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 is a platform that collects and shares clean trial data and ratings using PRECIS-2, allowing for multiple and diverse meta-epidemiological research studies to compare treatment effects estimates across trials that employ different levels of pragmatism and other design features.
Background
Pragmatic studies provide real-world evidence that can be used to make clinical decisions. The term "pragmatic" however, is a word that is often used in contradiction and its definition and assessment need further clarification. Pragmatic trials must be designed to guide clinical practice and policy decisions, rather than to prove an hypothesis that is based on a clinical or physiological basis. A pragmatic trial should aim to be as close as is possible to real-world clinical practices which include the recruiting participants, setting up, implementation and delivery of interventions, determining and analysis results, as well as primary analyses. This is a major difference between explanation-based trials, as described by Schwartz & Lellouch1 which are designed to test a hypothesis in a more thorough way.
Truely pragmatic trials should not conceal participants or the clinicians. This can result in a bias in the estimates of the effect of treatment. Practical trials should also aim to enroll patients from a variety of health care settings, so that their results can be compared to the real world.
Finally the focus of pragmatic trials should be on outcomes that are important to patients, like quality of life or functional recovery. This is especially important when trials involve invasive procedures or have potentially harmful adverse consequences. The CRASH trial29 compared a two-page report with an electronic monitoring system for hospitalized patients suffering from chronic cardiac failure. The catheter trial28, however, used symptomatic catheter associated urinary tract infections as its primary outcome.
In addition to these characteristics the pragmatic trial should also reduce the trial's procedures and requirements for data collection to reduce costs. Additionally, pragmatic trials should seek to make their findings as applicable to clinical practice as they can by making sure that their primary analysis follows the intention-to treat approach (as described in CONSORT extensions for pragmatic trials).
Many RCTs that don't meet the criteria for pragmatism, however, they have characteristics that are contrary to pragmatism have been published in journals of different kinds and incorrectly labeled pragmatic. This could lead to misleading claims of pragmaticity and the usage of the term needs to be standardized. The creation of the PRECIS-2 tool, which offers a standard objective assessment of pragmatic characteristics is a good initial step.
Methods
In a practical trial the goal is to inform clinical or policy decisions by demonstrating how an intervention would be implemented into routine care. This is distinct from explanation trials that test hypotheses regarding the cause-effect relationship in idealised conditions. In this way, pragmatic trials may have less internal validity than explanation studies and are more susceptible to biases in their design analysis, conduct, and design. Despite these limitations, pragmatic trials can 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 domains of recruitment, organisation as well as flexibility in delivery flexibility in adherence, and follow-up scored high. However, the principal outcome and method of missing data were scored below the practical limit. This suggests that it is possible to design a trial with excellent pragmatic features without harming the quality of the results.
However, it's difficult to judge how practical a particular trial is since pragmaticity is not a definite attribute; some aspects of a study can be more pragmatic than others. The pragmatism of a trial can be affected by changes to the protocol or logistics during the trial. Koppenaal and colleagues found that 36% of the 89 pragmatic studies were placebo-controlled or conducted prior to licensing. Most were also single-center. They are not in line with the usual practice, and can only be referred to as pragmatic if the sponsors agree that the trials aren't blinded.
Additionally, a typical feature of pragmatic trials is that researchers attempt to make their findings more meaningful by analysing subgroups of the sample. This can lead to unbalanced analyses that have lower statistical power. This increases the chance of omitting or ignoring differences in the primary outcomes. This was the case in the meta-analysis of pragmatic trials due to the fact that secondary outcomes were not adjusted for covariates' differences at baseline.
Additionally, studies that are pragmatic may pose challenges to gathering and interpretation of safety data. This is due to the fact that adverse events are typically reported by participants themselves and are prone to reporting errors, delays or coding deviations. It is therefore important to improve the quality of outcomes ascertainment in these trials, and ideally by using national registries instead of relying on participants to report adverse events in a trial's own database.
Results
While the definition of pragmatism doesn't require that all clinical trials be 100% pragmatic There are advantages of including pragmatic elements in trials. These include:
By including routine patients, the results of trials can be more quickly translated into clinical practice. However, pragmatic studies can also have disadvantages. For instance, the right kind of heterogeneity can allow a study to generalize its results to many different settings and patients. However, the wrong type of heterogeneity may reduce the assay's sensitiveness and consequently reduce the power of a study to detect even minor effects of treatment.
A variety of studies have attempted to categorize pragmatic trials, with various definitions and scoring systems. Schwartz and Lellouch1 created an approach to distinguish between explanatory trials that confirm a clinical or physiological hypothesis, and pragmatic trials that aid in the choice of appropriate therapies in the real-world clinical setting. The framework was comprised of nine domains scored on a 1-5 scale with 1 being more lucid while 5 was more practical. The domains included recruitment, setting up, delivery of intervention, flexible adherence and primary analysis.
The initial PRECIS tool3 featured similar domains and a scale of 1 to 5. Koppenaal and colleagues10 created an adaptation of the assessment, known as the Pragmascope that was simpler to use for systematic reviews. They discovered that pragmatic systematic reviews had a higher average scores across all 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 approach data. Some explanatory trials, however don't. The overall score was lower for pragmatic systematic reviews when the domains of organisation, flexible delivery and follow-up were combined.
It is important to remember that a pragmatic study does not mean that a trial is of poor quality. In fact, there is a growing number of clinical trials that use the term 'pragmatic' either in their abstract or title (as defined by MEDLINE however it is neither sensitive nor precise). 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 reflected in the contents of the articles.
Conclusions
In recent years, pragmatic trials have been increasing in popularity in research because the importance of real-world evidence is becoming increasingly acknowledged. They are randomized clinical trials that compare real-world care alternatives instead of experimental treatments in development. They involve patients that more closely mirror the ones who are treated in routine medical care, they utilize comparisons that are commonplace in practice (e.g., existing drugs) and rely on participant self-report of outcomes. 프라그마틱 플레이 has the potential to overcome limitations of observational studies, such as the biases that arise from relying on volunteers and limited accessibility and coding flexibility in national registry systems.
Pragmatic trials offer other advantages, such as the ability to leverage existing data sources, and a greater likelihood of detecting meaningful distinctions from traditional trials. However, pragmatic tests may be prone to limitations that undermine their reliability and generalizability. Participation rates in some trials could be lower than anticipated because of the healthy-volunteering effect, financial incentives, or competition from other research studies. Practical trials are often restricted by the necessity to recruit participants quickly. Additionally certain pragmatic trials do not have controls to ensure that the observed differences are not due to biases in trial conduct.
The authors of the Pragmatic Free Trial Meta identified RCTs published from 2022 to 2022 that self-described themselves as pragmatic. The PRECIS-2 tool was used to determine the degree of pragmatism. It includes domains such as eligibility criteria and flexibility in recruitment as well as adherence to interventions and follow-up. They found that 14 of these trials scored pragmatic or highly practical (i.e., scoring 5 or higher) in one or more of these domains, and that the majority of them were single-center.
Trials with high pragmatism scores are likely to have broader criteria for eligibility than traditional RCTs. They also contain patients from a variety of hospitals. These characteristics, according to the authors, can make pragmatic trials more useful and useful in the daily practice. However, they don't guarantee that a trial will be free of bias. The pragmatism principle is not a fixed characteristic; a pragmatic test that does not have all the characteristics of an explanation study may still yield valuable and valid results.