Question:

1: Define randomisation. Outline the three reasons why randomization is important for designing trials to assess intervention outcomes

2: Define and discuss allocation concealment.

3: Discuss the intent to treat analysis. What makes it superior to other types?

4: Compare, contrast and compare pragmatic and explanatory trials.

Explain why a pragmatic test might be more beneficial than an explanatory one.

Answer to Question: NURSING 746 Evidence-Based Practice And Implementation

Randomised Control Trial participants randomly are assigned to either the control group, which is the group receiving standard treatment, or the treatment under investigation.

This is what we call randomization. It reduces bias and allows the researcher compare the results with the no treatment group, while keeping other variables constant.

It is useful in assessing interventions as it provides information regarding the adverse effects of the treatment, while also eliminating bias in the treatment assignment.

The results of trials can be used as scientific evidence, since they reduce the chance of spurious casualties (Schulz and colleagues 1995).

Randomisation allows for blinding participants, investigators, assessors and others to see the “identity or treatment”.

The concealment of the nature of intervention is important to ensure fair results and limit the chance of contamination (Day & Altman2000).

Randomisation also allows for the application of probability theory.

It suggests that the “differences between the outcomes” of the treated groups is merely an indication of “chance”.

Randomization is an important design element when assessing interventions in trials (Gore, 1981).2.

Allocation concealment is a method of protecting randomization so that patients do not know the identity of the treatment being allocated.

The treatment allocation system is created in such a way that the individual enrolling them does not know which treatment they will receive.

If investigators know about the adverse effects of the intervention, they may reveal the allocation to the assessors. This may lead to bias (Altman & Schulz (2002).

However, allocation concealment is a different concept from blinding.

Blinding trial participants as well as their families, caregivers or adductors, makes it difficult for investigators to discover the treatment identity.

The allocation concealment is only for trial participants. Only the person enrolling them and their families are informed. Blinding stops clinicians treating patients based upon the allocation.

Blinding also helps to prevent observer bias.

Blinding is not a way for assessors and patients to introduce bias when evaluating subjective outcomes.

Patients can’t introduce bias during flow up (Sedgwick (2013)).

Blinding and Allocation concealment differ in that the former ensures that participants are not told their treatment identities before they enroll into the study.

Ruxton, 2017, states that blinding ensures that the physician or patient does not learn the treatment allocation after enrolment in the study.

Allocation concealment prevents selection bias.

Ruxton, 2017 states that this concealment facilitates the “enrolment and comparison of similar participants” in each group.

Blinding or masking has the purpose of preventing biases related performance or attrition.

Blinding facilitates the provision of comparable care and evaluates each participant (Pocock (2013)).3.

Intention to Treat Analysis or ITT is the inclusion of all patients in an analysis who were randomly assigned to the group or enrolled in that group.

This process is intended to prevent different misleading artifacts from occurring in interventional research (Hollis & Campbell, 1999).

The effect of treatment is “offered/assigned” in this way.

In this case, inclusion is made regardless of possible deviations from the randomisation process such as withdrawal or non-compliance.

This analysis is preferred over any other type because it preserves a “prognosis balanced” that was generated by the original random treatment allocation.

This analysis can be used to estimate the effectiveness of real treatment by replicating what is actually happening in actual practice.

This analysis eliminates biases in outcomes and minimizes type one statistical error.

Dossing et.al. (2016) show that the estimates of the treatment effect were more conservative than the PP analysis.

This analysis is much simpler than other forms.

ITT is different from other types of analysis because it provides information about the “potential effects” of treatment policies, rather than the specific treatment.

The protection against “unmeasured conflusion” is another reason for this analysis’s validity.

This method does not adjust to non-adherence and maximizes external validity.

Because of its superior external validity, it’s preferred over other modes of analysis in randomised trials (Hollis & Campbell 1999).4.

Definition

A clinical trial to determine if an intervention is beneficial in a particular situation is called an explanatory trial (Sedgwick & Associates, 2014).

A pragmatic trial (Schulz, 1995) is a clinical trial that measures the effectiveness and extent of an intervention in real clinical practice.

Comparison of pragmatic trials and explanational trials

Explanatory studies are done in large referral-based healthcare centres or in tertiary services.

The pragmatic trials on the other side are conducted in real world conditions.

The pragmatic trials determine if a therapy, or drug, works. Explanatory tests are used to evaluate whether or not a drug or treatment is effective.

