Table 1

Summary of the main types of RWE studies and their key characteristics2 5 10 11

Study type	Design	Conventional uses	Key characteristics compared with RCTs
Non-interventional studies, including pragmatic trials	Prospective or retrospective, non-interventional, observational Includes cohort, cross-sectional and case–control studies	Incidence, cause and prognosis (cohort) Prevalence and cause (cross-sectional) Predictors of outcome (case–control)	Advantages Cohort: important in assessing risk factors where an RCT may be unethical; chronology enables clear distinction between cause and effect; several outcomes may be studied simultaneously; quick and inexpensive. Cross-sectional: most efficient way to determine prevalence; quick and inexpensive; several outcomes may be studied simultaneously. Case–control: case-efficient; useful for studying rare conditions or those with a long latency between exposure and disease; can assess many variables. Disadvantages Cohort: recall bias; inefficient for studying rare outcomes; loss to follow-up can significantly affect outcomes; data quality issues (potential for missing data) especially in retrospective studies; prospective studies with comparator arm may be subject to treatment-allocation bias because of lack of randomisation. Cross-sectional: difficult to clearly distinguish cause and effect; may be inefficient for very rare conditions; uses questionnaires. Case–control: susceptible to sampling bias, observational bias and recall bias; can only assess one outcome; risk of cross-contamination between studies.
Patient registries	Prospective, observational cohort study	Natural history of disease Real-world safety and effectiveness Prognosis and quality of life Quality of care Cost-effectiveness	Advantages Larger and more diverse population; longer follow-up. Few or no required study centre visits, evaluations or procedures. Can identify the most cost-effective treatment approaches. Data are captured in real time. Disadvantages Lack of randomisation means that patient groups may not be comparable; problems of dose adjustment. Data quality issues: potential for missing data; variance in the quality of data between registries, due to differences in audit and control measures. Limits to the amount of data that can be collected. Data may not be collected at fixed time intervals.
Administrative and claims database studies	Retrospective	Longitudinal and cross-sectional analyses of clinical and economic outcomes Natural history of disease Real-world safety and effectiveness	Advantages Very large in size; can be used to identify rare events more easily, assess economic impact of various interventions and gain insight into associations between interventions and outcomes. Quick and inexpensive. Useful in assessing healthcare resource utilisation and costs. Disadvantages Lack of randomisation means patient groups may not be comparable. Data quality issues: missing data; coding errors; inconsistency of coding/outcome definitions between centres or countries. Limited information on health outcomes, health status and symptoms. Limited validation. Disadvantages specific to claims database studies Absence of a population denominator. Patients can switch between insurance companies, which may limit duration of follow-up.
Electronic health record studies	Retrospective, observational, medical record study	Clinical treatments, procedures and outcomes	Advantages Capture real-time clinical treatment, outcomes, techniques and procedures. Can study rare conditions or those with a long latency between exposure and disease. Quick and inexpensive. Disadvantages Requires sophisticated data management and statistical tools. Data quality issues: missing data, recording/coding errors, interpretive or recall biases. Lack of randomisation means patient groups may not be comparable. Typically limited to a small number of study centres.
Patient surveys	Online, interview or paper-based questionnaire	Health status and well-being Patient preferences Healthcare resource utilisation Treatment patterns and expenditure	Advantages Methodologically rigorous in their collection of data. Can provide information on the generalisability of treatments, their impact, healthcare utilisation and costs. Disadvantages Lack of relevant data on specific treatments/products. Recall and subjectivity bias.

RCT, randomised controlled trial; RWE, real-world evidence.