Pragmatic Free Trial Meta
Pragmatic Free Trial Meta is a non-commercial open data platform and infrastructure that supports research on pragmatic trials. It gathers and distributes clean trial data, ratings and evaluations using PRECIS-2. This permits a variety of meta-epidemiological analyses to evaluate the effects of treatment across trials of different levels of pragmatism.
Background
Pragmatic studies are increasingly acknowledged as providing evidence from the real world to support clinical decision-making. The term "pragmatic", however, is used inconsistently and its definition and evaluation need further clarification. Pragmatic trials are intended to inform clinical practices and policy choices, rather than confirm a physiological hypothesis or clinical hypothesis. A pragmatic trial should also aim to be as similar to the real-world clinical environment as possible, including in its recruitment of participants, setting up and design of the intervention, its delivery and execution of the intervention, as well as the determination and analysis of outcomes as well as primary analyses. This is a major distinction from explanatory trials (as described by Schwartz and Lellouch1) which are designed to provide more complete confirmation of a hypothesis.
Studies that are truly pragmatic should not attempt to blind participants or healthcare professionals in order to result in bias in estimates of treatment effects. Pragmatic trials should also seek to attract patients from a variety of health care settings to ensure that the results can be compared to the real world.
Additionally, clinical trials should be focused on outcomes that matter to patients, such as quality of life and functional recovery. This is particularly relevant when trials involve invasive procedures or have potentially dangerous adverse impacts. The CRASH trial29 compared a 2 page report with an electronic monitoring system for patients in hospitals suffering from chronic cardiac failure. The catheter trial28 on the other hand utilized symptomatic catheter-related urinary tract infection as its primary outcome.
In addition to these features, pragmatic trials should minimize trial procedures and data-collection requirements to reduce costs and time commitments. Finaly, pragmatic trials should aim to make their results as relevant to real-world clinical practices as possible. This can be achieved by ensuring that their primary analysis is based on an intention-to treat approach (as described in CONSORT extensions).
Despite these criteria, many RCTs with features that defy pragmatism have been incorrectly self-labeled pragmatic and published in journals of all kinds. 프라그마틱 공식홈페이지 could lead to false claims about pragmatism, and the use of the term should be standardized. The development of the PRECIS-2 tool, which provides a standard objective assessment of pragmatic characteristics is a great first step.
Methods
In a practical trial the goal is to inform clinical or policy decisions by showing how an intervention could be integrated into everyday routine care. Explanatory trials test hypotheses about the causal-effect relationship in idealized settings. In this way, pragmatic trials could have a lower internal validity than explanatory studies and be more prone to biases in their design analysis, conduct, and design. Despite their limitations, pragmatic studies can provide valuable information for decision-making within the healthcare context.
The PRECIS-2 tool evaluates the level of pragmatism that is present in an RCT by assessing it on 9 domains ranging from 1 (very explanatory) to 5 (very pragmatic). In this study, the recruitment, organization, flexibility in delivery, flexible adherence and follow-up domains received high scores, however, the primary outcome and the method for missing data were not at the limit of practicality. This suggests that it is possible to design a trial using high-quality pragmatic features, without damaging the quality of its outcomes.
It is hard to determine the level of pragmatism in a particular trial since pragmatism doesn't possess a specific attribute. Some aspects of a research study can be more pragmatic than others. A trial's pragmatism can be affected by changes to the protocol or the logistics during the trial. Koppenaal and colleagues discovered that 36% of 89 pragmatic studies were placebo-controlled or conducted prior to licensing. They also found that the majority were single-center. They aren't in line with the standard practice, and can only be called pragmatic if the sponsors agree that these trials aren't blinded.
A typical feature of pragmatic studies is that researchers try to make their findings more meaningful by analyzing subgroups within the trial sample. This can lead to unbalanced analyses that have less statistical power. This increases the possibility of omitting or misinterpreting differences in the primary outcomes. In the case of the pragmatic studies included in this meta-analysis, this was a significant problem because the secondary outcomes weren't adjusted for variations in the baseline covariates.
