PRECIS) tools in low- and middle-income countries (LMICs), focusing on successes, challenges, and potential improvements to enhance applicability across diverse settings. A systematic search of PubMed to identify peer-reviewed articles applying PRECIS tools to LMIC-based research. Data extraction focused on trial characteristics, modifications, and use of PRECIS tools. Narrative synthesis was used to outline successes, challenges, and recommendations. A total of 40 articles met the selection criteria. The PRECIS tools were mostly (n = 39, 97.5%) used for purposes other than trial design. Significant variation was seen in methods of use and reporting. Most (n = 32, 80%) used PRECIS-2, valued for its reliability, ability to quantify pragmatism, assess trial design, and identify research gaps. Challenges included the tools’ subjectivity, absence of information needed for scoring, interpretation of scores, and application to non-Western contexts and multinational trials. Recommendations for improvement included refining scoring criteria, translating guidance, and developing additional educational resources. The PRECIS tools have successfully supported research globally and are perceived as reliable research tools with multiple strengths. Further guidance and refinement would enable consistent application and reporting, particularly as the tools have frequently been used for purposes other than their original intention. Most challenges were similar to high-income settings; however, translation and application of the tools to traditional medicine, international trials, and research-naïve settings were highlighted as LMIC-focused issues requiring consideration. The pragmatic-explanatory continuum indicator summary (PRECIS) tools were created to help researchers design better studies. The tools were developed mainly by researchers from developed Western nations. Therefore, it is possible that the PRECIS tools are not as relevant to other places. To help improve the usefulness of the tools in all settings, our team wanted to learn from the experiences of people who had already used PRECIS in low- and middle-income countries. We systematically searched for academic papers on this topic published before May 2022 and found 40 relevant articles. The articles showed that the PRECIS tools had been successfully used in many, often unexpected, ways to support research. Some researchers struggled with using the tool to assess research conducted by others, as relevant information was not available. Researchers recommended translating the tools to other languages and asked for more guidance to use the tool in specific circumstances, such as Chinese herbal medicine and large international research projects. Advice on the best ways to use the PRECIS tools and report the findings would also be beneficial. We share these findings to help those designing the next version of the tool make it useful for researchers working in all parts of the world. •PRECIS tools have successfully supported trials in low- and middle-income countries.•The use of PRECIS has extended beyond the initial intended purpose of trial design.•Guidance on training, use, and reporting of the tools is needed to ensure optimal use.•Application to non-Western medicine and international trials requires consideration.

A randomized controlled trial (RCT) may be intended either to support real-world decisions on choice between alternative interventions or to help researchers understand mechanisms of action of an intervention. PRECIS-2 is widely used to help investigators match detailed design elements to their main intention for that RCT. PRECIS-2 is increasingly being used retrospectively for assessing RCTs within reviews. In this commentary, we counter arguments that RCTs with a placebo control group, masking/blinding of participants or providers, or conducted in a single center should be retrospectively assessed as completely explanatory, overriding a detailed PRECIS-2 assessment. We also counter arguments that a trial cannot be assessed using only the main peer-reviewed trial report. This is a commentary on the use of PRECIS-2 for systematic reviews. Although placebos are seldom openly prescribed in real-world care, knowing that an intervention achieves its impact via the placebo effect might change some clinical and policy decisions, which means that this feature does not always preclude decision-making use and so should not override a full PRECIS-2 assessment. A domain describing the comparator should be added to PRECIS-2. Conduct of an RCT in only a single centre should also not override PRECIS-2 as the decision support value of a single-centre RCT could be high for decision makers in that centre and others like it. Many journals require that submitted RCT reports meet CONSORT reporting guidelines, which standardizes the available information for all RCTs in systematic reviews; whereas information from registration and protocol documents is unstandardized and undermines comparison between RCTs and across reviews. Published RCT reports are thus more suitable for retrospective PRECIS-2 assessments, but PRECIS-2 domains with missing information should be scored as blank. Wider use of the CONSORT extension specific to pragmatic trials may reduce domains with missing data. PRECIS-2 can be used for retrospective assessments of trials in systematic reviews. The PRECIS-2 instrument should be expanded by including a domain describing the control group(s). Published RCT reports are suitable for retrospective PRECIS-2 assessments.

