A forum for discussion: "The emergence of regulatory science gave us the opportunity to reach out to others"

RSNN’s unique network of experts from industry, academia, government bodies, and the broader regulatory science field owes much to the vision and work of Christine Gispen-de Wied. She was instrumental in bringing together disparate bodies which had very different priorities.

Gispen-de Wied is very pleased with what the RSNN network has achieved already, and said there is now the potential to achieve much more: “Establishing this network in 2015 was extremely rewarding. We were able to set out a clear vision of what regulatory science can do, and this happened in a historical context where different parties often had competing needs – and where trust could be a barrier to progress. Our work at RSNN has meant that industry, regulators and academia have a forum for informal discussion and planning.”

High profile issues

Some issues were receiving a lot of attention in the media, presenting a major potential barrier to success.  Gispen-de Wied said that there was often an atmosphere of distrust that needed to be addressed: “We faced publicity around drugs being prescribed in ways other than intended, and the holding back of important information, for example in the case of anti-depressant prescriptions in children. At the same time, pharma was continuing to grow, becoming ‘big pharma’. More oversight was needed to restore trust.”

Pharma industry needs also had to be addressed. Regulators were seen in a poor light by companies developing drugs, because the bar was set very high, with too many hurdles to bringing drugs to market. The focus for many bodies involved in drugs research was on things that were going wrong, rather than ways to put them right.

Collaboration and transparency

Gispen-de Wied was at the Medicines Evaluation Board (MEB) over the last 10 years, as regulators opened up to society, and she concentrated on making the environment more transparent: “I started the MEB science program in 2007, which was designed to create close collaboration with university partners in research programs. This resulted in more transparency and dialogue with the outside world. We also started a regulatory science program at the FIGON. From there I was asked to create a network by the FIGON board, and I subsequently started RSNN.”

From data to real-world change

While science is conducted by many bodies and for all kinds of reasons, the priority for regulatory science is the impact that data have on the regulatory process. If everyone is publishing and nobody is interpreting, beneficial outcomes are lost.
So, what are some of the main achievements of regulatory science to date? Gispen-de Wied said that it’s a big question: “We are still seeing our approach being picked up on a relatively small scale, although improvements are continuing. The Escher project is illustrative. For example, we asked to what extent and how drugs with specific cardiotoxicity such as QT prolongation should be monitored throughout their use. QT prolongation (and the risk of heart rhythm disturbance) associated with long-term use of some anti-psychotics led to authorities asking if monitoring for changes via regular EKGs would be productive and cost effective. It turned out that a huge number of EKGs are needed to prevent one adverse outcome, and we have been able to discuss the issue in an ICH (International Council for Harmonisation) context, covering Europe, Japan and the US.”

Future priorities

Revisiting what a clinical end point should be will be an important focus in the future, especially the use of biomarkers as surrogates for the true endpoint – for example, should cancer drugs prolong life, or improve quality of life?

Gispen-de Wied said that data that are not from traditional randomised clinical trials (RCTs) will also be crucial, and not just in fields such as orphan diseases. “Different types of data can be important where RCTs are challenging, including lifecycle monitoring based on Real World Evidence such as data around a patient's wellbeing in real life, using new instruments to measure that. This cuts across all medical disciplines – for example, will drugs that lower blood glucose (anti-diabetics) effectively also prove effective against the development of cardiovascular morbidity? Such questions cannot be solved by RCTs alone, and so we need to look at data in new ways.

What next?

Gispen-de Wied plans to devote some time to education next: “I see myself as a scientist who loves education, and I will be working on language development in children as part of my next phase. Of course I will also be responding to training or advisory requests in the regulatory field – whether in pharma, academia or government.”

RSNN wants to thank Christine for all of her hard work and for her dedication over the last three years – it has been a highly productive period. The Steering Committee position of Vice Chair on behalf of the CBG-MEB will be filled by Peter van Meer.