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 cleaned trial data, ratings, and evaluations using PRECIS-2. This allows for a variety of meta-epidemiological studies to examine the effect of treatment across trials of various levels of pragmatism.
Background
Pragmatic trials are becoming more widely 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 require clarification. Pragmatic trials are intended to guide clinical practices and policy decisions, not to prove a physiological or clinical hypothesis. A pragmatic trial should try to be as similar to the real-world clinical environment as possible, including in the selection of participants, setting up and design of the intervention, its delivery and implementation of the intervention, and the determination and analysis of outcomes and primary analysis. This is a significant distinction from explanatory trials (as described by Schwartz and Lellouch1) that are intended to provide a more thorough proof of a hypothesis.
The most pragmatic trials should not be blind participants or clinicians. This can lead to a bias in the estimates of treatment effects. The trials that are pragmatic should also try to attract patients from a variety of health care settings to ensure that the results can be compared to the real world.
Finally, pragmatic trials must focus on outcomes that matter to patients, like quality of life and functional recovery. This is particularly important when it comes to trials that involve surgical procedures that are invasive or have potential serious adverse events. The CRASH trial29 compared a two-page report with an electronic monitoring system for hospitalized patients with chronic cardiac failure. The trial with a catheter, however, used symptomatic catheter associated urinary tract infection as its primary outcome.
In addition to these aspects pragmatic trials should also reduce the procedures for conducting trials and requirements for data collection to cut down on costs and time commitments. Finally pragmatic trials should strive to make their findings as applicable to clinical practice as they can by ensuring that their primary analysis is the intention-to-treat approach (as described in CONSORT extensions for pragmatic trials).
Despite these criteria however, a large number of RCTs with features that defy pragmatism have been incorrectly self-labeled pragmatic and published in journals of all kinds. This can lead to misleading claims of pragmatism and the term's use should be made more uniform. The creation of a PRECIS-2 tool that provides a standardized objective evaluation of pragmatic aspects is the first step.
프라그마틱 게임
In a pragmatic study the aim is to inform policy or clinical decisions by showing how an intervention can be integrated into routine care in real-world situations. This differs from explanation trials that test hypotheses about the causal-effect relationship in idealized situations. In this way, pragmatic trials may have less internal validity than explanation studies and are more susceptible to biases in their design analysis, conduct, and design. Despite these limitations, pragmatic trials may provide valuable information to decision-making in the context of healthcare.
The PRECIS-2 tool scores an RCT on 9 domains, with scores ranging from 1 to 5 (very pragmatic). 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 method for missing data were below the pragmatic limit. This suggests that a trial could be designed with well-thought-out practical features, yet not compromising its quality.
It is hard to determine the amount of pragmatism in a particular trial since pragmatism doesn't possess a specific characteristic. Some aspects of a research study can be more pragmatic than others. A trial's pragmatism could be affected by modifications to the protocol or logistics during the trial. Koppenaal and colleagues discovered that 36% of 89 pragmatic studies were placebo-controlled, or conducted prior to the licensing. The majority of them were single-center. This means that they are not very close to usual practice and are only pragmatic in the event that their sponsors are supportive of the lack of blinding in such trials.
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 unbalanced comparisons with a 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 studies included in this meta-analysis, this was a serious issue since the secondary outcomes were not adjusted for variations in the baseline covariates.
In addition practical trials can present challenges in the gathering and interpretation of safety data. This is due to the fact that adverse events are usually self-reported and are prone to reporting delays, inaccuracies or coding errors. It is essential to increase the accuracy and quality of outcomes in these trials.
Results
Although the definition of pragmatism may not mean that trials must be 100% pragmatic, there are benefits to incorporating pragmatic components into clinical trials. These include:
Increased sensitivity to real-world issues which reduces study size and cost and allowing the study results to be faster translated into actual clinical practice (by including patients who are routinely treated). But pragmatic trials can have disadvantages. The right type of heterogeneity for instance, can help a study expand its findings to different patients or settings. However, the wrong type can reduce the assay sensitivity, and therefore decrease the ability of a study to detect small treatment effects.
Many studies have attempted classify pragmatic trials using a variety of definitions and scoring methods. Schwartz and Lellouch1 developed an approach to distinguish between explanation-based trials that support a physiological or clinical hypothesis, and pragmatic trials that inform the selection of appropriate treatments in the real-world clinical setting. The framework was comprised of nine domains evaluated on a scale of 1-5 which indicated that 1 was more lucid while 5 was more pragmatic. The domains were recruitment and setting, delivery of intervention with flexibility, follow-up and primary analysis.
The original PRECIS tool3 had similar domains and a scale of 1 to 5. Koppenaal et al10 developed an adaptation of the assessment, called the Pragmascope that was simpler to use for systematic reviews. They discovered that pragmatic reviews scored higher on average across all domains, however they scored lower in the primary analysis domain.
This distinction in the primary analysis domains can be due to the way in which most pragmatic trials approach data. Certain explanatory trials however do not. The overall score was lower for pragmatic systematic reviews when the domains on the organization, flexibility of delivery and follow-up were combined.
It is important to understand that a pragmatic trial doesn't necessarily mean a poor quality trial, and in fact there is an increasing rate of clinical trials (as defined by MEDLINE search, but it is neither sensitive nor specific) that use the term 'pragmatic' in their title or abstract. The use of these terms in titles and abstracts could indicate a greater understanding of the importance of pragmatism however, it is not clear if this is evident in the content of the articles.
Conclusions
As the importance of real-world evidence becomes increasingly popular the pragmatic trial has gained popularity in research. They are randomized clinical trials which compare real-world treatment options rather than experimental treatments under development. They involve patients which are more closely resembling the patients who receive routine medical care, they utilize comparisons that are commonplace in practice (e.g., existing drugs), and they rely on participant self-report of outcomes. This approach can help overcome the limitations of observational studies that are prone to biases that arise from relying on volunteers and limited availability and the variability of coding in national registry systems.
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 still have limitations which undermine their effectiveness and generalizability. The participation rates in certain trials could 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 restricts the sample size and the impact of many pragmatic trials. Some pragmatic trials also lack controls to ensure that any observed differences aren't due to biases in the trial.
The authors of the Pragmatic Free Trial Meta identified RCTs that were published between 2022 and 2022 that self-described as pragmatic. The PRECIS-2 tool was used to evaluate the degree of pragmatism. It includes areas such as eligibility criteria and flexibility in recruitment and adherence to intervention and follow-up. They discovered that 14 of the trials scored highly or pragmatic pragmatic (i.e. scoring 5 or more) in any one or more of these domains and that the majority were single-center.
Trials with a high pragmatism score tend to have more expansive eligibility criteria than traditional RCTs that have specific criteria that are unlikely to be found in the clinical environment, and they contain patients from a broad variety of hospitals. These characteristics, according to the authors, could make pragmatic trials more useful and applicable in everyday clinical. However, they don't guarantee that a trial will be free of bias. The pragmatism characteristic is not a fixed characteristic the test that doesn't have all the characteristics of an explanation study may still yield valid and useful outcomes.