Why Real-World Evidence is Key in Medical Cannabis Research

For the last 50 years, randomised controlled trials (RCTs) have been considered the ‘gold standard’ research methodology for measuring the safety and efficacy of new healthcare interventions. 

But experts say that this reliance on RCTs overlooks the value of other approaches which may be better suited to cannabis-based medicines, and is preventing patients from accessing potentially life-changing treatments.

This doesn’t just apply to cannabis-based medicines, but all new healthcare interventions.

Back in 2008, Sir Michael Rawlins, former head of the MHRA and NICE, criticised the regulators’ reliance on RCTs.

“Randomised controlled trials have been put on an undeserved pedestal,” he said. “They should be replaced by a diversity of approaches that involve analysing the totality of the evidence base.”

Real-world evidence (RWE) is collected from everyday clinical practice, through patient registries, electronic health records, and reported outcomes, rather than from trials conducted under tightly controlled settings.

It is typically more cost-effective and allows researchers to collect data on larger sample sizes, over longer periods of time, to get a more accurate understanding of long-term safety and efficacy. It also captures how medicines actually perform across diverse patient populations, including those typically excluded from RCTs, such as patients with multiple health conditions.

However, RWE lacks the robustness of RCTs and factors such as bias, lack of control group and a reliance on patients self-reporting may affect the data quality. 

A growing body of RWE, from the UK and overseas, has linked CBPMs to reduced symptoms and improvements in quality of life across a range of conditions, including anxiety, chronic pain and PTSD.

Researchers, such as Dr Anne Schlag, head of research at Drug Science, say this could help bridge gaps in our understanding of cannabis-based medicines and provide evidence not addressed by RCTs. 

The limitations of RCTs are well documented. As well as being expensive and time-consuming to conduct, they are designed to study one active ingredient to measure its specific effects. This method works well for conventional pharmaceutical drugs, but not for cannabis-based medicines, which contain hundreds of active compounds that may work together in complex ways.

The strict design of RCTs also means many patients are excluded from participating — including those taking multiple medications, people with several chronic conditions, and underrepresented groups such as women and ethnic minorities. 

“RCTs do not lend themselves well to the study of whole plant medicines,” says Dr Schlag, and colleagues, in their 2022 paper, The Value of Real-World Evidence: The Case of Medical Cannabis, challenges the dominance of this research model. 

“In relation to CBMPs, RWE has a broad range of advantages. These include the study of larger groups of patients, the use of a broader range and ratio of components of CBMPs, and the inclusion of more and rarer medical conditions.” 

The UK’s Medicines and Healthcare products Regulatory Agency (MHRA) and the National Institute for Health and Care Excellence (NICE) have both acknowledged the role that RWE can play in improving patient access and guiding clinical decision-making. 

The MHRA has called it a way to “broaden and streamline” the evidence generation process, while NICE acknowledges that real-world data could be used “more routinely” to “fill evidence gaps and speed up patient access”.

Experts including Dr Schlag believe that regulators must start giving “greater weight” to RWE when licensing new medicines.

Findings from real-world data can inform future clinical trials by identifying areas of research and indications worthy of further investigation, potentially reducing the costs and speeding up the process.

Real-world data, they say, should not replace RCTs, but complement them.

Dr Schlag will be presenting her research and discussing the importance of RWE in the study of cannabis-based medicines at Cannabis Health Symposium on Tuesday 25 November.