Once a new drug has been developed, it must be reviewed by both the regulators (for the decision on marketing authorisation) and health technology assessment (HTA) bodies (for the decision on access to patients). The regulators draw on data, mostly from clinical trials, to determine if a drug is safe and works well enough to be authorised for use in patients. For their part, HTA organisations assess more broadly the value of a new drug for a given healthcare system. For this, they need real-world evidence (RWE) to support the assessment of ‘relative effectiveness’: that is the extent to which a treatment does more good than harm when compared to one or more alternative treatments when provided under normal healthcare circumstances.
However, while there are clear, detailed guidelines on how to carry out clinical trials and what is required to achieve marketing authorisation, there is little guidance on how to generate RWE and integrate this into drug development. This is a serious issue: even if a drug is approved as safe and effective by the regulators, insufficient evidence supporting relative effectiveness may delay, or restrict (partially or entirely) patient access to new treatments. The challenge, therefore, is to incorporate relative effectiveness research into the earlier stages of drug research and development. IMI’s GETREAL project set out to bridge that gap.
The project broke ground in that it brought together companies, healthcare decision-makers, patient representatives and other stakeholders to begin to work towards building a consensus on best practices in the use of RWE in drug development, as well as regulatory and reimbursement decision-making. The project developed tools, recommendations and guidance for incorporating RWE earlier in the drug development process.
Getting to grips with RWE: the Navigator tool
One of the main project achievements was the launch of RWE Navigator. This online resource helps users from a broad range of research and healthcare backgrounds get to grips with the need for and the generation of RWE, and understand how this can be used to inform decision-making.
The RWE Navigator is designed to help users from industry define and implement a robust RWE generation plan; HTAs and regulators to better understand the analytical models used; and patients to understand concepts related to RWE and the challenges faced when using or generating RWE. It directs users to the TOOLBOX, which in turn guides them on how to define the attributes of the medicine that may drive a difference in the efficacy seen in a clinical trial setting, compared to the effectiveness when used in routine healthcare (often referred to as the efficacy-effectiveness gap). It also informs users on the specific types of analyses or study designs that can be used to generate or model RWE, including their pros and cons, and includes a comprehensive directory of resources to support users in implementing their RWE generation plans.
Pragmatic trials and the PRAGMAGIC tool
Pragmatic trials offer an opportunity to generate high-quality evidence on relative effectiveness prior to and (soon) after drug launch. However, many people are still reluctant to conduct such studies as they are very challenging to implement and there is some uncertainty regarding the acceptability of pragmatic trial data in decision-making.
In order to aid researchers in pragmatic clinical trial design, the GETREAL project developed an innovative online tool called PRAGMAGIC. It is a decision support tool designed to help users understand how the choices that they make when designing a pragmatic trial can impact the operational feasibility of the study, and how reflective the data generated will be of the effectiveness of the medicine in routine healthcare. The tool draws on guidance and recommendations accumulated through methods reviews, case studies and stakeholder feedback. The project hopes that the new tool will increase the understanding of the value and feasibility of conducting pragmatic trials in the future.
Demystifying relative effectiveness assessments
Both network meta-analysis (NMA) and multi-criteria decision analysis (MCDA) are useful methods for assessing the relative effectiveness of medicines by using data generated from randomised controlled trials. These methods are gaining acceptance among industry, academia, HTA agencies, and regulatory bodies. However, continued efforts are required to embed these approaches in decision-making. To this end, GETREAL developed the ADDIS tool, which provides users access to clinical trial data and the software required to apply NMA and MCDA to the data. Additionally, GETREAL improved the NMA and MCDA methods further by developing a methodology to include real-world data.
Webinars, courses and other achievements
Other important project achievements include:
- An interactive online course entitled ‘Real-world evidence in medicine development’. Under the supervision of leading academics from the project, the course provides students with an understanding of current techniques, opportunities and challenges for the use of real-world evidence in medicine development.
- RWE policy recommendations written by the project’s Policy Expert Group, setting out seven key themes that require further attention to advance the use of RWE and RWD in drug development.
- A network of regulators, HTA organisations, companies, academics, healthcare professionals, patients and other societal stakeholders. This network is important because the challenges faced by the pharmaceutical industry, regulators and other healthcare decision makers are all interlinked.
GETREAL also hosted a series of webinars to support the dissemination of information and organised many cross-sector workshops and events attracting participants from academia, industry, regulatory bodies and patient organisations from across Europe.
For the benefit of industry, academia and SMEs
All of the partners in the project benefitted from the network which was created and collaboration with different stakeholders. This was a unique opportunity for the different stakeholders to share experiences and perspectives in RWE generation and use in decision-making, and all of them will benefit from a greater consensus on the issue.
As the funding for methodology development can be scarce, the academic partners also benefited from IMI funding, which enabled them to drive the development of innovative RWE analytical approaches, published in high-impact journals.
Last but not least, the SME in the project was able to demonstrate their leadership in this field, and had the opportunity to work with leading academics and major pharmaceutical companies who ultimately are their key customers. Through publications and meeting attendance, they were also able to increase their company’s visibility.
GETREAL project partners applied for additional funding through IMI2 - Call 11 for the exploitation of project results. The follow-up project will start in June 2018 and will build on the success of GETREAL. In particular, the follow-up project will be used to continue building the research community, drive forward some of the project’s policy recommendations, and take forward the global debate regarding the opportunities for and the barriers to the use of RWE in healthcare decision-making.
Read the interview with the project coordinator.