Pragmatic Free Trial Meta
Pragmatic Free Trail Meta is an open data platform that facilitates research into pragmatic trials. It is a platform that collects and shares clean trial data and ratings using PRECIS-2, permitting multiple and varied meta-epidemiological studies that evaluate the effect of treatment on trials with 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 evaluation need further clarification. Pragmatic trials must be designed to inform policy and clinical practice decisions, rather than confirm the validity of a clinical or physiological 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 up and design as well as the implementation of the intervention, determination and analysis of outcomes as well as primary analysis. This is a key distinction from explanatory trials (as described by Schwartz and Lellouch1) which are intended to provide a more thorough proof of a hypothesis.
Truly pragmatic trials should not conceal participants or the clinicians. This can lead to a bias in the estimates of treatment effects. The trials that are pragmatic should also try to attract patients from a wide range of health care settings to ensure that their findings can be compared to the real world.
Furthermore, trials that are pragmatic must be focused on outcomes that matter to patients, such as the quality of life and functional recovery. This is especially important when it comes to trials that involve surgical procedures that are invasive or have potentially dangerous adverse events. The CRASH trial29 compared a 2-page report with an electronic monitoring system for patients in hospitals with chronic cardiac failure. The catheter trial28 however was based on symptomatic catheter-related urinary tract infection as the primary outcome.
In addition to these features the pragmatic trial should also reduce the trial's procedures and requirements for data collection to reduce costs. Finaly, pragmatic trials should aim to make their results as applicable to current clinical practices as possible. This can be achieved by ensuring that their primary analysis is based on the intention to treat approach (as defined in CONSORT extensions).
Many RCTs that don't meet the criteria for pragmatism, but have features that are contrary to pragmatism have been published in journals of various types and incorrectly labeled as pragmatic. This could lead to misleading claims of pragmatism and the use of the term should be standardized. The creation of the PRECIS-2 tool, which provides 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 implemented into routine care. Explanatory trials test hypotheses about the cause-effect relation within idealized environments. In this way, pragmatic trials can have a lower internal validity than explanatory studies and are more susceptible to biases in their design analysis, conduct, and design. Despite their limitations, pragmatic research can be a valuable source of data for making decisions within the context of healthcare.
The PRECIS-2 tool evaluates the degree of pragmatism within an RCT by assessing it on 9 domains that range from 1 (very explicit) to 5 (very pragmatic). In this study, the areas of recruitment, organization as well as flexibility in delivery flexible adherence, and follow-up received high scores. However, the principal outcome and the 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 compromising the quality of its outcomes.
It is hard to determine the level of pragmatism in a particular trial since pragmatism doesn't possess a specific characteristic. Certain aspects of a research study can be more pragmatic than other. Moreover, protocol or logistic changes during a trial can change its score in pragmatism. 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 in line with the norm and can only be called pragmatic if the sponsors agree that these trials are not blinded.
A common aspect of pragmatic studies is that researchers try to make their findings more meaningful by analyzing subgroups within the trial sample. This can lead to unbalanced analyses with lower statistical power. This increases the possibility of missing or misdetecting differences in the primary outcomes. In the instance of the pragmatic trials that were included in this meta-analysis this was a major issue because the secondary outcomes weren't adjusted for the differences in baseline covariates.
In addition practical trials can have challenges with respect to the collection and interpretation of safety data. It is because adverse events tend to be self-reported, and are prone to errors, delays or coding errors. It is therefore crucial to improve the quality of outcomes ascertainment in these trials, and ideally by using national registry databases instead of relying on participants to report adverse events in a trial's own database.
Results
While the definition of pragmatism does not require that all trials be 100 100% pragmatic, there are benefits to incorporating pragmatic components into clinical trials. These include:
Increased sensitivity to real-world issues as well as reducing the size of studies and their costs, and enabling the trial results to be more quickly implemented into clinical practice (by including patients who are routinely treated). However, pragmatic trials can also have disadvantages. The right type of heterogeneity, for example, can help a study expand its findings to different settings or patients. However the wrong kind of heterogeneity can decrease the sensitivity of the test and thus lessen the power of a trial to detect minor treatment effects.
A variety of studies have attempted to classify pragmatic trials using a variety of definitions and scoring methods. Schwartz and Lellouch1 have developed a framework for distinguishing between research studies that prove the clinical or physiological hypothesis and pragmatic trials that aid in the selection of appropriate therapies in clinical practice. The framework was comprised of nine domains that were scored on a scale ranging from 1 to 5, with 1 being more informative and 5 suggesting more pragmatic. The domains were recruitment setting, setting, intervention delivery with flexibility, follow-up and primary analysis.
The initial PRECIS tool3 featured similar domains and scales from 1 to 5. Koppenaal and colleagues10 developed an adaptation to this assessment dubbed the Pragmascope that was simpler to use in systematic reviews. They found that pragmatic systematic reviews had higher average score in most domains, with lower scores in the primary analysis domain.
The difference in the primary analysis domain could be due to the fact that most pragmatic trials analyse their data in the intention to treat way however some explanation trials 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 poor quality trial, and in fact there is an increasing number of clinical trials (as defined by MEDLINE search, however this is neither sensitive nor specific) that employ the term 'pragmatic' in their title or abstract. These terms may signal that there is a greater understanding of pragmatism in abstracts and titles, but it isn't clear if this is reflected in content.
Conclusions
As appreciation for the value of evidence from the real world becomes more widespread, pragmatic trials have gained traction in research. They are randomized clinical trials which compare real-world treatment options rather than experimental treatments under development, they involve populations of patients which are more closely resembling those treated in routine medical care, they utilize comparisons that are commonplace in practice (e.g., existing drugs), and they rely on participant self-report of outcomes. This method can help overcome the limitations of observational research such as the biases associated with the use of volunteers and the lack of coding variations in national registries.
Other advantages of pragmatic trials are the ability to use existing data sources, as well as a higher likelihood of detecting meaningful changes than traditional trials. However, pragmatic trials may still have limitations that undermine their validity and generalizability. Participation rates in some trials may be lower than anticipated due to the healthy-volunteering effect, financial incentives, or competition from other research studies. The necessity to recruit people in a timely fashion also limits the sample size and the impact of many practical trials. 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-described themselves as pragmatist and published until 2022. They assessed pragmatism using the PRECIS-2 tool, which includes the domains eligibility criteria as well as recruitment, flexibility in adherence to intervention, and follow-up. They discovered that 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 more expansive eligibility criteria than traditional RCTs, which include very specific criteria that are unlikely to be found in the clinical setting, and comprise patients from a wide variety of hospitals. The authors suggest that these traits can make pragmatic trials more meaningful and useful for everyday practice, but they do not necessarily guarantee that a trial conducted in a pragmatic manner is free of bias. 프라그마틱 게임 is not a fixed attribute and a test that does not possess all the characteristics of an explicative study could still yield valuable and valid results.