Pragmatic Free Trial Meta
Pragmatic Free Trial Meta is a free and non-commercial open data platform and infrastructure that supports research on pragmatic trials. It shares clean trial data and ratings using PRECIS-2, allowing for multiple and diverse meta-epidemiological research studies to evaluate the effect of treatment on trials with different levels of pragmatism, as well as other design features.
Background
Pragmatic trials are increasingly acknowledged as providing evidence from the real world to support clinical decision-making. However, the use of the term "pragmatic" is not uniform and its definition and evaluation requires further clarification. The purpose of pragmatic trials is to inform clinical practices and policy decisions rather than verify a physiological hypothesis or clinical hypothesis. A pragmatic trial should aim to be as similar to actual clinical practice as possible, such as the recruitment of participants, setting up and design of the intervention, its delivery and execution of the intervention, determination and analysis of outcomes as well as primary analysis. This is a significant difference between explanation-based trials, as described by Schwartz and Lellouch1 that are designed to prove the hypothesis in a more thorough manner.
Studies that are truly pragmatic should avoid attempting to blind participants or healthcare professionals in order to result in distortions in estimates of treatment effects. Pragmatic trials will also recruit patients from different health care settings to ensure that their outcomes can be compared to the real world.
Additionally, clinical trials should concentrate on outcomes that are important to patients, such as the quality of life and functional recovery. This is especially important in trials that require the use of invasive procedures or could have harmful adverse effects. The CRASH trial29, for example, focused on functional outcomes to compare a 2-page case-report with an electronic system for monitoring of patients in hospitals suffering from chronic heart failure, and the catheter trial28 used symptomatic catheter-associated urinary tract infections as its primary outcome.
In addition to these features pragmatic trials should also reduce the procedures for conducting trials and requirements for data collection to reduce costs and time commitments. Additionally, pragmatic trials should aim to make their results as applicable to current clinical practices as they can. This can be achieved by ensuring their primary analysis is based on the intention-to treat approach (as defined in CONSORT extensions).
Despite these guidelines however, a large number of RCTs with features that challenge the notion of pragmatism were incorrectly labeled pragmatic and published in journals of all types. This could lead to misleading claims of pragmatism and the use of the term must be standardized. The creation of the PRECIS-2 tool, which offers an objective standard for assessing pragmatic characteristics is a great first step.
Methods
In a pragmatic trial the goal is to inform clinical or policy decisions by demonstrating how an intervention would be incorporated into real-world routine care. Explanatory trials test hypotheses regarding the cause-effect relation within idealized settings. In 프라그마틱 슬롯 환수율 , pragmatic trials could have less internal validity than studies that explain and be more susceptible to biases in their design, analysis, and conduct. Despite these limitations, pragmatic trials can provide valuable information to decisions in the context of healthcare.
The PRECIS-2 tool scores an RCT on 9 domains, with scores ranging from 1 to 5 (very pragmatist). In this study, the recruit-ment organization, flexibility in delivery, flexible adherence and follow-up domains were awarded high scores, but the primary outcome and the procedure for missing data were not at the practical limit. This suggests that a trial could be designed with good pragmatic features, 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 single characteristic. Certain aspects of a study can be more pragmatic than other. The pragmatism of a trial can be affected by modifications to the protocol or the logistics during the trial. Koppenaal and colleagues found that 36% of 89 pragmatic studies were placebo-controlled, or conducted prior to licensing. They also found that the majority were single-center. They are not close to the usual practice and are only referred to as pragmatic if their sponsors accept that these trials are not blinded.
Furthermore, a common feature of pragmatic trials is that the researchers try to make their results more meaningful by analysing subgroups of the trial sample. This can result in unbalanced analyses with lower statistical power. This increases the possibility of omitting or misinterpreting differences in the primary outcomes. In the case of the pragmatic trials that were included in this meta-analysis this was a serious issue because the secondary outcomes were not adjusted for variations in baseline covariates.
