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 permits a variety of meta-epidemiological analyses to evaluate the effects of treatment across trials with different levels of pragmatism.
Background
Pragmatic studies provide real-world evidence that can be used to make clinical decisions. However, the use of the term "pragmatic" is inconsistent and its definition as well as assessment requires clarification. Pragmatic trials are designed to guide clinical practices and policy decisions, not to prove a physiological or clinical hypothesis. A pragmatic trial should strive to be as close to the real-world clinical environment as possible, including in the selection of participants, setting up and design as well as the execution of the intervention, and the determination and analysis of outcomes and primary analyses. This is a significant distinction from explanation trials (as described by Schwartz and Lellouch1) which are designed to provide more complete confirmation of an idea.
Truly pragmatic trials should not blind participants or clinicians. This can result in an overestimation of treatment effects. The pragmatic trials also include patients from various health care settings to ensure that their outcomes can be compared to the real world.
Furthermore, trials that are pragmatic must concentrate on outcomes that are important to patients, like the quality of life and functional recovery. This is particularly important when trials involve the use of invasive procedures or could have harmful adverse effects. The CRASH trial29, for example was focused on functional outcomes to evaluate a two-page case report with an electronic system to monitor the health of patients admitted to hospitals with chronic heart failure, and the catheter trial28 focused on urinary tract infections caused by catheters as the primary outcome.
In addition to these features pragmatic trials should reduce the procedures for conducting trials and data collection requirements in order to reduce costs. Finally, pragmatic trials should seek to make their findings as relevant to actual clinical practice as possible by making sure that their primary method of analysis follows the intention-to treat approach (as described in CONSORT extensions for pragmatic trials).
Many RCTs that don't meet the criteria for pragmatism, but contain features contrary to pragmatism have been published in journals of various types and incorrectly labeled as pragmatic. This can lead to false claims of pragmatism and the usage of the term should be standardised. The development of the PRECIS-2 tool, which offers an objective and standard assessment of pragmatic characteristics, is a good first step.
Methods
In a pragmatic research study it is the intention to inform policy or clinical decisions by showing how an intervention could be integrated into routine care in real-world contexts. Explanatory trials test hypotheses concerning the causal-effect relationship in idealized conditions. In this way, pragmatic trials can have lower internal validity than explanatory studies and be more prone to biases in their design analysis, conduct, and design. Despite their limitations, pragmatic research can be a valuable source of information for decision-making within the healthcare context.
The PRECIS-2 tool evaluates an RCT on 9 domains, with scores ranging between 1 and 5 (very pragmatist). In this study, the recruit-ment, organization, flexibility in delivery, flexible adherence and follow-up domains scored high scores, but the primary outcome and the procedure for missing data were below the practical limit. This suggests that a trial could be designed with good pragmatic features, without damaging the quality.
It is, however, difficult to determine the degree of pragmatism a trial is, since the pragmatism score is not a binary attribute; some aspects of a trial can be more pragmatic than others. A trial's pragmatism could be affected by changes to the protocol or the logistics during the trial. In addition 36% of the 89 pragmatic trials discovered by Koppenaal et al were placebo-controlled or conducted before licensing, and the majority were single-center. They aren't in line with the standard practice and are only considered pragmatic if their sponsors accept that such trials aren't blinded.
A common aspect of pragmatic research is that researchers try to make their findings more meaningful by analyzing subgroups of the trial sample. However, this can lead to unbalanced results and lower statistical power, which increases the risk of either not detecting or misinterpreting the results of the primary outcome. In the case of the pragmatic trials included in this meta-analysis, this was a major issue because the secondary outcomes were not adjusted for variations in baseline covariates.
Furthermore, pragmatic studies may pose challenges to collection and interpretation safety data. This is due to the fact that adverse events are usually self-reported, and therefore are prone to delays, inaccuracies or coding differences. It is crucial to improve the quality and accuracy of outcomes in these trials.
프라그마틱 순위
While the definition of pragmatism does not require that all clinical trials are 100% pragmatic there are benefits of including pragmatic elements in trials. These include:
Increased sensitivity to real-world issues which reduces study size and cost, and enabling the trial results to be faster implemented into clinical practice (by including patients who are routinely treated). However, pragmatic studies can also have disadvantages. For example, the right kind of heterogeneity can allow the trial to apply its results to many different patients and settings; however, the wrong type of heterogeneity can reduce assay sensitiveness and consequently decrease the ability of a study to detect minor treatment effects.
Several studies have attempted to classify pragmatic trials using different definitions and scoring methods. Schwartz and Lellouch1 have developed an approach to distinguish between explanatory trials that confirm a physiological or clinical hypothesis as well as pragmatic trials that inform the selection of appropriate therapies in clinical practice. Their framework included nine domains, each scoring on a scale of 1-5, with 1 indicating more explanatory and 5 indicating more practical. The domains covered recruitment of intervention, setting up, delivery of intervention, flex adhering to the program and primary analysis.
The initial PRECIS tool3 included similar domains and scales from 1 to 5. Koppenaal et. al10 devised an adaptation of this assessment, dubbed the Pragmascope which was more user-friendly to use for systematic reviews. They discovered that pragmatic reviews scored higher in all domains, but scored lower in the primary analysis domain.
This difference in primary analysis domains can be explained by the way most pragmatic trials analyse data. Some explanatory trials, however, do not. The overall score was lower for systematic reviews that were pragmatic when the domains of organisation, flexible delivery, and follow-up were combined.
It is important to understand that the term "pragmatic trial" does not necessarily mean a low quality trial, and indeed there is an increasing rate of clinical trials (as defined by MEDLINE search, but this is neither sensitive nor specific) which use the word 'pragmatic' in their abstracts or titles. These terms may signal an increased appreciation of pragmatism in abstracts and titles, but it's not clear whether this is reflected in content.
Conclusions
In recent years, pragmatic trials have been becoming more popular in research as the importance of real-world evidence is becoming increasingly acknowledged. They are randomized trials that compare real world alternatives to experimental treatments in development. They are conducted with populations of patients that are more similar to those who receive treatment in regular care. This approach can overcome the limitations of observational research, such as the biases associated with the use of volunteers as well as the insufficient availability and coding variations in national registries.
Other advantages of pragmatic trials are the ability to utilize existing data sources, and a greater chance of detecting meaningful changes than traditional trials. However, pragmatic trials may still have limitations that undermine their validity and generalizability. The participation rates in certain trials may be lower than anticipated because of the healthy-volunteering effect, financial incentives, or competition from other research studies. The requirement to recruit participants in a timely fashion also limits the sample size and the impact of many practical trials. In addition, some pragmatic trials don't have controls to ensure that the observed differences are not due to biases in trial conduct.
The authors of the Pragmatic Free Trial Meta identified RCTs published from 2022 to 2022 that self-described as pragmatic. They assessed pragmatism by using the PRECIS-2 tool, which includes the eligibility criteria for domains and recruitment criteria, as well as flexibility in intervention adherence and follow-up. They discovered that 14 of these trials scored as highly or pragmatic sensible (i.e. scoring 5 or more) in one or more of these domains and that the majority of them were single-center.
Studies that have high pragmatism scores tend to have broader criteria for eligibility than traditional RCTs. They also contain populations from various hospitals. These characteristics, according to the authors, can make pragmatic trials more relevant and relevant to the daily clinical. However, they cannot guarantee that a trial will be free of bias. The pragmatism is not a fixed attribute the test that does not have all the characteristics of an explanation study may still yield reliable and beneficial results.