The pragmatic trials do not follow the strict exclusion criteria of the explanatory ones.

The former has strict eligibility criteria.

The criteria for eligibility are strict and only high-responsive, high-risk patients with high compliance levels (Pocock, 2013,).

All patients who have the condition of concern can take part in pragmatic tests.

Explanatory trials have rigid instructions and require the intervention to be implemented.

Both the participant and the practitioner are often blind during these trials.

These trials do not allow for crossovers.

The pragmatic trials, which are used in routine health care, allow crossovers to be prohibited.

This trial does not allow for blinding and allows for cross-overs.

Many times, the placebo in comparison trials is used with other conditions that are the same as experimental intervention.

The usual care for this condition is provided in pragmatic trials (Sedgwick 2014.

Explanatory trials require high levels of expertise from the settings and practioners. In pragmatic trials, the full range is available to the practitioners in the setting where successful interventions are applied.

Explanatory trials monitor the compliance of participants to the intervention and are a prerequisite to entry into study.

Both prophylactic and emergency strategies are used to ensure high compliance.

Practical trials are not able to measure compliance (Larson, et al. 2016).

Explanatory trials ensure that practioners follow the protocol strictly and are notified of any deviations.

This is not the case in pragmatic trials (Roland & Torgerson 1998)

Explanatory trials require frequent follow up and extensive data collection.

Sometimes, the primary outcome is determined by blinded specialists. However, there are also surrogate outcomes.

It is possible that the primary analysis will justify exclusion of non-responders.

A pragmatic trial has a regular follow up intensity. The primary outcome is determined in routine healthcare.

Sedgwick 2014 says that the primary analysis is always based on the intention to treat all patients.Usefulness

Pragmatic studies are more effective than explanatory trials, as the outcomes directly relate to patients, healthcare professionals, funders, and the communities.

Because it doesn’t use placebo-like explanations, its effectiveness is assessed.

These conditions are very similar to clinical practice.

Accordingly, these results are more applicable for the average patient (Larson et. al., 2016).

Refer toAltman, D. G., & Schulz, K. F. (2001).

In randomised trials, concealing treatment allocation. Bmj, 323(7310), 446-447.Day, S. J., & Altman, D. G. (2000).

Blinding in clinical studies and other studies. Bmj, 321(7259), 504.Dossing, A., Tarp, S., Furst, D. E., Gluud, C., Wells, G. A., Beyene, J., … & Christensen, R. (2016).

Modified intention–to-treat analysis was not biased in trial results.

Journal of clinical epidemicology, 72.Gore, S. M. (1981).

Assessment of clinical trials-Why randomise?

British medical journal, Clinical research ed. ), 282(6280), 1958.Hollis, S., & Campbell, F. (1999).

What is intention to treat analysis?

Survey of controlled, randomised trials. Bmj, 319(7211), 670-674.Johnston, B. C., & Guyatt, G. H. (2016).

It is important to remember the following best practices: treatment adherence, intention-to–treat, and missing participants outcome data from nutrition literature.

The American Journal of Clinical Nutrition. 104(5). 1197-1201.Larson, E. B., Tachibana, C., Thompson, E., Coronado, G. D., DeBar, L., Dember, L. M., … & Septimus, E. (2016, September).

Trials without trials: Reducing the burden and complexity of practical research on healthcare systems. In Healthcare (Vol. 4, No. 3, pp. 138-141). Elsevier.Paludan-Muller, A., Laursen, D. R. T., & Hrobjartsson, A. (2016).

Mechanisms of bias and direction in randomised clinical trials.

BMC Medical Research Methodology. 16(1):133.Pocock, S. J. (2013).

Clinical trials: A practical approach.

John Wiley & Sons.Roland, M., & Torgerson, D. J. (1998).

Understanding controlled trials. What are pragmatic trials.

BMJ. British Medical Journal. 316(7127), 285.Ruxton, G. D. (2017).

Allocation concealment can be a valuable aspect of randomised experiments.

Behavioral Ecology & Sociobiology. 71(2), 31.Schulz, K. F. (1995).

Subverting randomization for controlled trials Jama, 274(18), 1456-1458.Sedgwick, P. (2013).

Blinding vs. concealment in randomised controlled studies. Bmj, 347, f5518.Sedgwick, P. (2014).

Explanatory trials or pragmatic trials?

BMJ: British Medical Journal. 349.