Understanding the Challenges of Real Life Research

Pragmatic Trials

Pragmatic trials offer greater external validity than classical RCTS but at the expense of internal validity.
Pragmatic trials still require patient consent, collaboration of ‘trial-minded’ physicians, adherence to a strict trial protocol and treatment plan, and higher than usual monitoring and patient-clinician interaction.
Pragmatic trials do not replace, but rather complement RCTs, by testing a hypothesis in a more naturalistic real life setting.
Some of these limitations can be overcome by observational studies, which allow evaluation of naturalistic outcomes achieved by real life patient populations treated in routine care.

Observational Studies

Many patients with varied, potentially confounding, characteristics may be included in the study.
Lack of randomisation can potentially introduce selection bias and lead to an overestimation of the effects of the treatment.
There may potentially be recall bias; when assessment of treatment exposure and/or outcomes depends on patients’ or caregivers’ recall.
Quality standards for real-world research are still being refined.
High-quality, well-designed observational studies define a priori the hypothesis, objectives, patient cohort, analysis plan, and outcomes, resulting in useful hypothesis testing.
Statistical techniques can minimise this bias, including adjusted analyses and matching processes. Further subgroup analyses can be carried out.
This bias is minimised by the use of prospectively recorded databases instead of clinical observation. We have access to global databases such as the CPRD and OPCRD. ↗
Several checklists have been published to establish quality standards for real world research, such as that published by the Respiratory Effectiveness Group. ↗