1. Define randomisation. Outline the three main reasons that randomisation is an important design component in trials assessing interventions.
2: Define allocation concealment, and explain how it differs form blinding.
3: Discuss and define intention to treat an analysis. And why is this the preferred method of analysis in trials, compared to other types.
4: Compare and contrast the pragmatic and explicatory trials.
Explain why a pragmatic trial is more valuable than an explicatory trial.
Randomised Control Trials randomly assign participants to one of two groups: the control (group receiving standard treatment), or the treatment group under investigation.
This is also known as randomization. It reduces bias and allows the researcher compare the results with the no treatment group, while keeping other variables constant (Paludan Muller and al., 2016).
It can be used to assess intervention because it provides information on adverse effects and removes bias from the treatment assignment.
Because of the low number of cases of accidental death, the results of trials can be used as scientific evidence. (Schulz and Associates 1995).
Randomization facilitates the blinding of the “identity” of treatment from participants, investigators and assessors.
As it minimizes contamination, the nature and extent of the intervention can be concealed. Day & Altman, 2000.
Randomisation also allows you to use probability theory.
It indicates the likelihood that there will be no differences in the outcome between the treated groups.
Randomization is therefore an important design component in trials evaluating interventions (Gore 1982).
Allocation concealment refers to the protection of randomisation so that patients do not know the identity of the treatment being allocated.
Allocation concealment is simply the process of hiding the identity of the participant who will receive the treatment.
It is possible for investigators to reveal the allocation to assessors if they are aware of adverse effects. This could in turn lead (Altman & Schulz, 2001).
The concept of allocation concealment, however, is not the same as blinding.
Blinding the trial participants, their family members, caregivers and investigators means that they are not aware of the treatment identity.
Blinding, on the other hand, keeps the participants in trial and their family members from knowing the allocation. It also prevents the clinicians (consciously or subconsciously), from treating the patients based upon the allocation.
It also eliminates observer bias.
Blinding does NOT allow assessors or patients to introduce biases when evaluating subjective outcomes.
Even patients cannot introduce bias during flow-up (Sedgwick 2013).
Blinding and allocation concealment have one major difference. Blinding ensures that participants do not know their treatment identity prior to entering the study.
Ruxton, 2017: The blinding method ensures that either the patient or physician do not know the treatment allocation until they enroll in the study.
The purpose of allocation concealment is to stop selection bias.
Ruxton, 2017, explains that it allows for “enrolment by comparable participants” in each study.
The purpose of masking or blinding is to hide any biases, ascertainment or other information related to performance or attrition.
Blinding facilitates similar concomitant treatment and evaluates participants in each study (Pocock 2013).
Intention-to-treat analysis or ITT refers to including all patients who were randomly allocated or enrolled into the randomised group.
This method aims to eliminate different misleading artifacts which could arise in intervention research (Hollis & Campbell (1999).
The method is a simple way to estimate the effect of treatment when it is “offered or assigned”.
In this case, inclusion is made regardless of any deviations that could occur following randomisation (e.g. withdrawal from the trial or non-compliance).
This analysis is preferable to any other because it preserves the original random treatment allocation’s “prognosis equilibrium”.
This analysis is reliable in estimating the true effectiveness of treatment. It replicates what happens in actual practice.
This analysis reduces biases in outcomes and minimizes type 1 statistical error.
Dossing et.al., 2016, found that treatment effects estimates are more conservative than PP analyses.
This analysis is more straightforward than other forms of analysis.
ITT provides information on the “potential consequences of treatment policy”, rather than on the possible effect of “specific treatment”, unlike other forms.
In this analysis, the validity of the sample results from the protection against “unmeasured cluttering”.
This allows for maximum external validity and does not adjust for non-adherence (Johnston & Guyatt 2016).
It is preferred over other modes of analysis in randomised control trial because of its advantages on external validity (Hollis, Campbell, 1999).
An Explanatory Trial is a clinical trial that tests whether an intervention will have a beneficial effect in an ideal situation (Sedgwick (2014)).
Pragmatic trials are clinical trials that measure the effectiveness of interventions in clinical practice.
Comparison of pragmatic and explicatory trials
Explanatory tests are carried out in large referral-based health centers or in tertiary healthcare.
However, pragmatic trials are performed under real-world conditions.
Explanatory studies are used to determine if a treatment or drug can be effective, while pragmatic trials evaluate if it actually works.
The pragmatic tests, unlike the explanatory trial, do not have strict exclusion criteria.
The latter applies strict eligibility criteria to participants.
Eligibility is limited to patients who are highly responsive, high risk, highly compliant, and highly responsive (Pocock 2013).
However, anyone with a condition of interest can participate in the pragmatic tests.
The instructions for each component of an experimental intervention in the case of explanatory trials are rigid and non-translatable.
The participants and the practising physician are often blind in these trials.
Crossovers are prohibited in these trials.
These pragmatic trials are, on the other hand, used in routine medical care and allow for flexibility.
The trial is not blind and allows crossovers.
Explanatory trials frequently use placebo, with other conditions being the same as experimental.
There is an usual care for this condition in pragmatic trials (Sedgwick 2014).
Explanatory trials employ highly skilled settings and practitioners, whereas pragmatic trials use a full range of practitioners.
Participant compliance with the intervention is monitored closely in the explanatory trial and is required to be admitted into the study.
High compliance is required for both prophylactic strategies as well as rescue strategies.
However, pragmatic trials do not measure compliance (Larson, et al. 2016).
Explanatory trials require that the compliance of practioners to the protocol be closely monitored. If there are any deficiencies, intervention is initiated.
The pragmatic trials do not have such an action (Roland & Torgerson 1998)
Explanatory trials are characterized by frequent follow up and extensive data collection.
Surrogate outcomes are often determined by blinded experts.
Sometimes, the primary analysis might justify exclusion of non-responders.
Practical trials have a standard follow up intensity, and the primary outcome is determined in the regular course of healthcare.
Sedgwick 2014 states that the primary analysis does not alter the intent to treat all patients.
Pragmatic trials have a higher value than those that are explanatory because the results are relevant to patients, health care professionals, funders, communities, and others.
The effectiveness of the trial is not based on placebo-like explanatory.
These trials simulate routine clinical practice.
These results are therefore more applicable to the average patient (Larson, et al. 2016).
In randomised trials, concealing treatment allocation.
Blinding in clinical trials, and other studies.
Modified intention-to treat analysis didn’t bias the trial results.
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What does it mean to intend to treat analysis?
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One of the most important (and often overlooked) practices is intention-to treat, treatment adherence and missing participant outcome information in the nutrition literature.
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Allocation concealment is a potential useful aspect of randomised trials.
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Blinding versus concealment in randomised controlled trial.
Explanatory trials and pragmatic trials.
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