Pragmatic Free Trial Meta
Pragmatic Free Trail Meta is an open data platform that facilitates research into pragmatic trials. It gathers and distributes clean trial data, ratings, and evaluations using PRECIS-2. This allows for diverse meta-epidemiological studies to compare treatment effect estimates across trials of various levels of pragmatism.
Background
Pragmatic trials are increasingly recognized as providing real-world evidence to support clinical decision-making. The term "pragmatic" however, is a word that is often used in contradiction and its definition and measurement need further clarification. The purpose of pragmatic trials is to inform clinical practices and policy decisions, not to confirm a physiological hypothesis or clinical hypothesis. A pragmatic trial should also try to be as similar to real-world clinical practice as is possible, including its participation of participants, setting up and design, the delivery and implementation of the intervention, determination and analysis of outcomes as well as primary analysis. This is a major difference between explanation-based trials, as described by Schwartz and Lellouch1, which are designed to test a hypothesis in a more thorough manner.
The trials that are truly pragmatic should not attempt to blind participants or the clinicians as this could result in distortions in estimates of the effects of treatment. Practical trials should also aim to recruit patients from a wide range of health care settings to ensure that their findings can be applied to the real world.
Finally studies that are pragmatic should focus on outcomes that are crucial to patients, such as quality of life or functional recovery. This is especially important when trials involve the use of invasive procedures or could have harmful adverse impacts. The CRASH trial29, for example, focused on functional outcomes to compare a two-page report with an electronic system for the 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 minimize the procedures for conducting trials and data collection requirements to reduce costs. In the end the aim of pragmatic trials is to make their results as applicable to current clinical practice as is possible. This can be accomplished by ensuring that their analysis is based on the intention to treat method (as described within CONSORT extensions).
Despite these requirements however, a large number of RCTs with features that challenge the concept of pragmatism have been mislabeled as pragmatic and published in journals of all kinds. This could lead to misleading claims of pragmaticity, and the use of the term should be standardized. The development of a PRECIS-2 tool that provides an objective and standardized assessment of pragmatic features is a first step.
Methods
In a practical study, the goal is to inform policy or clinical decisions by demonstrating how an intervention could be integrated into routine treatment in real-world situations. Explanatory trials test hypotheses regarding the cause-effect relation within idealized conditions. In this way, pragmatic trials may have a lower internal validity than explanation studies and be more prone to biases in their design as well as analysis and conduct. Despite their limitations, pragmatic studies can provide valuable data for making decisions within the healthcare context.
The PRECIS-2 tool scores an RCT on 9 domains, with scores ranging from 1 to 5 (very pragmatist). In this study the areas of recruitment, organization, flexibility in delivery, flexible adherence, and follow-up received high scores. However, the main outcome and method of missing data was scored below the pragmatic limit. This suggests that it is possible to design a trial using excellent pragmatic features without harming the quality of the outcomes.
It is, however, difficult to determine how pragmatic a particular trial really is because pragmatism is not a binary characteristic; certain aspects of a trial can be more pragmatic than others. The pragmatism of a trial can be affected by modifications to the protocol or the logistics during the trial. Koppenaal and colleagues discovered that 36% of 89 pragmatic studies were placebo-controlled, or conducted prior to licensing. They also found that the majority were single-center. Thus, they are not 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 feature of pragmatic studies is that researchers try to make their findings more meaningful by analyzing subgroups within the trial sample. This can lead to imbalanced analyses and lower statistical power. This increases the possibility of omitting or misinterpreting differences in the primary outcomes. This was a problem during the meta-analysis of pragmatic trials as secondary outcomes were not corrected for covariates that differed at baseline.
Furthermore practical trials can present challenges in the gathering and interpretation of safety data. This is due to the fact that adverse events are usually self-reported and prone to reporting errors, delays or coding errors. It is important to increase the accuracy and quality of outcomes in these trials.
Results
While the definition of pragmatism may not require that all clinical trials are 100% pragmatist there are benefits when incorporating pragmatic components into trials. These include:
Increased sensitivity to real-world issues as well as reducing study size and cost as well as allowing trial results to be more quickly implemented into clinical practice (by including patients who are routinely treated). However, pragmatic trials have disadvantages. For example, the right type of heterogeneity can help a trial to generalise its findings to a variety of patients and settings; however the wrong kind of heterogeneity could reduce assay sensitivity, and thus decrease the ability of a trial to detect minor treatment effects.
Several studies have attempted to classify pragmatic trials using different definitions and scoring methods. Schwartz and Lellouch1 created a framework to discern between explanation-based studies that support a physiological hypothesis or clinical hypothesis and pragmatic studies that inform the selection of appropriate treatments in real world clinical practice. The framework was composed of nine domains that were scored on a 1-5 scale, with 1 being more explanatory while 5 being more pragmatic. The domains included recruitment, setting up, delivery of intervention, flex compliance and primary analysis.
The initial PRECIS tool3 had similar domains and a scale of 1 to 5. Koppenaal and colleagues10 created an adaptation of this assessment, known as the Pragmascope, that was easier to use for systematic reviews. They discovered that pragmatic reviews scored higher across all domains, however they scored lower in the primary analysis domain.
This distinction in the primary analysis domains could be explained by the way most pragmatic trials analyse data. Some explanatory trials, however don't. The overall score for systematic reviews that were pragmatic was lower when the areas of organisation, flexible delivery and follow-up were merged.
프라그마틱 슬롯버프 is crucial to keep in mind that a pragmatic study should not mean a low-quality trial. In fact, there are increasing numbers of clinical trials that use the term 'pragmatic' either in their abstracts or titles (as defined by MEDLINE, but that 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 isn't clear if this is reflected in the content of the articles.
Conclusions
As the value of evidence from the real world becomes more popular the pragmatic trial has gained traction in research. They are randomized trials that evaluate real-world care alternatives to experimental treatments in development. They involve patient populations more closely resembling those treated in regular medical care. This approach could help overcome limitations of observational studies which include the limitations of relying on volunteers and the lack of availability and the variability of coding in national registries.
Pragmatic trials have other advantages, including the ability to draw on existing data sources, and a greater probability of detecting meaningful differences than traditional trials. However, pragmatic tests may be prone to limitations that undermine their validity and generalizability. For example the participation rates in certain trials might be lower than expected due to the healthy-volunteer effect as well as incentives to pay or compete for participants from other research studies (e.g., industry trials). The requirement to recruit participants in a timely fashion also limits the sample size and the impact of many practical trials. Some pragmatic trials also lack controls to ensure that any observed differences aren't due to biases during the trial.
The authors of the Pragmatic Free Trial Meta identified 48 RCTs self-labeled as pragmatic and that were published until 2022. The PRECIS-2 tool was used to determine the pragmatism of these trials. It covers areas such as eligibility criteria as well as recruitment flexibility and adherence to intervention and follow-up. They discovered 14 trials scored highly pragmatic or pragmatic (i.e. scoring 5 or above) in at least one of these domains.
Trials with a high pragmatism rating tend to have more expansive eligibility criteria than traditional RCTs, which include very specific criteria that are not likely to be used in the clinical environment, and they comprise patients from a wide range of hospitals. According to the authors, may make pragmatic trials more relevant and useful in the daily practice. However they do not guarantee that a trial will be free of bias. Furthermore, the pragmatism of the trial is not a predetermined characteristic and a pragmatic trial that doesn't have all the characteristics of a explanatory trial may yield valuable and reliable results.