Natural History Studies and Your Rare Disease Child

Natural History Studies and Your Rare Disease Child

Approximately 50% of rare diseases occur in children. A rare disease may present differently in different children at different ages. The same disease in a 5 year old, may look different in that same child at 10 years old. This is why Natural History Studies are so important.

Natural History Studies enable us to understand the course of a rare disease. For instance, how does it present itself at the outset? What symptoms do patients complain about? What happens to the patient after two years of living with the disease? What happens after five years of living with the disease? Does the disease become worse, or even out in terms of the symptoms?

Many patients with rare diseases suffer for a long time without receiving an accurate diagnosis.  One of the reasons for this is that the course of the disease is not well documented. As a result, the ability to accurately diagnose the disease in relation to the presentation of the disease is poor. This is especially troubling in children. Without an accurate diagnosis, it would not be possible to alleviate the child’s suffering. It would also not be possible to understand the prognosis, and what interventions might be appropriate to slow down the progression of the disease. It would be unethical to give a drug to a child if it would not help them. In this situation, the risks would outweigh the potential for benefit.

Conducting natural history studies in children presents some challenges. There are ethical challenges as well as practical challenges. Within the different age groups of childhood, there are different challenges. A baby is a very different research subject to a teenager. A teenager has to a certain extent learned to think for themselves, although some parents would debate that. They can generally provide feedback about levels of pain, and discomfort during bouts of illness. A baby cannot provide input except by e.g. crying, laughing and other forms of expression that have to be interpreted by a parent, nurse, doctor or carer.

While seeking to understand the natural course of a disease, we have to ensure that we are not denying someone treatment that is already available. This would be unethical. At the same time, we do not want to be studying the course of a disease that has effectively been modified and that does not really reflect the true course of the disease because pharmacological methods are being used to modify it.

How should Natural History studies be designed for children?

  1. They should be designed in such a way that they are not placing stress on the child. We do not want the child to dread the visit to the doctor’s office for the evaluation. That would place an undue level of stress on the child, as well as the parent.
  2. They should not require that the child be denied effective treatment that is currently available. This presents the challenge that any treatments may alter the course of the disease and therefore bias the natural history study.
  3. They should take into account the child’s normal day to day activities. The natural history study should avoid interfering with fun activities that the child wants to take part in. Nursing services that can visit the child in the home to take measurements are invaluable because they can work around the child’s schedule.
  4. Technology should be used where possible to take measurements. Using Apps to collect data from the child directly would be invaluable. For instance, very small children are very tech savvy. They can respond to questions about how they feel on a scale of 1 to 5, especially if pictorial representations and games are incorporated into the App.
  5. A natural history study must be practical. A design that is so onerous that it cannot be conducted is a waste of everyone’s time.
  6. Standardization of data from one natural history study in the same disease to another, would increase the usefulness of the natural history study, and avoid the need to duplicate efforts.
  7. Funding is a tremendous challenge for patient organizations that are interested in setting up natural history studies.
    1. Pharma and biotech companies should find ways to strategically provide small amounts of funding to ensure natural history studies are being conducted in all the 7000 rare diseases that exist.
Putting Rare Diseases Patients First! will be running a free Webinar on 25th February at 8 am PST. The title is Natural History Studies and Your Rare Disease Child. If you have a rare disease or have a child with a rare disease, please feel free to register by clicking onto the following link:




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