Rare diseases are often chronic conditions that begin to manifest during childhood.1 The effects of disease change everything from direct consequences of having the condition to impact on the child’s growth patterns and development, behaviour, psychology, self-worth, and self-belief. All these alongside the untold impact on the families who support them. At the current time, there are very few treatments available for rare conditions, but even with supportive therapies, the earlier that medical and supportive intervention takes place, the bigger the impact because it not only helps to slow the disease but also gives the child the opportunity to mature and integrate into diverse friendship groups for longer. This is why paediatric trials in rare diseases are so important; they help to develop the treatments of the future and by targeting the treatment of pediatric patients, they also provide the chance to live a positive childhood with as much normal development as possible.
Every individual is affected differently by the condition and therefore mainstream trial design, analysis, and real-world data methods are suboptimal. Collaboration between all stakeholders are essential for studies that are feasible to run and treatments that matter most to those who take them.
In this whitepaper, we discuss the complexities of agreeing to the definitions and approaches used to measure trial success, that are meaningful for all involved. Experts might imply we are missing out on the family/patient voice.
Success Means Different Things to Different People
Measure – What to look at and the robust method that is going to be used to record how much the drug is impacting this.
Endpoint – The defined amount of change that tells us whether the drug is working well enough or not.
When combined, these terms help to define what to look for and how to record change, as well as the degree of change that is important.
Trials must characterise both the benefits and risks of a new treatment. Working out what potential benefits are possible and then which are most important to measure is a complicated task. There are many people who have opinions on what should be chosen to study, and what level of change in this is meaningful. These include but are not limited to: (See Figure 1)
Traditionally two main factors have influenced what is chosen. Firstly, giving regulators what they expect to see when they review the drug at the end of development. This is important because if they don’t see something that they believe is valid then the drug will not be approved, and people will not be able to access it. Secondly, what clinical experts state is required to best tackle the disease. Again, this is logical. If the drug is not changing the disease, then it’s not working.
