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 clean trial data, ratings and evaluations using PRECIS-2. This permits a variety of meta-epidemiological studies to examine the effect of treatment across trials of various levels of pragmatism.
Background
Pragmatic studies are increasingly recognized as providing real-world evidence for clinical decision-making. However, the use of the term "pragmatic" is not uniform and its definition and assessment requires clarification. Pragmatic trials are intended to guide clinical practices and policy decisions, not to prove a physiological or clinical hypothesis. A pragmatic trial should also aim to be as similar to the real-world clinical environment as is possible, including its recruitment of participants, setting and design of the intervention, its delivery and implementation of the intervention, as well as the determination and analysis of outcomes as well as primary analysis. This is a major distinction between explanation-based trials, as defined by Schwartz & Lellouch1, which are designed to prove a hypothesis in a more thorough way.
The trials that are truly pragmatic should be careful not to blind patients or the clinicians as this could lead to bias in estimates of treatment effects. 프라그마틱 슬롯 추천 that are pragmatic should also try to recruit 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 especially important in trials that require the use of invasive procedures or could have dangerous adverse impacts. The CRASH trial29 compared a 2 page report with an electronic monitoring system for hospitalized patients with chronic cardiac failure. The catheter trial28, on the other hand, used symptomatic catheter associated urinary tract infections as its primary outcome.
In addition to these aspects, pragmatic trials should minimize the requirements for data collection and trial procedures to reduce costs and time commitments. Furthermore pragmatic trials should strive to make their results as relevant to actual clinical practice as is possible by making sure that their primary method of analysis is based on the intention-to-treat method (as described in CONSORT extensions for pragmatic trials).
Despite these requirements, many RCTs with features that challenge the notion of pragmatism were incorrectly labeled pragmatic and published in journals of all types. This can lead to false claims of pragmaticity 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 good initial step.
Methods
In a practical trial the goal is to inform clinical or policy decisions by demonstrating how the intervention can be implemented into routine care. This is distinct from explanation trials, which test hypotheses about the cause-effect connection in idealized conditions. Therefore, pragmatic trials might have lower internal validity than explanatory trials and might be more susceptible to bias in their design, conduct and analysis. Despite these limitations, pragmatic trials may contribute valuable information to decisions in the context of healthcare.
The PRECIS-2 tool scores an RCT on 9 domains, ranging between 1 and 5 (very pragmatist). In this study, the recruitment, organisation, flexibility: delivery and follow-up domains were awarded high scores, however the primary outcome and the method of missing data fell below the limit of practicality. This suggests that it is possible to design a trial that has good pragmatic features without damaging the quality of its results.
However, it is difficult to assess the degree of pragmatism a trial is, since pragmatism is not a binary characteristic; certain aspects of a trial may be more pragmatic than others. The pragmatism of a trial can be affected by changes 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 the licensing. The majority of them were single-center. This means that they are not quite as typical and can only be described as pragmatic in the event that their sponsors are supportive of the lack of blinding in these trials.
Furthermore, a common feature of pragmatic trials is that the researchers attempt to make their findings more valuable by studying subgroups of the trial sample. However, this often leads to unbalanced results and lower statistical power, thereby increasing the risk of either not detecting or misinterpreting the results of the primary outcome. This was the case in the meta-analysis of pragmatic trials due to the fact that secondary outcomes were not corrected for differences in covariates at the baseline.
In addition, pragmatic studies may pose challenges to gathering and interpretation of safety data. This is due to the fact that adverse events are typically self-reported, and therefore are prone to delays, inaccuracies or coding variations. It is therefore important 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 a trial's own database.
Results
While the definition of pragmatism may not mean that trials must be 100 percent pragmatic, there are advantages to including pragmatic components in clinical trials. These include:
By including routine patients, the trial results can be translated more quickly into clinical practice. But pragmatic trials can have disadvantages. For example, the right type of heterogeneity can help a study to generalize its results to many different patients and settings; however, the wrong type of heterogeneity can reduce assay sensitiveness and consequently lessen the ability of a study to detect even minor effects of treatment.
A variety of studies have attempted to classify pragmatic trials using a variety of definitions and scoring methods. Schwartz and Lellouch1 developed a framework for distinguishing between research studies that prove a physiological or clinical hypothesis and pragmatic trials that inform the selection of appropriate treatments in clinical practice. Their framework included nine domains, each scoring on a scale of 1 to 5, with 1 being more informative and 5 indicating more pragmatic. The domains were recruitment, setting, intervention delivery and follow-up, as well as flexible adherence and primary analysis.
The initial PRECIS tool3 had similar domains and a scale of 1 to 5. Koppenaal et. al10 devised an adaptation of this assessment, called the Pragmascope, that was easier to use for systematic reviews. They found that pragmatic systematic reviews had a higher average scores in the majority of domains but lower scores in the primary analysis domain.
The difference in the primary analysis domains could be explained by the way most pragmatic trials analyse 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 remember that a pragmatic trial does not necessarily mean a low-quality trial, and there is an increasing rate of clinical trials (as defined by MEDLINE search, however this is not sensitive nor specific) which use the word 'pragmatic' in their abstract or title. 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 reflected in the contents 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 clinical trials randomized that compare real-world care alternatives instead of experimental treatments under development. They involve patient populations that more closely mirror the patients who receive routine care, they use comparisons that are commonplace in practice (e.g. existing medications), and they depend on participants' self-reports of outcomes. This method can help overcome the limitations of observational research, such as the biases that are associated with the use of volunteers and the limited availability and codes that vary in national registers.
Pragmatic trials offer other advantages, like the ability to draw on existing data sources, and a greater chance of detecting significant differences from traditional trials. However, these trials could still have limitations that undermine their credibility and generalizability. For instance the participation rates in certain trials might be lower than expected due to the healthy-volunteer influence 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 enroll participants on time. Certain pragmatic trials lack controls to ensure that any observed variations aren't due to biases during the trial.
The authors of the Pragmatic Free Trial Meta identified RCTs published from 2022 to 2022 that self-described as pragmatic. They evaluated pragmatism using the PRECIS-2 tool, which includes the domains eligibility criteria, recruitment, flexibility in intervention adherence, and follow-up. They discovered 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 aren't likely to be found in clinical practice, and they contain patients from a broad range of hospitals. The authors argue that these characteristics can help make pragmatic trials more meaningful and useful for daily practice, but they do not guarantee that a trial using a pragmatic approach is free from bias. The pragmatism characteristic is not a fixed attribute and a test that doesn't have all the characteristics of an explanatory study may still yield valuable and valid results.