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 studies to examine the effect of treatment across trials with different levels of pragmatism.
Background
Pragmatic studies provide real-world evidence that can be used to make clinical decisions. 프라그마틱 슬롯 체험 ", however, is a word that is often used in contradiction and its definition and measurement need further clarification. Pragmatic trials must be designed to inform clinical practice and policy decisions, not to confirm an hypothesis that is based on a clinical or physiological basis. A pragmatic trial should aim to be as close as possible to actual clinical practices that include recruitment of participants, setting, designing, delivery and implementation of interventions, determination and analysis results, as well as primary analyses. This is a major distinction between explanation-based trials, as described by Schwartz and Lellouch1 which are designed to prove a hypothesis in a more thorough manner.
The most pragmatic trials should not conceal participants or clinicians. This can lead to a bias in the estimates of the effects of treatment. The trials that are pragmatic should also try to recruit patients from a wide range of health care settings, so that their results can be applied to the real world.
Additionally, clinical trials should be focused on outcomes that matter to patients, like quality of life and functional recovery. This is especially important for trials that involve the use of invasive procedures or could have harmful adverse impacts. The CRASH trial29 compared a 2-page report with an electronic monitoring system for patients in hospitals with chronic cardiac failure. The catheter trial28, on the other hand was based on symptomatic catheter-related urinary tract infection as the primary outcome.
In addition to these aspects pragmatic trials should reduce the procedures for conducting trials and requirements for data collection to reduce costs and time commitments. Finaly the aim of pragmatic trials is to make their findings as applicable to current clinical practices as possible. This can be achieved by ensuring that their primary analysis is based on an intention-to treat method (as described within CONSORT extensions).
Despite these requirements, many RCTs with features that defy pragmatism have been incorrectly self-labeled pragmatic and published in journals of all types. This can lead to false claims of pragmatism, and the use of the term needs to be standardized. The development of a PRECIS-2 tool that offers an objective, standardized evaluation of pragmatic aspects is a good start.
Methods
In a pragmatic study the aim is to inform policy or clinical decisions by showing how an intervention could be integrated into routine treatment in real-world situations. This is distinct from explanation trials, which test hypotheses about the causal-effect relationship in idealized settings. Consequently, pragmatic trials may have lower internal validity than explanatory trials and may be more susceptible to bias in their design, conduct, and analysis. Despite their limitations, pragmatic research can provide valuable information for decision-making within the context of healthcare.
The PRECIS-2 tool evaluates the degree of pragmatism within an RCT by scoring it across 9 domains that range from 1 (very explicative) to 5 (very pragmatic). In this study, the domains of recruitment, organisation and flexibility in delivery, flexible adherence and follow-up were awarded high scores. However, the main outcome and method of missing data scored below the pragmatic limit. This suggests that it is possible to design a trial using good pragmatic features without damaging the quality of its results.
It is difficult to determine the degree of pragmatism that is present in a trial since pragmatism doesn't have a single characteristic. Some aspects of a study can be more pragmatic than other. The pragmatism of a trial can be affected by changes to the protocol or logistics during the trial. In addition 36% of the 89 pragmatic trials identified by Koppenaal and co. were placebo-controlled or conducted prior to approval and a majority of them were single-center. This means that they are not quite as typical and are only pragmatic in the event that their sponsors are supportive of the lack of blinding in such trials.
A common aspect of pragmatic research is that researchers try to make their findings more meaningful by studying subgroups of the trial sample. However, this often leads to unbalanced comparisons and lower statistical power, which increases the likelihood of missing or misinterpreting the results of the primary outcome. This was a problem in the meta-analysis of pragmatic trials because secondary outcomes were not adjusted for covariates that differed at the time of baseline.
Additionally, studies that are pragmatic can present challenges in the collection and interpretation safety data. This is because adverse events are typically reported by participants themselves and are susceptible to reporting errors, delays or coding errors. It is therefore important to enhance the quality of outcomes for these trials, in particular by using national registries rather than relying on participants to report adverse events on the trial's database.
