Pragmatic Free Trial Meta
Pragmatic Free Trial Meta is a non-commercial, open data platform and infrastructure that facilitates research on pragmatic trials. It collects and distributes clean trial data, ratings, and evaluations using PRECIS-2. This allows for diverse meta-epidemiological analyses that compare treatment effect estimates across trials of different levels of pragmatism.
Background
Pragmatic trials provide real-world evidence that can be used to make clinical decisions. The term "pragmatic", however, is not used in a consistent manner and its definition and assessment need further clarification. The purpose of pragmatic trials is to inform clinical practice and policy decisions, not to confirm an hypothesis that is based on a clinical or physiological basis. A pragmatic study should try to be as similar to the real-world clinical environment as possible, such as its participation of participants, setting and design of the intervention, its delivery and execution of the intervention, as well as the determination and analysis of the outcomes, and primary analysis. This is a major distinction between explanatory trials as defined by Schwartz and Lellouch1 which are designed to prove the hypothesis in a more thorough manner.
The most pragmatic trials should not be blind participants or clinicians. This can result in bias in the estimations of treatment effects. The pragmatic trials also include patients from different health care settings to ensure that their results can be applied to the real world.
Additionally, pragmatic trials should focus on outcomes that are important to patients, like quality of life or functional recovery. This is especially important in trials that involve the use of invasive procedures or potential serious adverse events. The CRASH trial29, for example focused on the functional outcome to compare a 2-page case-report with an electronic system to monitor the health of hospitalized patients with chronic heart failure, and the catheter trial28 used urinary tract infections caused by catheters as its primary outcome.
In addition to these aspects, pragmatic trials should minimize the trial's procedures and data collection requirements in order to reduce costs. Finally pragmatic trials should try to make their findings as applicable to real-world clinical practice as is possible by making sure that their primary analysis follows the intention-to treat approach (as described in CONSORT extensions for pragmatic trials).
Despite these requirements, a number of RCTs with features that defy the notion of pragmatism were incorrectly labeled pragmatic and published in journals of all kinds. This can lead to false claims of pragmatism and the usage of the term should be standardized. The development of a PRECIS-2 tool that can provide an objective and standardized evaluation of the pragmatic characteristics is the first step.
Methods
In a pragmatic trial it is the intention to inform policy or clinical decisions by demonstrating how the intervention can be integrated into everyday routine care. This is different from explanatory trials that test hypotheses regarding the cause-effect relationship in idealised settings. Therefore, pragmatic trials might have less internal validity than explanatory trials, and could be more susceptible to bias in their design, conduct and analysis. Despite their limitations, pragmatic studies can provide valuable information for decision-making within the context of healthcare.
The PRECIS-2 tool scores an RCT on 9 domains, with scores ranging between 1 and 5 (very pragmatist). In this study, the domains of recruitment, organisation, flexibility in delivery, flexibility in adherence, and follow-up received high scores. However, the main outcome and the method for missing data were scored below the practical limit. This suggests that it is possible to design a trial using excellent pragmatic features without damaging the quality of its outcomes.
However, it's difficult to judge how pragmatic a particular trial is, since pragmatism is not a binary quality; certain aspects of a trial can be more pragmatic than others. Furthermore, logistical or protocol modifications made during a trial can change its pragmatism score. Koppenaal and colleagues discovered that 36% of 89 pragmatic studies were placebo-controlled, or conducted prior to the licensing. Most were also single-center. They are not close to the norm, and can only be called pragmatic if their sponsors accept that the trials aren't blinded.
Furthermore, a common feature of pragmatic trials is that the researchers attempt to make their findings more valuable by studying subgroups of the sample. This can lead to imbalanced analyses and less statistical power. This increases the chance of missing or misdetecting differences in the primary outcomes. In the instance of the pragmatic trials included in this meta-analysis this was a major issue since the secondary outcomes were not adjusted for variations in the baseline covariates.
