Pragmatic Free Trial Meta
Pragmatic Free Trail Meta is an open data platform that enables research into pragmatic trials. It collects and distributes cleaned trial data, ratings, and evaluations using PRECIS-2. This permits a variety of meta-epidemiological analyses that evaluate the effects of treatment across trials of different 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 a word that is often used in contradiction and its definition and evaluation require clarification. Pragmatic trials are intended to guide the practice of clinical medicine and policy choices, rather than prove a physiological or clinical hypothesis. A pragmatic trial should also aim to be as similar to real-world clinical practice as is possible, including its selection of participants, setting and design of the intervention, its delivery and implementation of the intervention, as well as the determination and analysis of the outcomes, and primary analyses. This is a major difference from explanatory trials (as described by Schwartz and Lellouch1), which are designed to provide more thorough proof of a hypothesis.
Studies that are truly pragmatic must be careful not to blind patients or 프라그마틱 무료 healthcare professionals in order to cause bias in the estimation of treatment effects. The trials that are pragmatic should also try to recruit patients from a wide range of health care settings to ensure that the results can be compared to the real world.
Additionally, clinical trials should focus on outcomes that matter to patients, like the quality of life and functional recovery. This is particularly important for trials that involve surgical procedures that are invasive or may have serious adverse consequences. The CRASH trial29 compared a 2-page report with an electronic monitoring system for hospitalized patients with chronic cardiac failure. The catheter trial28, however, used symptomatic catheter associated urinary tract infections as its primary outcome.
In addition to these features, pragmatic trials should minimize the trial procedures and requirements for data collection to reduce costs. Finally pragmatic trials should strive to make their findings as relevant to actual clinical practice as they can by ensuring that their primary analysis follows the intention-to treat approach (as described in CONSORT extensions for pragmatic trials).
Many RCTs which do not meet the criteria for pragmatism, but contain features contrary to pragmatism have been published in journals of different kinds and incorrectly labeled pragmatic. This can lead to misleading claims of pragmatism, and the usage of the term should be standardised. The creation of a PRECIS-2 tool that can provide an objective and standardized evaluation of the pragmatic characteristics is a good start.
Methods
In a practical trial the goal is to inform policy or clinical decisions by demonstrating how an intervention would be implemented into routine care. Explanatory trials test hypotheses concerning the causal-effect relationship in idealized settings. Therefore, pragmatic trials could have less internal validity than explanatory trials, and could be more susceptible to bias in their design, conduct and analysis. Despite their limitations, pragmatic studies can provide valuable information for decision-making within the context of healthcare.
The PRECIS-2 tool evaluates the degree of pragmatism in an RCT by scoring it across 9 domains that range from 1 (very explicative) to 5 (very pragmatic). In this study, the recruit-ment, organisation, flexibility: delivery, flexible adherence and follow-up domains were awarded high scores, but the primary outcome and the procedure for missing data fell below the pragmatic limit. This indicates that a trial can be designed with well-thought-out pragmatic features, without compromising its quality.
It is difficult to determine the amount of pragmatism in a particular trial because pragmatism does not possess a specific attribute. Some aspects of a research study can be more pragmatic than others. The pragmatism of a trial can be affected by modifications to the protocol or logistics during the trial. Koppenaal and colleagues discovered that 36% of the 89 pragmatic studies were placebo-controlled, or conducted prior to the licensing. They also found that the majority were single-center. Therefore, they aren't very close to usual practice and are only pragmatic in the event that their sponsors are supportive of the absence of blinding in these trials.
A common aspect of pragmatic research is that researchers attempt to make their findings more relevant by studying subgroups within the trial sample. This can result in imbalanced analyses and less statistical power. This increases the possibility of omitting or misinterpreting differences in the primary outcomes. In the instance of the pragmatic trials included in this meta-analysis this was a significant problem because the secondary outcomes were not adjusted to account for variations in the baseline covariates.
Furthermore, pragmatic trials can also 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 delays, errors or coding variations. It is therefore important to improve the quality of outcome for these trials, in particular by using national registries instead of relying on participants to report adverse events in the trial's database.
Results
Although the definition of pragmatism does not require that all trials be 100% pragmatic, there are benefits of including pragmatic elements in clinical trials. These include:
By including routine patients, the trial results can be more quickly translated into clinical practice. But pragmatic trials can be a challenge. The right amount of heterogeneity for instance, can help a study generalise its findings to many different settings or patients. However, the wrong type can decrease the sensitivity of the test, and therefore decrease the ability of a study to detect small treatment effects.
Many studies have attempted categorize pragmatic trials using various definitions and scoring methods. Schwartz and Lellouch1 created a framework to differentiate between explanation studies that confirm a physiological or clinical hypothesis, and pragmatic studies that inform the choice for appropriate therapies in real world clinical practice. The framework was comprised of nine domains, each scored on a scale of 1 to 5, with 1 indicating more lucid and 5 indicating more pragmatic. The domains were recruitment and setting, delivery of intervention with flexibility, follow-up and primary analysis.
The original PRECIS tool3 was based on a similar scale and domains. Koppenaal and colleagues10 developed an adaptation of this assessment dubbed the Pragmascope which was more user-friendly to use in systematic reviews. They discovered that pragmatic reviews scored higher in all domains, but scored lower in the primary analysis domain.
The difference in the primary analysis domain could be due to the fact that most pragmatic trials analyze their data in the intention to treat manner while some explanation trials do not. The overall score for systematic reviews that were pragmatic was lower when the areas of management, flexible delivery and follow-up were merged.
It is important to remember that a pragmatic study does not mean a low-quality trial. In fact, there are an increasing number of clinical trials that employ the word 'pragmatic,' either in their title or abstract (as defined by MEDLINE, but that is neither precise nor sensitive). The use of these terms in abstracts and titles could suggest a greater awareness of the importance of pragmatism but it is unclear whether this is manifested in the contents of the articles.
Conclusions
In recent times, pragmatic trials are increasing in popularity in research because the value of real world evidence is increasingly recognized. They are clinical trials that are randomized that compare real-world care alternatives instead of experimental treatments under development. They involve populations of 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 depend on the self-reporting of participants about outcomes. This approach has the potential to overcome the limitations of observational studies that are prone to biases associated with reliance on volunteers and the lack of availability and the variability of coding in national registries.
Pragmatic trials also have advantages, including the ability to draw on existing data sources and a greater probability of detecting meaningful distinctions from traditional trials. However, they may have some limitations that limit their validity 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. A lot of pragmatic trials are limited by the need to enroll participants in a timely manner. Some pragmatic trials also lack controls to ensure that observed differences aren't caused by biases during the trial.
The authors of the Pragmatic Free Trial Meta identified 48 RCTs that self-described themselves as pragmatist and published until 2022. They assessed pragmatism by using the PRECIS-2 tool that includes the eligibility criteria for domains as well as recruitment, flexibility in intervention adherence, and follow-up. They found that 14 of these trials scored highly or pragmatic sensible (i.e. scores of 5 or higher) in one or more of these domains, and that the majority of them were single-center.
Trials with high pragmatism scores are likely to have more lenient criteria for eligibility than conventional RCTs. They also have patients from a variety of hospitals. The authors claim that these traits can make pragmatic trials more meaningful and useful for everyday clinical practice, however they don't necessarily mean that a pragmatic trial is free of bias. Furthermore, the pragmatism of trials is not a definite characteristic A pragmatic trial that doesn't possess all the characteristics of an explanatory trial can produce reliable and relevant results.