Blending RWE with RCTs for deeper insights

Increasing patient representation in research

A study by Raynor et al¹ compared real-life sleep clinic OSA patients with those included in RCTs and found that only 1 to 20% of patients in sleep clinics are typically represented in RCTs.

The sleep clinic patients tended to be younger and sleepier, were more likely to be female and were less likely to have established cardiovascular disease compared to the RCT participants.

Unlike in RCTs where patient samples are meticulously selected, RWE analysis focuses on all patients irrespective of any differences. Evaluating data from both forms of research not only encapsulates more patients but also blends theory and practice for a more complete view.

As the broad scope of RWE could potentially skew findings, RWEs often employ a technique called propensity score matching² to counteract selection bias and effectively assess the effect of an intervention. It works by dividing the study population into two groups that share a large number of similar characteristics, reducing the differences between the control group and the intervention group.

The value of long-term trends and subtle correlations

Real-world evidence is often based on the analysis of large volumes of data from large numbers of patients. Gathering equivalent data through an RCT would not generally be feasible due to the time, cost and logistics involved. The large RWE sample sizes can help researchers identify subtle differences between patient groups or confirm trends identified through RCTs.

For example, one study³ analyzed nearly half a million French patients with obstructive sleep apnea (OSA) to understand the role of comorbidities in the termination of PAP therapy. Multivariate analysis showed that patients in certain age groups, female patients and patients with COPD or diabetes had a significantly higher risk of PAP termination, while patients with hypertension were more likely to continue with PAP therapy. Additionally, termination rates were highest in younger and older patients with one or more comorbidities.

Evidence like this could help clinicians better identify the patients who might struggle to comply with therapy and provide them with tailored support so they could remain on therapy and gain the needed benefits.

Complementary data for a more complete picture

In addition to providing useful insights on its own, RWE can complement the findings of RCT by confirming—or even contradicting—those findings.

For example, results from multiple RCTs exploring the effects of PAP treatment on cardiovascular risk and mortality found the use of PAP therapy had no significant impact on cardiovascular disease.^4-6 These same studies have been criticized for their methodology in terms of patient selection and device use.⁷

In contract, multiple studies based on real-world data have shown a positive link between PAP use and reduced mortality.^8-13 One study that gained great attention analyzed 5,138 French patients in the Pays de la Loire cohort. It scrutinized the association between PAP usage, mortality and cardiovascular morbidity and found that better adherence to treatment correlated with improved survival rates. This finding allows clinicians to educate patients about the potential ramifications of inadequate PAP use. The authors of the study suggest that patient support programs could be an effective strategy to boost adherence⁸, enabling them to stay on therapy and achieve the needed benefits.

A new approach to research

The collection and analysis of real-world data to generate real-world evidence is changing the way researchers and clinicians think about and perform scientific research. RWE can provide valuable new insights, bringing details and correlations to light that simply cannot be identified with traditional research.

As a result, the use of RWE is growing rapidly. For example, from 2019 to 2021, the number of Health Technology Assessment (HTA) records where RWE was used almost doubled from 20% to 39%.¹⁴

Nevertheless, real-world data comes from real-world people who require the same level of respect and privacy afforded to participants in clinical trials. Data collection and analysis must be performed to standards that ensure this and the quality and reliability of the resulting RWE. To this end, regulatory bodies in Asia, North America and Europe have issued guidelines on real-world study methods and data quality over the last decade.¹⁵ Privacy regulations like the European GDPR also set high standards for the use and protection of personal and medical data.

More and more, RWE is poised to take its rightful place alongside RCTs and traditional research as a cornerstone of medical knowledge and understanding. As this happens, more and more clinicians and patients can benefit from the expanded, holistic view this combination of research can afford.