In addition, pragmatic trials can also have challenges with respect to the gathering and interpretation of safety data. It is because adverse events are typically self-reported and are susceptible to delays, inaccuracies or coding errors. It is therefore crucial to improve the quality of outcomes ascertainment in these trials, and ideally by using national registry databases instead of relying on participants to report adverse events in the trial's own database.
Results
Although the definition of pragmatism may not require that clinical trials be 100% pragmatic there are benefits of including pragmatic elements in trials. These include:
By incorporating routine patients, the results of the trial can be translated more quickly into clinical practice. However, pragmatic trials may also have disadvantages. The right kind of heterogeneity for instance, can help a study expand its findings to different patients or settings. However the wrong kind of heterogeneity can reduce the sensitivity of an assay and, consequently, decrease the ability of a study to detect minor treatment effects.
Numerous studies have attempted to categorize pragmatic trials, using various definitions and scoring systems. Schwartz and Lellouch1 developed a framework for distinguishing between research studies that prove a physiological or clinical hypothesis as well as pragmatic trials that help in the selection of appropriate therapies in the real-world clinical setting. The framework was comprised of nine domains that were scored on a scale of 1 to 5 with 1 indicating more explanatory and 5 suggesting more pragmatic. The domains covered recruitment, setting up, delivery of intervention, flexible adherence and primary analysis.
The original PRECIS tool3 was built on the same scale and domains. Koppenaal and colleagues10 developed an adaptation to this assessment dubbed the Pragmascope that was easier to use in systematic reviews. They discovered that pragmatic reviews scored higher in all domains, but scored lower in the primary analysis domain.
This difference in the primary analysis domain could be due to the fact that most pragmatic trials process their data in an intention to treat way, whereas some explanatory trials do not. The overall score for systematic reviews that were pragmatic was lower when the domains of organization, 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 that use the term "pragmatic" either in their title or abstract (as defined by MEDLINE, but that is not precise nor sensitive). The use of these words in abstracts and titles could indicate a greater understanding of the importance of pragmatism however, it is not clear if this is reflected in the contents of the articles.
Conclusions
In recent times, pragmatic trials are gaining popularity in research as the value of real world evidence is becoming increasingly acknowledged. They are randomized clinical trials that evaluate real-world alternatives to care instead of experimental treatments in development. They include patients that are more similar to the patients who receive routine medical care, they utilize comparators that are used in routine practice (e.g., existing medications), and they rely on participant self-report of outcomes. This method has the potential to overcome the limitations of observational research that are prone to biases associated with reliance on volunteers and limited availability and coding variability in national registries.
Pragmatic trials have other advantages, such as the ability to leverage existing data sources and a greater likelihood of detecting meaningful differences than traditional trials. However, they may be prone to limitations that undermine their validity and generalizability. Participation rates in some trials may be lower than anticipated due to the health-promoting effect, financial incentives, or competition from other research studies. Practical trials are often limited by the need to recruit participants on time. Practical trials aren't always equipped with controls to ensure that any observed differences aren't due to biases during the trial.
The authors of the Pragmatic Free Trial Meta identified 48 RCTs that self-labeled themselves as pragmatist and published until 2022. They assessed pragmatism by using the PRECIS-2 tool that includes the domains eligibility criteria, recruitment, flexibility in intervention adherence and follow-up. They found 14 trials scored highly pragmatic or pragmatic (i.e. scoring 5 or above) in at least one of these domains.
Trials that have a high pragmatism score tend to have more expansive eligibility criteria than traditional RCTs, which include very specific criteria that aren't likely to be used in the clinical setting, and comprise patients from a wide variety of hospitals. These characteristics, according to the authors, may make pragmatic trials more relevant and relevant to the daily practice. However, they cannot ensure that a study is free of bias. Moreover, the pragmatism of the trial is not a fixed attribute A pragmatic trial that does not possess all the characteristics of an explanatory trial may yield valid and useful results.