Real World Data & Patient Registries
Medical cannabis researchers are still playing catchup as significant barriers and challenges to clinical research still need to be overcome in determining its role in condition-specific guidelines
Dr Simon Erridge | Business Development Director at Sapphire Medical Clinics and Academic Clinician at Imperial College London
Dr Mikael H Sodergren | Research Director at EMMAC Life Sciences, Managing Director & Academic Lead at Sapphire Medical Clinics and Academic Clinician at Imperial College London
Medical cannabis has faced numerous socio-political challenges in both the development of robust research programmes and ultimately acceptance as a potential therapeutic.
Over the early part of the 21st century we have seen a gradual, yet sustained, shift in attitudes towards cannabis globally. This has been achieved largely through patient and public pressure towards therapeutic use exemptions for those chronic health conditions which have benefited from using cannabis in its various forms for improvement of symptoms and quality of life. However, with this changing tide we have also seen the potential list of conditions for which medicinal cannabis may be beneficial grow substantially. Medical cannabis researchers are still playing catchup as significant barriers and challenges to clinical research still need to be overcome in determining its role in condition-specific guidelines. The utilisation of real-world evidence (RWE) derived from data being generated by patients presents an opportunity to accelerate clinical translation and supplement pre-clinical studies and randomised controlled trials, which are still awaited.
What is Real-World Data?
Real-world data (RWD) is defined by the United States Food and Drug Administration as ‘data relating to patient health status and/or the delivery of health care routinely collected from a variety of sources’(1). The European Medical Association however defines it as ‘health care related data that is collected outside of randomised clinical trials’(2). These sources include electronic health records, patient registries, patient-generated health data and insurance claims. RWE is the evidence and insights gained through analysis of this data(1-3).
RWD is generated through traditional clinical practice and outside of the rigid setting of randomised clinical trials (RCTs). It is typically unstructured and requires frameworks, governance and appropriate statistical methodology to derive appropriate outcomes(4). Whilst it is a term that is only recently been established as part of the lexicon for clinical researchers due to support from recent regulator-supported initiatives, it has been an integral part of clinical care for a number of years as part of post-marketing drug safety monitoring(2).
The data available depends greatly upon the source from which it is derived and therefore can give varying insights. It is important therefore that the dataset is appropriately configured to answer the question set out by the researchers. Electronic healthcare records, for example, generate granular healthcare data on individuals which can help determine reasons for specific outcomes. However, they are often specific to individual healthcare settings and not transferrable when patients transfer between care settings(3). Contrastingly patient registries can transfer across settings containing uniformly collected data set (3). The true value of RWD arguably lies in patient generated health data, however. Often clinical research is focused on clinician or researcher designated outcomes of interest, whilst patient generated health data often turns this on its head aiming to collect patient-centric outcomes about the impact of disease and quality of life. This is done through instruments such as validated patient reported outcome measures or performance outcomes which are collected remotely through computers, phones and wearables (3,5,6).
In the absence of readily available data to inform policy and clinical decisions, how can real world data bridge the evidence gap in cannabinoid science and clinical research?
There has been a shift in regulatory agencies’ assessment of RWE with increasing acceptance of its role in enhancing the drug development and approval process(2,3). There is an acknowledgement that drugs, including those outside the field of medical cannabis, may have indications beyond those studied within clinical trials and for which they are already being used in clinical practice(2). In the UK, cannabis-based medicinal products (CBMPs), with a few notable exceptions, are largely used off-license and without the support of National Institute for Health and Care Excellence (NICE) guidance(7). However, prescriptions for CBMPs are continuing to rise, particularly in the private sector(8). Collecting, analysing and interpreting this data will be important to better delineate the role of medical cannabis in each condition for which it is currently prescribed, ultimately reducing improving access and lessening the inequalities currently associated with obtaining a prescription. This data will continue to be important even after appropriate RCTs are performed.
Why is RWD seen as inferior to RCTs, and is such thinking justified?
When considering RWE within traditional hierarchies of evidence, RCTs are the standard bearer against which they are compared(9). However, these hierarchies are not best placed to provide definitive judgement on evidence quality and cannot assess the applicability of trial design to specific patient cohorts or indeed therapeutics. Instead RWE and RCTs should be seen as complementary to one another and assessed on individual study merits. Guidance on CBMPs in clinical practice has typically fallen short in the UK by failing to consider non-RCT evidence.
CBMPs are a complex class of pharmaceuticals which comprise a broad range of active pharmacological ingredients that can be administered either in isolation or in combination compounds and administered via a number of differing routes. The result of a clinical trial for one or two formulations is subsequently inappropriate to extrapolate for the entire class of medications, regardless of a positive or negative result. Continuing to perform RCTs without learning the insights from RWE will only add to the financial and resource waste associated with clinical research(10).
RWE incorporates a broader range of patient and therapeutic factors. They can subsequently be used improve the efficiency of clinical trials by helping define outcomes, inclusion characteristics and treatment. A blended approach whereby clinical trials are embedded within a registry has previously can reduce associated costs to run multiple trials without affecting evidence quality(11). RWE can also be used in novel study designs such as single arm trials with RWD comparators or augmented RCTs, where control arms are filled with RWD to reduce the number of participants that need to be recruited(12). This is particularly beneficial in rare diseases, such as childhood epilepsy syndromes.
Is RWE the future of evidence?
Rather than being the future, it appears as if RWE is the current innovation driving forward clinical research of CBMPs. In the United Kingdom there are two current clinical registries in the form of the UK Medical Cannabis Registry and Project TWENTY21. The UK Medical Cannabis Registry, set up by Sapphire Medical Clinics, is a registry platform which captures pre-clinical characteristics, CBMP preparations and monitors outcomes at distinct time periods through validated patient reported outcome measures and adverse events. The UK Medical Cannabis Registry is not limited by condition, CBMP preparation or time period. Project TWENTY21 by Drug Science aims to recruit 20,000 patients for focused analysis across six specific conditions with medications provided by 5 licensed producers. Initial data analysis is due in 2022(13). In Canada registries have also evolved to study medicinal cannabis patient outcomes in Quebec and Toronto(14,15).
There have been significant barriers in developing research programmes, which have been to the detriment of patients who may otherwise have benefitted from an additional treatment for chronic diseases. RWE presents a meaningful opportunity to improve the quality and timeliness of clinical medical cannabis research. With the correct analysis the data generated through routine clinical care can provide the insights needed to inform clinical trials, licensing arrangements and clinical guidelines. Ultimately RWE helps define a more comprehensive picture of the efficacy and risks associated with medicinal cannabis treatment and is an important component of a national research strategy.