Furthermore the pragmatic trials may be a challenge in the gathering and interpretation of safety data. This is because adverse events are typically reported by participants themselves and prone to delays in reporting, inaccuracies, or coding variations. It is important to improve the accuracy and quality of the outcomes in these trials.
Results
While the definition of pragmatism may not require that all trials are 100% pragmatic, there are benefits to incorporating pragmatic components into clinical trials. These include:
Enhancing sensitivity to issues in the real world which reduces study size and cost, and enabling the trial results to be faster translated into actual clinical practice (by including patients from routine care). However, pragmatic trials can also have disadvantages. The right amount of heterogeneity for instance, can help a study generalise its findings to many different settings or patients. However the wrong kind of heterogeneity can reduce the sensitivity of an assay and thus reduce a trial's power to detect small treatment effects.
Several studies have attempted to classify pragmatic trials using a variety of definitions and scoring methods. Schwartz and Lellouch1 developed a framework for distinguishing between research studies that prove a clinical or physiological hypothesis, and pragmatic trials that aid in the selection of appropriate treatments in the real-world clinical setting. The framework was composed of nine domains that were evaluated on a scale of 1-5 which indicated that 1 was more lucid while 5 being more pragmatic. The domains were recruitment setting, setting, intervention delivery and follow-up, as well as flexible adherence and primary analysis.
The original PRECIS tool3 was based on a similar scale and domains. Koppenaal et. al10 devised an adaptation of the assessment, dubbed the Pragmascope which was more user-friendly to use for systematic reviews. They found that pragmatic systematic reviews had a higher average scores in the majority of domains but lower scores in the primary analysis domain.
This distinction in the analysis domain that is primary could be due to the fact that the majority of pragmatic trials analyse their data in the intention to treat way however some explanation trials do not. 프라그마틱 공식홈페이지 was lower for systematic reviews that were pragmatic when the domains of organisation, flexible delivery, and follow-up were merged.
It is crucial to keep in mind that a pragmatic study should not mean a low-quality trial. In fact, there is an increasing number of clinical trials which use the term "pragmatic" either in their abstracts or titles (as defined by MEDLINE however it is not precise nor sensitive). The use of these terms in titles and abstracts could suggest a greater awareness of the importance of pragmatism but it is unclear whether this is evident in the contents of the articles.
Conclusions
As appreciation for the value of evidence from the real world becomes more popular the pragmatic trial has gained popularity in research. They are randomized trials that evaluate real-world treatment options with experimental treatments in development. They involve patient populations closer to those treated in regular care. This approach could help overcome the limitations of observational studies, such as the biases associated with reliance on volunteers and the lack of availability and the variability of coding in national registry systems.
Pragmatic trials offer other advantages, such as the ability to use existing data sources and a higher chance of detecting significant distinctions from traditional trials. However, pragmatic trials may have some limitations that limit their reliability and generalizability. Participation rates in some trials may be lower than anticipated due to the healthy-volunteering effect, financial incentives or competition from other research studies. The need to recruit individuals quickly restricts the sample size and the impact of many pragmatic trials. Some pragmatic trials also lack controls to ensure that the observed differences aren't due to biases during the trial.
The authors of the Pragmatic Free Trial Meta identified RCTs published up to 2022 that self-described as pragmatic. The PRECIS-2 tool was used to assess the degree of pragmatism. It covers domains such as eligibility criteria, recruitment flexibility, adherence to intervention, and follow-up. They discovered that 14 of the trials scored as highly or pragmatic practical (i.e. scoring 5 or more) in any one or more of these domains and that the majority were single-center.
Trials with high pragmatism scores are likely to have more lenient criteria for eligibility than conventional RCTs. They also have populations from many different hospitals. The authors claim that these characteristics could make pragmatic trials more meaningful and useful for daily practice, but they do not necessarily guarantee that a trial conducted in a pragmatic manner is free from bias. The pragmatism is not a fixed characteristic; a pragmatic test that doesn't have all the characteristics of an explanatory study can still produce valuable and valid results.