Results
Although the definition of pragmatism does not mean that trials must be 100 percent pragmatic, there are some advantages to including pragmatic components in clinical trials. These include:
Increased sensitivity to real-world issues as well as reducing study size and cost and allowing the study results to be more quickly implemented into clinical practice (by including routine patients). However, pragmatic trials may have their disadvantages. For example, the right type of heterogeneity can help a trial to generalise its results to different settings and patients. However the wrong kind of heterogeneity could reduce assay sensitivity and therefore reduce the power of a study to detect even minor effects of treatment.
Numerous studies have attempted to categorize pragmatic trials with a variety of definitions and scoring systems. Schwartz and Lellouch1 have developed a framework to distinguish between explanation-based trials that support the clinical or physiological hypothesis, and pragmatic trials that inform the choice of appropriate therapies in the real-world clinical setting. The framework was comprised of nine domains, each scoring on a scale of 1 to 5 with 1 indicating more lucid and 5 indicating more pragmatic. The domains were recruitment setting, setting, intervention delivery with flexibility, follow-up and primary analysis.
The original PRECIS tool3 was an adapted version of the PRECIS tool3 that was based on the same scale and domains. Koppenaal and colleagues10 created an adaptation of the assessment, dubbed the Pragmascope, that was easier to use for systematic reviews. They found that pragmatic reviews scored higher on average in most domains, but scored lower in the primary analysis domain.
This difference in primary analysis domains can be explained by the way that most pragmatic trials analyze data. Certain explanatory trials however, do not. The overall score for systematic reviews that were pragmatic was lower when the domains of organization, flexible delivery, and following-up were combined.
It is important to note that a pragmatic trial does not necessarily mean a low quality trial, and indeed there is an increasing rate of clinical trials (as defined by MEDLINE search, but this is not specific nor sensitive) that employ the term "pragmatic" in their abstracts or titles. The use of these terms in titles and abstracts could indicate a greater understanding of the importance of pragmatism, however, it is not clear if this is reflected in the content of the articles.
Conclusions
As appreciation for the value of evidence from the real world becomes more widespread and pragmatic trials have gained traction in research. They are randomized clinical trials that compare real-world care alternatives rather than experimental treatments under development. They involve populations of patients that are more similar to the ones who are treated in routine care, they employ comparators which exist in routine practice (e.g. existing drugs) and rely on participant self-report of outcomes. This approach can overcome the limitations of observational research such as the biases that come with the reliance on volunteers and the limited availability and codes that vary in national registers.
Pragmatic trials have other advantages, like the ability to draw on existing data sources and a greater probability of detecting meaningful differences than traditional trials. However, these tests could still have limitations which undermine their effectiveness and generalizability. The participation rates in certain trials could be lower than expected due to the health-promoting effect, financial incentives, or competition from other research studies. The requirement to recruit participants in a timely manner also reduces the size of the sample and the impact of many pragmatic trials. Practical trials aren't always equipped with controls to ensure that any observed variations aren't due to biases in the trial.
The authors of the Pragmatic Free Trial Meta identified 48 RCTs that self-labeled themselves as pragmatist and published from 2022. They assessed pragmatism by using the PRECIS-2 tool, which includes the domains eligibility criteria and recruitment criteria, as well as flexibility in adherence to interventions, and follow-up. They discovered 14 trials scored highly pragmatic or pragmatic (i.e. scoring 5 or more) in at least one of these domains.
Trials that have a high pragmatism score tend to have more expansive eligibility criteria than traditional RCTs, which include very specific criteria that aren't likely to be present in clinical practice, and they include populations from a wide range of hospitals. The authors claim that these characteristics could make pragmatic trials more effective and applicable to everyday practice, but they don't necessarily mean that a pragmatic trial is free of bias. The pragmatism characteristic is not a definite characteristic; a pragmatic test that does not have all the characteristics of an explanation study may still yield valuable and valid results.
