Pragmatic Free Trial Meta
Pragmatic Free Trial Meta is a non-commercial open data platform and infrastructure that supports 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 analyses that evaluate the effects of treatment across trials with different levels of pragmatism.
Background
Pragmatic trials provide evidence from the real world that can be used to make clinical decisions. The term "pragmatic", however, is used inconsistently and its definition and evaluation require further clarification. The purpose of pragmatic trials is to inform clinical practices and policy decisions rather than prove a physiological or clinical hypothesis. A pragmatic study should aim to be as similar to the real-world clinical environment as is possible, including the selection of participants, setting up and design as well as the execution of the intervention, as well as the determination and analysis of the outcomes, and primary analyses. This is a major difference between explanatory trials as defined by Schwartz & Lellouch1, which are designed to test a hypothesis in a more thorough manner.
The most pragmatic trials should not be blind participants or clinicians. This can result in an overestimation of the effects of treatment. Pragmatic trials will also recruit patients from different healthcare settings to ensure that the outcomes can be compared to the real world.
Furthermore, pragmatic trials should focus on outcomes that are vital to patients, like quality of life or functional recovery. This is especially important when trials involve invasive procedures or have potentially serious adverse effects. The CRASH trial29 compared a 2 page report with an electronic monitoring system for hospitalized patients with chronic heart failure. The trial with a catheter, on the other hand was based on symptomatic catheter-related urinary tract infection as its primary outcome.
In addition to these aspects pragmatic trials should also reduce the requirements for data collection and trial procedures to cut down on costs and time commitments. Additionally these trials should strive to make their results as applicable to current clinical practices as possible. 프라그마틱 슬롯 사이트 can be accomplished by ensuring their primary analysis is based on an intention-to treat approach (as described within CONSORT extensions).
Many RCTs that do not meet the criteria for pragmatism, but contain features in opposition to pragmatism, have been published in journals of different types and incorrectly labeled pragmatic. This could lead to false claims of pragmatism and the term's use should be standardized. The development of a PRECIS-2 tool that can provide an objective and standardized evaluation of the pragmatic characteristics is a first step.
Methods
In a pragmatic research study it is the intention to inform policy or clinical decisions by demonstrating how an intervention could be integrated into routine treatment in real-world settings. This is distinct from explanation trials, which test hypotheses about the causal-effect relationship in idealized conditions. In this way, pragmatic trials could have less internal validity than explanatory studies and are more susceptible to biases in their design as well as analysis and conduct. Despite their limitations, pragmatic studies can provide valuable information for decision-making within the healthcare context.
The PRECIS-2 tool scores an RCT on 9 domains, ranging from 1 to 5 (very pragmatist). In this study, the recruit-ment, organization, flexibility in delivery, flexible adherence and follow-up domains received high scores, however, the primary outcome and the method of missing data were not at the practical limit. This suggests that it is possible to design a trial that has excellent pragmatic features without harming the quality of the outcomes.
However, it is difficult to assess how pragmatic a particular trial is since the pragmatism score is not a binary characteristic; certain aspects of a trial may be more pragmatic than others. A trial's pragmatism can be affected by modifications to the protocol or the logistics during the trial. In addition 36% of the 89 pragmatic trials identified by Koppenaal and colleagues were placebo-controlled or conducted before licensing and most were single-center. Therefore, they aren't quite as typical and can only be described as pragmatic in the event that their sponsors are supportive of the absence of blinding in these trials.
Additionally, a typical feature of pragmatic trials is that researchers attempt to make their findings more relevant by analyzing subgroups of the trial sample. However, this can lead to unbalanced results and lower statistical power, increasing the risk of either not detecting or misinterpreting the results of the primary outcome. This was a problem in the meta-analysis of pragmatic trials as secondary outcomes were not adjusted for covariates' differences at the baseline.
Additionally, pragmatic trials can also present challenges in the collection and interpretation of safety data. It is because adverse events tend to be self-reported and are susceptible to errors, delays or coding errors. It is important to increase the accuracy and quality of the outcomes in these trials.
Results
While the definition of pragmatism may not require that all trials are 100 percent pragmatic, there are benefits of including pragmatic elements in clinical trials. These include:
By incorporating routine patients, the results of trials can be translated more quickly into clinical practice. However, pragmatic trials can also have drawbacks. For instance, the right kind of heterogeneity can allow a trial to generalise its results to many different patients and settings; however the wrong kind of heterogeneity could reduce assay sensitivity, and thus reduce the power of a study to detect even minor effects of treatment.
A number of studies have attempted to categorize pragmatic trials with a variety of definitions and scoring systems. Schwartz and Lellouch1 developed a framework to discern between explanation-based studies that confirm a physiological or clinical hypothesis, and pragmatic studies that inform the choice for appropriate therapies in the real-world clinical practice. The framework was comprised of nine domains that were assessed on a scale of 1-5 with 1 being more lucid while 5 being more pragmatic. The domains included recruitment of intervention, setting up, delivery of intervention, flexible adhering to the program and primary analysis.
The original PRECIS tool3 was based on a similar scale and domains. Koppenaal et al10 developed an adaptation of this assessment, called the Pragmascope that was simpler to use for systematic reviews. They discovered that pragmatic systematic reviews had higher average scores in the majority of domains, but lower scores in the primary analysis domain.
The difference in the primary analysis domains can be due to the way in which most pragmatic trials analyze data. Certain explanatory trials however, do not. The overall score was lower for pragmatic systematic reviews when the domains on organisation, flexible delivery, and follow-up were combined.
It is important to understand that the term "pragmatic trial" does not necessarily mean a poor quality trial, and there is an increasing rate of clinical trials (as defined by MEDLINE search, however this is not specific nor sensitive) which use the word 'pragmatic' in their abstracts or titles. The use of these words in abstracts and titles may suggest a greater awareness of the importance of pragmatism however, it is not clear if this is evident in the content of the articles.
Conclusions
In recent years, pragmatic trials are increasing in popularity in research because the value of real-world evidence is becoming increasingly acknowledged. They are randomized clinical trials that evaluate real-world alternatives to care instead of experimental treatments in development. They have patient populations which are more closely resembling the ones who are treated in routine care, they employ comparators that are used in routine practice (e.g., existing drugs) and depend on participants' self-reports of outcomes. This approach can overcome the limitations of observational research for example, the biases associated with the reliance on volunteers as well as the insufficient availability and coding variations in national registries.
Pragmatic trials have other advantages, including the ability to draw on existing data sources, and a greater chance of detecting significant distinctions from traditional trials. However, these tests could have some limitations that limit their reliability and generalizability. The participation rates in certain trials may be lower than expected because of the healthy-volunteering effect, financial incentives, or competition from other research studies. The need to recruit individuals in a timely fashion also reduces the size of the sample and the impact of many pragmatic trials. Additionally, some pragmatic trials don't have 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 pragmatist and published from 2022. They assessed pragmatism by using the PRECIS-2 tool, which consists of the eligibility criteria for domains and recruitment criteria, as well as flexibility in adherence to interventions and follow-up. They found 14 trials scored highly pragmatic or pragmatic (i.e. scoring 5 or higher) in at least one of these domains.
Trials with a high pragmatism score tend to have broader eligibility criteria than traditional RCTs which have very specific criteria that are not likely to be present in clinical practice, and they contain patients from a broad range of hospitals. These characteristics, according to the authors, may make pragmatic trials more relevant and applicable in the daily clinical. However, they cannot ensure that a study is free of bias. In addition, the pragmatism that is present in trials is not a definite characteristic and a pragmatic trial that does not contain all the characteristics of an explanatory trial may yield reliable and relevant results.