Pragmatic Free Trial Meta
Pragmatic Free Trial Meta is a free and non-commercial open data platform and infrastructure that supports research on pragmatic trials. It collects and shares cleaned trial data and ratings using PRECIS-2, allowing for multiple and diverse meta-epidemiological studies that examine the effects of treatment across trials with different levels of pragmatism as well as other design features.
Background
Pragmatic trials are becoming more widely acknowledged as providing evidence from the real world for clinical decision making. However, 무료 프라그마틱 of the term "pragmatic" is not uniform and its definition and assessment requires further clarification. Pragmatic trials should be designed to inform clinical practice and policy decisions, not to confirm the validity of a clinical or physiological hypothesis. A pragmatic trial should aim to be as similar to real-world clinical practice as is possible, including its participation of participants, setting and design of the intervention, its delivery and execution of the intervention, determination and analysis of the outcomes, and primary analyses. This is a major difference between explanatory trials, as defined by Schwartz and Lellouch1, which are designed to test a hypothesis in a more thorough way.
Studies that are truly pragmatic should not attempt to blind participants or healthcare professionals, as this may lead to bias in the estimation of the effects of treatment. Pragmatic trials should also seek to recruit patients from a wide range of health care settings to ensure that their findings can be compared to the real world.
Furthermore, trials that are pragmatic must be focused on outcomes that matter to patients, such as quality of life and functional recovery. This is particularly relevant for trials involving the use of invasive procedures or potential dangerous adverse events. The CRASH trial29 compared a 2-page report with an electronic monitoring system for hospitalized patients with chronic cardiac failure. The catheter trial28, on the other hand utilized symptomatic catheter-related urinary tract infections as its primary outcome.
In addition to these characteristics pragmatic trials should also reduce the procedures for conducting trials and requirements for data collection to cut costs and time commitments. Furthermore, pragmatic trials should seek to make their findings as applicable to real-world clinical practice as they can by making sure that their primary analysis is the intention-to-treat approach (as described in CONSORT extensions for pragmatic trials).
Despite these criteria, a number of RCTs with features that challenge the concept of pragmatism have been mislabeled as pragmatic and published in journals of all kinds. This could lead to misleading claims of pragmaticity and the usage of the term should be standardized. The development of a PRECIS-2 tool that provides a standardized objective evaluation of the pragmatic characteristics is a good start.
Methods
In a pragmatic study it is the intention to inform clinical or policy decisions by showing how an intervention can be integrated into routine care in real-world contexts. Explanatory trials test hypotheses regarding the cause-effect relationship within idealised settings. Therefore, pragmatic trials could have less internal validity than explanatory trials and may be more susceptible to bias in their design, conduct, and analysis. Despite their limitations, pragmatic research can be a valuable source of data for making decisions within the context of healthcare.
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 explicative) to 5 (very pragmatic). In this study, the recruitment, organisation, flexibility: delivery, flexible adherence and follow-up domains were awarded high scores, but the primary outcome and the method for missing data were below the limit of practicality. This suggests that a trial could be designed with effective pragmatic features, without harming the quality of the trial.
It is, however, difficult to assess the degree of pragmatism a trial is, since pragmatism is not a binary attribute; some aspects of a trial can be more pragmatic than others. Furthermore, logistical or protocol modifications made during the trial may alter its score in pragmatism. Additionally, 36% of the 89 pragmatic trials discovered by Koppenaal and co. were placebo-controlled, or conducted prior to licensing and most were single-center. They aren't in line with the norm and can only be referred to as pragmatic if their sponsors agree that these trials aren't blinded.
Additionally, a typical feature of pragmatic trials is that researchers try to make their results more meaningful by analysing subgroups of the sample. This can lead to unbalanced analyses that have lower statistical power. This increases the risk of omitting or ignoring differences in the primary outcomes. This was a problem during the meta-analysis of pragmatic trials because secondary outcomes were not adjusted for covariates' differences at the time of baseline.
