Generating real-world evidence

Conventional randomised controlled trials (RCTs) alone may not provide very good evidence of the relative effectiveness of a new medicine to meet the needs of reimbursement decision-makers. However, it may be possible to generate ‘earlier’ estimates of the relative effectiveness of the new medicine in time to inform reimbursement decision-making, by analysing existing real-world data sources or by conducting new studies to generate real-world evidence (RWE).

For more information about the limitations of RCTs to estimate relative effectiveness, see
What is Real World Evidence? and Effectiveness Issues

For an overview of methods for predicting relative effectiveness in the real world using RCT data, see Methods for Predicting Outcomes

For more information about existing real-world data sources, see Sources of Real World Data

Some types of experimental and observational study design that may be used to provide RWE are summarised in the table below. Not all types of observational study design are suitable for providing direct evidence of elative effectiveness. but they may be useful to help define the disease area of interest, to understand the natural disease progression, or to provide information about a relevant comparator therapy.

The quality and credibility of a study may have an impact on the reported effect of a medicine and its interpretation. So, it is important to assess each study individually, whether or not it is based on a randomised design. See Assuring Quality and Credibility of RWE for more information.

Table. Study designs that may provide RWE

Experimental study designs
Pragmatic RCT A pragmatic trial aims to measure the relative effectiveness of treatments in real-world clinical practice. It combines the strength of RCTs with evidence of the added value of a treatment strategy in routine clinical practice. See Pragmatic Trial
Population enrichment RCT A population enrichment RCT includes patients with characteristics that are typically under-represented or excluded from RCTs. Predictive modelling techniques may be applied to trial data to better estimate relative effectiveness in a real-world population. See Population Enrichment RCT
Cohort multiple RCT (cmRCT) (also known as or trials within cohorts) cmRCTs are a type of pragmatic RCT that use a large cohort of patients as a source of participants for a variety of RCTs, providing a more generalisable study sample. See Cohort Multiple Randomised Controlled Trial
Comprehensive cohort study (CCS) CCS is a type of pragmatic RCT that includes participants who do not consent to be randomised to the treatment group. This facilitates reduction in selection bias and improves the generalisability of study results. See Comprehensive Cohort Study
Cluster RCT Cluster RCTs randomise groups or clusters rather than individual participants as in traditional RCTs. This can reduce the possibility of contamination of the comparator (usual care) group. See Cluster RCT
Non-randomised controlled trial Any experimental study allocating participants to different treatments using a method other than randomisation, such as clinician or patient preference.
Observational study designs
Cohort A cohort study follows a group of individuals over a period of time to consider associations between risk factors, exposures (or interventions received) and outcomes.
Case-control A study that examines associations between outcomes and prior exposures by comparing people with an outcome of interest to those without the outcome. These generally do not give measures of relative risk and so are not used to estimate the relative effectiveness of interventions.
Cross-sectional In a cross-sectional study, data are collected from a population or a representative subset of a population at one specific point of time (or over a short time period) to examine current associations between health status and exposures (use of interventions). The cross-sectional relationships revealed are generally not good evidence of relative effectiveness, which requires longitudinal data.
Case series, interrupted time-series or before-and-after Recorded observations on a series of individuals before and after receiving an intervention.
Controlled before-and-after Similar to a case series, in which observations are recorded on a series of individuals before and after receiving an intervention, but this study design includes a control group.
Case report AA detailed report on an individual patient, typically describing symptoms an unusual or new occurrence, including outcomes after a treatment.