Real-world evidence regulations are on the way

Richard Tadd Blog

The last decade has seen increasing emphasis worldwide on the importance of well-regulated, real-world data collection and analysis as a follow-up to clinical trials for new medicines and medical devices. China is now taking steps to make regulatory changes of its own in this area. On 7 January 2020, the National Medical Products Association (NMPA) released a paper entitled Guiding Principles for Real-World Evidence to Support Drug Development and Review (Trial), which has the potential to bring about significant improvements in the quality and efficiency of the drug development process.

What is real-world evidence?

China clinical trials are producing increasingly high-quality data, but real-world data and the evidence developed from it allow for a more thorough understanding of how drugs impact populations in practice. The key difference between this type of data and clinical research data is that it comes from observations made ‘in the wild’, as it were, with contributions from death registers and organisations such as the China ADR Sentinel Surveillance Alliance (CASSA). Combining this aggregate data with data based on pre-set questions addressed in a clinical context enables researchers to identify any gaps between how a new drug or device was expected to work and how it actually works. This can provide pointers for further research aimed at identifying the factors responsible for those gaps.

What the guidelines do

China’s new guidelines cover a variety of situations but focus primarily on six objectives:

  • Providing evidence that new drugs are safe and effective – establishing the way that treatments work on the different diseases they target, within different demographics, and how accessible they are to end users, as well as identifying any other factors relevant to how they should be regulated and marketed.
  • Providing evidence for changes in drug labelling – where randomised controlled trials are not sufficient to support new indications, real-world evidence may be used to add or modify indications, address changes in dosage, identify new groups suitable for treatment, update safety guidelines and so forth.
  • Provide indicators for any necessary post-marketing requirements or re-evaluations – regulators recognise that even with the high standards now expected of RCT, China clinical trials may not provide enough data to address all concerns about a new product, and real-world evidence can often enable a more comprehensive evaluation of usage in practice, safety and economics.
  • Guiding clinical research design – real-world evidence can provide a useful guide for the design of new clinical trials, for instance by helping to establish optimum sample sizes or inclusion and exclusion criteria, as well as proving useful at the review stage for determining the feasibility of the trial and its likelihood of producing useful results.
  • Refining the positioning of target groups – observing how the therapeutic benefits and side-effects of a product pattern out across different sub-groups within the original target population in the real world, as well as identifying patterns of off-label use and the effects thereof, can make it possible to target a drug more precisely at those patients for whom it is likely to give the best results.
  • Facilitating communication with review agencies – China drug registration is becoming increasingly strict and the use of real-world evidence alongside clinical trial results can be important in getting it approved, as long as the appropriate application has been submitted in advance and effective channels of communication established to support the review process.

The international picture

How does all this fit into the bigger picture? The European Medicines Agency (EMA) first set up a project to improve the collection and synthesis of real-world data in 2013 and is currently working on bringing this up to date through the integration of the opportunities to work with big data that have since been brought about by technological advances. The US Food and Drug Administration (FDA) has been responsible for collecting and analysing real-world data in that country since 2016. The work now being done in China has the advantage of being able to draw on lessons learned from these projects so that the NMPA can put together a more refined model at the outset. Presently, in China medical device registration is being tightened and there has never been a better time to implement real-world evidence into the product licensing review process.

China’s developing real-world evidence regulations will set the standard for the next decade of medical development in the country, and with the government primed to invest heavily in this, we can expect that no stone will be left unturned. This is a country keen to be a world leader in clinical research, and fully regulated real-world data collection and analysis will have an important role to play in that.