PDCO and Industry Working on a New Relationship

Dr. Irja Lutsar Professor of Medical Microbiology, University of Tartu and Member, PDCO discuss the current challenges facing paediatric clinical development , and how PDCO and the industry are working together to overcome them.

How do you feel the industry is responding to changes to the regulatory environment?

I have to say that the industry is responding very well. At the moment, maybe it is too early to say how many plans actually are ongoing right now, as we do not have that data. It is too early to find the publications that have been triggered by the new paediatric regulation, but at least in the paediatric committee we have had a lot of new requests and nicely designed trials. We are hopefully that in a couple of years, we will see much more new paediatric data, especially in pharmacokinetics and pharmacodynamics, and we can prescribe medicines for children in a much more scientific way or thought through way.

How are PDCO addressing the challenges with Paediatric Investigation Plans (PIPs)?

I think that PDCO, as also industry are trying to do their best. Obviously the workload for PDCO at the moment is very high, because everybody is aware that paediatric trials have not been conducted in this intensity. At the moment with PIPs there is a huge volume coming in, and have to admit that there are quality worries. There are some PIPs which are absolutely excellent, and you can have challenging scientific conversation and commentary, and there are other PIPs that are not that good. The industry does not yet have experience on how to fill in a paediatric investigation plan, what is important, what is less important in this plan. PDCO and industry still haven’t developed a well working relationship, but both sides are working on that.   

What would you say are the 3 main difficulties in conducting trials in neonates?

Luckily the number of sick neonates is very small. Most newborn babies worldwide are born healthy and do not need any treatment. This is actually a very fortunate story. That the number of neonates in different diseases is relatively small, and we specifically need the data in premature babies, who weigh sometimes 500-600 grams, and have a very limited amount of blood. We do not know how they react in the brain or to pain, so I think that this is a very vulnerable population. You really you need to go to specialised units to specialised neonatologists, who have experience in conducting clinical trials. I am myself conducting trials in extremely premature babies, most of my time in the clinic, but there is certainly experience in the field needed.

Ethics, with regards to ethics, the better ethics committees have paediatricians in their team. They know paediatric trials can be conducted, and this leads to very fruitful in discussion within the committee, in order to conduct these trials in the most ethical way.

These I would say are the difficulties, the whole concept I sometimes feel. That people think this little baby you can’t do trials on them, but always my answer is if you can’t do the trials how can you give the drugs? In which you don’t know what is the correct dose, what is the correct dosing regiment, what side effects you are supposed to be expecting. So those are the main issues which I feel are important to mention. 

In what ways do you think that we can look to overcome these difficulties, how is the industry addressing these challenges?

I think that it all boils down to the training, and training industry people. Some companies, both large and small have paediatricians in their own teams, and others have very good relationships with societies. For example, the Cystic Fibrosis Society and companies that have new developments in Cystic Fibrosis field have developed very good relationships.

It is learning process at all sides, industry and maybe also at the university level. We have discussed in our university, that maybe we need to teach our students more on evidence-based medicine, not only in paediatrics or paediatric trials, but in general, also in adults. This would involve how to read reports of clinical trials, what clinical trials show us and also what they don’t show. Maybe a new trend in teaching, starting from the undergraduate level. 

What opportunities do you think there are for paediatric clinical development in the next five years?

I think that there are going to be more trials, and I hope very much that people working in academia and industry cooperate to come up with more and better study designs. Where you would need smaller sample sizes and take fewer samples.

I am really looking forward to new statistical methods, new methodologies in the paediatric field, because we cannot over study trials, or not do trials, and we need to come up with the best dosing recommendations for children. However, I am certainly not the best one to b forecasting what is going to happen.

I understand that you will be presenting a case study on Planning and Conducting Clinical Trials in Children with Anti-infective Agents, on the 6th July at Paediatric Clinical Development in London UK. What will be your key take home message?

The main message is how to navigate between regulatory requirements, and the limited amount of children to be included into the trials. I will be talking about how to design the trial, which trials are essential. As I already mentioned, the pharmacokinetic and pharmacodynamic trials are most likely needed in every new agent, but sometimes the efficacy can be extrapolated. I will be most likely be discussing where you can extrapolate efficacy, where you can’t, how big the safety trials should be, and how to plan. I want to share my experience in PDCO, what PDCO is looking for when there is a PIP on anti-infectives.

Interview by Andrea Charles

[inlinead]