In addition, pragmatic studies may pose challenges to gathering and interpretation of safety data. This is because adverse events are typically reported by participants themselves and prone to reporting errors, delays or coding deviations. Therefore, it is crucial to improve the quality of outcomes assessment in these trials, in particular by using national registries rather than relying on participants to report adverse events on the trial's database.
Results
While the definition of pragmatism may not mean that trials must be 100 percent pragmatic, there are benefits to incorporating pragmatic components into clinical trials. These include:
Increased sensitivity to real-world issues, reducing study size and cost, and enabling the trial results to be faster implemented into clinical practice (by including routine patients). However, pragmatic trials may have disadvantages. The right amount of heterogeneity for instance could allow a study to expand its findings to different settings or patients. However, the wrong type can decrease the sensitivity of the test and, consequently, reduce a trial's power to detect small treatment effects.
Several studies have attempted to categorize pragmatic trials using various definitions and scoring methods. Schwartz and Lellouch1 have developed an approach to distinguish between explanatory trials that confirm a clinical or physiological hypothesis as well as pragmatic trials that help in the selection of appropriate treatments in the real-world clinical setting. The framework was composed of nine domains that were scored on a 1-5 scale with 1 being more lucid while 5 was more practical. The domains were recruitment setting, setting, intervention delivery with flexibility, follow-up and primary analysis.
The initial PRECIS tool3 featured similar domains and an assessment scale ranging from 1 to 5. Koppenaal et al10 created 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 on average in most domains, but 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 analyse data. Certain explanatory trials however, do not. The overall score for pragmatic systematic reviews was lower when the areas of organization, flexible delivery, and follow-up were merged.
It is important to remember that a pragmatic study should not necessarily mean a low-quality study. In fact, there are increasing numbers of clinical trials that employ the term "pragmatic" either in their title or abstract (as defined by MEDLINE however it is neither sensitive nor precise). The use of these words in abstracts and titles could indicate a greater understanding of the importance of pragmatism but it is unclear whether this is reflected in the content of the articles.
Conclusions
In recent years, pragmatic trials are gaining popularity in research as the value of real world evidence is becoming increasingly acknowledged. They are randomized clinical trials that compare real-world care alternatives instead of experimental treatments under development. They involve patient populations that more closely mirror the ones who are treated in routine care, they employ comparators which exist in routine practice (e.g. existing medications), and they depend on participants' self-reports of outcomes. This method is able to overcome the limitations of observational research, for example, the biases associated with the reliance on volunteers, as well as the insufficient availability and the coding differences in national registry.
Pragmatic trials also have advantages, including the ability to draw on existing data sources and a greater chance of detecting significant differences from traditional trials. However, pragmatic tests may have some limitations that limit their effectiveness and generalizability. For instance the participation rates in certain trials might be lower than anticipated due to the healthy-volunteer effect and financial incentives or competition for participants from other research studies (e.g. industry trials). Many pragmatic trials are also restricted by the necessity to recruit participants on time. Practical trials aren't always equipped with controls to ensure that the observed variations aren't due to biases that occur during the trial.
The authors of the Pragmatic Free Trial Meta identified 48 RCTs that self-labeled themselves as pragmatist and published until 2022. They evaluated pragmatism using the PRECIS-2 tool, which includes the eligibility criteria for domains as well as recruitment, flexibility in adherence to intervention 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 higher eligibility criteria than traditional RCTs that have specific criteria that are unlikely to be found in the clinical environment, and they include populations from a wide variety of hospitals. The authors claim that these characteristics can help make pragmatic trials more meaningful and applicable to everyday practice, but they do not guarantee that a trial conducted in a pragmatic manner is free of bias. Moreover, the pragmatism of the trial is not a fixed attribute and a pragmatic trial that doesn't have all the characteristics of an explanatory trial can yield reliable and relevant results.