Over half a century ago, the terms “pragmatic” and “explanatory” were introduced to biomedicine by Schwartz and Lellouch, presenting two distinct conceptual approaches to trial design. Today, we frequently say that there are pragmatic trials and there are explanatory trials. Pragmatic trials inform decision-making in practice, and explanatory trials aim to understand the mechanism of an intervention. They are often perceived as diametral extremes of a continuum. In this commentary, we argue that with the digitalization of health care and clinical research, ways for modern trial designs were paved and new avenues opened, and that there is no such continuum. Since the groundbreaking work of Schwartz and Lellouch, new approaches and methods have become available that allow researchers to address pragmatic and explanatory questions in parallel in the same trial. Emerging availability of routinely collected “real-world” data, development of decentralized trial techniques, and creation of digital biomarkers allow to observe health outcomes with minimal or no interference in real-world care. This overcomes previous limitations to studying mechanisms of interventions in routine care and makes the idea of a continuum obsolete. We argue that pragmatism and explanatorism need to be understood as two distinct but compatible conceptual dimensions to open new perspectives for using novel technologies to design the most informative clinical trials and make better clinical and regulatory decisions. We base our argument on an analysis of the concept of a continuum and highlight its limitations. We review key trial design features and introduce a new concept that sees explanatory design features as fundamental, invasive or noninvasive, or sufficient or insufficient. We describe their impact on pragmatism and explanatorism and show how multidimensional pragmatic explanatory trials that are most useful are possible today. •Modern trial designs and approaches have emerged allowing to address pragmatic and explanatory questions in parallel in the same trial.•Pragmatism and explanatorism are not extremes of a continuum.•Pragmatism and explanatorism need to be understood as two distinct but compatible conceptual dimensions.•Pragmatic trials can include noninvasive explanatory trial design features to not only inform decisions but also to understand the mechanisms of interventions.•Multidimensional trials combining pragmatic and explanatory attitudes that are most useful are now possible by leveraging the digitalization of health care and clinical research.

Pragmatic trials are increasingly gaining recognition. However, what pragmatic trials are is frequently misunderstood. They are frequently described superficially by their manifestation and surface only, as studies conducted in “real world” settings, having wide inclusion criteria, and less complicated study procedures. However, these features are neither necessary nor defining characteristics. They also do not guarantee that trials sharing them are useful to inform medical practice. There is a danger of losing sight of the essence of the powerful pragmatic approach. Here we describe the key elements of the pragmatic approach and the close relationship with the original nature of randomized trials. Our aim is to refocus teaching, research and interpretation of evidence, not as a novel approach but as a return towards the essence of pragmatic evidence and the nature of randomized trials. We first go back to the origin of pragmatism in philosophy and its introduction in medicine and revisit the nature of randomized trials in their pure form. We highlight the critical distinction between assessing treatment decisions and understanding the mechanisms of these decisions. We show why the current view on randomized trials in medicine has lost a pragmatic focus, with the explanatory design features blinding and adherence control often seen as defining characteristics or quality criteria of randomized trials. We then highlight common misunderstandings of pragmatic trials and conclude with an overview of their key features to provide pragmatic evidence. Key•Knowing what is form and what is function avoids misconceptions about pragmatic trials.•Trials are not simply pragmatic due to their integration into routine care.•The nature of RCTs is not testing interventions with controls but comparing decisions.•Avoiding blinding or adherence control, often used by explanatory trials, eases conduct but does not define design.•Pragmatic randomized trials compare real-world decisions on practical outcomes.

Background First articulated by Schwartz and Lellouch (1967), randomized controlled trials (RCTs) can be conceptualized along a continuum from more explanatory to more pragmatic. The purpose and intent of the former is to test interventions under ideal contexts, and the purpose and intent of the latter is to test interventions in real-world contexts. The PR agmatic E xplanatory C ontinuum I ndicator S ummary-2 (PRECIS-2) is a validated tool that helps researchers make decisions about the elements of the trial to match the overall purpose and intent of the trial along the continuum. The PRECIS-2 tool has guided the design of hundreds of RCTs. However, a few aspects of the tool would benefit from greater clarity, including its application to provider-focused implementation trials rather than patient-focused intervention trials. Main text We describe the newly developed PRECIS-2-Provider Strategies (PRECIS-2-PS) tool, an extension of the PRECIS-2 tool, which has been adapted for trials testing provider-focused strategies. We elaborate on nine domains that can make a provider-focused trial more explanatory or more pragmatic, including eligibility, recruitment, setting, implementation resources, flexibility of provider strategies, flexibility of intervention, data collection, primary outcome, and primary analysis. We detail the complementary roles that researchers and stakeholders play in the trial design phase, with implications for generalizability of trial results to the contexts in which they are intended to be applied. Conclusions The PRECIS-2-PS tool is designed to help research and practice teams plan for provider-focused trials that reflect the overall intent and purpose of the trial. The tool has potential to help advance the science of provider-focused strategies across a range of trials, with the ultimate goal of facilitating the adoption, integration, and sustainability of provider-focused strategies outside the context of trials.

Randomized trials may be designed to provide evidence more strongly related to efficacy or effectiveness of an intervention. When systematic reviews are used to inform clinical or policy decisions, it is important to know the efficacy–effectiveness nature of the included trials. The objective of this study was to develop a tool to characterize randomized trials included in a systematic review on an efficacy–effectiveness continuum. We extracted rating domains and descriptors from existing tools and used a modified Delphi procedure to condense the domains and develop a new tool. The feasibility and interrater reliability of the tool was tested on trials from four systematic reviews. The Rating of Included Trials on the Efficacy–Effectiveness Spectrum (RITES) tool rates clinical trials on a five-point Likert scale in four domains: (1) participant characteristics, (2) trial setting, (3) flexibility of interventions, and (4) clinical relevance of interventions. When RITES was piloted on trials from three reviews by unaffiliated raters, ratings were variable (intraclass correlation coefficient [ICC] 0.25–0.66 for the four domains); but, when RITES was used on one review by the review authors with expertise on the topic, the ratings were consistent (ICCs > 0.80. RITES may help to characterize the efficacy–effectiveness nature of trials included in systematic reviews.