In addition, pragmatic studies can present challenges in the collection and interpretation safety data. This is due to the fact that adverse events tend to be self-reported, and therefore are prone to delays, errors or coding differences. It is essential to improve the quality and accuracy of the outcomes in these trials.
Results
While the definition of pragmatism does not require that all clinical trials are 100% pragmatist There are advantages to including pragmatic components in trials. These include:
Increasing sensitivity to real-world issues which reduces the size of studies and their costs and allowing the study results to be faster transferred into real-world clinical practice (by including patients from routine care). However, pragmatic trials may be a challenge. For instance, the right type of heterogeneity could help the trial to apply its results to different patients and settings; however the wrong kind of heterogeneity may reduce the assay's sensitivity and therefore lessen the ability of a trial to detect small treatment effects.
Many studies have attempted categorize pragmatic trials using various definitions and scoring methods. Schwartz and Lellouch1 developed an approach to distinguish between explanatory trials that confirm the clinical or physiological hypothesis, and pragmatic trials that inform the choice of appropriate therapies in clinical practice. The framework consisted of nine domains scored on a 1-5 scale which indicated that 1 was more explanatory while 5 was more practical. The domains included recruitment setting, setting, intervention delivery, flexible adherence, follow-up and primary analysis.
The initial PRECIS tool3 had similar domains and an assessment scale ranging from 1 to 5. Koppenaal and colleagues10 created an adaptation of this assessment, called the Pragmascope which was more user-friendly to use for systematic reviews. They found that pragmatic systematic reviews had higher average score in most domains, with lower scores in the primary analysis domain.
This difference in the main analysis domain could be explained by the fact that the majority of pragmatic trials analyze their data in an intention to treat manner however some explanation trials do not. The overall score was lower for systematic reviews that were pragmatic when the domains on the organization, flexibility of delivery and follow-up were merged.
It is crucial to keep in mind that a study that is pragmatic does not mean that a trial is of poor quality. In fact, there is a growing number of clinical trials which use the term "pragmatic" either in their abstract or title (as defined by MEDLINE but which is neither sensitive nor precise). These terms may indicate that there is a greater appreciation of pragmatism in abstracts and titles, however it's not clear if this is reflected in content.
Conclusions
In recent years, pragmatic trials are gaining popularity in research as the value of real world evidence is becoming increasingly acknowledged. They are clinical trials that are randomized that evaluate real-world alternatives to care instead of experimental treatments under development, they include populations of patients that are more similar to those treated in routine care, they employ comparators that are used in routine practice (e.g. existing medications), and they depend on participants' self-reports of outcomes. This approach has the potential to overcome limitations of observational studies that are prone to biases that arise from relying on volunteers, and the limited accessibility and coding flexibility in national registries.
Other advantages of pragmatic trials are the ability to use existing data sources, and a greater probability of detecting significant changes than traditional trials. However, they may be prone to limitations that undermine their effectiveness and generalizability. Participation rates in some trials could be lower than anticipated because of the healthy-volunteering effect, financial incentives or competition from other research studies. Practical trials are often restricted by the need to enroll participants quickly. Practical trials aren't always equipped with controls to ensure that any observed variations aren't due to biases that occur during the trial.
The authors of the Pragmatic Free Trial Meta identified 48 RCTs self-labeled as pragmatist and published until 2022. The PRECIS-2 tool was employed to evaluate the pragmatism of these trials. It includes areas like eligibility criteria as well as recruitment flexibility as well as adherence to interventions and follow-up. They discovered that 14 of the trials scored as highly or pragmatic practical (i.e. scores of 5 or more) in one or more of these domains, and that the majority of them were single-center.
Trials with a high pragmatism rating tend to have higher eligibility criteria than traditional RCTs which have very specific criteria that aren't likely to be present in the clinical setting, and include populations from a wide range of hospitals. These characteristics, according to the authors, may make pragmatic trials more relevant and useful in everyday practice. However, they don't guarantee that a trial is free of bias. The pragmatism characteristic is not a fixed characteristic and a test that does not have all the characteristics of an explanation study can still produce valuable and valid results.