Pragmatic Free Trial Meta
Pragmatic Free Trial Meta is a non-commercial open data platform and infrastructure that supports research on pragmatic trials. It is a platform that collects and shares clean trial data and ratings using PRECIS-2 which allows for multiple and varied meta-epidemiological studies to compare treatment effects estimates across trials that have different levels of pragmatism as well as other design features.
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 evaluation require clarification. Pragmatic trials are designed to guide the practice of clinical medicine and policy decisions rather than verify a physiological hypothesis or clinical hypothesis. A pragmatic trial should aim to be as close as it is to actual clinical practices which include the recruiting participants, setting up, delivery and implementation of interventions, determining and analysis outcomes, and primary analyses. This is a significant distinction from explanation trials (as described by Schwartz and Lellouch1) that are designed to provide more thorough proof of a hypothesis.
Truly pragmatic trials should not blind participants or clinicians. This could lead to an overestimation of the effects of treatment. Pragmatic trials should also seek to enroll patients from a wide range of health care settings to ensure that their findings can be applied to the real world.
Furthermore studies that are pragmatic should focus on outcomes that are vital to patients, such as quality of life or functional recovery. This is especially important in trials that require surgical procedures that are invasive or may have harmful adverse effects. The CRASH trial29 compared a two-page report with an electronic monitoring system for hospitalized patients suffering from chronic cardiac failure. The catheter trial28 on the other hand utilized symptomatic catheter-related urinary tract infection as the primary outcome.
In addition to these features, pragmatic trials should minimize the procedures for conducting trials and requirements for data collection to reduce costs and time commitments. Finaly, pragmatic trials should aim to make their findings as relevant to actual clinical practices as they can. This can be accomplished by ensuring that their analysis is based on the intention to treat method (as described within CONSORT extensions).
Many RCTs that don't meet the requirements for pragmatism but have features that are contrary to pragmatism have been published in journals of varying types and incorrectly labeled as pragmatic. This can lead to false claims of pragmatism, and the usage of the term must be standardized. The creation of the PRECIS-2 tool, which offers an objective and standard assessment of practical features is a great first step.
Methods
In a pragmatic 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 cause-effect relationship within idealised conditions. In this way, pragmatic trials may 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 research can be a valuable source of data for making decisions within the healthcare context.
The PRECIS-2 tool assesses the degree of pragmatism within an RCT by scoring it across 9 domains, ranging from 1 (very explicative) to 5 (very pragmatic). In this study, the areas of recruitment, organisation as well as flexibility in delivery flexibility in adherence, and follow-up scored high. However, the principal outcome and method of missing data scored below the pragmatic limit. This suggests that a trial can be designed with effective practical features, but without harming the quality of the trial.
It is difficult to determine the level of pragmatism within a specific study because pragmatism is not a have a binary characteristic. Some aspects of a study may be more pragmatic than others. A trial's pragmatism can be affected by modifications to the protocol or logistics during the trial. Koppenaal and colleagues found that 36% of 89 pragmatic studies were placebo-controlled, or conducted prior to the licensing. They also found that the majority were single-center. They are not in line with the standard practice and are only referred to as pragmatic if the sponsors agree that such trials aren't blinded.
Another common aspect of pragmatic trials is that researchers try to make their results more valuable by studying subgroups of the trial sample. This can lead to imbalanced analyses and less statistical power. This increases the possibility of omitting or misinterpreting differences in the primary outcomes. This was a problem in the meta-analysis of pragmatic trials as secondary outcomes were not adjusted for differences in covariates at the time of baseline.
In addition practical trials can have challenges with respect to the gathering and interpretation of safety data. This is due to the fact that adverse events are usually self-reported, and therefore are prone to errors, delays or coding differences. It is therefore crucial to improve the quality of outcome ascertainment in these trials, ideally by using national registry databases instead of relying on participants to report adverse events on the trial's database.
Results
Although the definition of pragmatism does not mean that trials must be 100 100% pragmatic, there are benefits to incorporating pragmatic components into clinical trials. These include:
Increased sensitivity to real-world issues as well as reducing cost and size of the study, 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 drawbacks. For instance, the appropriate type of heterogeneity can help the trial to apply its findings to a variety of patients and settings; however, the wrong type of heterogeneity could reduce assay sensitivity and therefore reduce the power of a study to detect even minor effects of treatment.
Several studies have attempted to categorize pragmatic trials using various definitions and scoring methods. Schwartz and Lellouch1 have developed a framework for distinguishing between research studies that prove a clinical or physiological hypothesis, and pragmatic trials that help in the selection of appropriate treatments in real-world clinical practice. Their framework comprised nine domains that were scored on a scale ranging from 1 to 5, with 1 indicating more lucid and 5 indicating more pragmatic. The domains included recruitment, setting, intervention delivery with flexibility, follow-up and primary analysis.
The original PRECIS tool3 was based on a similar scale and domains. Koppenaal et. al10 devised an adaptation of this assessment, dubbed the Pragmascope which was more user-friendly to use for systematic reviews. They found that pragmatic reviews scored higher in most domains, but scored lower in the primary analysis domain.
This difference in primary analysis domains could be explained by the way most pragmatic trials analyze data. Certain explanatory trials however, do not. The overall score for systematic reviews that were pragmatic was lower when the areas of organization, flexible delivery, and follow-up were merged.
It is crucial to keep in mind that a pragmatic study does not necessarily mean a low-quality study. In fact, there are a growing number of clinical trials that employ the term "pragmatic" either in their title or abstract (as defined by MEDLINE, but that is not precise nor sensitive). The use of these terms in abstracts and titles could suggest a greater awareness of the importance of pragmatism, however, it is not clear if this is evident in the contents of the articles.
Conclusions
In recent years, pragmatic trials have been becoming more popular in research as the value of real world evidence is increasingly recognized. They are randomized studies that compare real-world alternatives to new treatments that are being developed. They include patient populations that are more similar to those who receive treatment in regular care. 프라그마틱 환수율 is able to overcome the limitations of observational research, such as the biases associated with the reliance on volunteers, and the lack of codes that vary in national registers.
Other advantages of pragmatic trials are the ability to utilize existing data sources, and a greater probability of detecting significant changes than traditional trials. However, pragmatic trials may still have limitations that undermine their reliability and generalizability. For instance the participation rates in certain trials might be lower than anticipated due to the healthy-volunteer influence and financial incentives or competition for participants from other research studies (e.g., industry trials). A lot of pragmatic trials are restricted by the need to enroll participants on time. Additionally some pragmatic trials lack controls to ensure that the observed differences aren't due to biases in trial conduct.
The authors of the Pragmatic Free Trial Meta identified 48 RCTs self-labeled as pragmatic and were published up to 2022. The PRECIS-2 tool was employed to assess the pragmatism of these trials. It includes areas like eligibility criteria and flexibility in recruitment and adherence to intervention and follow-up. They discovered that 14 trials scored highly pragmatic or pragmatic (i.e. scoring 5 or higher) 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 have very specific criteria that are not likely to be present in the clinical setting, and comprise patients from a wide variety of hospitals. The authors suggest that these characteristics could make pragmatic trials more meaningful and useful for daily practice, but they don't necessarily mean that a trial using a pragmatic approach is free from bias. Furthermore, the pragmatism of trials is not a fixed attribute A pragmatic trial that doesn't have all the characteristics of an explanatory trial may yield valid and useful results.